Course Instructors: Dr. Francis, Dr. Wolf and Dr.

Bautista

PASS PROGRAM
USMLE REVIEW STEPS 1, 2 AND 3
Course Instructors: Dr. Francis, Dr. Wolfe & Dr. Bautista
Lecture

Page

Note Pages

Welcome to the Program

45

Low Energy State

53

Vitamins, Minerals, Trace Elements

55

Cellular Physiology

64

Membrane Physiology

71

Inflamation

76

Electrolyte Physiology

80

Pulmonary Physiology

87

Neuromuscular Physiology

105

Vascular Physiology

116

Cardiac Physiology

125

Gastrointestinal Physiology (GI)

135

Endocrinology

159

Rheumatology

171

Reproductive Endocrinology

184

Renal Physiology

192

Nephritic-Nephrotic

218

Neurophysiology

220

Hematology

238

Hemostasis

244

Lymphoma & Leukemia

248

Biochemistry

251

Amino Acids

254

Protein Structure and Function

262

Enzymes

277

Anabolic Pathways

282

Catabolic Pathways

292

Cancers

303

Immunology

329

Immunodeficiencies

335

Leukocytes

344

Lymphocytes

351

Granulocytes

358

The Four Hypersensitivities

366

Antibiotics

369

Microbiology

371

Viruses

408

Note Pages

413

Obstectrics and Gynecology

453

Surgery & Trauma (Dr. Cordova)

477

Antibiotics (Dr. Cordova)

Biochemistry, Glycolysis,
Gluconeogenesis & TCA

497
515

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4/30/2008

Making the most

out of your time
here at the PASS
program !!!

Study smart
not hard

NBME- National Board

of Medical Examiners

Power is in
g !
knowledge

For
profit
company
NBME- National
Board
of Medical Examiners

What do you want to do when

you finish medical school?

Shortage of family
doctors throughout
US

Youre the next cutting edge

physician
20,000 new residents
Your p
pay?
y
Radiology, Dermatology,
Ortho.

Shortage of OB/GYN
physicians
p
y
in Fl,
Texas, California, and
Michigan

Those making decisions,

control how many come
across the bridge

Cutoff for USMLE

Steps were raised
from 182 to 185?

45

4/30/2008

How do they comprise a test

that is written for you to fail?

Why do so many fail the

test?

A physician sits and writes a question based

off of the discipline they want to test you on

ZOO
THEORY

A psychologists
h l i t rewords
d th
the question
ti th
the way
your mind thinks
This is why the wrong answers always look
good

55 PASS
PASS rules
rules in
in answering
answering
question
question

A 38 y/o woman has congestive heart failure,

premature ventricular contractions and
repeated episodes of ventricular tachycardia.
Her blood pressure is normal and there are no
murmurs. Her heart is markedly enlarged.
Coronary angiography shows no abnormalities.

1.
1. Cover
Coverthe
theanswers
answers
2. Read the last sentence and decide if it is
2. Read the last sentence and decide if
a clue or concept question
it is a
clue or concept
3. Read the vignette, and isolate the facts
question
of the vignette
3. Comprise
Read the
vignette,
and isolate the
4.
a thought
process
facts
the click vignette
5.
Lookof
down,
and move !!!!!!!

Which of the following is the

most likely diagnosis ?

4. Comprise a thought process

5. Look down, click and move !!!!!!!

[Link] rheumatic fever

[Link] fibroelastosis
[Link] pericarditis
[Link] infarction
[Link] cardiomyopathy

[Link] rheumatic fever

[Link] fibroelastosis
[Link] pericarditis
[Link] infarction
[Link] cardiomyopathy

46

4/30/2008

A 23 y/o man who is HIV positive has a 2 week

history of midsternal chest pain that is aggravated
by eating spicy foods; the pain is unrelated to
exertion or position and he reports no dysphagia.
Treatment with H2 receptor blocking agents has
provided no relief. He takes clotrimazole for
thrush and zidovudine ((AZT).
) He has a CD4+ T
lymphocyte count of 220/mm3 (N>500).

USMLE Step 2 and Step 3 approach

What is the next best step in management?

Is the patient stable? (based on hemodynamics)

- Unstable: ABCs
- Stable: read the vignette
Do you have enough information to make a
definitive diagnosis?
- Yes- treat
- No- order a test (BLIS)
blood/labs/image/surgery

Which of the following is the most

appropriate next step in
management?

[Link] trial of acyclovir

B.24 Hour pH probe
[Link] perfusion test
[Link] manometry
[Link]

[Link] trial of acyclovir

B.24 Hour pH probe
[Link] perfusion test
[Link] manometry
[Link]

Procrastination in doing
questions

Procrastination in doing questions

How many read all the choices
in the explanation?

How many read before doing

questions?
Wh t are you ttesting
What
ti ?
2 weeks later, what
happens?

Prior exposure to future

f
questions
I have a lot of
details in my head

47

4/30/2008

Its ok to be wrong !!!!

Procrastination in doing
questions

Block of 50 question and get

45/50 correct, are you any more
prepared for the boards from the
moment you started that test?

How many do the questions

in tutor mode?

If you get 30 /50 wrong, you will

not be very happy

Driving a car
and lost

Found a hole, that can be fixed

Remember every time you fall

Why do we not listen to our first

thought?

My friends told me to do as
many questions as I can
before I take the test

We are scared of being wrong

6000 questions
Multiple banks
You are doing questions to learn
from them
Do we order test to learn about a
pathology
(i.e. Hypothyroidism TSH panel)

We do not want our over all

average to be lower than the mean

3 steps to studying:
1. Obtain the information
2. Questions
3. Results of the bank

Questions: Organ
50 question

What bank to use?

Q-Bank

USMLE Rx.

USMLEworld

system based

Do they ask you 50 new things?

Do you see a pattern?

Pathological presentation does not

change, just the story line (clues are
so important)

At the end of your first week,

you will be evaluated by several
tutors to determine which is the
best test bank for you to use.

Will you see the pattern in mixed

blocks?

48

4/30/2008

What do most students do

What should I do, with the

results of my question bank?

Vignette.. Downs syndrome

Answer: Endocardial cushion defect

50 questions completed
(what is right or wrong)

Example: Polyhydramnios: Down syndrome

What is the most common cardiac
abnormality?
Write the subject matter
Look for patterns in the question
This is what you will read about

Read about it from the author

Transcribe to note cards on ECD
Read the notes about ECD
Read the CMDT about ECD
Harrisons and read about ECD

Are you any more prepared for

Downs syndrome on the boards?

NBME practice exam

Not enough time in the day !!!!!!!

- Exercise
- 210 score
- Proper sleep hygiene
-Take time out to
reward yourself

On line at [Link]
Step 1 5 forms (do not take form 3)
Step 2 3 forms
Step 3 1 form

When should I take

may NBME ?

Tutoring:

PASS program clues vs. class notes

This is your time to ask questions that

you may have with the material

You should drill the PP-clues with a

partner for at least 1 hour a night.
( hour new, hour random review)

Do questions with your tutor (remember

its ok to be wrong)

Caution in drilling class notes:

Teacher vs. Student

Your tutor is there to help

you find and fix your weakness

49

4/30/2008

Tutoring cont.
Try several tutors to find the chemistry that
works for you
If you can not make it to your secession, please
inform your tutor, so they can fill the spot with
another student
Once you are comfortable with a
couple of tutors, there is a request
book in the back.
(The key word, just a request book)

50

Physiology:
Weeks One & Two

51 51

52 52

WHO USES ENERGY?

INTRODUCTION: THE MOST

POWERFUL CONCEPT IN
MEDICINE

THE LOW ENERGY STATE

BRAIN
MUSCLES
PRIMARY ACTIVE TRANSPORT
HEART
MEMBRANE MOVEMENT

RAPIDLY DIVIDING CELLS

SKIN
HAIR
GI
RESPIRATORY
RENAL(PCT)
BLADDER
ENDOMETRIUM
ENDOTHELIUM
BREASTS
SPERM
GERM CELLS
CUTICLES
BONE MARROW
RED BLOOD CELLS
WHITE BLOOD CELLS
PLATELETS

SIGNS OF DISEASE: WHAT YOU

PRESENTATION OF A DISEASE

CAN SEE

When it bothers the patient enough, he or

she will see the doctor as soon as possible

TACHYPNEA and DYSPNEA

Weakness so that the patient can not go to

work
Shortness of breath scares people; they think
they might die

SYMPTOMS: THE PATIENTS

MOST COMMON INFECTIONS

COMPLAINTS
WEAKNESS
SHORTNESS OF BREATH

PULMONARY INFECTIONS
URINARY TRACT INFECTIONS

1
53 53

OTHER COMPLICATIONS

COMPLICATIONS, cont
Endothelium atrophic
Endometrium
atrophic
Breasts atrophic
Sperm count low
GI nausea, vomiting
and diarrhea
Renal- PCT shuts
down

Dry skin
Hair dry and brittle
Nails brittle
Bone marrow suppressed
Anemia
Leukopenia
Thrombocytopenia

Bladder atrophic;
leads to UTIs
Respiratory weak
cough > infections
Germ cells unable to
replicate > leads to
skin and GI cancers
CNS: MR (children)
and dementia (adults)
CV heart failure

ANYTIME YOU CAN CONNECT TO THE LOW

ENERGY STATE
APPLY THE ENTIRE CONCEPT
THIS ACCOUNTS FOR
APPROXIMATELY 98% OF ILLNESSES
WHENEVER IN DOUBT > ASSUME IT IS
A LOW ENERGY STATE

MOST COMMON CAUSE OF DEATH?

HEART FAILURE!!!

STOP GUESSING!!!

2
54 54

Vitamin A
A cofactor for PTH
Necessary for CSF production
Used for epithelial maturation, especially
hair, skin, and eyes
Most unique function is night vision
A mild antioxidant

VITAMINS, MINERALS and

TRACE ELEMENTS
THE BEGINNING

Vitamin A deficiency

Vitamin A excess

Poor night vision

Decreased CSF production: asymptomatic
Hypoparathyroidism
Epithelial cells fail to mature

Pseudotumor cerebri: excess CSF

production
Hyperparathyroidism: moans, groans,bones
and stones

Vitamin B1: Thiamine

Pseudotumor Cerebri
Sign: papilledema
Symptom: headache
Evaluation: CT scan ( shows enlarged
ventricles)
Treatment: d/c vitamin A; serial LPs (30cc at a
time)
Main complication: blindness
This is the only cause of increased ICP where
you dont have to worry about herniation

Necessary for four important enzymes:

Pyruvate dehydrogenase
Alpha-ketogluterate dehydrogenase
Branched chain amino acid dehydrogenase
Transketolase

55 55

Vitamin B2: Riboflavin

Thiamine Deficiency
Beriberi

Used in cofactors ( FAD)

Best source is milk
Sunlight breaks riboflavin down

Dry beriberi
Wet beriberi

Wernickes Encephalopathy
Receptive aphasia

Wernicke-Korsakoff syndrome
Mamillary bodies now also involved
Confabulation
Inability to move short-term memory to long-term
memory

Vitamin B3: Niacin

Riboflavin deficiency
Angular Cheilosis

Necessary for cofactors ( NAD, NADH,

NADP, NADPH)
Needed by pyruvate dehydrogenase,
alpha-ketogluterate dehydrogenase, and
branched chain amino acid
dehydrogenase

Vitamin B4: Lipoic acid

Niacin deficiency
Pallegra : 4 Ds diarrhea, dermatitis,
dimentia and death
Hatnups disease: presents just like pallegra

Needed by pyruvate dehydrogenase,

alpha-ketogluterate dehydrogenase, and
branched chain amino acid
dehydrogenase

Defective renal transport of tryptophan

No deficiency state

56 56

Vitamin B5: Panthotenic Acid

Vitamin B6: Pyridoxine

Needed by all transaminases
INH pulls pyridoxine out of the body
Forms the cofactor pyridoxalphosphate

Needed by pyruvate dehydrogenase,

dehydrogenase, alpha-ketogluterate
dehydrogenase, and branched chain
amino acid dehydrogenase
No deficiency state

Vitamin B9: Folate

Pyridoxine deficiency
neuropathy

The first vitamin to run out whenever you

have rapidly dividing cells
Used to make tetrahydrofolate (THF) from
which you make nucleotides

Vitamin B12: Cyanocobalamin

Folate deficiency

Megaloblastic anemia
Hypersegmented neutrophils
Neural tube defects in fetuses
Mcc: overcooked vegetables

Needed by two enzymes:

Homocysteine methyltransferase
Methylmalonyl-CoA mutase

Used to make tetrahydrofolate

Used to recycle odd-numbered carbon
fatty acids

57 57

Vitamin B12 deficiency

Vitamin C

Megaloblastic anemia
Hypersegmented neutrophils
Neuropathy, especially involving the dorsal
column pathways and corticospinal tracts
Mcc: pernicious anemia (type A gastritis)

Used for hydroxylation

Hydroxylates proline and lysine in collagen
and elastin
Main antioxidant in the GI system

Vitamin C deficiency

Vitamin D

Scurvy
Bleeding from hair follicles and gums

Necessary for bone and teeth formation

Stimulates osteoblastic activity
Stimulates calcium AND phosphorous
absorption and reabsorption
Mineralizes bones and teeth

Vitamin E

Vitamin D deficiency
Rickets: in children
Lateral bowing of the legs
Osteomalacia: in adults

The main antioxidant in your blood

Absorbs free radicals

Vitamin D resistant rickets

Defective renal reabsorption of phosphorous
As phosphorous leaks out, it pulls calcium
with it

58 58

Diseases involving oxidation

Antioxidants

Cancer
Alzheimers disease
Coronary artery disease
Hemolytic anemia ( esp. G6PD)

Biotin

Vitamin E: in blood
Vitamin C: in GI tract
Vitamin A
Beta-Carotene

Biotin deficiency

Necessary for carboxylation

Many carboxylases would lose their

function

Vitamin K

Warfarin

Needed for gamma-carboxylation

Adds a third (gamma) carboxyl group to
the vitamin k dependent clotting factors

Clotting factors II, VII, IX, X, Protein C &

Protein S
Protein C has shortest half life, followed by
factor VII

59 59

Competitive inhibitor of vitamin K

Given orally
Always give heparin first
Crosses the placenta
Teratogenic
Follow PT ( prothrombin time )
INR 2 to 3x normal

Heparin

What are germs good for?

Acts as a cofactor for antithrombin III

Blocks thrombin, as well as clotting factors
IX, X, XI, and XII
Follow by measuring PTT ( INR 2 3X NL)
To reverse the action: protamine sulphate
If patient acutely bleeding: give FFP to
reverse immediately

MINERALS

Vitamins related to gut flora

They make: 90% of vitamin K
Biotin
Folate
Panthotenic acid

They help absorb

Vitamin B12

Calcium

Minerals

Intracellular calcium needed for all muscle

contraction
Smooth muscle uses extracellular calcium
for second messenger systems
Atrium is ONLY membrane that uses
calcium to depolarize
Cardiac ventricle depends on extracellular
calcium to trigger off its intracellular
calcium release

Calcium
Magnesium
Zinc
Copper
Iron

60 60

Magnesium

Calcium, cont
Used for axonal transport
Presynaptic influx of calcium necessary for
release of ALL neurotransmitters
Needed for normal bone and teeth
development

A cofactor for ALL kinases

A cofactor for PTH
Interacts with potassium as well, but
location currently unknown

Zinc

Copper

Needed by hair, skin, sperm and taste

buds

Needed by lysine hydroxylase in the

formation of collagen
Also needed by complex IV of electron
transport system

Zinc deficiency: dysguisia

Movement disorder in a middleaged person

Copper excess
Wilsons disease

HUNTINGTONS
DISEASE (90%)

Autosomal recessive
Ceruloplasmin deficiency
Copper deposition in lenticular nucleus (basal
ganglia), iris (Kayser-Fleischer rings) and in
the liver (causing cirrhosis)
Tx: penicillamine

Autosomal dominant
Trinucleotide repeats
Involves caudate
nucleus
Has anticipation
Treat with
antipsychotics
Mcc of death: suicide

61 61

WILSONS DISEASE
Autosomal recessive
Ceruloplasmin def
Copper deposition in
lenticular nucleus, liver
and iris
Treat: penicillamine

Trinucleotide repeats

Iron

Huntingtons disease
Fragile X
Fredriecks ataxia
Prader Willi syndrome
Myotonic dystrophy

Needed for formation of heme and

hemoglobin
Ferrous iron binds oxygen
Needed by complex III and IV of electron
transport system

And finally the trace elements

Trace Elements

Chromium

Chromium
Selenium
Molebdenum
Manganese
Tin
Flouride

Selenium

Enhances insulin action

Def: causes diabetes

Needed primarily by the heart

Excess: breath smells like garlic ( arsenic
as well)
Def: dilated cardiomyopathy

62 62

Molebdenum and Manganese

Tin

Needed by many enzymes in glycolysis

Xanthine oxidase: needs both elements

Needed for hair growth

Flouride
Needed for teeth and bone growth
Excess: blocks enolase of glycolysis

THE END
BUT, it is really the beginning

63 63

CELLULAR PHYSIOLOGY
CELL ORGANELLS

NECROSIS

IRREVERSIBLE CELLULAR INJURY

APOPTOSIS

NECROSIS

CELL MEMBRANE
DISSOLVES FIRST
PROGRAMMED CELL
DEATH
NONINFLAMMATORY

NUCLEUS
DISSOLVES FIRST
UNEXPECTED
INVOLVES
INFLAMMATION

PYKNOSIS
KARYORHEXXIS
KARYOLYSIS

PYKNOSIS
KARYORHEXXIS
KARYOLYSIS

NECROSIS

ISCHEMIC(COAGULATIVE)
PURULENT
GRANULOMATOUS
FIBRINOUS
CASEOUS
FAT
HEMORRHAGIC
LIQUEFACTIVE

NECROSIS

ISCHEMIC(COAGULATIVE)
PURULENT
GRANULOMATOUS
FIBRINOUS
CASEOUS
FAT
HEMORRHAGIC
LIQUEFACTIVE

64 64

ISCHEMIC(COAGULATIVE)
PURULENT
GRANULOMATOUS
FIBRINOUS
CASEOUS
FAT
HEMORRHAGIC
LIQUEFACTIVE

NECROSIS

NECROSIS

ISCHEMIC(COAGULATIVE)
PURULENT
GRANULOMATOUS
FIBRINOUS
CASEOUS
FAT
HEMORRHAGIC
LIQUEFACTIVE

NECROSIS

NECROSIS

ISCHEMIC(COAGULATIVE)
PURULENT
GRANULOMATOUS
FIBRINOUS
CASEOUS
FAT
HEMORRHAGIC
LIQUEFACTIVE

ISCHEMIC(COAGULATIVE)
PURULENT
GRANULOMATOUS
FIBRINOUS
CASEOUS
FAT
HEMORRHAGIC
LIQUEFACTIVE

MESS WITH THE

CHROMOSOMES

NECROSIS

ISCHEMIC(COAGULATIVE)
PURULENT
GRANULOMATOUS
FIBRINOUS
CASEOUS
FAT
HEMORRHAGIC
LIQUEFACTIVE

ISCHEMIC(COAGULATIVE)
PURULENT
GRANULOMATOUS
FIBRINOUS
CASEOUS
FAT
HEMORRHAGIC
LIQUEFACTIVE

MONOSOMIES: DIE! DIE! DIE!

MCC: NONDISJUNCTION
90% IN DAD, USUALLY IN MEIOSIS 1; BUT
SPERM DIE ON A DAILY BASIS
FEWER OCCUR IN MOM; BUT MOM KEEPS
HER EGGS FOR LIFE AND IS THEREFORE
MORE LIKELY TO TRANSMIT HERS
IF ONE WERE TO SURVIVE TO BE BORN, IN
THE LEAST, THINGS WILL NOT GROW

65 65

TURNER SYNDROME

WEBBED NECK
CYSTIC HYGROMA
GONADAL STREAKS
SHIELD-SHAPED CHEST
COARCTATION OF AORTA

TRISOMIES

TRISOMIES
TRISOMIE 18: EDWARDS SYNDROME

DIE! DIE!
FEW LIVE
TRISOMIE 13: PATAU SYNDROME

ROCKERBOTTOM FEET (IN 95%)

POLYDACTYLY
PALATE IS HIGH-ARCHED
PEE-ING SYSTEM ABNORMALITY

TRISOMIES

DOWNS SYNDROME

TRISOMIE 21: DOWNS SYNDROME

MENTAL RETARDATION 100%

IQ: AVERAGE IS 85 TO 100 WITH A STANDARD
DEVIATION OF 15
SUPERIOR INTELLIGENCE: IQ > 130
MILD MR: IQ < 70
MODERATE MR: IQ < 55
SEVERE MR: IQ < 40
PROFOUND MR: IQ < 25 NEEDS 24HR CARE
MILD TO MODERATE MR CAN BE TAUGHT BASIC
ADLS

MCC: NONDISJUNCTION
ROBERTSONIAN TRANSLOCATION:
HIGHEST INCIDENCE (33% OF
OFFSPRING)
HAS MANY THINGS TO CONSIDER

66 66

DOWNS SYNDROME
EARLY-ONSET ALZHEIMER DISEASE
HIGHER FREQUENCY OF AML;BUT ALL IS THE
MOST COMMON LEUKEMIA
20 TO 40% HAVE congenital heart
DISEASE
-ENDOCARDIAL CUSHION DEFECTS
VSD and ASD
VSD
ASD

DOWNS SYNDROME

DOWNS SYNDROME

CYANOTIC CONGENITAL HEART

DISEASE

TRANSPOSITION OF GREAT ARTERIES

TETROLOGY OF FALOT

50% HAVE HYPOTHYROIDISM

WIDELY-PACED CRANIAL SUTURES
MACROGLOSSIA
DUODENAL ATRESIA
HIRSCHSPRUNGS DISEASE
CLUES:
MONGLIAN SLANT TO EYES
WIDELY SPACED FIRST AND SECOND TOES
SIMIAN CREASE

Chemotherapy

TRISOMIES
XXX: Normal female; has two barr bodies
XXY: Klinefelters syndrome. Tall male
with gynecomastia, small penis and
testicles
X- Fragile X syndrome
Mcc of chromosomal induced MR
Short stature; macrochordism
Collagen disorder (increased risk of MVP)
Isolated using the drug METHOTREXATE

67 67

ANTIMETABOLITES

CHEMOTHERAPY

ARA-A
ARA-C
5-FU: blocks thymidylate synthetase
6-MERCAPTOPURINE: promotes gout; recognized by
xanthine oxidase
THIOGUANINE
METHOTREXATE: inhibits dihydrofolate reductase(as
does TRIMETHOPRIM and PYREMETHAMINE)

Stops rapidly dividing cells

Attacks the nucleus in some way
Causes irreversible cellular death
WILL kill some patients
No such thing as safe chemo

Most commonly used antimetabolite

Used to treat molar pregnancies
Used to treat STEROID RESISTANT disease( followed by
AZOTHIOPRINE and CYCLOSPORINE)

ANTIMETABOLITES

ANTIMETABOLITES

METHOTREXATE

AZOTHIOPRINE

Causes folate deficiency and megaloblastic

anemia
Give LEUCOVORIN > FOLINIC ACID to
prevent the anemia

Used for steroid resistant diseases( behind

METHOTREXATE and before
CYCLOSPORINE)

ALKYLATING AGENTS

ALKYLATING AGENTS

Bind to double stranded DNA

Used primarily for slow growing cancers
Cause the most nausea and vomiting
ONDANSETRON: serotonin blocker used to treat
nausea and vomiting in chemotherapy

68 68

Bleomycin
Busulphan
Adriamycin
Cisplatnin
Cyclophosphamide
Isophosphamide
Mitomycin
Antimycin
Acridine dyes

Hydroxyurea
Melphalan
Mechlorethamine
Procarbazine
Dacarbazine
Chlorambucil

FOR RESCUES
Desroxzasane
Mesna

MICROTUBULE INHIBITORS

NUTRIENT DEPLETION

Vinblastine
Vincristine
Paclitaxel

L-ASPARAGINASE

IMMUNEMODULATORS
LEVAMISOLE

IRREVERSIBLE CELLULAR
DEATH
NUCLEAR DAMAGE
LYSOSOMAL DAMAGE
MITOCHONDRIAL DAMAGE
OCCURS IN 6 HOURS in all tissues

69 69

IRREVERSIBLE CELLULAR
DEATH

IRREVERSIBLE CELLULAR
DEATH

NUCLEAR DAMAGE
LYSOSOMAL DAMAGE
MITOCHONDRIAL DAMAGE

OCCURS IN 20 MINUTES IN THE

OCCURS IN 6 HOURS in all tissues

except the brain

The End?
To Be Continued

70 70

BRAIN

WHAT A MEMBRANE DOES

PROVIDE SHAPE
AMPHIPATHIC

MEMBRANE PHYSIOLOGY

HYDROPHILIC and HYDROPHOBIC

WATER SOLUBLE and FAT SOLUBLE
HYDROPHOBIC wants to be INSIDE away from
water
HYDROPHILIC wants to be OUTSIDE in contact
with water

A MEMBRANES JOB IS NEVER

DONE

FAT SOLUBLE COMPOUNDS

STEROID HORMONES

DO NOT interact with the outer cell

membrane. They go right through and
head for the nucleus
HAVE NUCLEAR MEMBRANE
RECEPTORS
Concentration gradient is only limiting
factor

MADE FROM CHOLESTEROL

FAT SOLUBLE( hydrophobic)
Do NOT interact with cell membrane
ALL have a nuclear membrane receptor
except CORTISOL
CORTISOL has a cytoplasmic receptor;
but it still translocates to the nuclear
membrane

71 71

WATER SOLUBLE COMPOUNDS

Factors affecting diffusion

WATER SOLUBLE HORMONES

HYDROPHILIC
CAN NOT simply go through a fat soluble
membrane
Must bind to the outside membrane to a
receptor
Requires a SECOND MESSENGER
But first, what about ANY water soluble
compound?

CONCENTRATION GRADIENT
SIZE of molecule
Net charge on molecule
pH (affects the net charge of a molecule)
THICKNESS of membrane
SURFACE AREA of membrane
FLUX (dx/dt)
REFLECTION COEFFICIENT
NUMBER OF PARTICLES RETURNED / NUMBER
OF PARTICLES SENT TO MEMBRANE

FICKS EQUATION

OTHER FUNCTIONS OF A
MEMBRANE

Factors that FAVOR diffusion go in the

NUMERATOR
Factors that NEGATIVELY affect diffusion
go in the DENOMINATOR

CREATE and MAINTAIN concentration

gradients
SELECTIVE permeability
Has SATURATED fats( no double bonds)
Has UNSATURATED fats( double bonds)
Easier to break down
Better temperature regulation
More fluidity of movement, especially lateral

ESSENTIAL FATS

OTHER MEMBRANE FUNCTIONS

Can get them ONLY through the diet

LINOLENIC
LINOLEIC

PHAGOCYTOSIS: requires energy

ENDOCYTOSIS: primarily for nutrition
EXOCYTOSIS: primarily for getting rid of
waste products ( i.e. lipofuscin )
PINOCYTOSIS: for movement of fluids and
electrolytes

Used to make ARACHADONIC ACID

Arachadonic acid becomes essential if linoleic
acid is missing from the diet

SKIN is only organ that does this process

72 72

OTHER MEMBRANE FUNCTIONS

OTHER MEMBRANE FUNCTIONS

TEMPERATURE REGULATION

ALL membranes can depolarize

Resting membrane potentials

RADIATION > concentration gradient

CONDUCTION > requires contact
CONVECTION > movement of environment
drags heat out of the body

ELECTROLYTE MOVEMENT

CONCENTRATION GRADIENT
ELECTRICAL GRADIENT
DRIVING FORCE
NERNST NUMBER (E-ion)
CONDUCTANCE (G-ion)
PERMEABILITY
CHANNELS: small ions
PORES: medium-sized molecules (sweat)
TRANSPORT PROTEINS

TRANSPORT PROTEINS

SECOND MESSENGERS

PRIMARY ACTIVE TRANSPORT

>requires an ATPase. Going against a
gradient
SECONDARY ACTIVE TRANSPORT

C-amp > most common second messenger

Requires sodiums gradient

SYNPORT or COTRANSPORT >moving in
the same direction as sodium
ANTIPORT > movement in opposite direction
as sodium

73 73

PHOSPHODIESTERASE INHIBITORS

SECOND MESSENGERS, cont

CAFFIENE
THEOPHYLLINE

IP3 -DAG

SILDENAFIL
VARDENAFIL
TADALAFIL

IP3-DAG SYSTEM

CALCIUM CALMODULIN SYSTEM

All HYPOTHALAMIC HORMONES, except

CRH
All SMOOOTH MUSCLE CONTRACTION
by hormone or neurotransmitter

4 calcium molecules: 1 calmodulin

All SMOOTH MUSCLE CONTRACTION
by DISTENTION

CALCIUM

TYROSINE KINASE

Used as a second messenger by

GASTRIN only

INSULIN and all GROWTH FACTORS

74 74

NITRIC OXIDE

NITRATES

NITRIC OXIDE > GUANYLATE CYCLASE

> elevates c-GMP

VASODILATORS
TACHYPHYLAXIS; rapid tolerance

NITRATES
ENDOTOXIN
ANP

Nitroglycerin
Dinilatrate
Sodium Nitroprusside

The End
Insane in the membrane

75 75

INFLAMMATION

SHUTTING DOWN THE Na-K ATPase

Potassium still leaks out
Cell becomes more negative > less likely
to depolarize

EKG CHANGES

SHUTTING DOWN THE Na-K ATPase, cont

With Na trapped within the cell, calcium
also gets trapped within the cell

Na-K ATPase shuts down when a vessel

is 70% stenosed
Potassium leaks out, making cells more
negative
This is why you get ST-wave
DEPRESSION

This increases contractility

DIGITALIS
DIGITOXIN
OUBAIN

ST-WAVE DEPRESSION

FOLLOW-UP FOR ANGINA

Early ischemia
70% stenosis
SYMPTOMS BEGIN
Subendocardial ischemia
STABLE ANGINA

PAIN GOES AWAY

Hospitalize for 24hours
Do serial EKGs and CIEs (Q6h x 24h)
If negative workup, then discharge home
Do a regular STRESS TEST in 6 weeks
Do STRESS THALLIUM test in 6 weeks

Comes on with exertion; goes away with rest

30% flow is enough at rest, but not on exertion
TX: VASODILATORS > increase radius increases
flow

Thallium flows through the coronary arteries

Look for COLD AREAS: NO FLOW( ISCHEMIC)

76 76

FOLLOW-UP FOR ANGINA, cont

FOLLOW-UP FOR ANGINA, cont

If you think they might have had an MI,

then do a Ca-PYROPHOSPHATE scan

IF PATIENT UNABLE TO PERFORM THE

STRESS TEST:

Cells that die calcify

Dead cells will take up the CaPYROPHOSPHATE

DOBUTAMINE STRESS TEST

DIPYRIDAMOLE STRESS TEST

Look for a HOT SPOT

EKG CHANGES

UNSTABLE ANGINA

Na gets trapped within a cell when there is

at least 90% stenosis
Cells become more POSITIVE

90% stenosis
EVENTS OCCUR
PLAQUE RUPTURED, and platelets are
closing off the rest of the lumen
TX: Aspirin > Nitrates> Oxygen > Heparin
> tPa > Morphine > B-blockers > Take to
CATH LAB for angiogram

ANGIOGRAM FINDINGS

ANGIOGRAM FINDINGS, cont

LEFT MAIN CORONARY ARTERY

OCCLUSION ( 70% stenosis or more)
THREE OR MORE VESSELL DISEASE

ANY SINGLE OR DOUBLE VESSELL

DISEASE
TX: PTCA with STENT placement coated
with CLOPIDOGREL

TX: GO STRAIGHT TO SURGERY

77 77

CELLS ARE MORE LIKELY TO

DEPOLARIZE WHEN ISCHEMIC

WITH Na and Ca trapped within the

cell

After a stroke: SEIZURES

After an MI: ARRYTHMIAS
After ischemic bowel: BLOODY DIARREA
After a DVT: CRAMPS

Since atria use Ca to depolarize, the

trapped Ca may cause atrial arrythmias
Contractility of muscles increases

WITH CELL DYING,

SWELLING

Sodium continues to accumulate inside

cell
Chloride will follow
WATER will follow next
SWELLING is therefore the FIRST visible
change of cellular injury

Cerebral edema
Papilledema
Hydropic changes
Dilated lymphatics
Third spacing

INFLAMMATION TIME LINE

WHEN TOO MUCH SODIUM

INSIDE CELL.

< 24 hours: SWELLING

AT 24 hours: NEUTROPHILS show up
and peak at 3 days
T-cells and MACROPHAGES: show up at
day 4 and peak at day 7
FIBROBLASTS: show up at day 7, peak at
day 30, and take 3 to 6 months to
complete their work ( chronic
inflammation)

Sodium begins to leak OUT of the cell now

that concentration gradient is reversed
The only way for sodium to get out is to
use the Na-Ca exchange protein which is
concentration driven

78 78

IF BLOOD SUPPLY NEVER

RETURNS TO THE CELL

WHEN ALL CALCIUM NOW

TRAPPED WITHIN THE CELL

The sodium can pull ALL the calcium into

the cell
WHILE calcium is moving into cell, more
atrial arrythmias may develop

Cells that depend on EXTRACELLULAR

calcium will lose function
SMOOTH MUSCLE
ATRIUM
VENTRICLE

SIGN OF CHRONIC DISEASE

ON BIOPSY: you see evidence of fibrosis
ON X-RAY: you see calcifications

ALL inflammatory processes

DONE!!!

79 79

Electrolyte Movement

Electrolyte Physiology

Something in the way she moves

me

CHANNELS: small ions

PORES: medium-sized molecules (sweat)
TRANSPORT PROTEINS

Electrolyte Movement

Electrolyte Movement

CONCENTRATION GRADIENT
ELECTRICAL GRADIENT
DRIVING FORCE
NERNST NUMBER (E-ion)
CONDUCTANCE (G-ion)
PERMEABILITY

CHANNELS: small ions

PORES: medium-sized molecules (sweat)
TRANSPORT PROTEINS

CONCENTRATION GRADIENT
ELECTRICAL GRADIENT
DRIVING FORCE
NERNST NUMBER (E-ion)
CONDUCTANCE (G-ion)
PERMEABILITY
CHANNELS: small ions
PORES: medium-sized molecules (sweat)
TRANSPORT PROTEINS

Electrolyte Movement

CONCENTRATION GRADIENT
ELECTRICAL GRADIENT
DRIVING FORCE
NERNST NUMBER (E-ion)
CONDUCTANCE (G-ion)
PERMEABILITY

Electrolyte Movement

CONCENTRATION GRADIENT
ELECTRICAL GRADIENT
DRIVING FORCE
NERNST NUMBER (E-ion)
CONDUCTANCE (G-ion)
PERMEABILITY

CHANNELS: small ions

PORES: medium-sized molecules (sweat)
TRANSPORT PROTEINS

CONCENTRATION GRADIENT
ELECTRICAL GRADIENT
DRIVING FORCE
NERNST NUMBER (E-ion)
CONDUCTANCE (G-ion)
PERMEABILITY
CHANNELS: small ions
PORES: medium-sized molecules (sweat)
TRANSPORT PROTEINS

80 80

Electrolyte Movement

Electrolyte Movement
Depolarize: to become positive from
baseline
Overshoot: more positive than the
threshold potential
Repolarization: to become negative from a
positive potential
Hyperpolarization ( or undershoot): to
become more negative than baseline
potential

CONCENTRATION GRADIENT
ELECTRICAL GRADIENT
DRIVING FORCE
NERNST NUMBER (E-ion)
CONDUCTANCE (G-ion)
PERMEABILITY
CHANNELS: small ions
PORES: medium-sized molecules (sweat)
TRANSPORT PROTEINS

Sodium Channels

81 81

HEART BLOCKS
NORMAL PR-interval : <0.2sec
FIRST DEGREE HEART BLOCK: fixed
and prolonged PR-interval
Problem is AT the SA node or BETWEEN the
SA node and the AV node
NO treatment necessary
Speeding up the heart rate( exercise) will
make the block disappear

HEART BLOCKS, cont

HEART BLOCKS, cont

SECOND DEGREE HEART BLOCK

MOBITZ 1: progressive lengthening of PRinterval until QRS is dropped

MOBITZ II: PR-interval is normal; QRS

complexes are dropped erratically
Late ischemia at the AV node
Some cells are negative; some cells are
positive
ALL must have a pacemaker

Early ischemia at the AV node

Also called WENCKEBACKS
Put in pacemaker if symptomatic; do nothing if
asymptomatic

82 82

HEART BLOCKS, cont

QRS COMPLEXES
Premature ventricular complex (PVC)

THIRD DEGREE HEART BLOCK

No P- wave; wide QRS complex; a pause

following the QRS complex
BIGEMINY: A PVC every other beat
TRIGEMINY: A PVC every third beat
VENTRICULAR TACHYCARDIA: three or
more consecutive PVCs with a minimum heart
rate of 150
VENTRICULAR FIBRILLATION: NO
recognizable QRS complexes

COMPLETE AV DISSOCIATION
AV-node has INFARCTED
P-waves and QRS complexes have NO
relationship
ALL must have a pacemaker

VENTRICULAR TACHYCARDIA

VENTRICULAR FIBRILLATION

IF PATIENT STABLE: treat with

medication
IF PATIENT UNSTABLE:

EPINEPHRINE
TREAT LIKE VENTRICULAR
TACHYCARDIA

SHOCK with 200joules

SHOCK with 300joules
SHOCK with 360(max)joules
LIDOCAINE
SHOCK
BRETYLIUM or AMIODORONE

ELECTROLYTES AFFECT
DEPOLARIZATIONS

ATRIAL ARRHYTHMIAS

Premature atrial contraction (PAC)

Multifocal atrial tachycardia
Paroxysmal supraventricular tachcardia
Atrial flutter
Atrial fibrillation

FOUR SPECIALIZED MEMBRANES

NEURONS
SKELETAL MUSCLES
SMOOTH MUSCLES
CARDIAC MUSCLE

If ACUTE and STABLE: treat with medication

If ACUTE and UNSTABLE: DEFIBRILLATE
If CHRONIC: treat medically; put on coumadin
May defibrillate after minimum 2 weeks on coumadin

ATRIUM: uses calcium to depolarize

VENTRICLE: uses sodium to depolarize; uses
intracellular calcium to contract; depends on
extracellular calcium to trigger off intracellular
calcium release

TX: use synchronized button

83 83

HYPERMAGNESEMIA

HYPOMAGNESEMIA

LESS LIKELY TO DEPOLARIZE

AFFECTS CALCIUM AND POTASSIUM
GETS IN THE WAY OF SODIUM
TX: IV normal saline; loop diuretic

MORE LIKELY TO DEPOLARIZE

AFFECTS CALCIUM and POTASSIUM
AFFECTS all KINASES
TX: magnesium sulphate

HYPERCALCEMIA

HYPOCALCEMIA

LESS LIKELY TO DEPOLARIZE

everywhere except the atrium( more likely)
SMOOTH MUSCLE: initially less likely
(blocks nerve) to depolarize, then more
likely to CONTRACT (due to second
messenger systems)
TX: IV normal saline; loop diuretics

MORE LIKELY TO DEPOLARIZE

everywhere except the atrium( less likely)
WILL AFFECT SECOND MESSENGER
SYSTEMS
SMOOTH MUSCLE: initially more likely to
depolarize( nerve fires more) followed by
less likely to CONTRACT (affects second
messenger systems)

HYPERKALEMIA

HYPOKALEMIA

Initially MORE LIKELY TO DEPOLARIZE

Potassium will flow into the cell, taking the
membrane potential closer to threshold
Potassium gets trapped INSIDE the cell during
repolarization; repolarization therefore takes
longer > LESS LIKELY TO DEPOLARIZE

LESS LIKELY TO DEPOLARIZE

Potassium will rush out of the cells,
making them more negative
Cells repolarize even faster
Cells repolarize too much

Peaked T waves
Widened T waves
Prolonged QT interval
Predisposes to arrythmias

84 84

Narrow T waves
Flat T waves
Flipped and inverted T wave
The U wave( exaggerated flipped T wave)

HYPERNATREMIA

HYPONATREMIA
MORE LIKELY TO DEPOLARIZE
SODIUM will now leak out of a cell by Na-K
exchange
When calcium leaks INTO cell in exchange for
sodium leaking OUT, cells become more
positive
TX: IV normal saline; correct slowly

MORE LIKELY TO DEPOLARIZE

SODIUM rushes into the cells, making
them more positive
After sometime, the NA-K ATP-ase kicks
Into high gear, making the cells more
negative( less likely to depolarize)
TX: IV normal saline; correct slowly

Use 3% saline if sodium under 120 with symptoms

Use fluid restriction if hyponatremia due to SIADH

Hyponatremia

The End: Turn off the lytes

Antiarrhythmics

Class 1: Na channel blockers

1a
Quinidine
Procainamide
Disepyramide

1b

Lidocaine
Tocainide
Mixelitine
Phenytoin

1c
Encainide
Flecainide
propofenone

85 85

Class II: Beta Blockers

Class II: Beta Blockers

All end in lol

Specific beta 1: begins with A thru M, but
NOT L or C
Nonspecific: begins with N thru Z,
including L and C

Class III: K Channel blockers

Class IV: Ca Channel blocker

Napa ( from procainamide)

Sotalol
Bretylium
Amiodorone

IF YOU PLAY WITH LYTES

Propanolol
Esmalol
Sotalol
Timalol
Butexalol
Labetalol
Carvedilol

Verapamil
Diltiazem
Nifedipine
Nicardipine
Nimodipine
Femlodipine
Amlodipine

Acebutalol
Atenalol
Pindalol

Quinidine
Procainamide
Phenytoin

You may go down IN FLAMES

86 86

PULMONARY PHYSIOLOGY
PULMONARY PHYSIOLOGY
TAKING A DEEP BREATH

Foregut Endoderm

Neural Crest

Respiratory Tract
GI Tract > from the mouth to the second
part of the duodenum

Tracheal cartilage
Laryngeal cartilage

Embryogenesis

Surfactant

Develops in the first trimester like every

other organ
Surfactant production is NOT complete
until approximately 32 to 34 weeks
Brain develops first in embryo: notochord
visible by 3 weeks; brain formed by 8
weeks

Decreases atmospheric pressures effect

on the alveoli > PREVENTS
ATELECTASIS
Increases compliance of alveoli
Compliance = change in volume / change
in pressure

87 87

You know surfactant production is

complete when
Lecithin / sphyngomyelin ratio is 2:1 or
greater or
You detect phosphatidylglycerol, a
breakdown product of surfactant

When there was NO surfactant

If mom comes in with preterm labor

Check L / S ratio
Check for phosphatidylglycerol
If both of the above are negative
Beclamethasone
Betamethasone
If baby still born early, then there is synthetic
surfactant that can be applied

Alveoli would collapse: Atelectasis

> leads to very poor compliance
> increases work of breathing
> weakness and shortness of breath
> oxygen is given
> oxygen has difficult time diffusing across
> oxygen builds up, causing free radical
formation > alveoli develop hyaline membrane in
order to protect themselves

Restrictive Lung Disease

Have poor
compliance
Have trouble
breathing in
Have poor diffusion
Have increased A-a
gradient
pO2 =low pCO2 =low
pH =high

Develop a secondary
perfusion problem
LOW ENERGY state
LOW VOLUME state
ALL die from heart
failure known as COR
PULMONALE = right
sided heart failure
due to pulmonary
HTN (severe RVH)

Hyaline Membrane Disease

THE FIRST RESTRICTIVE LUNG
DISEASE

88 88

Complications, cont

COMPLICATIONS of HMD ( or RLD)

As compliance drops, the need for
pressure support increases
As diffusion decreases, the need for
oxygen increases
More oxygen means more free radicals,
which means more hyaline membrane
Bring in the JET VENTILATOR

More pressure support can lead to a

PNEUMOTHORAX
Kussmaul sign: increased JVD on inspiration
Pulsus paradoxicus: exaggerated drop in BP
( more than 10mm) or in pulse rate ( more
than 10 bpm)
Loss of pulse and BP
Cyanosis
Hammans sign: subcutaneous emphysema

As free radicals traumatize the

AIRWAY

Pneumothorax
Spontaneous
Traumatic

Asymptomatic
symptomatic

Airway produces mucus to protect itself

Airway thickens
Goblet cell hyperplasia
Airway lumen narrows
Increased REID index
BRONCHOPULMONARY DYSPLASIA
The first obstructive lung disease

EVERY lung disease presents with

Obstructive Lung Disease

the SAME signs and symptoms!!!

Difficulty breathing OUT

Problem with VENTILATION
ABG: pO2 = nl or low pCO2 = high pH=low
Too much airway mucus
Airway thickening
Goblet cell hyperplasia
Increased Reid Index
Mcc of death is BRONCHIECTASIS

89 89

Can it really be this easy???

Amniotic Fluid Production

Role of Amniotic Fluid

80% is a filtrate of moms plasma

To SUBTRACT:

Main function is shock absorption

Secondary action is to prevent
atmospheric pressure from affecting the
fetus, especially the lungs

Swallow ( a reflex)
Digest ( need patent UGI)

20% comes directly from the fetus

To ADD:
Process the swallowed fluid, then add 20%
more than was swallowed, then URINATE

Potters Syndrome

Problem with amniotic fluid

POLYHYRAMNIOS
Autonomic dysfunction
( Riley-Day syndrome)
Neuromuscular
disease ( WerdnigHoffman syndrome)
UGI atresia

OLIGOHYDRAMNIOS
RENAL agenesis or
obstruction

When OLIGOHYDRAMNIOS leads to

pressure effects on the fetus ( everything
is flattened)
Will lead to pulmonary aplasia or
hypoplasia due to the positive pressure

Esophageal atresia
Duodenal atresia

90 90

It is important to have negative

pressure in the thoracic cavity!

Prune Belly Syndrome

Absence of abdominal wall musculature
Fetus is unable to urinate in utero
Fetus is unable to bear down and raise
abdominal pressure for urination
OLIGOHYDRAMNIOS
Unable to urinate due to neuromuscular
weakness?
Teach to (self) catheterize

Diaphragmatic Hernias
The diaphragm forms from Ventral to
Dorsal
Bochtalek defect: rear defect
Morgagni defect: anterior, midline defect
Visible by sonography in utero
Bowel sounds in chest exam
Must repair surgically immediately after birth

Extrathoracic Airway

Intrathoracic Airway

From the lips to the glottis

Narrows on inspiration; expands on
expiration
NOT protected by the thoracic cage

From the glottis to the alveoli

Expands on inspiration; narrows on
expiration
Protected by the thoracic cage
Has a vacuum surrounding it

91 91

Trachea

Aspiration

Has 16 to 20 C-shaped cartilage rings,

with the opening to the C facing posteriorly

If patient is unable to speak, then the

object is lodged in the trachea
LARGE OBJECTS tend to lodge at the
glottis 90% of time
Perform the Heimlick Maneuver
Perform Back Thrusts if less than 2 y/o
If still unable to dislodge the object

This allows partial collapse of the airway

during swallowing to prevent aspiration

Has three anatomic narrowings

The glottis
Midway: due to anterior compression by aorta
Carina: located at T4 (level of nipple)

Perform emergency cricothyroidotomy

Aspiration, cont

Evaluation for aspiration

Small objects tend to lodge in the right

lower lobe

Inspiratory film: all lobes are inflated

Expiratory film: the lobe with the aspirated
object does NOT collapse
Tx: bronchoscopy

Recurrent RLL pneumonia: R/O FB aspiration

Do inspiratory-expiratory films

Right mainstem bronchus is larger and

straighter than the left
If person is sitting or standing UP, the object will
lodge in the superior segment
If patient is lying DOWN, the object will lodge in the
posterior segment

Airway Anatomical Divisions

Dead space
Respiratory unit
Dead space ventilation
Alveolar ventilation
Total ventilation

92 92

Histology
Pneumocytes
Type 1: macrophages
Type 2: produce surfactant

Goblet cells: produce mucus to trap debris

Mucus moves 1 inch per cough

Smooth muscle
Clara dust cells
cartilage

Epithelium

Cilia

Upper 1/3 of trachea has squamous cells

Mid 1/3 of trachea is a combination
Main respiratory epithelium is tall columnar
ciliated epithelium
The more you smoke, the longer the zone
of squamous cells

Line the entire airway

Beat in one direction > orad
Has the 9 + 2 configuration (9
microtubules surrounding 2 actin proteins)
Need a Dynein arm to have flexibility

Kartageners Syndrome

Lung Sounds

Dynein arm is defective

An obstructive lung disease

Bronchiectasis
Infertility
Situs Inversus

Stridor: narrowing in extrathoracic airway

Wheeze: narrowing in intrathoracic airway
Rhonchi: air moving over mucus
Crackles: collapsed airways popping
open
Surfactant is missing
Alveoli have been scarred down

93 93

Lung Sounds, cont

Lung Sounds, cont

Decreased breath sounds: space between

alveolus and chest wall is occupied
Dullness to percussion: as above
Increased fremitus: consolidation on same
side or atelectasis on opposite side
Bronchophony, egophony, or e to a
changes: as above

Tracheal deviation: towards atelectasis

and away from a pneumothorax
Hyperresonance: pneumothorax on same
side or atelectasis on opposite side

Lung Infections

Airway Infections
Epiglotitis: H. Influenza B
Tracheitis: C. Diptheria
Pneumonia

Croup
Bronchiolitis
Bronchitis
Acute
chronic

Rusty colored sputum: Strep Pneumonia

Curant jelly sputum: Klebsiella Pneumonia
Sulphur granules: Actinomyces Israelii
Frequent after the flu: Staph Aureus
Malodorous smell or gas formation:
Anaerobes

Pneumonia
Airway
interstitial

tracheitis

Interstitial Pneumonias

Interstitial pneumonias
Fungus, cont

Atypicals

Paracoccidiomycosis: South America

Aspergillus: moldy hay or moldy basement
Sporothrix: rose thorn

Chlamydia: from 0 to 2 mo
Mycoplasma: from 10 to 30 y/o
Legionella: over 40 y/o

Pneumoconioses

Fungus

Asbestosis
Silicosis
Bissinosis
berrylliosis

Histoplasmosis: midwest
Blastomycosis: northeast
Coccidiomycosis: southwest

94 94

Lung Masses

Interstitial pneumonias, cont

Nocardia: the only G+ that is partially acid
fast
Sarcoidosis: noncaseating granulomas;
large hilar adenopathy; high ACE levels

Most common MASS in children:

hamartoma
Most common MASS in adults:
granulomas
Most common TUMOR: adenoma

Central Cancers

Peripheral Cancers

Squamous Cell Carcinoma: produces PTH

Small Cell Carcinoma

Bronchogenic adenocarcinoma
Bronchioalveolar adenocarcinoma

Anaplastic
Located at the carina
Produces 4 hormones:

Carcinoid syndrome
flushing, wheezing and diarrhea
Too much serotonin
Measure 5-HIAA in the urine

ACTH: 90%
ADH: 5%
PTH: 3%
TSH: 2%

Large cell adenocarcinoma

Risk factors for lung cancer

Time for the PHYSIOLOGY of the lung!!

Primary smoking
Risk increases with amount AND duration
If you STOP smoking: 5 yrs > reversal of
damage visible; 15 yrs > risk back to baseline

Radon
Second hand smoke
(1) sidestream smoke (2) mainstream smoke

Pneumoconioses

95 95

Three PHYSIOLOGIC parts to the lung

Intrathoracic space
Chest wall
Pleural space

Pulmonary vasculature
Pulmonary airway

Lung Volumes

Lung Volumes, cont

RV: the amount of air left in the lungs AFTER

TV: the amount of air you take IN during a

forced expiration

NORMAL inhalation effort

IRV: the amount of air you can FORCE

Can not be physiologically forced out

Maintains some compliance in the airway

INSPIRE after a normal inhalation effort

ERV: the amount of air that can still be FORCED

TLC: ALL the air in your lungs at the END of a

out AFTER a normal exhalation

deep breath ( RV + ERV +TV + IRV)

Fills up the dead space; decreases the tidal volume

that you would have to take in

VC: all the air you can breathe in AFTER forced

FRC: a combination of RV and ERV

exhalation ( ERV + TV + IRV)

96 96

Compliance and Air Flow

Inspiration
Beginning: expansile forces of the CHEST
WALL is greater ( 0 to 49%)
Middle: expansile forces of the LUNG is
greater ( 50 to 99%)
End: recoil force of the chest wall
EQUALS the expansile force of the lung

Expiration

Breathing in
FRC: baseline > intrathoraxic pressure is
negative ( - 3 to 5)
TV: intrathoraxic pressure gets more
negative ( -10 to -12)
TLC: intrathoraxic pressure most negative
(-20 to -25)
Intrathoraxic Pressure should always be
NEGATIVE

Beginning: recoil forces of the CHEST

WALL are greater ( 0 to 49%)
Middle: recoil forces of the LUNG are
greater ( 50 to 99%)
End: the recoil force of the lung EQUALS
the expansile force of the chest wall

Intrathoracic Pressure

Intrathoraxic Pressure
Should ALWAYS remain negative
Should decrease with inspiration
If it gets positive, then it will resist any
blood or air from entering the thorax
If you do not breathe in, there will be NO
pressure gradient for blood to enter the
thorax

97 97

Pericardial Tamponade

Positive Intrathoracic Pressure

Kussmaul sign: increased JVD with
inspiration
Pulsus paradoxicus: exaggerated drop in
BP( more than 10mmHg) or pulse ( more
than 10bpm) on inspiration

Mcc: trauma or cancer

CXR: enlarged cardiac shadow
ECHO: compressed small heart
Tx: pericardiocentesis
If recurrent: put in a pericardial window

Mcc: pericardial tamponade or

pneumothorax

Pneumothorax
Traumatic
Spontaneous
Associated with estrogen use or collagen
disease
Less than 25% occupation & asymptomatic
More than 25% occupation or symptomatic

Tx: chest tube placement

Pulmonary Vasculature

Flow ( Q )
As you breathe in, the lung Inflates, pulling
on traction fibers attached to vessels
As vessels DILATE, flow increases
As flow increases, oxygen dilates the
vessels, significantly increasing Q
The increased Q keeps the pulmonary
valve open longer, INCREASING S-2
splitting

98 98

Flow ( Q ) is greater to the bottom of

the lungs because

S-2 Splitting

(1) gravity
(2) less resistance
(3) more oxygen goes to the bottom of the
lungs with each breath
Normal RR = 12 to 16 breaths/min
Q increases on inspiration and decreases
on expiration.

Increases on inspiration due to Increased

pulmonary blood flow
Decreases on expiration due to decreased
pulmonary blood flow
This is why RIGHT sided heart sounds
increase on INSPIRATION
This is why LEFT sided heart sounds
increase on EXPIRATION

Oxygenation

Ventilation (V)

Directly related to DIFFUSION and

PERFUSION
More oxygenation is accomplished at the
bottom of the lungs only on inspiration
Most of oxygenation is accomplished at
the top of the lungs > ALWAYS OPEN!

Inversely related to pCO-2

Definition: patent airway
Measurement: pCO-2 ( on ABGs)
More V to the bottom of the lungs only on
inspiration
Most V at the top of the lungs because it is
ALWAYS PATENT

The Law of V / Q

Pulmonary Airway

V /Q is greatest at the top of the lungs,

equally matched in the middle, least at the
bottom
If you change one, you MUST change the
other in the SAME direction
ANY V / Q mismatch will lead to hypoxia

99 99

Pulmonary Airway Pressure

The Only Pressure That Gets
Positive With Each Breath

How The Brain Monitors Pulmonary

Physiology

Signals from the lungs and chest wall

J-receptors: found in the interstitium of
lungs
Senses interstitial particles
Increases respiratory rate

Slow adapting receptors: found in the ribs,

especially the sternocostal junctions
Senses stretch and inflation
Causes exhalation

100100

SINUSES

BODIES

Maxillary
Ethmoid
Sphenoidal
Frontal

AORTIC BODY: found in the arch of the

aorta
Measures pCO-2, pH, and H+ ions

CAROTID BODY: located at the

bifurcation of the internal and external
carotids
Measures PO2, PCO2, pH, and H+ ions

BRAIN
More sensitive to elevated pCO-2
Hypoxia and Hypercarbia are synergistic
Forms of pCO-2:
90% in the form of HCO-3
7% as carbaminohemoglobin and
carboxyhemoglobin
3% is dissolved ( .03pCO2 )

Medulla
Responsible for BASIC functions; has a
RR of 8 to 10
BRAIN DEAD: no function above the
medulla
COMATOSE: cerebral cortex is still alive,
but patient unable to respond

101101

Pons
RESPONDS to the environment
Locked-In syndrome: damage to pons; patient
only able to blink as response
Most sensitive to osmotic shifts > Central Pontine
Demylinolysis
Apneustic center: senses hypoxia; causes
inspiration
Pneumotactic center: senses hypercarbia;
causes exhalation

Kussmaul Breathing
RAPID, DEEP breathing
Means METABOLIC ACIDOSIS

Apneustic Breathing
Pneumotactic center is desensitized, as in
COPD
A lesion below the pneumotactic center
but above the apneustic center

102102

Apnea
Central Apnea: NO inspiratory effort, with or
without bradycardia, in 20 seconds or more
Apnea monitor
Tx: Caffiene; theophylline

Obstructive Apnea: occlusion of airway during

sleep, usually caused by obesity

Weight loss
Progesterone
CPAP
Surgery: Uvulopalatoplasty

Lesions to MEDULLA

THE END

Lesions to MEDULLA
Hypoglycemia
Ischemia
Thoracic outlet syndrome
Subclavian steal syndrome

103103

Obstructive Lung Diseases

And now for a few good CLUES

Bronchitis
Acute
chronic

Bronchiolitis
Asthma
Intrinsic
extrinsic

Cystic fibrosis
Bronchiectasis

Really! The End!!

104104

Emphysema

Panacinar
Centroacinar
Distoacinar
Bullous
Staph aureus
Pseudomonas

NEUROLOGICAL CONTROL
NEUROMUSCULAR
PHYSIOLOGY
I WANT A CONTRACT

Central Nervous System

Inhibitory Neurotransmitters

Involves the BRAIN and SPINAL CORD

GABA: brain; causes an influx of chloride

PARASYMPATHETIC system

GLYCINE: spinal cord; causes an influx of

chloride

Controls the craniosacral divisions

SYMPATHETIC system
Controls the thoracolumbar divisions

PARASYMPATHETIC SYSTEM

SYMPATHETIC SYSTEM

Uses acetylcholine for preganglionic fibers

and postganglionic fibers
DEPOLARIZES the head and neck as well
as below the belt
HYPERPOLARIZES the thoracolumbar
areas
Has long preganglionic fibers, short
postganglionic fibers

Uses acetylcholine for preganglionic

fibers; uses primarily NE for postganglionic
fibers
Some pathways use DA or SEROTONIN
DEPOLARIZES the brain and the
thoracolumbar areas
HYPERPOLARIZES the sacral area
Has short preganglionic fibers, long
postganglionic fibers

105105

Second Messengers
PARASYMPATHETIC: c-GMP
SYMPATHETIC: c-AMP
Smooth muscle contraction by
neurotransmitter or hormone: IP3/DAG
Smooth muscle contraction by distention:
calcium-calmodulin

Sympathetic Receptors

Parasympathetic Receptors
Most are MUSCARINIC except at ganglia
or neuromuscular junctions which are
NICOTINIC

Many are NICOTINIC, except for sweat

glands which are muscarinic or

Alpha 1 Receptors

Alpha 2 Receptors

Arteries: vasoconstriction
Sphincters: tighten
Radial muscles of the eyes: mydriasis w/o
cycloplegia

All presynaptic sympathetic fibers: inhibit

NE release
Islet cells of pancreas: inhibit insulin
secretion

106106

Beta 1 Receptors

Beta 2 Receptors

CNS: increased activity

SA NODE: increase heart rate and
contractility
JG Apparatus: increased renin release
Alpha cells of pancreas: increased
glucagon release

CNS: increased activity

Ventricles: increased contractility but NOT
rate
Lungs: bronchodilation
Arterioles: vasodilation
Islet cells of pancreas: increased insulin
Uterus and Bladder: relaxation

If you want to stimulate

If you want to inhibit

You want to depolarize

Make the cell more positive
Make Na move INTO the cell
Make Ca move into SA node

CNS: make CL move into cell

PNS: make K move out of cells
In either case, cells become more
NEGATIVE and are less likely to
depolarize

NOW FOR THE MUSCLES!

TYPES of MUSCLES
CARDIAC muscle
SKELETAL muscle
SMOOTH muscle

107107

STRIATED MUSCLES

Smooth Muscle

Cardiac muscle
Skeletal muscle

Appear smooth due to lack of striations

Striations due to sarcomeres

Skeletal Muscle

Cardiac Muscle

Use intracellular calcium for contraction

100% electrochemically coupled
Function as motor units( one nerve fiber
and all the muscle fibers it innervates
Demonstrate RECRUITMENT
NO AUTONOMICS
NO SYNCYTIAL activity

Uses intracellular calcium for contraction

Needs extracellular calcium to trigger off
intracellular calcium release
Complete SYNCYTIAL activity
The most gap junctions
Complete AUTONOMICS
Can function without innervation,
neurotransmitters or hormones

Smooth Muscle

NEUROMUSCULAR TRANSMISSION

Uses intracellular calcium for contraction

Needs extracellular calcium for its second
messenger system ( when it flows inside
the cell)
Has AUTONOMICS
Has partial SYNCYTIAL activity
Can function without innervation,
neurotransmitters or hormones

108108

MUSCLE CONTRACTION
Calcium binds trop-C
Trop-C releases trop-I
Trop-I releases
tropomyosin
Tropomyosin releases
actin binding sites
Myosin heads bind actin
CONTRACTION occurs

MUSCLE CONTRACTION, cont

Myosin heads release

ADP from previous rd
Myosin heads bind
new ATP
Myosin heads
hydrolyze ATP
RELEASE occurs
Myosin heads return
to start position

Clinical Application

Tropomyosin binds actin

Trop-I binds tropomyosin
Trop-C binds trop-I
Ca-ATPase pumps Ca back into SR
Phospholambin inhibits Ca-ATPase when
it is done pumping

Diagnosis of a Myocardial
Infarction

Management of an MI

EKG: Na-K pump stops > peaked T-wave > STwave depression > ST-wave elevation > T-wave
depression, then inversion > Q-wave
Troponin I: rises at 2 hours > peaks in 2days >
positive up to 7 days
CK-mb: rises in 6 hours > peaks in 12 hours >
gone in 24 to 36 hours
LDH 1: rises in 24 hours > peaks in 48hours >
gone in 72 hours

109109

24 hour hospitalization
Check EKG Q6
Check CIEs Q6
Monitor for arrythmias
Discharge after 24 hours IF asymptomatic
Re-evaluate in 6 weeks

In 6 Weeks
Exercise stress test
Positive IF: chest pain is reproduced; ST-wave
changes; drop in BP

The Functional Unit of Muscles

Stress Thallium test

A perfusion test; looking for a COLD spot

Dobutamine or Dipyridamole stress test

Use when patient unable to exercise

THE SARCOMERE

Calcium Pyrophosphate scan

Taken up by DEAD tissue; looking for HOT spot

2-D echo

Evaluates anatomy of heart; measures SV and CO

MUSCLE DIFFERENCES

CARDIAC MUSCLE

Smooth Muscle

In addition to wave of depolarization,

calcium MUST flow into the T-tubules
during phase 2 for contraction to occur
Ventricle depends on EXTRACELLULAR
calcium to trigger its contraction

Has NO sarcomeres
Contains NO troponin > actin and myosin
are always bound ( LATCHING)
Contains BASAL BODIES
Has NO myosin ATPase activity
Has MLCK and MLCP working together

110110

As Muscle Contracts

Length/Tension Curve

LENGTH decreases
FORCE and TENSION increase
A band stays the same
Amount of OVERLAP increases
The H band and I band therefore shrink

Golgi Tendon Organs

Muscle Strain

Located at muscle insertions

Monitor the force of muscle contractions
Allows muscle to hold MAXIMUM muscle
contraction force for only one second
Once it fires, muscle fibers MUST relax
Prevents destruction of sarcomeres

Overstretching or tearing a muscle

When a muscle is torn, it goes into spasm
to keep the fibers together for proper
healing
Tx: rest it > apply heat > NSAIDS > muscle
relaxants

JOINT SPRAIN

Frank-Starling Curve

TORN tendon or ligament

Tx: Rest it > Ice Compression > Elevate
the extremity

111111

Congestive Heart Failure after a

myocardial infarction

Congestive Heart Failure

Over 50% mortality in 5 years

Most common medicare diagnosis
Muscle fibers are overstretched
Dilated ventricle
Increased EDV and ESV
Decreased contractility > decreased CO
and EF

AT LEAST 40% of myocardium lost

EJECTION FRACTION is less than 45%
Due to left coronary artery infarcts 90% of
time

Treating CHF: Applying

Frank-Starling Curve

NEUROMUSCULAR PROFILE

Decrease volume
Restrict sodium intake
Restrict volume intake

Increase contractility
Digitalis
Dobutamine
Dopamine

Decrease TPR
Ace inhibitors

ALL YOU NEED NOW IS THE

CLUE

Inflammatory Myopathies

Myositis
Polymyositis
Dermatomyositis
Fibrositis
Fibromyalgia
Polymyalgia
rheumatica
Temporal Arteritis

112112

ALL HAVE:

High ESR
High WBC count
Myoglobinemia
High AST, ALT and
Aldolase

Muscular Dystrophies

Neuropathies

Duchennes

Gowers sign
Waddling gait
Pseudohypertrophy of the calf
Dystrophin protein
X-linked recessive; onset BEFORE age 5

Guillian Barre
Diabetes mellitus
Syphilis
Myesthenia Gravis / Myesthenic or Eaton
Lambert syndrome

Beckers
Onset AFTER age 5

Myotonic

Acetylcholinesterase inhibitors:
reversible

Acetylcholinesterase inhibitors:
irreversible

Edrephonium
Neostigmine
Pyridostigmine
Physostigmine

AKA Organophosphates
End in .phate ( diflorophate; echothiophate)
End in .thion ( malathion; nalathion;
parathion)

If they come back complaining

about more weakness

Anticholinergic Drugs

Myesthenia Gravis has gotten worse or

Cholinergic crisis

Side effects are sympathetic except for

HOT, DRY SKIN!

REPEAT EDREPHONIUM TEST!!

IF patient gets better > disease is worse
Increase neostigmine

IF patient gets worse > cholinergic crisis

Hold neostigmine > give atropine > decrease
neostigmine

113113

Atropine
Glycopyrollate
Pilocarpine
Benztropine
Trihexyphenidyl
ipratropium

Neoplastic Associations

Neuropathies, cont

Myesthenia Gravis: THYMOMA

Multiple sclerosis
Metachromatic leukodystrophy

Myesthenic syndrome: SMALL CELL

CARCINOMA; a paraneoplastic syndrome
Sarcoplasmic reticulum is slow to sequester
calcium; cancer blocks some calcium
channels

Treatment of MS

Lower Motor Neuron Disease

STEROIDS
IV GAMMGLOBULINS
PLASMAPHARESIS

Amyotrophic lateral sclerosis

Werdnig-Hoffman Disease
Polio

Cerebellar Disease in 5 to 10 Y/O

children

Cerebral Palsy
Any permanent neurological damage suffered
PRIOR to age 21 years

Ataxia Telangiectasia
Fredricks Ataxia
Adrenoleukodystrophy

Spastic Diplegia
Midline cortical problem

Spastic Hemiplegia
Cortical problem on ONE SIDE of the brain

Choreoathetosis
BASAL GANGLIA is involved: kernicterus

Atonic
FRONTAL CORTEX: involves the CST

114114

THE END

115115

VASCULAR PHYSIOLOGY

Im Talking About
SMOOTH

YOU GOTTA HAVE SOME FLOW

SMOOTH MUSCLE, that is

Smooth Muscle

Arterioles

THICKEST layer of smooth muscle is

found in the aorta
MOST smooth muscle by surface area
found in the arterioles
LEAST smooth muscle found In the veins
and veinules

Considered the STOPCOCKS of the

vascular tree
MOST smooth muscle by surface area
allows most vasodilatation and
vasoconstriction
Maintain AUTOREGULATION
Do the MOST to regulate BP, up or down

AUTOREGULATION

Veins and Veinules

Between BP 60 to 160 systolic : cerebral,

coronary, and renal perfusion remains
constant

Have the most CAPACITANCE

Have the least smooth muscle
60% of blood ( the most) is pooled here
Depend on skeletal muscle contractions to
squeeze blood upward
Have one-way valves which move blood
from superficial to deep veins

ISCHEMIC infarct: BP went below 60

systolic
HEMORRHAGIC infarct: BP went above
160 systolic

116116

CONTROL of vessels

If Hypovolemia Develops

VEINS: under parasympathetic control

This is why veins are usually dilated
Blood flow rate is quite slow
example: subdural hematomas

VENOCONSTRICTION is first response to

loss of volume > gets volume back into
circulation
Venoconstriction is most significant in skin
and GI
Poor skin turgor
Loss of bowel sounds and ileus

A-V Anastamoses

CONTROL of vessels, cont

Shunt blood away from nonessential

organs
More concentrated in fingertips, tips of
toes, tip of nose, lips and earlobes

ARTERIES: under sympathetic control

This is why arteries are usually constricted
Reactive hyperemia: cutting an artery or
the nerve to that artery causes immediate
vasodilatation
i.e. epidural hematoma

Severe vasoconstriction
hypothermia

Receptors

Capillaries

ARTERIES: alpha one ( IP3/DAG)

Have the thinnest membranes

Made for diffusion
Have the greatest surface area

vasoconstriction

ARTERIOLES: beta 2 ( c-AMP)

vasodilatation

VEINS: alpha 1 ( IP3/DAG)

venoconstriction

117117

As Blood Flows Through the

Capillaries

In the Veins and Venules

Fluid diffuses out; large proteins (albumin)

stay in
Osmotic pressure rises in the capillaries
Concentration gradient pushes particles
out of capillaries

Osmotic pressure is now high enough to

PULL waste products into vessels
Blood PULLS waste products back into
circulation

Total Pressure in a vessel

As a Vessel Narrows

Velocity increases
Flow decreases
Resistance increases
Blood Pressure rises

Resistance in Series

118118

Resistance in Parallel

During Diastole

Ventricles are relaxing

Very LOW RESISTANCE in coronaries
Aortic valve is closed
Aorta has MORE TRANSMURAL
PRESSURE

MORE CORONARY BLOOD FLOW

In Summary

During Systole
Ventricles are CONTRACTING
There is HIGH RESISTANCE in coronary
vessels
Velocity in aorta is too high
Aortic valve is open
LOW TRANSMURAL PRESSURE

LESS blood flow through coronary arteries

during SYSTOLE
MORE blood flow through coronary
arteries during DIASTOLE
Most work is done in systole!
A-V O2 difference created during systole
Therefore: MOST O2 EXTRACTION
occurs in systole

LESS CORONARY BLOOD FLOW

Lets Look at FLOW

A-V O2 Difference

At REST: the heart extracts 97% of O2

With EXERCISE: skeletal muscle
After EATING: GI system
During INTENSE CONCENTRATION: the
brain

LOWEST A-V O2 difference: the kidneys,

at all times

119119

POISSOILE LAW

NEUROLOGICAL control of blood

pressure

Regulation of Radius

CNS: pCO2 pO2

LUNGS: pO2
MUSCLES: pCO2
pH
CV: adenosine
SKIN: temp pCO2
GI: food, especially fats
RENAL: PGE2; dopamine; ANP

Carotid Sinus

REMEMBER!

Located at the bifurcation of the common

carotid
Responds to FLOW or STROKE VOLUME
Increased STRETCH means increased
FLOW
Sensory nerve : CN IX
Efferent nerve : CN X

Stroke volume, carotid sinus stretch, CN

IX firing and CN X firing ALWAYS go in
the same direction
CN IX and CN X are ALWAYS firing
Amount of firing varies always in SAME
DIRECTION as the stroke volume

120120

Autonomic Dysfunction

Low Volume State

Low stroke volume >
low carotid stretch >
low CN IX firing >
decreased CN X firing
>increased heart rate
> increased NE from
NTS in medulla >
increased TPR >
decreased RBF >
decreased GFR >

Mcc: DIABETES MELLITUS

In Newborns: Riley-Day syndrome
In Parkinsonism: Shy-Dragger syndrome
In elderly: Sick Sinus syndrome

Low Volume State

> increased renin,

angiotensinogen,
aldosterone secretion
> increased Na
reabsorption >
increased total body
Na > decreased
urinary Na >
decreased FENa >
increased urinary K >
>>>

Decreased serum Na( dilutional)

Decreased serum Cl ( dilutional)
Decreased serum K (real and dilutional)
Decreased urine pH ( aldosterone
excretes H)
Increased serum Ph (metabolic alkalosis)
Increased TPR

Most common cause of

hyponatremia?

Most common cause of

hypokalemia?

LOW VOLUME STATE

LOW VOLUME STATE

121121

Most common cause of

hypochloremia?

Most common cause of high TPR ?

LOW VOLUME STATE

LOW VOLUME STATE

Most common cause of metabolic

alkalosis?

Ace Inhibitors

LOW VOLUME STATE

ALKALOSIS favors calcium precipitation
with phosphate
KIDNEY STONES !!!!

Angiotensin Receptor Blockers

Ace Inhibitors

Stop conversion of AT-1 to AT-II

Increased bradykinin
VASODILATION and VENODILATION
Decreased preload and afterload
BALANCED dilation
Contain sulphur
Decrease mortality in CHF; decreases
proteinuria in diabetic nephropathy

Captopril
Lisenopril
Enalopril
rinilopril

Losartan
Vosartan
Do not contain sulphur
NO elevation in bradykinin

122122

What is a VASCULITIS?

Vasculitis

Schistocytes ( Burr cells; helmet cells)

Petechiae, purpura and ecchymoses
LOW ENERGY STATE
LOW VOLUME STATE
Restrictive lung disease profile
CELL MEDIATED inflammation

Ig-A nephropathies

All You Need Now is the Clue!!!

Bergers
Henoch-Schonlein Purpura
Alports

More vasculitides

More vasculitides

Buergers
DIC
HUS
TTP
DM
Syphilis
Takayasu
kawasaki

123123

Temporal arteritis
Ankylosing Spondylitis
PAN
Wegeners
Goodpastures
Leukocytoclastic
Churg-Strauss

Collagen Vascular Diseases with

LOW COMPLEMENT

Collagen Vascular Diseases

CREST syndrome
Scleroderma
Progresive Systemic Sclerosis
MCTD
RA / JRA (Stills disease)

Feltys: RA & leukopenia and splenomegaly

Becets : RA & GI ulcerations
Sjogrens : RA & xeropthalmia, xerostomia

THIS IS THE END

124124

PSGN
Serum Sickness
SBE
SLE
MPGN : type l, ll
Cryoglobulinemia

CARDIAC PHYSIOLOGY
THE HEART OF THE MATTER

PRESSURE is the GRADIENT of the

organs!

OPENING SNAP
A valve is popping open during diastole
TRICUSPID STENOSIS
MITRAL STENOSIS

EJECTION CLICK

MIDSYSTOLIC CLICK

A valve is popping open during systole

Blood is coming at high velocity, slapping

the mitral valve on the way out
Occurs closer to S-1 with standing and
closer to S-2 with lying down

AORTIC STENOSIS
PULMONARY STENOSIS

MITRAL VALVE PROLAPSE

Occurs in 7% of normal women (estrogen
connection)

125125

SOFT S-1

LOUD S-1

One of the two valves that contribute to

this sound is NOT closing

Either you have a stiff valve that bangs

shut: TRICUSPID or MITRAL STENOSIS
Or the ventricle is contracting harder

TRICUSPID REGURGITATION
MITRAL REGURGITATION
VALVE IS NOT THERE!
Tricuspid atresia
Mitral atresia
BOTH ARE CYANOTIC

SOFT S-2

LOUD S-2
Either one of the valves is stiff and
BANGS shut when it tries to open

One of the two valves that contribute to

this sound is NOT closing
AORTIC REGUGITATION
PULMONARY REGURGITATION
OR the valve is not present

AORTIC STENOSIS
PULMONARY STENOSIS
Or there is HIGH pressure in front of the
valves (systemic or pulmonary
hypertension)

AORTIC ATRESIA
PULMONARY ATRESIA
BOTH ARE CYANOTIC

S-3

S-3

Sound made by a noncompliant ventricle

????????????????

VOLUME overload
DILATED ventricle
DECOMPENSATION
S-3 said to be normal ONLY in an
adolescent female

126126

ESTROGEN CONNECTION

S-4

Estrogen is a muscle relaxant

Causes liver to produce many proteins

Sound made by an atrial kick

High ESR or CRP

Lipoproteins
TBG
Angiotensinogen
Clotting factors

PRESSURE overload
HYPERTROPHY
COMPENSATION
Most common gallop (atherosclerosis)

Especially fibrinogen, but not factor 11

MURMURS CAUSED BY

MURMURS! MURMURS! MURMURS!

TERBULENCE
Reynolds number > 2500
Murmur: if it is in the heart
Bruit: if it is in a vessel
Occurs when you have 70% stenosis

127127

MURMUR GRADES

A SYSTOLIC MURMUR

Grade 1: barely audible

Grade 2: easily audible
Grade 3: pretty loud
Grade 4: palpable thrill
Grade 5: able to hear with stethoscope off
the chest
Grade 6: able to hear across the room
without stethoscope

Valves that are supposed to be open are

stenotic ( PULMONARY or AORTIC
STENOSIS)
OR valves that should be closed are not
closing ( MITRAL REGURGITATION or
TRICUSPID REGURGITATION)

HOLOSYSTOLIC ( PANSYSTOLIC)
MURMURS

SYSTOLIC MURMURS

Aortic stenosis
Pulmonary stenosis
Mitral regurgitation
Tricuspid regurgitation
Ventricular septal defect

Tricuspid regurgitation
Mitral regurgitation
VSD

PANSYSTOLIC increases on
INSPIRATION

PANSYSTOLIC increases on
EXPIRATION

Tricuspid regurgitation

Mitral regurgitation
VSD
Radiates into the axilla: MITRAL

128128

AORTIC STENOSIS

SYSTOLIC EJECTION MURMURS

Radiates to the carotids( neck)

LOUDER with leaning forward, making a
fist, blowing up a blood pressure cuff, or
squatting

Aortic stenosis
Pulmonary stenosis

Crescendo decrescendo or diamond

shaped murmur
PULSUS TARDUS
DELAYED CAROTID UPSTROKE

IHSS

IHSS, cont

Autosomal dominant
Muscle fibers are hypertrophied but
disorganized
Any young athlete who dies suddenly,
especially during peak exercise
Septum is asymmetrically thick, especially
the top > causes SUBAORTIC stenosis

Excessive hypertrophy compresses the

coronary arteries
Excessive hypertrophy obliterates the
ventricular space
Murmur is LOUDER with standing or with
Valsalva; decreased with increased TPR
PULSUS BISFERIENS

IHSS, cont

DIASTOLIC MURMURS

Tx: need to decrease contractility; allow

time for adequate ventricular filling

Either the valves that should be open are

stenotic (MITRAL STENOSIS or
TRICUSPID STENOSIS)
Or the valves that should be closed are
regurgitant ( AORTIC REGURGITATION
or PULMONARY REGURGITATION)

Beta blockers
Adequate fluid intake
Bar from organized sports
Do an ECHO on entire family

129129

DIASTOLIC BLOWINNG or
DECRESCENDO MURMUR

Aortic Regurgitation
Radiates to carotids; LOUDER with leaning
forward, making a fist, blowing up a blood
pressure cuff, or squatting
Austin-Flint murmur: mitral regurgitation
Widens the pulse pressure
bounding pulses
waterhammer pulse
head-bobbing
Quinckes pulses

AORTIC REGURGITATION
PULMONARY REGURGITATION
Increases on inspiration: Pulmonary
regurgitation
Increases on expiration: Aortic
regurgitation

Pulmonary Regurgitation

Diastolic Rumbles

Radiates to the back

Louder on inspiration
Graham-Steele murmur: tricuspid
regurgitation

TRICUSPID STENOSIS
MITRAL STENOSIS
Increases on inspiration: tricuspid
regurgitation
Increases on expiration: mitral
regurgitation

CARDIAC PATHOLOGY

CARDIOMYOPATHIES
DILATED
HYPERTROPHIC
RESTRICTIVE
CVD
Amyloidosis
Hemochromatosis

CONSTRICTIVE
Tamponade ( Kussmaul sign; Pulsus Parodoxicus)
Trauma
cancer

130130

EFFUSIONS
Transudate: mostly water
Exudate: mostly protein
Transudate: sp. G < 1.012
Protein < 2grams

Exudate: sp. G > 1.012

Protein > 2grams

Congenital Heart Diseases

Cyanotic Congenital Heart Disease

VSD
ASD
PDA
Coarctation

VALVULAR DISEASES: most common

Transposition of Great Arteries

Tetrology of Falot
Tricuspid Atresia
Total Anomalous Pulmonary Venous Return
Truncus arteriosus
Pulmonary Atresia
Aortic Atresia
Hypoplastic Left Heart
Ebstiens Anomaly

Pulmonary Disease

causes

Aortic stenosis: aging

Aortic regurgitation: aging
Mitral stenosis: Rheumatic fever
Mitral regurgitation: MVP, SBE, collagen
diseases
Tricuspid stenosis: Rheumatic fever,
carcinoid syndrome
Tricuspid regurgitation: acute endocarditis

Most common cause is ALWAYS

congenital
Pulmonary valve is protected on BOTH
sides

131131

Flow Volume Loops

Antiarrhythmics

132132

Na Channel Blockers
Class Ia
Quinidine
Procainamide
Disepyramide

Wolf-Parkinson-White Syndrome

Class Ic
Encainide
Flecainide
Propofenone

Class Ib

Lidocaine
Tocainide
Mixeletine
Phenytoin

Class II Beta Blockers

Class IV Ca Channel Blockers

Verapamil
Diltiazem
Nefedipine
Nicardipine
Nimodipine
Amlodipine
Femlodipine

End in lol
Specific B-1: begin with A thru M (not L,C)
Specific B-2: begin with N thru Z (incl L,C)

133133

Class II Beta Blockers

Propanolol
Esmalol
Timolol
Butexalol
Sotalol
Labetalol
Carvidalol

Class III: K channel Blockers

Acebutalol
Atenalol
Pindalol

THE END

134134

Napa
Sotalol
Bretylium
Amiodorone

4/29/2008

Foregut (rotation 90)

Celiac artery

Parasympathetic:
Vagus

Sympathetic:splanchnic
nerves T5-T9

Midgut (rotation 270)

PHYSIOLOGY

Superior mesenteric

Parasympathetic:
Vagus

Sympathetic: splanchnic
nerves T9-T12

Hindgut ( Septation)
Inferior mesenteric

Parasympathetic: pelvic
splanchnic nerves

Sympathetic: lumbar
splanchnic nerves:
L1-L2

Extends from the second part of duodenum

to the spleenic flexure

Gives rise to the GI, from mouth to second

part of duodenum, including the respiratory
tract

Develops in the YOLK SAC

Must go through a 270 degree rotation as it
migrates from yolk sac into abdominal cavity

Lungs and upper GI have many congenital

connections

MIDGUT ROTATION requires ciliary action

KARTAGENERS: SITUS INVERSUS

CNS
ORAL
PHARYNGEAL
ESOPHAGEAL
UGI
LGI

FROM splenic flexure to the anus

WATERSHED AREA: the spleenic flexure
l
t bl
d supply
l
H
Has th
the least
blood
Most susceptible to ischemic infarcts

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4/29/2008

SENSORY INFORMATION

Cortex can over ride any basic urge:

(outer layer of the cerebrum-forgut)

THINKING about food

HEARING about food
SMELLING food
TOUCHING food
TASTING food

ALL sensory information must reach the cortex;

Response is via the CORTOCOBULBAR pathway via the vagus

LIMBIC SYSTEM- responsible for basic urges

Hippocampus long term memory
Amygdala- reward and fear, mating

No longer do a vagotomy for peptic ulcer disease (cant enjoy

food)
Highly selective parietal cell vagotomy now

Responsible for setting time: Circadian rhythms

Melatonin from tryptophan- milk and turkey

Neurotransmitter: melatonin
Light outside- melatonin low- DAYTIME
Dark outsideoutside melatonin highhigh NIGHT

- Bright lights in companies, casinos

- 1st, 2nd, 3rd shift workers/ workers comp

Morning- catabolic processes are in their highest

function- working out in the morning is the best

Feeding Center
(HUNGER)
Location:

Lateral hypothalamus

Stimulus:

Feeding (hunger) Glucose

If sugar remains normal the
center will not fire

Destruction: Anorexia

Satiety Center

ANOREXIA NERVOSA

Starvation
Desentasize your
hunger center
Body
ody dys
dysmorphic
o p c
disorder
Small body frame and
thinks they are over
weight
Young female trying to
please her mother
BMI < 17

Location:

Vento-medial nucleus of
the hypothalamus

Stimulus:

Stop feeding: Glucose

Stomach stretch will
stimulate satiety center
Can override- Cortex

Destruction:

Bulimia

Enjoys eating
Chunky female
Trying to please her
b f i d
boyfriend
Purging
Abrasion on knuckles
Tooth enamel erosion
Laxative abuse
BMI > 25

Hypothalamic obesity syndrome

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4/29/2008

Lesion of the satiety center (Ventormedial)

Men: 5 feet = 106 lbs

Women: 5 feet= 100 lbs

Uniparental disomy- one parent carrying lesion

Paternal in origin
T i
Trinucletide
l id repeats
Chromosome 15

Add 5 lbs for each inch past that

Small frame: add 15 lbs
Large frame: add 30 lbs

Very aggressive appetite

Die due to over eating

(i.e. male 510: 106 + 50 +30 = 186 lbs)

Norepinephrine or Serotonin (more important),

so many people use Amphetamines for weight
loss

They are taken up presynaptically, causing release

of all catecholamines

80% of time > stimulates satiety center

Nausea/ vomiting -(DA)

(DA) stimulates

Increase DA, NE and Serotonin

Neuromuscular- basal ganglia- tics (DA)

20% of time > stimulates hunger center

Amphetamine tox. clue vertical nystagmus

Methylphenidate- ritilan (1st line) [drug dependence]

Controls MENSES- progesterone stimulates

hunger system

Narcolepsey (hipnogogic)hallucinations as you fall asleep

Pemolinehepatic necrosis (hepatitis)- off the market 2005

Pregnancy- due to corpus luetum

DexadrineD
d i
d
dexatrim
t i - weight
i ht loss
l
OTC

FOOD craving.

LSD- hallucinations from Seratonin (slow, lazy)

PCP- hallucinations from Seratonin (violent, aggressive)
ECSTACY- hallucinations from Seratonin (stimulate thirst)

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4/29/2008

STRESS RESPONSE:

Controls TEMPERATURE:
ANTERIOR Hypothalamus: cools (inhibits NE)

Parasympathetic first (HR dec.) increased

gastric motility, increase acid production

Lesion anterior- die from: hyperthermia

Sympathetic second (B/P inc) constipation,

POSTERIOR Hypothalamus: warms

pulls blood from GI, so you can not buffer acid

Lesion posterior- die from hypothermia

Stress from burn- Curlings ulcer

ICP- Cushing's ulcer

Acetametaphen: for use with fever

(stimulate anterior hypothalamus- cools), then it
blocks posterior so you do not go back up again

Seizure- foam at the mouth, defecate, urinate

(all parasympathetic)

Toxicity- microsteatosis, Reye syndrome in children

Tx: N-acetylcystine-reducing agent

- 4 hour level will determine if you use it

Hollywood and sphincter control

Put food into mouth- salivary glands respond

SALIVARY GLANDS

Parotid [ in front of ear ](serous)-water - CN 9

Lingual [ on tongue ] (most serous)
CN 7
Sublingual [under tongue] (most mucus)
CN 7
Submandibular [jaw] (mucus)
CN 7

Saliva in your mouth has to be HYPOTONIC (cracker)

Food on your cheek- food will get stuck (gummy bear)

Acetylcholine- CNS: excitatory, PNS: activates

muscles

Norepinephrine- and 1
Epinephrine- has methyl group (hormone)
Ephedrine- OTC med
Pseudoephedrine stress incont.
Phenylephrine- neurogenic shock Tx (constrict)

Methacholine- dx asthma (old), beta 2 agonist to

bring you out
Pilocarpine- sweat test ( > 60), open angle
glaucoma (chronic)

RESULT: remove the blood supply to the GI causing

a decreased saliva that has increased osmolarity
(less saliva- more salt)

Carbachol- post op urinary retention (stimulate

bladder emptying)
Bethanecol- post op urinary retention

Exercise- mouth dry, white film in corner

4
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4/29/2008

MCC: of malabsorption in children

Meconium ileus: first presentation in neonate

Malabsorption develops as pancreatic ducts
become clogged

CFTR gene on chromosome 7

Defective CHLORIDE transport

Infertility in men develops as epididymus is

clogged (unable to ejaculate)

Chloride traps sodium, increasing the salt

content and thickness of secretions

Obstructive lung disease develops over the

years (unable to cough up thick mucus)

Affects GI tract, lungs, pancreatic duct, sweat

glands and epididymus

Worst bacterial enemies:

IgA
Lipase- little fat break down
Amylase: breaks alpha 1,4 bonds
Lysozyme: a detergent
HCO3:
sources off acid
HCO3 three
h
id

Staph Aureus and Pseudomonas Auregenosa

MUST cover Staph Aureus with one
antibiotic and Pseudomonas Auregenosa
with two antibiotics

From food- drinks

Produced by bacteria ( strep mutans)
Reflux

Dx: Pilocarpine: Cl sweat test

< 40 Normal
40 60 Heterozygous
> 60 CF

A normal phenomenon: GERD

INCISORS: cut 10 15 months
BICUSPIDS: chop 15- 18 months
MOLARS: grind 18 24 months

ESOPHAGITIS- tissue inflammation (T-cell/Mac)

BARRETTS ESOPHAGUS- short to long
columnar

P i
h fall
f ll out by
b age 8 and
d are
Primary
teeth
replaced by permanent teeth

MALORY WEIS SYNDROME- tears in submucosa

(ETOH, vomiting)
BOORHAAVES SYNDROME- Rupture of
esophagus

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4/29/2008

Tip of tongue rises >

Sides of tongue rise and fold medially >
Tip of tongue rises to hard palate >
Gravity begins bolus rolling >
When bolus approaches trachea
trachea, epiglottis
Closes off glottis >
Bolus rolls over epiglottis/touches the pharynx>
CN 9, 10 sense the bolus >
UES opens relaxes >
Bolus drops into esophagus

Masseter- closes
Temporalis- (closes) moves jaw forward and back
Medial Pterygoids (closes)
Lateral Pterygoids- (opens) lowers jaw
Innervated by cranial nerve 5 (Trigeminal)mandibular V3
Develop from first branchial arch

Nucleus Ambiguus: innervates the UESefferent vagus (motor CN 10)

UPPER ESOPHAGEAL SPHINCTER

Voluntary
Skeletal muscle in upper 1/3 of esophagus
Constrictors of the pharynx

Dorsal motor nucleus: innervates the rest

of GI efferent vagus (motor CN 10)

y p
y g
Stylopharyngeus

Primary peristalsis: requires vagus nerve

and Auerbachs plexus; begins just distal
to the UES only

Develops from 4th pharyngeal arch

Innervated by

CN 9(stylopharyngeus)
CN10(all others)

Nucleus
Ambiguous

Secondary peristalsis: intrinsic to smooth

muscle; can begin anywhere in GI

1 Peristalsis
UES

- Vagus CN 10
- Auerbauch (VIP)

2 Peristalsis
- Stretch from food

No receptive
relaxation:
Achalasia

Dorsal motor nucleus

of CN 10 (Vagus)
LES

Receptive
relaxation

6
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4/29/2008

Esophageal Pathology

Choanal atresia: lack apoptosis /bluefeeding

Esophageal atresia w/ distal TE fistula
Vomit on first feeding

Zenckers: congenital
Traction diverticula: occurs due to large bolus

UES

Schatzki rings:
-Intermittent
dysphagia
- Around LES

LES

Plummer
Vinson
Syndrome

UES

Iron deficiency

Zenckers
Diverticulium C
Congenital
it l

Traction
Diverticulium

LES

Strips of mucosal tissue- lack apoptosis

Risk of esophageal cancer
Young woman
Microcytic anemia

Patients with a history of GERD > 5 years

(Screening for Barrettes esoph.-sq. to columnar)
Tx: PPIs, upper endoscopy every 2-3 years

Abnormal esophageal acid exposure

> 4 week trial of PPIs still having symptoms
E l d GERD iin patients
i
i h unexplained
l i d
Exclude
with
chest pain

Patients with long standing cirrhosis: screening for

varices
Tx: Propranolol- decreases risk of bleeding

GERD symptoms with a negative upper

endoscopy

7
141

4/29/2008

Best initial test for dysphagia

Diagnosis:
Dysphagia
Unexplained chest pain w/o mechanical obst.

Not the best test if the problem is due to an

obvious obstruction, then the best test is
upper endoscopy

Transducer
T
d
placed
l
d iin esophagous
h
to record
d
pressure

Achalasia- bird beak

Most accurate test for Achalasia, Esophageal spasm

Diffuse esophageal spasm- cork screw

Diagnosis: GERD
NGT placed at the esophageal junction
Dilute
hydrochloric
Dil
h
d
hl i acid
id iis iinjected
j
d through
h
h
the NGT to reproduce the symptoms of GERD
OLD TEST..PPIs and 24 hour pH monitor

ALWAYS THE WRONG ANSWER !!!!!!!!!

Orad
Region

Fundus
LES

Caudad
Region

Cardia

Orad region- fundus and proximal portion of

the body

FOOD

Thin muscle wall

Caudad region - distal portion of the body

and the antrum

Body

Pyloris

Thicker muscle wall

Region responsible for mixing the food

Antrum
G cells
Duod

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4/29/2008

Mechanoreceptors detect distension of

the stomach and relay this information
to the CNS via sensory neurons

Receptive relaxation: relaxation of the lower

esophagous sphinctor and the orad region to
accept food into the stomach.

CNS then sends efferent information to

the smooth muscle wall of the orad
stomach, causing it to relax

Vagovagal reflex
reflex- both afferent and efferent
limbs of the reflex are carried in the vagus
nerve

VIP

Neurotransmitter released from

f
the
postganglionic vagal nerve fibers is VIP

Afferent

Vagotomy eliminates receptive

relaxation

Vagus
Efferent

During fasting- periodic gastric contrations

occur MMC
migrating myoelectric complexes

Takes approximately 3 hours to empty

Mediated
d
d my Motilin
l

Rate must be regulated to provide adequate time to

neutralize the gastric H+ in the duodenum
adequate time for absorption of nutrients

Occur ever 90 minutes

Function to clear the stomach of any
residue remaining from a previous meal

Four major components:

Two factors slow or inhibit gastric emptying:

Hydrochloric acid (HCL)- function is to reduce pH for

the conversion of pepsinogen to pepsin

Fat and H+ in the duodenum

Fat- mediated by CCK (secreted by duodenum)

Pepsinogen (inactive) Low pH converts it to the active

form- pepsin for protein digestion

H+- mediated by reflexes of the enteric nerves (myenteric

plexus) ensures content is delivered to the duodenum
slowly

Intrinsic factor-for the absorption of Vit. B12 in the

ileum (essential)
Mucus- protects the gastric mucosa from HCL

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4/29/2008

Glands of the Antrum of the Stomach

Glands of the Body of the Stomach

Empty their secretory products via ducts
Opening of the glands are called pits
Lined with epithelial cells

Contain 2 cell type:

Mucus cells- mucus and HCO3 are

protective
G-cells (secrete gastrin into circulation)

Gastric
Lumen

Gastric
Lumen

Epithelial cells

Mucous cells

Parietal cells

Epithelial cells

Mucous cells
HCL & Intrinsic factor
G - cell

Chief cells

Mucus, Pepsinogen, and HCO3-

Gastrin

Pepsinogen

Mucus from goblet cells

Prostaglandins (PGE2)
HCO3: alkaline tide
Aspirinirreversible
block
Cox 1 & 2
A i i
i
ibl bl
kC
NSAIDs - reversible inhibit COX
Steroids

COX 1 GI

Misoprostyl- replace PGE

COX 2- Joints

Gastric ulcers due to lack of blood supply;

sympathetic output causes vasoconstriction

(Vasocon/Vasodilation- alprostadil)

CUSHINGS ULCER

Cox 2 inhibitors

Celecoxib- only one left

Rofecoxib- off the market
Valdecoxib off the market
(problem if on > 18 mo)- block

CURLINGS ULCER
STRESS ULCER

prostacyclins- inhibit platelet agg.

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Regulation of H+ Secretion

Type B gastritis (located in antrum)

Is the most common cause of upper GI

bleeding in older children and adults

Due to a breakdown in barrier protection

Superficial erosions

NOT TOO MUCH ACID!

Type A Gastritis (located in body)

Autoimmune etiology
Antiparietal cell antibody
Atrophic gastritis
Adenocarcinoma risk

Associated with Helicobacter Pylori

Body

Gastric Ulcer

Duodenal Ulcers

Pain is worse during the meal

Pain is worse 30 to 40 minutes after a meal and

also at night

Located in the antrum

Located in the second part of the duodenum

Associated with H. Pylori 70% of time

Associated with H. Pylori 95% of time

Associated with CANCER 20% of time

Cancer risk < 1%

Endoscopy on ALL patients

Treat empirically with medication

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Surgical indications:

Definition: a mass made of

undigestible materials

Intractable pain- meds fail

Hemorrhage massive UGB
HemorrhageObstruction- Scarring
Perforation- Retroperitoneal
R/O- CT

Most common type:

yp Hair
Causes a gastric outlet obstruction
TX: endoscopy and removal

SLIDING TYPE: 90%

ROLLING TYPE:

Involve sliding of the fundus into the esophageal

hiatus

Due to a defect in the diaphragm

q
g y
surgery
Requires

MCC: obesity; restrictive lung disease

Risk of strangulation and infarction

TX: conservative measures; medications;

surgery( Nissan fundoplication)- no belch

High incidence of GERD

Hypertrophy of the pyloric muscle

Rare

Presents at 3 to 4 weeks of life

Large RUGAL FOLDS on biopsy

PROJECTILE
vomiting
J
g

H
l i off goblet
bl cells
ll
Hyperplasia

Olive sign; string sign on Barrium;

Cells ooze out proteins

Like nephrotic syndrome
Low albumin

DX: ultrasound
TX: correct fluids and electrolytes
pyloromyotomy

12
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4/29/2008

PROTEIN: no protein digestion in the mouth;

significant digestion in the stomach;
completed in the small bowel
SUGARS: significant
g
digestion
g
in the mouth;; it
stalls in the stomach; completed in the small
bowel

Now we call it CHYME

FATS: negligible digestion in the mouth; it

stalls in the stomach; completes in the small
bowel

Zymogens: inactive enzymes

Secretin
CCK
Motilin
GIP
VIP
Somatostatin
Enterokinase

First trypsin activated by

enterokinase
Trypsin then activates all other
enzymes

Lactase
Sucrase
Maltase
Alpha-dextrinase

Breaks alpha 1,4 glycosidic bonds

Lactose
Sucrose
Maltose
Alpha-dextrins
p

Sucrase def is most common primary

disacharidase deficiency

Fructose is only sugar with its own transport system

Lactase def is most common secondary

disacharidase deficiency
First enzyme to disappear in gastroenteritis; last
one to return( in about 48 hours)

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147

4/29/2008

Phlegmon: inflamed pancreas with the

intestines wrapped around it

The most common severe abdominal pain

Causes a severe ileus

Pain is mid-epigastric, boring through to the

back
Children: MCC is

Severe dehydration

(1)abdominal trauma
(2) infections

Ransons criteria:
Age > 55 years

Cocksackie B, Mumps virus

Blood sugar rises above 200

WBC > 16,000

LDH > 350
AST > 250

Adults: MCC is (1) alcohol

(2) gallstones

MANAGEMENT: (for ANY abdominal pain)

Poor prognosis in first 24 hours if

NPO
NG tube
IV normal saline
Meperidine
Abdominal x-ray

Patient needs more than 6 liters of fluid

pO2 < 55 (ARDS)
Hemoglobin drops by 2 or more grams
Calcium drops to below 8

Hemorrhagic pancreatitis:

Pseudocyst: has no epithelial lining

Bleeding into the retroperitoneal

Grey-Turner sign
Cullen sign

Can become infected ( abscess)

Tx: connect it to skin or small bowel

TX: subtotal pancreatectomy

Characterized by persistent high amylase

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RUQ colic (stone): pain comes in waves

Virchows triangle

Murphys sign: cessation of inspiratory

effort with RUQ palpation

Lecithin

Bile
Salts

80% are made of cholesterol (not seen on x-ray)

20% are made of calcium bilirubinate (hemolytic
anemia) excess biliruben
90% get lodged in cystic duct (Alk phos normal)

Cholesterol

10% get lodged in the common bile duct

(Inc. Alk phos)

3 clues for common bile duct stone:

Dx:

Pancreatitis

Ultrasound;
HIDA scan (most specific)- injectable radioactive

- if an obstruction- non visualization of gall bladder

phosphatase common bile duct

High alkaline phosphatase-

Management: like ALL abdominal pains

High WBC count and fever- pus backs up

NPO
NGT
IV
Opiates- meperadine (always start with)
ABD xray

Stone in common bile duct

Surgery: ERCP (endoscopic retrograde
choleangopancreotophagraphy-pull it out by mouth;
Laporoscopic cholecystectomy- 90% of cases
Asymptomatic gallstones-ursodeoxycolic acid

(DM, OCP, pregnancy) and schedule for surgery (60 % will

progress)

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Helps EMULSIFY fats

Bile acids:

Cholesterol go to the liver and forms

Cholic and Chenodeoxycholic acids
which are conjugated to Glycine and
Taurine to form bile salts

Comes from Phosphatidylcholine

Modified to make surfactant

Help EMULSIFY fats

Cholestyramine
Colestipol

Micelle
Short chain fatty acids
Medium chain fatty acids
Long chain fatty acids
Chilomicrons
Chil
i
VLDL
IDL
LDL
HDL

Side effects: need cholesterol to make

Estrogen
Steroids
Malabsorption (diarrhea)
Fat for energy
Fat soluble vitamins
Cause gall stone

Atherosclerosis
LDL and B100 Clathrin Pits

Metabolism of the lipoprotein is

defective

Symptoms:
70% Stenosis
FOAM CELL

Triglycerides, cholesterol or both can

be elevated

Events:
90% Stenosis
Atheroma

Cholesterol

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4/29/2008

Predisposes to xanthelesma and

pancreatitis

Predisposes to early coronary artery

disease and xanthomas

Defective metabolism of VLDL, IDL

or Chilomicrons

Defective metabolism of LDL

TYPE 1: elevated chilomicrons

STATINS: block HMG-CoA reductase

Main side effects: myositis; hepatitis

TYPE 2A: elevated LDL

Lovastatin
Provostatin
Simvastatin
Atorvastatin
Cirivastatin
Valdestatin
Reduvastatin

TYPE 2B: elevated LDL & VLDL

TYPE 3: elevated IDL
TYPE 4: elevated VLDL
TYPE 5: elevated VLDL & CHILOMICRONS

Cholestyramine- binds bile and blocks

Works best after 8pm

Gemfibrozil : increases LPL

Clofibrate

reabsorption

Colestipol

Niacin
Probucol

Niacin : (-) VLDL

Probucol

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4/29/2008

Intravascular hemolysis

Direct hyperbilirubinemia: conjugated

Vasculitis
Schistocytes
Low haptoglobin
Fibrin deposition in vessels
tear RBCs and platelets

Extravascular hemolysis
Splenomegaly
Something is wrong
with RBC membrane
Mcc: autoimmune
hemolytic anemia

DIRECT

Criggler-Najjar syndrome, type 2

Rotors syndrome
Dubin
Johnson syndrome
Dubin-Johnson

Indirect hyperbilirubinemia: unconjugated

INDIRECT

Low albumin
Gilbert syndrome
Criggler-Najjar syndrome
Type 1

The Ileum: in children

The Sigmoid: in adults

Newborns: choledochal cyst; biliary atresia

Children and adults: pancreatitis; gallstones;
sclerosing cholangitis; primary biliary
cirrhosis

Diverticulosis
Diverticulitis
Volvulus
Intussusception

After age 40: pancreatic cancer

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The last part of the small bowel

Begins with pain around umbilicus

(visceral pain)

An organ with NO known function

Pain settles into RLQ ( McBurneys point)

somatic
somatic pain
Caused by a fecolith
Management: like ALL abdominal pains
30% perforate in 24 hours
Incidental appendectomies can be done

The first part of the colon

LAST chance to REABSORB fluids and

electrolytes

The largest part of the colon

Cecal cancer has poor prognosis

Many Na-K pumps controlled by

aldosterone

Haustration

Haustration

Mass movement

Mass movement

Watershed area: spleenic flexure

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Relax pubococcygeus muscle

Rectum falls in line with sigmoid colon
Gravity and distention start moving stool
down
Once stool touches internal anal sphincter,
f
f
first
urge to d
defecate
occurs
Once stool touches external anal sphincter,
last urge to defecate occurs
Relaxation of pelvic floor muscles relaxes
both sphincters
NO sympathetic input to defecation

Sits at a 90 degree angle with the

descending colon AND rectum
Pubococcygeus muscle forms the
sling that holds the rectum at 90
degree angle

Duodenum

Jejunum

Amino
Acids

90

FATS

80

Sugars

90

Iron

Ileum
Ca-carbonate
Aluminum hydroxide
Mg-hydroxide
Gaviscon
Sucralfate
Bismuth
h
H-2 Blockers

90

A,D,E,K,
B12
All else

100

PPI

Omeprazole
Esomeprazole
Pantaprazole
Robeprazole
lomeprazole

Cimetidine
Ranitidine
Famotidine
Nizatidine

90

Simethicone

Mineral oil

Loperamide
Diphenoxylate

Cisapride
Metachlopramide

Psillium
Sorbitol
Mg-citrate
Phenophthalien
Docussate sodium

Sulfasalazine
Sulfapyrazone

Abetalipoproteinemia
Ataxia telangiectasia
Selective Ig-A def
H
h i disease
di
Heavy
chain
Celiac Sprue
Tropical Sprue
Necrotizing enterocolitis

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Irritable bowel syndrome

Spastic colon
Whipples disease
Toxic megacolon
Ischemic bowel

Crohns disease

Women
Transmural
Melena
Granulomatous
Creeping fat
Cobblestoning
Skip lesions
From mouth to anus
Starts in ileum
Fistulas

Ulcerative Colitis

Men
Hematochezia
Mucosal
Starts in rectum > prox
Pseudopolyps
Continuous
HLA B-27
Sclerosing choolangitis
Toxic megacolon
Lead pipe colon
Colon cancer risk: 10%
at 10 years
Begin annual colonoscopy
at 7 years

Newborns: swallowed maternal blood

Children: epistaxis
Adults:
Ad l gastritis
ii
Massive UGI bleeding

Children: meckels diverticulum

Adults: Peptic ulcer disease

Newborns:

Newborns: swallowed maternal blood

Choanal atresia

Infants: anal fissure

C-type esophageal atresia

Child
l
Children:
polyps

Duodenal atresia

Adults: IBD
Elderly: Angiodysplasia
Diverticulosis
Cancer

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3 to 4 weeks old

4 to 6 months old

Pyloric
stenosis
y

achalasia

2 years to 40 years

6 months to 2 years of age

intussusception

Adhesions
Internal hernias

FIRST year of life

1 year to 40 years

Hirschsprungs
Hirschsprung s disease

Adhesions
Adhesions

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After age 40

GI
Management

Adhesions
Obstipation
Obstipation
Diverticulitis
Cancer

Measurement of radiolabeled carbon dioxide after

the oral ingestion of labeled urea

Detect steatorrhea as a sign of fat

malabsorption

H. pylori splits urea with urease

Pick Sudan black stain when you see a patient

with chronic pale
pale, greasy
greasy, malodorous
diarrhea and no evidence of infection

Confirm eradication of H
H. pylori
If ulcer is found on endoscopy, the test of choice
will be biopsy, not urea breath test

Suspect chronic pancreatitis in pts w/steatorrhea

Wheat or gluten (gliadin) antigens

Trypsinogen levels are low from a burned out

pancreas

DX of celiac disease

Pick trypsinogen level only after Sudan black stain has

confirmed a fat malabsorption

Small bowel biopsy is the most accurate test for

celiac disease

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Differentiate between intestinal malabsorption and

chronic pancreatitis

Best initial test for Wilsons disease

D-xylose is a sugar that should be absorbed if the small

bowel is intact

Unexplained hepatic and psychiatric abnormalities

with movement disorder

Low urine levels of D-xylose- defective intestinal mucosa

( Celiac, tropical sprue and Whipples disease)

Low ceruloplasmin levels = Wilsons disease

Most accurate test is a liver biopsy

Best initial test in the diagnosis of acute pancreatitis

Best initial test for autoimmune hepatitis

Lipase is more specific to the pancreas

Young female with liver disease

y
g to the salivary
y
Amylase
can be elevated from damage
glands, esophagus or small bowel

Liver biopsy most accurate test

Most accurate test for acute pancreatitis is abdominal

CT- indicator of the need for a pancreatic biopsy

Best initital test for primary biliary cirrhosis

(PBC)
Middle aged female with itching (pruritus) and
an elevated alkaline phosphatase with normal

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Endocrinology, cont

ENDOCRINOLOGY

Exocrine: secreted into a cavity (pancreas)

Paracrine: secreted, then works only in the vicinity
(somatostatin)
Autocrine: secreted by the cell it works on
(granulosa cells)
Apocrine ( merocrine) tip of cell is secreted with the
substance (sweat glands)
Holocrine: entire cell is secreted with the substance
(sweat glands of the arm pit and groin)

HORMONE

HORMONES

Name and where it comes from

Main stimulus
Main inhibitor
Where does it go?
g
What is the main action?
What is second messenger?
Miscellaneous syndromes

STEROID HORMONES PROTEIN HORMONES

Fat soluble
Nuclear membrane
receptor
Affect DNA replication,
transcription and
translation
Work via proteins
NO second messengers

Water soluble
Cell membrane
receptors
Work via second
messengers

ERYTHROPOETIN
Made by:

renal parenchymal cells

Signal:

hypoxia ( NOT anemia)

Inhibitor:

increased oxygen

Where it goes: bone marrow

What it does: erythropoiesis
Second messenger: tyrosine kinase

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POLYCYTHEMIA

POLYCYTHEMIA

[Link] erythropoietin

Increased erythropoietin: due to hypoxia

Normal erythropoietin:

Acute hypoxia: tachypnea and dyspnea

Chronic hypoxia: clubbing
(angiogenen new vessels)
(angiogenen-new
Restrictive LD; COPD;
RENAL CELL CARCINOMA- adults
Wilms tumor- children

Gaisbock syndrome;
Stress polycythemia;
Spurious (not real) ;
Due to loss of plasma volume

POLYCYTHEMIA
Decreased erythropoietin:
You have a cancer !!!!!!!!
Angiotensin II

g on its own
Bone marrow is acting

ACTH

POLYCYTHEMIA RUBRA VERA

Essential thrombocythemia
(platelets>600000)

ACTH

ADRENAL CORTEX

ALDOSTERONE, cont
Miscellaneous syndromes: (tumor)

Zona Glomerulosa: ALDOSTERONE

Stimulus: hypovolemia; hyponatremia; hyperkalemia

Too much: CONNS SYNDROME

Hypernatremia
Hypokalemia (K freely filters out)
Alkalosis (K/H exchange)
Hypertension (3 H2O for every Na+)

Inhibition: hypervolemia
Where it goes: late DCT
What it does: stimulate synthesis of Na-K pumps
Second messenger: none

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ALDOSTERONE, cont

21 Hydroxylase deficiency:
Decreased Aldosterone [mineral corticoid]

Too little: ADRENAL INSUFFICIENCY

(Na+ wasting)- hypotension

21 hydroxylase def
11 hydroxylase def

Lo cortisol
Low
co tisol [Gl
[Glucocorticoid]
coco ticoid]
no feedback by ACTH

In adults:
Abrupt withdrawal of steroids
Autoimmune adrenalitis

Increased Androgensvirilization

11 Hydroxylase deficiency:

Zona Fasciculata

Excess 11-Deoxycorticosterone-

CORTISOL

retain salt HTN

Stimulus: stress; hypoglycemia

Aldosterone decreased desmolase rate limiting

step
t iin th
the pathwayth
allosteric
ll t i activatorti t
AT II
AT-II

Inhibitor: hyperglycemia

(down regulated due to the HTN)

Where it goes: everywhere >PERMISSIVE

Low cortisol- no ACTH feedback

What it does: up regulates ALL receptors during stress

Increased Androgen production- virilization

Second messenger: none

Cortisol, cont

CORTISOL
Physiologic affects
Proteolysis
Gluconeogenesis
(break down protein
to make glucose)

Too little: Adrenal insufficiency ( Addisons )

Too much: CUSHINGS SYNDROME

Anti-inflammatory

Pituitary adenoma: Cushings disease (to much ACTH)

Small cell carcinoma: Cushings disease
Adrenal adenoma: Cushings syndrome

Kills T-cells and

eosinophil
Inhibit macrophage
migration
Stabilizes endothelium
Stabilizes mast cells
Inhibits phospholipase-A

Disease affects one organ

Syndrome affects many organs

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Dexamethasone suppression test

Dexamethasone suppression test

Lo-dose: 0.5mg IV Q6 x 4
If suppression occurs

Hi dose: 1 mg IV Q6 x 4
If suppression occurs
Pituitary adenoma

Obesity
Depression
Normal variant

If suppression does NOT occur

Check ACTH levels:
High ACTH: SMALL CELL CARCINOMA
Low ACTH: ADRENAL ADENOMA

ZONA RETICULARIS

TESTOSTERONE

Testosterone

DHT: made in testes by 5 alpha reductase

Stimulus:
Controls male external genitalia in utero
Increase in appetite
Aggression and violence
Increases libido and RBC count
Stimulated by ACTH

Leads to secondary male characteristics at

puberty.
Responsible for hair growth
Too much leads to hair loss, especially in the
middle and front of scalp

Male patterned baldness

FENESTERIDE blocks 5 alpha reductase
FLUTAMIDE blocks DHT receptors

Second messenger: none

ADRENAL MEDULLA

Pheochromocytoma or Neuroblastoma

Epinephrine:

An excess of NE and Epi

Intermittent palpitations, HTN, diaphoresis and headache

Stimulus: stress/hypoglycemia
Inhibition: hyperglycemia
Where it goes: liver and adrenal cortex
What it does: gluconeogenesis;
glycogenolysis
Second messenger: c-AMP
Misc. syndromes

Neuroblastoma:
hypsarrythmia (dancing eyes)
opsoclonus (dancing feet)

Dx: measure urinary VMA and metanephrines

( dopamine > HVA)
Phentolamine- short acting alpha blocker for diagnosis
Tx: phenoxybenzamine (longer acting, not specific)

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Pheochromocytoma or Neuroblastoma

Pheochromocytoma

Difficult to differentiate benign from malignant

on biopsy; they look alike

24 hr urine collection
Metanephrine
Vanillyl mandelic Acid (VMA)
Catecholamines

Neuroblastoma is MOST common abdominal

mass in children
Pheochromocytoma

If elevated CT or MRI

10% are malignant

10% are bilateral
10% are in children
10% are familial
10% are metastatic at diagnosis

If CT or MRI find nothing:

meta-iodo-benzyl-guanidine (MIBG) scinigraphy

(NE analogue that concentrates in the adrenals)

Stress Hormones
Epinephrine:
immediately
Glucagon: within 20
minutes
Cortisol: within 2 to 4
hours
GH: after 24 hours

Pancreatic Hormones

Insulin: within 30 min

ADH: within 30 min

Glucagon: from ALPHA cells

Insulin: from BETA cells

Insulin pushes the

i t cells
ll and
d
sugar into
ADH normalizes the
osmolarity

Somatostatin: from DELTA cells

THESE PRODUCE THE

SUGAR

Pancreatic Polypeptide: from F cells

Glucagon

Glucagonoma
Pancreatic tumor

From: pancreatic alpha cells (1 receptors)

Stimulus: hypoglycemia and stress
Inhibition: hyperglycemia
Where it goes: adrenal cortex, liver, and
adipose
di
tissue
ti
What it does: gluconeogenesis (raises
sugar), glycogenolysis (glycogen), lipolysis
(fat), and ketogenesis
Second messenger: c-AMP
Misc. syndromes

High glucose; high lipids; and high

ketones
Related to MEN I ( Wermers)
Hormone responsible for KETOACIDOSIS
in type 1 diabetes

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lnsulin

cells of the pancreas

From: pancreatic islet cells cells

(2 and 2 receptors)

Stimulus: hyperglycemia
Inhibition: hypoglycemia
Wh
Where
it goes: everywhere
h
exceptt BRICKLE
What it does: increase all anabolic
processes
Second messenger: tyrosine kinase
Misc syndromes

Somatostatin

Insulinoma vs Nessidioblastosis
INSULINOMA

NESSIDIOBLASTOSIS
Seen primarily in
seen primarily in
adults
infants
Causes hypoglycemia
causes
hypoglycemia
M
Measure
hi
high
h iinsulin
li
and high C-peptide
measure high insulin
and high C-peptide
Dx: cat scan
Tx: subtotal
Tx: remove surgically
pancreatectomy

From: pancreatic DELTA cells

Stimulus: insulin and glucagon
Inhibition: low insulin and glucagon
Where it goes: paracrine
Wh
What it does: inhibits insulin and glucagon
Second messenger: c-AMP
Misc. syndromes

Somatostatinoma

Pancreatic Polypeptide

Usually a pancreatic tumor

Severe constipation
Dx: cat scan
Tx: surgery

NO KNOWN FUNCTION!
Whatt iis the
Wh
th only
l know
k
organ with
ith no
known function?

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GI Hormones
Stomach

GI
HORMONES

Gastrin

Duodenum
Secretin
CCK
Motilin
GIP
VIP
Somatostatin

Secretin

CCK

From: duodenum
Stimulus: low pH
Inhibition: high pH
Where it goes: paracrine (pancreas &
gallbladder)
What it does: stimulates production and
secretion of bicarbonate ions from pancreas
& GB
Second messenger: c-AMP
Misc. syndromes: none

From: duodenum
Stimulus: food, especially fats
Inhibition: high pH
Where it goes: pancreas (digestive enzymes)
and gallbladder (bile)
What it does: primarily fat and protein
digestion
Second messenger: IP3/DAG
Misc. syndromes: none

GIP

GIP Syndromes

From: duodenum
Stimulus: glucose
Inhibition: high pH
Wh
Where
it goes: pancreatic
ti iislet
l t cells
ll
What it does: enhances insulin secretion
Second messenger: c-GMP
Misc. syndromes

Dumping Syndrome: seen after Bilroth ll

procedure
Increased osmotic load dumped Into duodenum
Causes osmotic diarrhea
Can also cause postprandial (reactive)
hypoglycemia

Causes insulin resistance over time (type 2

diabetes)

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Somatostatin

VIP

From: duodenum
Stimulus: duodenal hormones
Inhibition: high pH
Where it goes: paracrine
What it does: purely inhibitory
Second messenger: c-AMP
Misc. syndromes: somatostatinoma

From: duodenum (from Auerbachs

plexus)
Stimulus: duodenal hormones
Inhibition: high pH
Where it goes: paracrine
What it does: purely Inhibitory to all
duodenal hormones
Second messenger: c-AMP
Misc. syndromes

Vipoma

Gastrin
From: antrum of stomach
Stimulus: high pH
Inhibition: low pH
Where it goes: parietal cells of the
stomach (mostly in the body of stomach)
What it does: production of HCL and
intrinsic factor (for absorbing VIT B12)
Second messenger: calcium
Misc. syndromes

Usually a pancreatic tumor

WATERY or secretory diarrhea
Dx: cat scan
Tx: surgery

Gastrinoma

ANP ( B-type natriuretic peptide )

From: right atrium
Stimulus: high volume (stretch of right Atrium)
Inhibition: low volume
Where it goes: kidney
What it does: dilates the afferent renal artery;
inhibits aldosterone
Second messenger: nitric oxide
Misc. syndromeleads to polyuria, nocturia and
hyponatremia in right atrial distention

Usually a pancreatic tumor

Zollinger-Ellison syndrome
Gastrin levels are high all the time
Can be part of MEN-1 syndrome

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PTH

PTH
VITAMIN D
CALCITONIN

Superior parathyroids: 4th pharyngeal pouch

Inferior parathyroids: 3rd pharyngeal arch
Stimulus: low calcium; high phosphorus
Inhibition: high calcium; low phosphorus
Where it goes: (1) osteoclasts of bone (2)late
DCT
What it does:
(1) stimulate osteoclastic activity
(2) increases secretion of phosphorus
(3) activates 1-alpha hydroxylase

CALCIUM
METABOLISM

PTH, cont

PTH Syndromes

Second messenger: c-AMP

Misc. syndromes

HYPO-PARATHYROIDISM
Primary: due to thyroidectomy
Pseudo:
P
d receptor
t nott working;
ki
short
h t 3rd
th
and 5 digit
Pseudopseudo
HYPOPARATHYROIDISM : only
difference is that calcium is normal

PTH Syndromes

Vitamin D

HYPER-PARATHYROIDISM

From: skin > liver > renal

Stimulus: low calcium; low phosphorus
Inhibition: high calcium; high phosphorus
Where it goes: (1) kidney and (2) GI
What it does: (1) production of Ca-ATPase and
(2) production of CBP ;(3) stimulates
osteoblastic activity
Second messenger: none
Misc. syndromes

Primary: due to parathyroid adenoma;

MCC of isolated hypercalcemia in adults
Secondary: due to renal failure

Renal Osteodystrophy
Osteitis Fibrosa Cystica- fibrous tissue
Osteopenia- low density
Osteomalacia- nutrition
Osteosclerosis- trauma

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Calcitonin

Vitamin D syndromes

From: parafollicular cells

Deficiency: Osteomalacia in adults; Rickets in

children

Stimulus: high calcium

Excess: high
g calcium; high
g p
phosphorus
p

Inhibition: low calcium

Where it goes: bone
What it does: inhibit osteoclastic activity
Second messenger: c-AMP
Misc. syndromes

Bisphosphonates

MEN Syndromes

Inhibit osteoclastic activity like calcitonin

MEN 1: pituitary adenomas, parathyroid

adenomas, and pancreatic adenomas
(Wermer syndrome)

Second line drugs for osteoporosis

MEN 2: medullary carcinoma of thyroid (high

calcitonin), pheochromocytoma, plus or minus
parathyroid adenoma( Sipple syndrome)

Very corrosive in the GI

MEN 3: men 2 with neuroma/ganglioneuroma but

minus parathyroid adenoma

Stored in bone for up to 20 years

i.e. etidranate; elandronate; ibondranate,
residronate

Causes osteonecrosis (if received via IV)

Prolactin:

Hypothalamic Hormones

Stimulate PRL release- nipple

stimulation
Inhibit PRL release- DA

Pituitary Hormones

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Dopamine Agonists

Dopamine Blockers (D-2)

L-Dopa/Carbidopa
Bromocriptine- old (stop lactation)
Selegyline- MAO type B, increases extracellular
dopamine
Amantadine- antiviral (influenza A)

Phenothiazines

(-) prolactin- cant lactate

N/V CTZ
Movement disorders- gross motor

Thioxanthenes

Dopamine Blockers (D-2)

Pituitary Tumors

Chlorpromazine
Prochlorperazine (Compazine): anti-N/V
Promethazine
Fluphenazine
Thioridazine- pigment retinopathy

Thiothixene- long acting (>30 days)

Butyrephenones

Nonfunctional (chromophobic) adenomas: most

common pituitary tumor

Haloperidol- antipsychotic- schizophrenia, psychosis

Droperidol - antimetic

Prolactinoma: most common functional pituitary

tumor

At i l block
Atypicals:
bl k D
D-4
4 receptors
t
Used for negative symptoms
Used when pt has had extrapyramidal side effects
Clozapine- agranulocytosis
Onlazapine- wt. gain
Resperidone- neuroleptic anesth.
(fever, muscle stiffness)

ALL pituitary tumors associated with high prolactin

levels
High PRL > galactorrhea and amenorrhea

Hypothyroidism

Hypothyroidism:

Cretinism- Mom and fetus- hypo

T4

TSH

TRH

T4

TSH

TRH

T4

TSH

TRH

Iodine deficiency
Hashimotos disease
DeQuarvains disease- Virus (painful)-self limiting
Lymphocytic thyroiditis (postpartum )
Riedels Struma- capsule cancer (woody)
Tx: Thyroxine(T-4) or L-Thyronine (T-3)

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Hyperthyroidism

THE
END

Graves Disease ( autoimmune) < 50 y/o TSH

antibody
Plummers Syndrome: toxic multinodular goiter
> 50 y/o one area hot (iodine takeup)

Tx: propanolol
Propylthiouracil- blocks peroxidation
Methimazole- block peroxidation
I-131- destroy the tissue
Thyroxine- replacement

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First Step: Distribution

Polyarticular symmetric-

Rheumatology
gy

Monoarticular arthritis
Oligoarticular asymmetric-

Steps to evaluate a patient

Migratory arthropathy-

Polyarticular symmetric

First Step: Distribution

Polyarticular symmetric:

Rheumatoid arthritis (RA)

SLE (spares joint destruction)
Viral (Hep
(Hep. B,
B EBV,
EBV CMV
CMV, B19)

Monoarticular arthritis
Oligoarticular asymmetric
Migratory arthropathy

Monoarticular arthritis

First Step: Distribution

OA
Gout
Septic arthritis

Polyarticular symmetric:
Monoarticular arthritis:
Oligoarticular asymmetric:
Migratory arthropathy:

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Oligoarticular asymmetric joint

First Step: Distribution

Spondyloarthropathies

Polyarticular symmetric:
Monoarticular arthritis:
Oligoarticular asymmetric:
Migratory arthropathy:

Migratory arthropathy

Second step:

Rheumatic fever
Gonococcal arthritis (disseminated)
Lyme disease

Osteoarthritis

Pain move around the body

Septic arthritis

Acute or Chronic

Crystal induced

Third step:

Fourth step:

Is there any evidence of systemic

symptoms?

Any evidence of inflammation?

OA:

Lungs:
Kidney:
CNS:
Skin:
Hemotologic:

RA:

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Inflammation association

CASE 1

Morning stiffness > 1hr

72 y/o woman
presents with left
knee pain.

Red,, warm,, tender

Erythematous joint
Increased ESR and CRP

CASE 2

Monoarticular

30 y/o female
presents with wrist
wrist,
MCP and PIP
swelling and pain.

OA (chronic)
Septic (acute)
Crystal induced (acute)

CASE 3

32 y/o male presents with

knee swelling after you had
seen him for left wrist pain
the day before which has
now resolved.

Polyarticular
SLE
Viral
RA

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Case 4

Migratory arthropathy

25 y/o female presents

complaining of right
knee pain and swelling
and left hip pain.

GC
GC
Rheumatic fever
Lyme disease

Oligo-arthropathy

Test in
Rheumatologic
diseases

Spondyloarthropathy (Reiters)

Test:

Test:
Joint Aspiration: whenever there is fluid
in a joint, you need to aspirate it

Joint Aspiration: whenever there

is fluid in a joint, you need to
aspirate it

Exception: Contraindication
Bleeding disorders
Anticoagulants with bleeding diathasis
Cellulitis overlying

Exception: Contraindication

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Test:

WBC ranges
OA / Traumatic arthritis

Always order the 3 Cs and a

gram stain
1.
2.
3.

Inflammatory (RA, Gout)

Septic arthritis

Crystals:

Anti-Nuclear Antibodies (ANA)

Antibodies against part of the
nucleus

OA / Traumatic arthritis
RA
SLE
Gout
Pseudo gout
Septic

10% of normal people have + ANA

High AB titer

Anti-Nuclear Antibodies (ANA)

If you think the patient may have

SLE, what is your first step in
management?

97% of SLE patients have a + ANA

So
S if the
h test results
l come b
backk
negative, assume they dont have
SLE

If positive, order

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Ab association

Rheumatoid Factor (RF)

SLE (60%), lupus nephritis

SLE (30%)
Drug induced lupus
Neonatal lupus, Sjogrens
Sjogrens
CREST
Mixed connective tissue dz.

Antibodies against antibodies

Fc portion of IgG
Increase with age

Anti-Neutrophilic Cytoplasmic
Antibodies (ANCA)

Diseases:

Antibodies against certain

proteins in the cytoplasm of
neutrophils.

Rheumatoid Arthritis
Systemic Lupus Erythematosus
Scleroderma (SSc)
Sjogren Syndrome

(c) ANCA:
(p) ANCA:

Rheumatoid Arthritis

Rules of 6:

Chronic inflammatory disease

Morning stiffness > 1 hr - for at least 6 weeks

Target- Synovium

Swelling of wrist, MCP, PIP 6 weeks

Symmetric distribution

Swelling of at least 3 joints- 6 weeks

Potential to destroy cartilage and bone

erosion

Symmetric joint swelling 6 weeks

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Extra-articular manifestations

Labs for RA

Damage to tendon and ligaments

RF
Anemia
ESR

Boutinniere deformity- PIP flexion, DIP extension

Swan neck deformity- PIP extension, DIP flexion

X-ray:

Rheumatoid nodules- vasculitis

Synovial fluid analysis

Caplan syndrome- rheumatoid nodules in lungs

Mgt. for RA

CASE 5

Patient with RA presents

with a swollen painful calf.
Diagnosis?

Old Tx:
NSAIDS > Steroids > Methotrexate (2yrs later)
NEW TX: Start with MTX
after 1 week add prednisone for 1 week
only use for flare-ups
Antimalarial- hydroxychloroquine- MTX backup

Alentoaxial Subluxation in RA

Systemic Lupus Erythematosus (SLE)

Systemic disease
Tissue and multiple organ damage by
antibodies and immune complexes

C1, C2
Dx: X-ray
X ray / CT

Remember: you can have all the criteria for

SLE, but if the ANA is negative, the patient
does not have lupus

Must rule out before surgery

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Organs involved with SLE

Diagnosis of SLE
Best screening test

CNS: confusion, personality change

Skin:
Kidney:
Lungs:
Hematologic:
Immune:
Bone:

ANA

Specific Abs associated

Complement levels (C3,C4,CH50)
Active lupus
Lupus nephritis

Case 6

Pregnancy and SLE

Fertility rates:

26 y/o female, admitted for

confusion. Hx. SLE and was recently
pp
off p
prednisone ((10
tappered
mg/day). Pt was fine a couple of days
ago. PE- no focal deficits.
DDx?

Spontaneous abortions and still births

DOC Mgt.:
Exacerbation (flare up) DOC:
All pregnant women with SLE need to be
screened:

Mgt. SLE

Drug induced lupus

NSAIDs for arthritis

Limited form of lupus due to a drug

Antimalarials: Chloroquine

No major organ involvement

Steroids: for major organ involvement

Dx: rash + anti-histone antibodies

(complement normal)

Cytotoxins:

Mgt: Discontinue offending drug

Azathioprine
Cyclophosphamide

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Scleroderma (SSc)

CREST syndrome

Chronic multisystem disease

Thickening of the skin
Raunaud phenomenon
g involvement
Visceral organ

Limited form of scleroderma

Symmetrical skin thickening
C
R
E
S
T

GI: esophageal dysmotility, hypomotility of small

intestine
Pulmonary
Renal

Anti-centromere antibodies

Sjogren Syndrome

Spondyloarthropathies

Chronic auto-immune disease

Ankylosisng spondylitis

Xerostomia and dry eyes

Reactive Arthritis

Lymphoproliferative disease- Malignant lymphoma

Psoriatic Arthritis

Bilateral parotid enlargement

Enteropathic arthropathy

Itchy eyes, sand under their eyes

Keratoconjunctivitis sicca

Ankylosing spondylitis

Extra-articular manifestations AS

Inflammatory disorder of axial skeleton and peripheral

joints

Cardiac:

Rare after age 40

Spine:

90% of patients + HLA-B27

Eyes:

Young male 20s, chronic lower back pain, morning

stiffness > 1hr, get better with exercise

Skin:

Cervical spine involvement- late stage of the disease

Mgt: NSAIDs, Physical therapy, Exercise

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Reactive Arthritis:

Reactive Arthritis Mgt.

Complication of an infection somewhere in

the body.
Non-Gonococcal urethritis:

NSAIDs
Antibiotics (prompt)

1.
2.

Infectious diarrhea:
1.
2.
3.

Psoriatic Arthritis

Enteropathic Arthropathy
Ulcerative colitis
Crohns disease

DIP joint
Nail pitting
Sausage shaped digits

Skin lesions:
Pyoderma gangrenosium
Erythema Nodosum

Osteoarthritis (OA)

Osteoarthritis (OA)

Target- articular cartilage

Hypertrophy of bone
NOT an inflammatory disease

Target- articular cartilage

Hypertrophy of bone
NOT an inflammatory disease

MC joint affected?
2nd most common joint affected?
Joint involved with the greatest disability?

MC joint affected? Knee

2nd most common joint affected?
Joint involved with the greatest disability?

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Two forms of OA:

Association with OA

Idiopathic

Joint pain with exercise

Secondary (cause)

Relieved by rest

Arthropathies - gout
Endocrine dz
Desosition dz
Mechanical factors

Morning stiffness (< 20- 30 min)

Slow, progressive, irreversible
NO systemic manifestations

Labs with OA

Mgt. with OA

CRP and ESR : Normal

X-ray:

Non- pharmacological
Correct poor posture
Weight reduction
Physical therapy

Osteophytes
Unequal joint space
Bouchards nodules (PIP)
Heberdens nodules (DIP)

Drug therapy
First drug- Acetaminophen (contra: use ibuprofen)
Add Capsaicin

Orthopedic surgery and joint

arthroplasty

Crystal Induced Arthropathies

Monosodium urate (MSU)

Unsatisfactory medical Tx

Calcium phrophosphate (CPPD)

Quality of life decreased

Calcium oxylate (CaOx)

Calcium hydroxyapatite (CaHA)

11
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Gout:

Predispose to Gout:

Acute Monoarthritis
Tophi:

Excess ETOH
Trauma
Infection

Metaatarsophalangeal joint (first toe):

Diuretics: Hydrochlorthiazide, Furosemide

First episode:

Anti-TB meds: Pyrazinamide

Ethambutol

Red, tender, warm

Diagnosis of Gout:

Mgt. Acute Gouty Arthritis

It is made with fluid analysis of synovial fluid

NSAIDs
Indomethacin 50 mg 3 x day

MSU crystals
Negative
N
i Birefringent
Bi f i
Needle shape crystals
WBC 5,000-50,000

Colchicine: 0.6 mg every hr until symptoms

resolve
Steroids: intraarticular or oral (elderly)

Chronic Hypouricemic Therapy

Pseuod-gout:

Low urine levels of uric acid

Usually life long therapy
Follow uric acid levels here !!!

CPPD crystal formation

Probenecid- under secretors

May present acute like gout

Allopurinol- over producers

Knee most common joint affected

Elderly and pre-existing joint damage

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Diagnosis of pseudo-gout

Septic Arthritis

Arthrocentesis:

MCC gonorrhea

Rhomboid crystals
+ Birefrengent

70% of cases > age 40

X-ray: linear radiodense deposits in joint

menisci Condro- calcinosis

Elderly- Staph aureus (pre-existing joint

destruction)

Mgt: same as acute gout

Mgt. Septic Arthritis

Non-GC: (older) Staph aureus

THE END

GC (younger) sexually active

Both WBC > 50,000 and negative crystals
Staph aureus- IV Vancomycin
GC- IV Ceftriaxone
Therapeudic arthrocentesis

13
183

REPRODUCTIVE
ENDOCRINOLOGY

Menstrual irregularities
The number one reason an adult woman
goes to see a doctor
The number one reason a teenage female
misses work or school (dysmenorrhea)

Dr. Naegle

Naegles Rule
Assumed that a womans menstrual cycle
lasts 28 days long
Allows us to calculate the EDC
Begin with the last first day of menses, go
forward 9 months or go backward 3 months,
then add one week
If the womans menstrual cycle varies from 28
days, then you add/subtract the difference at
the end

Some Rules

Naegles rule also allows us to

Term pregnancy: 37 to 42 weeks

Average birth weight: 2500gms to
3500gms (5 to 7 pounds)
Preterm: birth prior to 37 weeks
Postterm: birth after 42 weeks
SGA: small for gestational age
LGA: large for gestational age

1
184185

Oogenesis

Oogenesis: The Steps

One round of mitosis first: 2n to 4n (occurs in
utero)

Begins in-utero at about 5mo gestation

At birth, a female ovary contains about
400k eggs
Beginning at puberty, 8 to 10 follicles
begin development; but, only ONE egg will
ovulate

Primary oocyte

Enters meiosis 1 and arrests in Prophase (cells

still at 4n)
Eggs remain arrested in meiosis 1 in prophase
until ovulation occurs
If egg ovulates, it will complete meiosis 1, give
off first Polar Body, and enter meiosis 2,
arresting again in Metaphase(4n to 2n)

The eggs that do not finish development will

turn into small white nodules (corpus
albicans)

Secondary oocyte

Oogenesis: The Steps

If fertilization occurs, egg will complete
meiosis 2, give off the second Polar Body,
and form a zygote (2n to 1n)

Because moms eggs remain

arrested for SO long

Tertiary oocyte

You can trace 80% of

chromosomal mutations to MOM

2
185186

OCPs

HRT

Norethindrone
Mestranol
Depo-provera
Estrone
Estradiol
Estriol

Decreases symptoms
Decreases osteoporosis ( decreases
osteoclastic activity)
Decreases risk of CAD ( increase HDL;
vasodilator)
Controversy!!

Other Hormonal Drugs

Now, introducingTYRONE!

Clomiphene
Leuprolide
RU-486 (mifeprostone)

Spermatogenesis

Sertoli Cells

Begins at puberty
First sign of puberty in a male is testicular
enlargement
Controlled by testosterone
LH > testosterone > spermatogenesis
FSH > Sertoli cells > produce inhibin

Produce inhibin
Maintain the blood-testes barrier
Protect and nourish the sperm to maturity

3
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Spermatogenesis

Spermatogenesis, cont

One round of mitosis: 2n to 4n

Each day 20 to 40 million sperm mature

Complete spermatogenesis takes 41 to 72
days
Sperm can live for 5 days in fallopian tube
while an egg can live for only 3 days

Primary spermatogonium

Meiosis 1: 4n to 2n
Secondary spermatocyte

Meiosis 2: 2n to 1n
Tertiary spermatid

One spermatogonium gives rise to 64 spermatids

As spermatogonia mature, they move from the basal
layer into the epididymus to finish maturing

Virility

Infertility

20 to 40 million sperm per cc of semen

4 to 5cc of semen per ejaculate
No more than 40% abnormal forms
30 to 60% of sperm must still be motile
after 5 minutes on a glass slide
The pH is basic

50% male factor

Always do sperm analysis first

30% female factor

Mcc is PID

20% miscellaneous

Before Sperm Can Leave

Seminal vesicles: semen; fructose
Bulbourethral ( Cowpers ) gland: HCO3
Prostate: Zn ; acid phosphatase;
hyaluronidase

4
187188

Sexual Response

Sexual Dysfunction

The Difference Between the Sexes

In young men: premature ejaculation

In older men: stress induced impotence
In the elderly: vascular impotence

Men have a longer refractory phase; short

excitement phase
Women have a longer excitement phase;
short refractory phase

Atherosclerosis decreases blood flow

Takes longer to establish an erection
Harder to maintain an erection
Need for more direct stimulation
Longer refractory phase

To Address Premature
Ejaculation
Apply the SQUEEZE TECHNIQUE
Gently squeeze the head of the penis; it starts
retrograde peristalsis in the ejaculatory duct
and epididymus

5
188189

Once the sperm are deposited in

the vagina

Once the sperm are deposited in

the vagina

Sperm hide under the semen

HCO3 is released to neutralize lactic acid
Zn is used for the Capacitation Reaction
Fructose is used for energy
70% of sperm are dead before reaching
the cervix
Acid phosphatase is used to eat through
cervical mucus

Sperm enter the uterus

They swim through the fallopian tubes
By the time the sperm approach the egg,
only a few thousand sperm remain
Sperm surround the egg
They dart in and out, opening their heads
to release enzymes ( Acrosomal Reaction)

Once the sperm are deposited in

the vagina

Stages to Know

Once one sperm head fuses with egg, a

wall forms behind the sperm (
Crystallization Reaction)

Zygote: 2 cell stage

90% fertilizations occur in the ampulla
It must now migrate into the fallopian tubes
Ectopic pregnancy: mcc is PID (forms scars)

This prevents Polyspermy

A ZYGOTE is formed when egg (1n) and the
sperm head (1n) fuse

Morula: 16 cell stage

This stage enters the uterus

Blastula: 256 to 512 cell stage

This is the stage that implants

Formation of the Placenta

Placental Hormones

HCG
PROGESTERONE
ESTRIOL
HUMAN PLACENTAL LACTOGEN
INHIBIN
RELAXIN

6
189190

HCG

HCG, cont

Detectable in BLOOD one week after

fertilization; in the URINE two weeks after
Has the same alpha subunit as FSH. LH,
and TSH ( check the beta-HCG)

Maintains corpus luteum production of

progesterone
Can lead to Hyperemesis Gravidarum
DES
Cervical incompetence
Adenomyosis
Clear cell carcinoma of the vagina

Maintains the corpus luteum

Increases GI motility and absorption
Sensitizes the TSH receptor

Increases BMR

HCG, cont

How to Follow the First Trimester

Doubles every 2 days until week 12

HCG of 600: viable fetus
HCG of 2000: fetus visible on abdominal
ultrasound

Fundal height rises 1cm per week

Pubic symphasis = 12 weeks
Umbilicus = 20 weeks

HCG doubles every 2days

Estriol level rises linearly
If fetus dies: estriol level falls first

Think of Molar Pregnancy if

Progesterone

Fundus growing higher than predicted

HCG rising faster than predicted
HTN in first trimester
Complete mole
Incomplete mole

Increase RR from pons

Increase appetite
Pica
Increase RBC mass by 30%
Causes acne
Hyperpigmentation
Cloasma or malasma
Helps increase plasma volume by 50%

7
190191

Estrogen

Inhibin

Smooth muscle relaxation

Stimulates protein synthesis in the liver

Inhibits FSH
Prevents another menstrual cycle from
beginning

High ESR
Hyperlipidemia
Increased TBG
Increased angiotensinogen
Increased clotting factors

Human Placental Lactogen

Relaxin

BLOCKS moms Insulin receptors

Creates insulin resistance
Gestational diabetes

Relaxes tendons and ligaments

Stretches the pelvis

The END

8
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4/29/2008

Renal Embryology:
At different points of gestation, various
organs are embryologically developed.
For example:
- Notochord at 2 wks
- Brain at 4 wks
- Renal system is formed at 12 wks

METANEPHROS - give rise to the kidney

Renal
Pelvis

URETERIC BUD - gives

i
rise
i to
t the
th entire
ti
collecting system

Calyx

Collecting duct, major and minor calices, papillae,

hilum and ureters
URETERIC BUD

Metanephros

Ureteric bud must make contact with the

metanephros or kidney will NOT develop

Gives rise to the GENITALIA in MALES

Gives rise to female genitalia

Paramesonephros
(never functional)
as a kidney

Has
H kidney
kid
function prior
to kidney
formation

Develops into the ovaries, fallopian tubes, uterus and

upper vagina

Develops into the testes, seminal vesicles, vas

deferens and epididymus

A female can develop either by DESIGN or by DEFAULT

To develop, you need a Y chromosome and MIF

1
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4/29/2008

Vitelline Duct:

Allantois:

Omphalomesenteric duct

IN MALES: becomes the PENIS

IN FEMALES: becomes the CLITORIS
Urogenital Sinus

IN MALES: prostate, prostatic urethra and

bulbourethral ( Cowpers) glands

Urogenital
Tubercle

IN FEMALES: lower vagina, and labia minora

Cortex: outermost layer of the kidney.

L1 and L2 levels:
right kidney is positioned
slightly
li htl lower
l
th
than the
th left
l ft
kidney

It contains the nephrons, PCT, and DCT

Cortical nephrons are shorter in length
compared to the medullary nephrons

Why?

Functions to maintain an isotonic urine

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4/29/2008

Medulla: deeper layer of the kidney

Pyramids collect urine from the collecting
ducts that drain into each renal papilla
p p
From the papilla > calyces > ureters
Responsible for hypertonic urine

Why do we sweat in different regions?

Renal Blood Supply

In hot places, we sweat and lose water.

Right renal artery

IIn cold areas, we do

d nott sweatt and
d thus
th do
d
not need to preserve this water.

Right renal vein

The nephrons elongate after 3-4 days

Allows for more water conservation
(hypertonic urine) and fluid replacement lost

Healthy
Kidney
Renal Blood Supply
Right gonadal vein
y drains into the
directly
IVC. Right sided
infection or cancer has
a worse prognosis

Sodium and
water
removal

Fluid
overload

Waste
removal

Elevated
waste- Urea,
Creatinine,
Potassium

Hormone
production
Renin
Erythropoietin's
Prostaglandins

Left gonadal vein

drains into the left
renal vein

Unhealthy
Kidney

Changes in
hormone levels
Blood pressure
Making red blood
cells
Uptake of calcium

3
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4/29/2008

Divide the kidney into 4 regions.

Blood
Vessels

When one of the 4 are affected, ultimately it will affect the others

20% off blood

bl d from
f
the
th CO is
i going
i to
t the
th kidneys
kid
Tubules

Glomeruli

90% of it, supplys the cortex

Only blood supply for the medulla - vasa recta
Blood
vessels

Medulla- first place to infarct in a low volume

state leading to medullary necrosis

Interstitium

Tubules

Glomeruli

Consist of visceral epithelial cells

(foot processes-podocytes)

Proximal convoluted tubule (80% of reabsorption)

Loop of Henely (triple transport)

Glomular basement membrane

(electron dense-type 4 collagen)

Distal convoluted tubule

Parietal epithelium lines bowman's space

Collecting tubule (for concentrating the urine).

Fenestrae (in the endothelium)

Most tubular diseases are frequently

caused by toxic or infectious agents

Most glomerular diseases are immunologically

mediated.

Interstitium

In the cortex, comprising mostly of fenestrating

capillaries (so any change in space, i.e. edema is
abnormal).

Most interstitial disorders are

frequently caused by toxic or infectious
agents.

4
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4/29/2008

Patient presents with polyuria and

polydyspia
You rule out diabetes based on glucose

What next?

Diagnosis

Cause
Excessive fluid intake

Psychogenic DI

Labs
Uosm/Posm > 0.7

i.e. As much as 10-12 gallons

Restrict H2O for 24 hours
of H2O a day

Urine will concentrate

Posterior pituitary does not

release the stored ADH

Central DI

Uosm/Posm < 0.7

ADH is
i nott present,
t but
b t

i.e. Infarction of the pituitary

when you give it, expect
gland

the urine to concentrate

Renal kidneys are

unresponsive to ADH

Nephrogenic DI

i.e. Renal failure, lithium,

low volume state infracting
the medulla of the kidney

Uosm/Posm < 0.7

ADH is present and wants
to work, but its a receptor
problem
Urine will not concentrate

For burn patients: Parkland formula

( to calculate fluid deficit only)
4cc x Wt (Kg) x % burned areas

Head and neck: 9%

Each arm: 9%
Front of torso: 18%
Back of torso: 18%
Each lower extremity: 18%
Genitalia: 1%

Never calculate more than 50% of burned

body area

For newborns: subtract 9% from each lower

extremity and add it to the head and neck

Replace fluids:
within the first 8 hrs ( from time of trauma)
Remainder over the next 16 hrs

Head 27%, legs 9%

5
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4/29/2008

A 36 y/o fire fighter (70 kg),was trapped in a

burning building and suffered 2nd and 3rd degree
burns to over 65% of his body. What will be the
fluid replacement management?

Urine Output: 1cc/kg/hr (70 kg male)

A. 15, 20, 15 ml/hr

Urine output : 1cc/kg/hr

B. 300, 250, 270 ml/hr

70 kg x 50 % = 3500 x 4cc = 14,000 ml (14L)

7 L first 8 hrs :

C. Over 48 hrs, urine output has been

between 50-100 ml/hr. Now on day 3,
urine output 250, 300. Next step in mgt.?

7 L remaining 16 hrs

2nd day that, 3rd day nothing

Never give a hypertonic solution this will pull fluids out of the
extracellular fluid to help fill the vascular space, which will be
replaced by the intracellular fluid.

Cell

H2O

Intracellular
H2O
Extracellular

Ok great job on getting patient Xs blood pressure back to the normal range, but
at what cost. the tissue (oops!!!)

Body water is broken down into fluid compartments:

Exception to the rule:

Intracellular fluid (2/3 of Body Water)

Extracellular fluid (1/3 of Body Water)

Hyponatremic patient ( Na <120) patients:

Interstitial fluid (ISF) 2/3 ECF

Vascular fluid (VF) 1/3 ECF

Use 3% (hypertonic) saline to get sodium

above 120

ISF

ICF

VF

ECF

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Loss of isotonic fluid:

Loss of hypotonic fluid:

Hemorrhage, Diarrhea, Vomiting

Dehydration, Diabetes Insipidus, Alcoholism

Osm

ICF

ECF

ICF

Gain of isotonic fluid:

Isotonic saline

ICF

ECF

Gain of hypotonic fluid:

Hypotonic saline, Water intoxication

ECF

ICF

ECF

Gain of Hypertonic fluid:

Hypertonic saline, Mannitol

ICF

Renin
Angiotensinogen
Pathway

ECF

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4/29/2008

Bartter's syndrome:
Renin
(JG cells-afferent)

JG cell hyperplasia with renin excess

No increase in blood pressure due to insensitivity
of the presser effects of AT-II

AT-II (stimulates)
alpha 1 vasoconstriction
Adrenals
Ad
l (Z
(Z. Gl
Glomerlus)l )
Aldosterone release
Posterior pituitary- ADH release
CNS- thirst center

Defect in the kidney's ability to reabsorb

p
potassium

Liver
(Angiotensinogen)release AT-I

Excessive amount of potassium is excreted from

the body. This is also known as potassium wasting

Lungs
(AT-I is converted
to AT-II via ACE)

Hypomagnesemia due to decreased

gastrointestinal (GI) absorption
(Diarrhea, malabsorption, diet)

DKA metabolic acidosis, which causes a

switch in H+/K+ pumps leading to K+
leaving the cells and intering the serum.

Not a true hyperkalemia, just ions shifted in

the wrong place.

or increased renal loss(diuresis due to

alcohol, thiazides and loop diuretics)

Kidneys will
Kid
ill recognize
i the
th high
hi h K+ and
d start
t t
to secrete it in the urine.
(Hyperkalemia to Hypokalemia)

Always look a pH first, then HCO3-

You should be able to differentiate

based off of these two

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4/29/2008

ACID / BASE Disorders:

For example

Respiratory
PaCO2

If the patients pH is acidic, you should

expect that patients HCO3- to be low
(buffering)

HCO3-
(compensations)
HCO3- normal

(non-compensation)

Acidosis
A id i
Metabolic
HCO3-

If not, then the problem has to be

respiratory

PaCO2
(compensation)
PaCO2 normal

(non-compensation)

ACID / BASE Disorders:

Respiratory
PaCO2

HCO3-
(compensating)
HCO3- normal

Arterial

(non-compensation)

Alk l i
Alkalosis
Metabolic
HCO3-

Serum

PaCO2
(compensating)
PaCO2 normal

pH
7.3
pCO2 30 mm Hg
pO2
95 mm Hg
HCO3- 14 mEq/L

What is the diagnosis?

(non-compensation)

Metabolic acidosis
Arterial
Serum

pH
pCO2
pO2
HCO3-

7.3 (ACID)
30 mm Hg
95 mm Hg
14 mEq/L (low)

Check anion gap... Na+ - (Cl- + HCO3-)

(N: 8-12 mEq/L)
Increased anion gap
MUD PILES
M- methanol
U- uremia
D- DKA
P- paraldehyde or phenformin
I- iron tablets or INH
L- lactic acidosis
E- ethylene glycol
S- salicylates

What is the diagnosis?

Metabolic Acidosis
w/respiratory compensation

Normal anion gap

Diarrhea
Renal tubular acidosis
Hyperchloremia

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4/29/2008

PCT

Diuretics

Acetazolamide, Dorzolamide:

Mannitol:

Ethacrynic Acid (no sulfa)

Furosemide (sulfa)

Hydrochlorothiazide (sulfa)
Indapamine (no hyperlipidemia)

Intra- Renal

Pre- Renal

Post-Renal

Spironolactone:
Amiloride:
Triamterene: (no anti-androgenic effects)

10
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4/29/2008

Volume depletion

Kidneys stop functioning properly: increase in

Creatinine
BUN and/ or
Decreased urine output

Oli
Oliguria
i : decrease
d
iin urine
i output ( < 400 cc/day)
/d )

Anuria ( < 100 cc/day)

PreRenal

(inflow to
the
kidneys)

Dehydration (nausea, vomiting)

Burns ( massive)
Third spacing (i.e. liver chirossis)
Diarrhea
Decrease in Aldosterone (Addisons)

Cardiovascular
Hypotension (CHF)
Coarctation / tamponade

Decrease in Oncotic pressure

Low Albumin
Nephrotic syndrome
Edematous states ( Cirrhosis)

Renal Artery Vasoconstriction

Medications ( NSAID's- block PG's, ACE-I)
Anatomical Renal Artery Stenosis

Decreased Vascular Resistance

Shock

Intra-renal problems

Pre-Renal

Drugs ( Gentamicin,
Amphoteracin B, Cisplatin) takes 5 to 7 days to damage

BUN/Cr > 20/1

Renal

Urine Na+ < 10

(Kidneys)

FeNa+ < 1%

Crushing injuries-cell lysis

dipstick positive (NO RBC's)

UOsm > 500

Thromboembolism, ATN

Renal
BUN/Cr < 20/1

PostRenal

Urine Na+ > 20

( out flow obstruction)

FeNa+

Crystals Uric acid - tumor lysis

Oxilate stones- antifreeze
or malabsorption

Both kindeys need

to be affected to
see any deficit

> 2%

Low specific gravity

(can not concentrate urine)

Bladder obstruction
Prostate enlargement
Pelvic tumors
Urethral strictures
(foley,retroperitoneal
fibrosis)
Urethral obstruction
Tumor
Stones

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4/29/2008

Post- Renal
If you suspect a pre-renal problemthe patients usually have

Obstruction
(hydronephrosis)

positive orthostatics
dry
d mucous membranes
b
increase for thirst
rapid heart rate
skin tenting (turgor)

Increased post void

residual volume

Consider (co-morbid) conditions that could

lead to their pre-renal problem

For a renal problem (intra-renal)consider drug history

Myoglobin is a normal intracellular proteins:

- toxic to the kidneys
- intra-renal damage

Knowing the patients drugs could prevent

unnecessary test for the patient and time
wasted in determining the cause.

If you suspect arteroemboli, look for

subcutaneous nodules
digital ischemia or immobility

With Glomerulonephritis:

Any recent history of exposure to possible

toxins that could be nephro-toxic.

red cast
edema (protein loss)
hypertension (renin pathway)

Check the urine (RBC's, WBC's, cast,

eosinophils), Electrolytes

If you suspect a post-renal problem,

check for

FeNa+ can destinguish between prerenal and renal problems

prostate disease (Prostitis, BPH, Prostatic CA)

DRE, urinary cath as well as ultrsound

can rule out an obstruction

all can lead to an enlarged bladder with pain

radiating to the flanks

Renal biopsy only when the cause of

intra-renal can not be determined

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4/29/2008

Urinalysis CLUES
Attempt to balance fluids and
electrolytes

Drug induced
hypersensitivity
Glomular
nephritis

Dialysis if necessarynecessary Hyperkalemia,

Hyperkalemia

Metabolic acidosis, Fluid overload, Pericarditis,

Encephalopathy

Infection
Discontinue medications if they are the cause of the
renal disease

Myoglobinuria

Nephrotic
syndrome

RBC cast
WBC's
Bacteria

Uric Acid (Gout) Crystals

Urinalysis CLUES
Multiple
myeloma

Eosinophils
(Most common causeCephlosporins)

Glomerular Disease:
Have you ever noticed, that when you
wake up in the morning and urinate,
there is a soapy appearance to your
urine in the toilet bowl?

Proteinuria (bence
jones)

Blood dipstick +, but

no red blood cells

Why is it, that when a nurse is going to

do a morning U/A on a patient, you ask
her to get a mid-steam catch?

Proteinuria >
3.5gm/d
Fat cast

When we look at nephritic or nephrotic

syndromes, we need to decide what sets
them apart from each other.
Aside from a few details, it just comes down
to protein loss and the magical number is
3 5g/day
3.5g/day.
If less than 3.5 g/day then we name that
Nephritic and if greater than 3.5 g/day, we
call that Nephrotic.

Hypertension

Macroscopic /
Microscopic
hematuria
(smokey brown
urine)

Oliguria

Edema

Why 3.5 g/day?

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4/29/2008

Treat any hypertension, fluid overload and

uremia with
Salt and water restrictions, diuretics and if
needed, dialysis

24 hour U/A ( best initial test) - look

for hematuria, proteinuria
If GFR is decreasethink auto
immune
auto-immune
check complement, ANCA and anti-GBM

Renal biopsy (most definitive) - LM, IF, or

EM to help in the diagnosis

If the underlying cause is inflammation of the

glouerular, the give corticosteroids

1. Post Strep GN
2. Good Pasture GN
3. RPGN
4. IgA Nephropathy
5. Membranoproliferative GN
(can be both)

Proteinuria (> 3.5 g/day)

Generalized edema
Hypoalbuminemia
Hyperlipidemia.

Approximately one-third of all cases are

the result of systemic diseases such as
DM, SLE, or amyloidosis.

Generalized
Edema

Foamy urine

Ascites

Hypercoagulable
state

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4/29/2008

U/A - proteinuria (>3.5 g/day),

lipiduria

Diet restrictions of salt and protein

Blood chemistry- decreased albumin

(<3g/dL), hyperlipidemia

Diuretics and antihyperlipidemics

If the patient is a diabetic- put them on an ACE-I for it
decreases the prograssion of the disease

Always look for secondary causes

Renal biopsy (definitive): LM, IF, EM

Vaccinate (PPV 23)- patients at risk of Streptococcus

pneumoniae infections

Nephrotic Syndrome

[Link] GN
[Link] change disease
[Link] Segmental GN
4. Amyloidosis
[Link] Glomular Sclerosis

Mcc in children: minimal change disease

Mcc in adults: membraneous nephropathy
Mcc in Blacks and Hispanics: FSGN
Fat cast

Block aldosterone
Have sulfur in them- anaphylaxis, hapton to RBCs
Angioedema- block C1 esterase inhibitor
Serum
Na- dec. , K -inc.,
pH dec (hangs
onto H+))
S
i
(

Captopril
Lisenopril
Enalopril

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Acute Renal Failure

Pa

FLOW

Pb

If you increase resistance at X

Pa pressure will increase
Pb pressure will decrease
GFR- look at Cr clearance:
Renal Blood Flow- assocated with Cr
clearance
(Lab) use inulin

Renal Plasma flow

BUN
(lab) use PAH

Flow will decrease throughout

GC

Glomerular
cap pressure

Peritubular
cap pressure

GFR

Post- efferent

Renal
plasma flow
Efferent

1. Constrict efferent

2. Dilate efferent

3. Constrict afferent

4. Dilate afferent

E
GC

GC

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E
GC

E
GC

Glomerula Filtration Rate (GFR)

Rate at which plasma is filtered into
bowmans capsule.

= Oncotic

Units of filtration:
(Volume filtered per unit of time)
e.g. ml/min, L/day

Decreased in
pregnancy, liver
failure, over
hydration
y

GFR = Kf [ (PGC-PBC)-( GC-BC)]

P= Hydrstatic
Inreased in
kidney stone,
obstruction

Breakdown of
bowmans
capsule

PGC is the main

factor that
determines GFR
(promotes filtration)

The negative charge of the filtering

membrane inhibits the filtering of
proteins [anions ((-)]
)]

GC

PGC

PBC opposes filtration

Does not affect the
rate of filtration,
except in obstruction

PBC

If the negative charge is not

present, significant protein
filtration takes place

Should not be a factor

BC

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Filtration fraction (FF) fraction of material that

enters the kidney, that is filtered normally (.20 or 20%)

Carriers are easily saturated

Carriers have high affinity for the substrate
Low back leak

The entire filtered load is reabsorbed until the

carriers are saturated, then the excess is excreted.

GFR 140 ml/min

RPF 400 ml/min
.35 or 35% FF
Constrict Efferents

Morning glucose is 600 mg/100ml,

how much will leave the kidneys?

Tubular Secretion (PAH):

(para-amino-hippurate)

120 (GFR) x 6 = 720mg

Secreted from the peritubular

capillaries into the PCT.

will be filtered

There are enough carrier to

secrete 4 times the amount
filtered.

How much will leave

in the urine?

If you inject 100 mg of PAH into

a patient, how much will be
excreted?

(normal carrier Tm 375 mg/min)

So urine dipstick will measure

345 mg/min

100 mg
(20% filtered and 80% secreted)

Protein
Lipid soluble

Inulin
Manitol
(filtered, not
secreted or
reabsorbed)

Glucose

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Theoretical volume of plasma from which a substance is removed over a

period of time

Calculate the clearance ?

V = 2ml/min
Px = 2mg/ ml
Ux = 2mg / ml
2 x 2 = 2 ml/ min
2

If the kidneys are too small

Kidney Pathology

Renal Artery Stenosis

atherosclerosis
fibromuscular dysplasia
Unilateral
Abdominal bruit
Low volume state

Each kidney measures about 3 to 7 inches

If kidneys too small
Renal Artery Stenosis
If kidneys too large
Polycystic kidney disease
Medullary sponge kidneys
Medullary cystic kidneys

Dx: ultrasound; renal vein renin elevated

( higher renin output indicates stenosis)

Treatment

Goldblat Kidney

Avoid ACE-inhibitors once HTN is severe

(AT-II Dependent)

Ipsilateral atherectomy
h
(or stent if not a surgical
candidate) and contralateral nephrectomy

RAS: most common cause of secondary

hypertention

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If you have large kidneys

Polycystic Kidney Disease

ADULT TYPE

Polycystic kidney disease

AD
Bilateral, HTN, RF
SAH - berry aneurysms
In posterior
communicating artery
CN 3- blown pupil
Worst headache
Tx: Transplant

Medullary sponge kidneys

Medullary cystic kidneys

INFANTILE TYPE
AR
Unilateral
NO HTN
NO RF

Medullary Sponge Kidneys

Medullary Cystic Kidneys

Multiple cysts destroy the medulla

Many holes develop in the medulla

Polyuria
Polydypsia
Low volume state

Polyuria
Polydypsia
Low volume state

Occasional kidney stone

Multiple kidney stones

Dx: Sonogram (bubbles)

Dx: Sonogram (holes)

Ureters: 3 anatomical narrowings

Kidney stones

Hilum

Most common type: calcium

Mid ureter: caused by going

over the iliac bones

MCC: hypercalciuria
Tx: Normal saline
Opiates for pain
Thiazides decrease hypercalciuria
by forcing the PCT and Loop to
increase Ca2+ absorption

Ureteropelvic junction
( where it enters the bladder)

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Urease Positive Bugs

Kidney stones
Struvite stones (Staghorn calculus)

Proteus
Pseudomonas
Ureoplasma
N
Nocardia
di
Cryptococcus
Helicobacter Pylori
Staph Saprophyticus
Brucellosis

Triple phosphate stones

C M NH4 Ph
Ca-Mg-NH4-Phosphate
h t
MCC: urease positive UTIs
Tx: normal saline; opiates for pain

Kidney stones

Kidney stones

Cystine stones

Uric acid stones

CYSTINURIA
Cysteine
Ornithine
Lysine
Arginine

The only stone NOT visible on xray

(radiolucent)
Associated with rapid cellular death
(burn pt, CA, massive trauma)
Tx:

AD
Coffin lid, enveloped
Defective renal transport of amino acids

normal saline
opiates for pain

Tx: normal saline; opiates for pain

Kidney Stones: management

Kidney stones
Oxalate stones

IV normal saline
Opiates for pain
< 5mm ( cm)

Due to malabsorption in GI tract

Let it pass

When you have malabsorption, calcium gets

trapped in the malabsorbed fat (saponification) and
do not therefore bind oxalates from proteins
breakdown. Oxalate get absorbed in the GI

5mm to 1cm

Can be hexagonal

> 1cm

Lithotripsy (whorl pool)

Open laparotomy (i.e. struvate)

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Kidney Stones: management

-Street- Heroin (short
-For

acting)
If pyelonephritis develops:
percutaneous nephrostomy stent placement
to drain the pus

withdraws- Methadone (long acting)

-Kidney stones
stones-

Morphine

Dx: KUB; spiral CT; IVP;

Sonogram (if with hydronephrosis)
Ureteroscopy- if stone is in the middle or
lower 1/3 of ureter

-Abdominal pain-

Meperadine
(no contraction of sphincter of odi)

HYDRONEPHROSIS

BPH

Newborns:
(1)malimplantation of the ureters (lack 2 90)
(2) posterior urethral valves

Most common cause of urinary obstruction in

adult men
Obstruction is periurethral (central) : Dx DRE

Children: UTIs

Tx: terazosin or doxazosin

(alpha 1 blockers) loosen sphinctor

Adolescents: urethral strictures ( from STDs)

Adult men: BPH

Tamsulosin (Flomax)- least side effects

2nd line - Fenesteride (block 5 alpha recductase)
Sx TURP (transurethral resection of prostate)

Adult women: uterine prolapse and cystocele

HYDRONEPHROSIS
UNILATERAL
Kidney stones

Bladder
Allantois develops into

BILATERAL
Retroperitoneal
fibrosis

Urachus develops in the

abdomen and descends into the
pelvis

Methysergide
(seretonin Rx for
migranes)
Nitrofurantoins

forming the Bladder

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Urachal Cyst

Exotrophy of the Bladder

Urachus retains attachment to the

umbilicus

Bladder was caught outside the abdominal

cavity

Clue: urine drains from the umbilicus

Predisposes to bladder cancer (MC

complication)

Tx: surgery

Risk for bladder cancer persists even after

surgery (UA and CT every year)
Tx: surgery

MCC: Atherosclerosis

< 4 cm diameter
- control HTN
- follow

Location: 90% occur below the renal arteries

Presentation:
1. Ripping, tearing pain down the lower back
2. Pulsating abdominal mass
(can only feel if they are thin)

> 6 cm in diameter
- control HTN
- surgery

Dx: Sono, CT scan

4 6 cm (surgery is the doctors call)

Incontinence
MCC: 1# Trauma , 2# Collagen disease
Presentation:
1. Ripping, tearing pain between the shoulder blades
Diagnosis: Spiral CT
Treatment: Type A control HTN, surgery
Type B- control HTN, pray
(not much connective tissue)

The involuntary loss of urine

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Urge Incontinence

Urge Incontinence, cont

Detrusser muscle activity is increased.

A spastic bladder ( UMN lesion)
Bladder capacity is low due to repetitive
bladder emptying
Sphincter pressure is normal
Gotta gogotta gogotta go

Tx: have patient urinate around the

clock beginning with
- hourly for 2 to 3 days
days,
- then every 2 hours for 2 to 3 days,
- then every 3 hours for 2 to 3 days,
- then every four hours (normal)

Tx:
Imipramine (in children) TCA
Oxybutynin (in adults) Blocks Ach (M)
(to decrease bladder contractions)

Stress Incontinence

Stress Incontinence, cont

Due to weak pelvic floor muscles

MCC: obesity; estrogen connection

Estrogen connection

Tx: weight loss; Kegle exercises to

tighten up pelvic floor muscles

Any increase in abdominal pressure

( like from sitting down, laughing, coughing,
sneezing, etc) causes a sudden loss of urine

Use pseudoephedrine to tighten up the

sphincter (alpha adrenergic)

Detrussor muscle function is normal

Bladder capacity is normal

Suggest diapers or panty liners in the

meantime

Sphincter pressure is decreased

Overflow Incontinence, cont

Overflow Incontinence
Due to an anatomical obstruction

Causes:

Detrussor muscle activity is decreased due to

stretching

In newborns: posterior urethral valves

Bl dd capacity
Bladder
it iis iincreased
d

In children: strictures

Sphincter pressure is increased

In adult men: BPH

Sx: a weak urine stream; dribbling after urination;

urgency; frequency

In adult women: uterine prolapse and

cystoceles

Tx: surgically remove the obstruction

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Urethra: Penis
Develops dorsal (top) to ventral
(bottom)

Hypospadia
yp p

Fuses from the tip to the base of penis or

clitoris

The most common congenital genitourinary abnormality!

Hypospadia ( still zipping)

Circumcision

Located at the base of the penis just next

to the anus

Done primarily for cosmetic reasons

UTI argument

Predisposes to UTIs
Penile cancer argument
Tx: surgical correction immediately to
prevent UTIs

Should be done in first 48 hours

Clean by pulling the foreskin up, then
clean; pull the foreskin back, then clean

Inflammatory Problems

Infections

Phimosis: foreskin is scarred and

adherent to the head of the penis

Ballanitis ( head of the penis )

Paraphimosis: foreskin is scarred and

adherent to the base of the penis

Urethritis ( dysuria)dysuria) infection of urethra

Staph Aureus

Chlamydia Trachomatis # 1 (90% asymp.)

Nisseria Gonorrhea # 2 (90% symp. Men)
(50% symp. Women)
Actinomyces Israelii

Tx: urology consult

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Infections, cont
Azythromycin 1gm or 2gm (Chlam + GC)

Cystitis: ( urgency and frequency)

Ceftriaxone (250 IM)

Cefixeme ( 400 PO)
Cefoxitin (250 IM)

Pyelonephritis: ( WBC Casts)- only nephron

can form cast
Causes:

Quinolones (400 PO)

Ciprofloxacin
Ofloxacin
Gatifloxacin

E. Coli
Proteus
Klebsiella
Enterococcus: nitrite negative

Nephritis

Casts
WBC casts: nephritis

Pyelonephritis: WBC Casts; sepsis

RBC casts: glomerulonephritis

Interstitial nephritis: drug allergy;

collagen vascular disease

Eosinophil casts: interstitial nephritis

Fat casts: nephrotic syndrome

Glomerulonephritis: RBC Casts; hematuria

Waxy casts: chronic renal failure

Hyaline and epithelial casts: normal findings;
represent sloughed off cells, most from the PCT
Crescents: RPGN. Goodpastures or Wegeners

RTAs
Type I: distal H/K exchange is defective
Urine pH is very high; renal stones; UTIs

Type II: proximal CA does not work

Urine pH is very high ( distal H/K exchange still

works)
Can not reabsorb HCO3-

THE END !

TYPE III: combines the above two

Urine pH is normal

Type IV: hyporenin-hypoaldosterone syndrome

Seen in diabetics; JG apparatus is infarcted

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4/29/2008

Embryology of the Brain

Primitive Streak
Making
Connections
M ki The
Th C
i

Notochord
Spinal cord

In the first trimester

Amniotic Fluid

Notochord: visible by 3 weeks

80% of amniotic fluid is filtrate from moms

plasma

Brain: fully formed by 8 weeks

Fetus SUBTRACTS by swallowing the

fluid
Fetus must absorb and digest the fluid

Brain is active early with movements,

especially reflexes

20% is added by the fetus

Brain is active in formation of amniotic fluid

Fetus then urinates the additional fluid into

the sac

Polyhydramnios

Oligohydramnios

AFI

Renal agenesis

Neuromuscular
N
l disease
di

Urinary outlet obstruction

Autonomic dysfunction: dry eyes- Riely Day syndrome

Muscle disease: in a newborn fasciculation- Wernig
Hoffman syndrome

GI obstruction

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Spinal Cord

Vertebral Arches

Develops from the notochord

Fuse ventral to dorsal

Goes down as far as L-1 or L-2

g at the cervical level

Begins

End : Conus Medullaris

Proceeds bi-directionally

Nerves: Cauda equina

If child born prematurely, a hole can

be still present at either end

Filum terminalis: anchors

Lower vertebral arch defects

Upper- vertebral arch defects

Spina Bifida Occulta

Anencephaly no contact to the brain

Only has the medulla
Breath 8-10 ipm

Spina Bifida Aperta

Encephalocele

1. Meningocele

Encephalo-meningocele

2. Meningomyelocele
Arnold Chiari Malformation (Type I and II)
Syringomyelia

Encephalo-meningo-myelocele

Now you need some CSF

How CSF differs from plasma

Less HCO3-

A filtrate of plasma
Made byy the Choroid

AFP

More CL-

Plexus in each ventricle

Lower pH 7.34 (acidic)

Requires Vitamin A
Up to 25 WBCs normal in first month of life normal
Requires Carbonic Anhydrase
>1 month, only up to 3 WBCs normal

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Lateral ventricles >

Vomiting Centers

foramen of Munro >

3rd ventricle >

Chemotactic Trigger Zone: located on

the floor of the 4th ventricle

aqueduct of Sylvius >

4th

ventricle >

foramina of Lushka & Magendie

Responds to any increase in ICP

subarachnoid layer >

CSF Flow

spinal canal >

dural sinuses >

Stimulated by dopamine

back into plasma

Vomiting Centers

Hydrocephalus

Area Postrema: located on the blood

side of the blood brain barrier (BBB)

Non-communicating:
due to an obstruction

Responds to offensive smells or

taste

Communicating:
overproduction of CSF

Stimulated by dopamine

Communicating Hydrocephalus

Communicating Hydrocephalus

Newborns: mainly premature newborns

Intraventricular hemorrhage

Adults: over ingestion of vitamin A

Pseudotumor Cerebri

Children: due to inflammation

Meningitis (posterior fossa) CN 3,
9,10,11,12

Elderly: due to brain atrophy

Normal Pressure Hydrocephalus
Ventricles enlarge

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Normal Pressure Hydrocephalus

Noncommunicating Hydrocephalus

Ventricles expands as the brain atrophies

Due to some form of obstruction

In newborns:
MCC: Aqueductal stenosis
2nd Dandy-Walker cyst
In children: meningitis, especially TB
In adults: cancer
In elderly: cancer

Enlarged ventricles then compress the long midline

fibers that go to the bladder and legs
Triad:
Dementia
Incontinence
Ataxia
Tx: VP shunt

The role of CSF

Neurocutaneous Syndromes

To add cushion for the brain

Shock absorption

Sturge Weber Syndrome:

Benign port wine stain- capillaries
Opthalmic branch of CN V
Mental retardation
Seizure

Head Injury
Coup lesions
Contracoup lesions worst than the
coup (brain makes CSF for repair)

Neurocutaneous Syndromes

Neurocutaneous Syndromes
Tuberous sclerosis: benign tumors
AD
Mental
M
l retardation
d i
Seizure
Retinal angiomyolipoma
Cardiac rhabdomyoma
Pancreatic cyst / Coloboma

Osler-Weber Rendu Syndrome

Small aneurysmal telangiectasia on
the
h skin
k and
d mucus membrane
b
Causes GI bleeding
Pulmonary AV fistula

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Embryology of the Brain

Neurocutaneous Syndromes
Von-Hippel Lindau
g
Cerebellar hemangioma
Retinal hemangioma
Renal cell carcinoma
(increased EPOs)

Prosencephalon

Telencephalon
Diencephalon

cerebrum
thalami and BG

Mesencephalon

Mesencephalon

midbrain

Rhombencephalon

Visual Cortex

Metencephalon
Myelencephalon

pons & cerebellum

medulla

Abnormalities of the Eyes

Light must hit the retina by 3 months of age

or the child is blind for life

Anisocoria: unequal pupil size

MCC: Congenital (AD) check parents
If it occurs in childhood- inc. ICP until proven
otherwise
h
i Dx:
D CT,
CT LP

You must verify that a child has a RED reflex

on eye exam at birth (retinal arteries, and if
you can see them- nothing is in the way)

Amblyopia: difference in visual acuity

Lazy eye
Tx: Patch the eye up to age 5
Weak muscles- CN: 3,4,6

Abnormalities of the Eyes

Vision Correction:
20/20 20/100 (5 times the difference)
20 ft. 4ft

Strabismus: misalignment of the eyes

Isotropia
Exotropia
Weak muscles of the eye.. Tx. Patch good eye

20/200 legally blind (no drivers license)

can not see details

Stigmatism: corneal defect

Straight line card (pt will see a blip in the line)
Convex or a concave defect in the cornea
Laser keratotomy

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Abnormalities of the Eyes

Myopia- can not see far away

My-opia: near sightedness (can not see far)

Focus of light is before the retina
Tx: Concave lens- disperses light

Hyperopia: far sightedness

Focus of light is behind the retina
Tx: Convex lens- focuses light earlier

Presbyopia: loss of accommodation seen with aging

Due to muscles weakening with age
Ability to focus on objects coming close

White Reflex

White Reflex

Cataracts: opacification of the lens

Does not allow light to hit the retina
Must be removed
Increased
with
high
or
d incidence
d
hh
h glucose
l
galactose ( sorbitol or galactitol accumulates)

Retinoblastoma (rare)
Rb gene
Cancer
High association with Ewings
sarcoma

Idiopathic: 90%
Diabetes or galactosemia
Rubella

Optic Nerve

Visual field deficits

Optic Tract
Meyers
Optic Chiasm
Optic Radiation

Calcarine
Fissure

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R
Monocular Visual Loss
Optic Nerve

Optic Radiation

Meyers Loop

Monocular blindness

Monocular blindness

Newborns: cataracts or retinoblastoma

Children: optic nerve gliomas

Bitemporal Hemanopsia

Neurofibromatosis
MEN III

Adults: embolic phenomena

TIA (Amaurosis Fugax)
Acute retinal artery occlusion
(white retina, macula has its own blood supply)

Acute retinal vein occlusion (bluish retina)

Elderly: macular degeneration

Optic Chiasm Lesions

Receives the smallest arteries of the retina - atherosclerosis

Optic Chiasm Lesions

Contralateral
Homonymous
Hemianopia

Pituitary tumors: 90%

Pituitary sits just beneath the chiasm
Pineal tumors
Pineal gland sits just lateral to the
chiasm
Circadian rhythm - Responds to light

Optic Tract Lesions

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Optic Tract Lesions

R
Contralateral Superior
Quadrantanopia

Mcc:
M
cancers or tumors

L
Contralateral Inferior
Quadrantanopia

Contralateral
Homonymous
Hemianopia with
Macula Sparing

Quadranopsia

Frontal Lobe ( Precentral Gyri)

Can get such a lesion in

the Optic radiation or
Meyer
Meyerss loop

CST (corticospinal tract) motor fibers

originates from here
Unique information:
Personality is stored in the frontal lobe
Abstract reasoning

Pie in the sky

(dont cry over spilled milk)

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Frontal Lobe Lesions

Temporal Lobe

Atonic seizures- generalized (knock out CST)

Hearing
Balance
Hallucinations ( released by serotonin)

Dementias
Alzheimer's
Al h i
'
Picks disease

PCP
LSD

Schizophrenia: loss of asymmetry

Posterior temporal lobe: Wernickes area
Frontal lobotomies

Amphetamines

Amphetamines

Used in ADD
Methylphenidate (use in Narcolepsy)
Pemoline Adderal
Dexadrine

Taken up presynaptically; cause release

of catecholamines

OTC for weight loss

Clue: vertical

Dexatrim

nystagmus

Cause hallucinations
LSD
PCP
ECSTACY

SSRIs

Parietal Lobes
Dominant lobe: long term memory; all the
things you learned since kindergarten
left side is dominant in 90% of right
righthanded and left-handed people

Fluoxetine
Paroxetine
Luvoxetine Depression, eating disorders
Sertraline
(MAOI- wait a month)
Nefazadone
Trazadone

Nondominant lobe: apraxia and hemineglect

Right side is nondominant in 90% of righthanded and left-handed people

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Anterior
Communicating

Anterior Cerebral

Lateral Pontine Syndrome

Occlusion AICA (anterior

inferior cerebellar artery)
Posterior Cerebral
Superior Cerebellar

CN 7- ipsilateral facial
paralysis

Anterior Inferior Cerebellar

Posterior Inferior Cerebellar
Vertebrals

CN 8- hearing loss

Lateral Medullary Syndrome

( Wallenberg)

Medial Medullary
Syndrome

Occlusion of PICA (posterior inferior

cerebellar artery )

Occlusion of vertebral artery

Cerebellar peduncle- ipsilateral limb

ataxia

Pyramid- contralateral spastic

hemiparesis

Descending hypothalamicsipsilateral horners

CN 12- tongue deviates

toward the lesion

Nucleus ambiguus- dysphagia

Median Midbrain Syndrome

(Weber)

Epidural Hematoma
Middle meningeal
artery

Occlusion of posterior cerebral

artery

Fracture of
temporal bone

CST- contralateral spastic

hemiparesis (upper limb)

Lucid interval

Corticobulbar tract- lower face

(contra)

Lenticular shape

CN3- eye (down and out)

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Subdural Hematoma

Subarachnoid Hemorrhage

Bridging vein

Aneurysm rupture

Venous bleed
Delayed onset

Worst headache of
their life

Shaken baby
Elderly

Bloody spinal tap

Crescent shape

THALAMI- SENSORY

Epithalamus

Epithalamus
The ONLY nucleus with NO known
function

Thalamus
Hypothalamus
Subthalamic Nucleus

Hypothalamus

Thalamus

Controls hunger
Hunger center: lateral
Satiety center: medial- 80% NE and 5HT (+)
You can override via cortex stimulus FOOD

ALL SENSORY information in and out of

the brain MUST stop here

Controls menstrual cycle

ALL information about the ARMS stay

LATERAL

Controls temperature
Anterior: cools
Posterior: warms

ALL information about the LEGS stay

MEDIAL

Controls stress response (NE release)

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Acetomenophen

Stress Response

Works at the level of the hypothalamus

Parasympathetic discharge always first

Sympathetic discharge always second

First, it cools the body (+ anterior hypothalamus)

2nd it resists fever (blocks posterior hypothalamus)

h pothalamus)

Stress ulcers
Curlings ulcers
Cushings ulcers (triad: bradycardia, HTN, Inc. ICP)
IBS

Oxidizes the liver (toxicity) by destroying bisulfur

groups
Treat with n-acetylcystiene ( reducing agent);
the four hour level is the most important factor

Subthalamic Nucleus
Final relay station for coordinating
fine motor movements

Lesion: Ballismus and Hemiballismus

Substantia Nigra

Parkinsons Disease
Loss of DOPAMINE fibers from substantia nigra
to striatum (caudate and putamen)

Responsible for INITIATING movements

Uses DOPAMINE for neurotransmitter

Unable to initiate activities

Receives inhibitory signals from basal ganglia via ACH

or GABA

Mask like facies

Bradykinesia
Shuffling gait
Pill rolling tremor
Autonomic dysfunction: Shy Dragger syndrome

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Movement disorder in middle-aged people

Parkinsons Disease, cont

Huntingtons disease

Treatment: L-dopa/ carbidopa

2nd

90%
AD
Trinucleotide repeats
Caudate nucleus involved
Anticipation
Decreased GABA fibers
Treat with DA blockers
(they have too much DA)

line: Bromocryptine (dopamine agonist)

Amantadine (Tx influenza A)- increase DA

release from nerve terminal
Selegyline (MAO-B inhibitor)- prevent DA
breakdown

Internal Capsule

Wilsons disease
< 10%
AR
Ceruloplasmin def
Copper excess
Lenticular nucleus
involved
Kayser-Fleischer rings
Liver involvement
Treat with penicillamine

Reticular Activating System (RAS)

ALL MOTOR fibers going in and out of the brain goes

through here

Maintain FOCUS on one item at a time

Blood
the
Bl d supply
l comes from
f
h lenticulostriate
l i l
i arteries
i
( smallest arteries in the brain)

Requires NE and Serotonin

cAMP second messenger (sympathetic)

Lacunar hemorrhages: due to HTN

Causes significant MOTOR deficits

Has a refractory period first thing in the

morning

BAT D

Sleep cycles

Attention Deficit Disorder

Beta waves wide awake (eyes open)

Alpha waves - Eyes close - awake not asleep

ADD or ADHD (Not focus).

RAS not working
Poor attention and focus
Restlessness
Unable to sit long enough to complete a task
Tx: methylphenidate (1st in children);
pemoline; dexadrine; adderal

Theta waves
light waves stage 1 and 2. (Stage 2: K complex and sleep spindles)

Delta waves Deep sleep big stage 4 all motor activities (teeth
griding, sleepwalking, enuresis).

Night terrors occur

Benzos, imipramine inhibts this fase

Beta waves - Rem sleep. Every 90 min. (REM latency) 5-7 x night
Parasympathetic. Most of the rest.
Dreams, penile/clitoral erection
NE, EtOH, Barbs, Age inhibts this
5-HT, Ach increase

13
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4/29/2008

Corticospinal Tract
Responsible for fine motor activity
Has to inhibit extension so that smooth flexion can
occur

Mid-brain
Mid brain

Spasticity- can not flex

Babinski extension of toes
Hyperreflexia
Clonus

Corticospinal Tract, cont

CST Pathology

Fibers originate from the frontal lobes,

the precentral gyri

Atonic seizures: depolarization

goes across the frontal cortex

Fibers descend through the internal

capsule and CROSS at the medullary
pyramids

B-12 deficiency
ALS

Increased Intracranial Pressure

First sign: papilledema (optic nerve)
First symptom: headache
Second sign: esotropia (CN VI paralysis)
abdusence

Second symptom: diplopia or blurred vision

Third sign: Sluggish pupils

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4/29/2008

If Herniation Continues

Decorticate Posturing

Second sign of herniation:

DECORTICATE posturing
Compression has occurred below CN
III but above the red nucleus
Red nucleus still makes the upper
extremities flex while the legs extend
UNTIL

The Final Push

DECEREBRATE posturing

Herniation goes beyond the red nucleus

CST and Corticorubral and rubrospinal
tracts are all lost
All extremities will extend by default
Medulla is pushed through the foramen
magnum.
DECEREBRATE posturing

Dorsal Columns, cont

Dorsal Columns
Vibratory sensation
Two-point discrimination
Position sense

Gracilis: carries leg fibers; located

MEDIALLY

(toe m0vement)

Conscious proprioception

Cuneatus: carries arm fibers; located

(eyes closed knowing what he is doing)

LATTERLY

The only sensory pathway with four

synapses

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4/29/2008

Dorsal Columns, cont

Dorsal Column Pathology

FIRST SYNAPSE: dorsal root ganglion

Syphilis
Vitamin B-12 Def
Brown-Sequard

Fasciculus gracilis: ( lower extremities)

Fasciculus cuneatus: ( upper extremities)

SECOND SYNAPSE: MEDULLA

THIRD SYNAPSE: THALAMUS
FOURTH SYNAPSE: parietal lobes
( postcentral gyri)- ALL SENSORY

Spinothalamic Tract

Spinothalamic Tract

Pain and Temperature

FIRST SYNAPSE: dorsal root ganglion

(opposite all other lesions)

SECOND SYNAPSE: thalamus

The only pathway that CROSSES in the

spinal cord (only one)

THIRD SYNAPSE: parietal lobes

( postcentral gyri)- Sensory

Fibers enter the spinal cord, ascend two

levels, then cross to opposite side via the
anterior white commisure

Spinocerebellar Pathway

Spinothalamic Tract Pathology

The only pathway in the spinal cord that crosses

Syringomyelia

twice ( equivalent to ipsilateral)

Responsible for depth perception

Signs of damage:
INTENTION TREMOR (during reach)
DYSMETRIA (heal to shin) or PRONATOR DRIFT
DYSDIODOKINESIS (rapid movement)
ROMBERG SIGN (loss of unconscious proprioception)

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Spinocerebellar Pathway Pathology

Spinocerebellar Pathway, cont

This pathway does NOT reach the cortex

Alcohol attacks the vermis (midline) of the cerebellum

while other diseases attack the hemispheres

Unconscious proprioception
(don
(dontt have to think about it)

Fredriecks Ataxia-retinitis pigmentosa

FIRST SYNAPSE: dorsal root ganglion

SECOND SYNAPSE: thalamus

Ataxia Telangiectasia- spider vein all over your body

THIRD SYNAPSE: cerebellum

Adrenoleukodystrophy- defective long chain FA

PONS

Pons Pathology

Responsible for responding to the environment

Locked-in Syndrome

Contains the
PNEUMOTACTIC (superior)inhibitory to the APNEUSTIC
(bottom) responds to pO2 dec., pCO2 inc.

Central Pontine Demyelinolysis

CNS area most sensitive to osmotic shifts

Medulla

Make sure you know the cranial nerves !

Midbrain 3,4

Controls ALL basic functions

Respiration of 8-10 ipm

Pons 5,6,7,8
Medulla 9,10,11,12

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You know its a spinal cord

lesion when

How Do I Figure
Out Any Lesion?

Pain and temperature loss is opposite to

all other deficits
Level of the lesion is two dermatomes above
where pain and temperature loss begins and on the
opposite side (Lesion L2- loss at L4)

You know its a CNS lesion

when
UMN signs on one side of the body
( upper and lower extremities)
Then the lesion is on the opposite side of the brain

Too slow grasshopper !!!!

THE END !

Use the cranial nerves to locate the level of the

lesion

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Red Blood Cell

Hematology
Hasenchecheg Qi MD
MD., Ph
Ph.D.
D

Hemoglobin

Hemoglobin

1. A Hb is composed of:

1). four globins, proteins

pair of alpha (a2): located on chromosome 16

1. Hb A

22

m.c.

2. Hb A2

2 2

2.5%

chain synthesis begins late in the

third trimester and in adults

3. Hb F

2 2

m.c. in the
fetus

small amounts in an adult, may be

abnormally elevated in certain forms
of anemia

pair of beta (b2): located on chromosome 11.

2). four heme groups, with the iron compound which binds with the O2
2. Hb has 2 forms:
T (taut) low affinity for O2
R (relaxed) high affinity for O2
3. Function

4. Hb S

1). In the lungs, each iron on Hb combines O2 reversibly.

2). Each Hb also has attached a single cysteine, which attracts nitric oxide (NO).
3). The enriched Hb circulates to the tissues, where the NO dilates the small capillaries,
allowing to deliver O2 to the tissues.
4). Then the O2- and NOfree Hb picks up CO2 and free NO and transports both back to
the lungs, where they are exhaled as waste.

sickle-cell
hemoglobin

5. Hb H

6. Barts

An abnormal Hb is not effectively

transport O2, it is usually associated
with a -thalassemia syndrome.
An abnormal Hb that is not effective in
O2 transport, found in -thalassemia.

5). When RBC are destroyed

the hema (iron) is stored in the liver for the manufacture of new red blood cells.
Globins is converted into bile and stored in the gall bladder

Anemia

Heme Synthesis (mitochondria)

Sideroblastic

Hb <11 mg/dl
MCV < 80

MCV (80100)

1. Thalassemia

4. Lead Poisoning
5. Sideroblastic
anemia
1. Sickle Cell Disease
2. Hemaglubin C
Disease
3. G-6-P-D deficiency
4. Thelassemia Major
5. PNH

-Aminolevulic acid

1. B12 deficiency

Reticulocyte

2. AOC
3. Iron deficiency
anemia
i

ALA Synthase

MCV > 100

> 2.0% high

1. Marrow failure

ALA dehydrase

3. Myelofibrosis
4. Ca matastasis
5. AOC
6. Renal failure

Prophobilinogen

3. Alcoholic Liver
disease

Uroporphyrinogen-I

4. Drug induce

2. Aplastic
Anemia
1. All the
hemolytic
anemia

Uroporphyrinogen-III

Extravascular

synthase
Acute Intermittent
Porphyria

2. All the
autoimmune
anemia

Protoporphyrin IX (protoheme)
Fe2+

Intravascular

+ B6
Lead (Pb)

2. Folate Deficiency
< 2.0 %Low

Anemia

Rate limited

Glycine + Succiny CoA

Hereditary
Spherocytosis

Iron Deficiency
Anemia

Ferrochelatase

Lead (Pb)

Heme

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10/13/2008

Microcytic Anemia

Microcytic Anemia

Sideroblastic Anemia

Lead Poisoning

cause

Symptoms

Acute Intermittent Porphyria

Porphyria Cutanea Tarda

1. decrease Vit B6 (m.c.)

1. Lead Line: in gums

2. isoniazid therapy

2. CNS : Encephapathy,

Uroprophyrinogen-1 Synthase
deficiency

Uroprophyrinogen
decarboxylase deficiency

3. Abdominal pain (lead colic)

Clinical Feature

Clinical Feature

1. AD, variable expression

1. Photosensitivity

2. acute abdominal p
pain
multiple laparoscopies (scars on
abdomen)

2. blistering
g of skin

4. PNS: wrist and foot Drop

Diagnosis:

Diagnosis:

1. BM: ring sideroblast

(most specific test)
An erythroblast containing
granules of ferritin

1. blood lead level > 10 g/dl

2. Lab

3. basophilic stippling (remnants of

RNA) :

Treatment

Treatment

Pyridoxine

succimer (PO), EDTA

[Link] changes

2. increase free erythrocyte

protoporhyrin

4. increase ALA and PBG

(prophobilinogen)
5. no photosensitivity
6. Contraindicate: barbiturate

Anemia of Chronic Disease (AOCD)

Anemia of Chronic Disease (AOCD)

Definition

Lab

1. Iron being trapped in

bone marrow
macrophages, causes
inability to use of iron in
stores.

1. serum ferritin
elevated
2. serum iron low

2. long term chronic

disease cause decreased
liver functions,

1. decrease protein
synthesis
2. Transferrin low =
TIBC low

Treatment

reticuloendothelial
system

3. reticulocyte count
low
lo

3. It can be microcytic or
normocytic

Iron deficiency Anemia

Iron deficiency Anemia

Cause

1. decrease intake or
Increase demand

elderly, children, pregnant women

2. decrease absorption:
(malabsorption)

1) decrease acid (Vc)

2) Dumping Syndrome: decrease
small intestine transit time
3) after gastrectomy

3. chronic blood loss

((m.c.))

1) GI Ca (m.c. in USA)
2) GYN bleeding
3) Hookworm (m.c. rest of the world)

Sequence
event due
to iron
deficiency:

1. decrease storage iron in

intestinal mucosa, spleen,
and liver

Decrease ferritin

2. decrease circulating iron

Decrease serum iron

Increase TIBC

3. formation of
microcytic/hypochromic
anemia

Decrease RBC size

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10/13/2008

Iron deficiency Anemia

Symptoms

1. General
2. others

Terminology

Low energy state, pallor of skin and nails,

1. Koilonychia: spooning of the fingernails

1. Hb

Hemoglobin

F12-15 g/dl,
M 13-16g/dl

2. Pica
Lab

Hb, MCV, Ht

Decrease

2. Ht (Hct)

Hematocrit % of RBC in the blood

40 --50%

RDW

decrease

3. MCV

mean cell (corpuscular) volume

80100

Serum iron

decrease

4. MCH

mean cell hemoglobin

25.435 pg/cell

5. MCHC

mean cell hemoglobin concentration

3136 g/dl

6. RDW

red cell distribution width (A measure

of the variation in size of red blood
cells)

612%)

7. Reticulocyte

immature RBC (1 day, normal 1.5%)

Transferrin (TIBC) increase

ferritin
microscope

Diagnosis
Treatment

decrease

microcyte
anisocytosis

abnormal size

poikilocytosis

abnormal shape

1. depend on lab
2. definitive Dx: bone marrow

< 1%, poor bone marrow response

1. diet

> 1%, good bone marrow response

2. ferrous sulfate tablets

Bluish color (polychromasia) due to

free ribosome RNA

3. parenteral iron
4. blood transfusion: most effective

Terminology
serum iron

100mg/dl

Ferritin

1. physiological storage iron form

2. intestinal mucosa, spleen, and liver

Hemosiderin

1. degraded ferritin + lysosomal debris

2. Prussian blue positive

Transferrin

A beta globulin in blood serum that combines with and

transports iron.

Total iron-binding
capacity (TIBC):

1. means transferrin level

2. Transferrin = TIBC = 300 mg/dl

% saturation of
transferrin

serum iron/TIBC = 1/3

Go Back

decrease decrease normal

increase

serum
ferritin

decrease

increase normal

increase

TIBC

increase

decrease normal

decrease

decrease normal

increase

B12 Deficiency Anemia

2. Decrease
absorption

Thalassemia Sideroblastic
minor
anemia

serum
Iron

%
decrease
saturation

B12 Deficiency Anemia

Causes
1. Dietary
deficiency

Microcytic Anemia
Iron
AOCD
deficiency

Diagnosis
1. B12 in red meat and fished

1. peripheral smear

Macroblastic anemia, hypersegmented

neutrophils

3. strict vegetarians, alcoholism

2. anti-IF: initial test

sensitivity 50-80% , specificity 100%

1. decrease IF, gastrectomy or pernicious anemia

3. serum homocysteine Due to folate or B12 deficiency

increase

2. B12 stores at body for more than 1 year supply.

2. Pancreatic insufficiency
3. intestinal malabsorption
a. p
parasites: fish tapeworm
p
diphyllobothrium
p y
latum
b. bacteria: blind-loop syndrome
c. Crohns disease

4. increase
methylmalonic acid

only due to B12 deficient

5. Schilling test:

Sign and symptom

over the 24 hours, a normal result shows at least

10% of the oral intake radioactive vitamin B12 will
be in the urine.

1. beefy tongue due to generalized epithelial atrophy

i. B12 injection + radiolabelled B12 orally

2. peripheral neuropathy

ii. B12 injection + radiolabelled B12 orally + IF

3. SCDSD: (Subacute combined degeneration of the spinal cord)

ii. demyelination of the posterior columns and lateral corticospinal tracts and
spinocerebellar tracts
iii. Urinary and fecal incontinence, impotence
iv. Dementia

Treatment

Treatment

B12 oral
Or parenteral

After give B12, may develop hypokalemia in 48

hrs, because potassium rapidly go into cells

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Autoimmune Hemolytic Anemia (AIHA)

Folate Deficiency

Go Back

Warm AIHA

Folate Deficiency

Cold AIHA

Mechanism

antibodies initiate
The IgG attach to a RBC,
complement lysis of
leaving their FC portion
sticking out. The FC is
red blood cells
recognized and grabbed onto
by monocytes and
macrophages in the spleen.

Antibody

1. IgG to Rh type
2. IgA

1. IgM

Cause

1. Methyldopa
2. Penicillin

1. Quinidine

1. serum homocysteine increase: due to both folate and B12 deficiency

coombs test +

IgG, or IgG + C3

C3

Treatment

Cold agglutinin

negative

positive

Treatment

1. steroid
2. splenectomy
3. treat causes
4. Cyclophosphamide

1. Cyclophosphamide
2. Chlorambucil

1. contain in green leaves vegetable

2. 3 month supply
Cause by
1. cause by tea and toast life-style
2. Methotrexate
3 Ph
3.
Phenytoin
t i
4. Pregnancy
Lab

Folic acid

Hereditary Spherocytosis

Normocytic Anemia
Intravascular (SH GTP)

Extravascular

Definition

Microangiopathic
Hemolytic Anemia

increase methemoglobin
(oxidized hemoglubin)
Rx; methylene blue

no methemoglobin 1. increase shictocytes

(fragmented RBC)
2. Helmet cell

markedly decrease
haptoglobin

decrease
heptoglobin

1. Sickle Cell Disease

2. Hemaglubin C Disease
3. G-6-P-D deficiency
4. Thelassemia Major
5. PNH

Hereditary
spherocytosis

2. defect spectrin in RBC membrane

Clinical
feature

1. splenomegaly

Lab

1. increase spherocytes

2. increase risk for acute aplastic crisis with Parovirus

B19 infection
2. normocytic hyperchronic
3. increase MCHC
4. increase osmotic fragility

1. DIC
2. TTP
3. HUS
4. Prosthetic Heart Valve
5. HELLP

Rx

Sickle Cell Disease

Sickle Cell Diasese

Hemoglobin C Disease

single nucleotide change in codon casues

valine (neutral) to replace normal glutamic
acid (acidic) at 6 position of the -globin
chain

single nucleotide change in

codon causes lysine (basic) to
replace normal glutamic acid
(acidic) at 6 position of the globin chain

Hemoglobin S

Sign:

1. become less soluble under decreasing

oxygen concentrations

1. splenomegaly

Sickle Cell Disease

Affecting factors

1. increase concentration (dehydration), make it

worse
decrease concentration make it better
2. Decrease pH decrease oxygen affinity: worse
3. increase HbF: better

Increase RBC
destruction cause

2. target cell
2. The deoxygenated molecules form rigid
rods called polymers into crystals that distort
the red blood cells into a sickle shape.
3. These abnormally sickle-shaped cells are
both rigid and sticky.

1. AD,

1 Erythroid hyperplasia
1.
2. increase bilirubin

3. rod-shaped crystals in RBCs

Genitic types
1. heterozygous (AS): trait
blood urine and resistance to malaria
2. Homozygous (SS):Sickle cell disease

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Sickle Cell Disease

Vaso-occlusion

1. Hand-foot syndrome (dactylitis)

1st sign of SD, in children

2. Vaso-occusive (painful) crisis

Rx: 1. Self limiting, last 2-7 days

2. hydration: NS
3. Morphine for pain
4. keep warm
5. Oxygen

3. Autosplenoectomy

1. Howell-Jolly bodies in peripheral blood:

remnantt off nuclear
l
chromatin
h
ti
2. increase infection of encapsulated
organisms, Rx: vaccinations

4. Leg ulcers

increase Salmonella osteomyelitis (leg pain)

5. Avascular necrosis of the joints

M.c. hip, 2nd shoulder

6. Priapism

Emergencies, Rx: transfusion

7. Acute chest syndrome

Emergencies, Rx: transfusion

8. Aplastic crisis

with infection of B19, Rx: folic acid

Treatment

1. Hydroxyurea; increase HbF

2. BM transplantation

G-6 PD Deficiency

Thalassemia Syndrome

G-6 PD Deficiency

Definition: quantitative, not qualitative, abnormalities of hemoglobin

G-6 PD deficiency causes decrease glutathione peroxidase

(antioxidant)
Clinical Feature
1. X-link R
i. African American type:
ii. Mediterranean type
2 H
2.
Heinz
i b
bodies:
di
oxidation
id ti off h
hemoglobin
l bi

1. -thalassemia

2. -thalassemia

1. decrease -globin chains ,

excess -chains

1. decrease -globin chains,

excess -chains

2. most commen in Asian population

2. most common in Mediterranean

3. expression in prenatally and

postnatally

expressed postnatally only

3. Bite cell: to eat heinz bodies by splenic macrophages

Treatment

-Thalassemia
Genetic
Normal

4 -chain (

Silent carrier

1. deletion 1 -chain
2. (- / ),

-Thal trait
(minor)

deletion 2 -chain

Genetic

1. -Thal minor

1. deletion 3 -chain
2. (--/- )

Hydrops fetalis 1. deletion 4 -chain,

2. lethal in utero (--/--)

1. normal: 2 chains,
2. point mutations,

asymptomatic, increased HbA2 or HbF

2. -Thal intermedia a severe anemia, but no transfusions needed

1. Genotype: cis (--/
in Asian

) type

3. -Thal major
(Cooley Syndrome)

1). normal at brith

2). develop at about 6 month as HbF decrease
3). severe hemolytic anemia
a. increase bilirubin, gallstones
b. Congestion heart failure is most common cause of
death
4). Erythroid hyperplasia in BM: x-ray: crewcut skull ,
chipmunk face
5). Peripheral in the blood: Numerous target cells

Treatment

1. do not require specific treatment

2. -major: blood transfusions 1 or 2 / month:
SE: Hemochromatosis, treat with deferoxamine
3. splenectomy eliminates severe hemolytic anemia:
4. Bone marrow transplantation

2 G
2.
Genotype:
t
trans
t
(( // )
type in African-American
Hb H disease
(major)

-Thalassemia

1. increase Hb H,
2. forms Heinz bodies
increase barts Hb

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PNH

Summery

Paroxysmal Nocturnal Hemoglubinuria

decreased glycosyl phosphatidyl inositol (GPI) linked proteins, especially
decay accelerating factor (DAF)
Function of DAF:
1. inhibit the activation of the complement cascade by breaking down C3
convertase
2. decrease O2, trigger complement pathway

RBC shapes

Diseases

Anisocytosis

Iron deficiency anemia

Poikilocytosis

Iron deficiency anemia

Shperocytes

1. hereditary spherocytosis

Target cells

Thalassemia, Hb C disease, Liver Disease

Symptoms and Complication

Bite cell

G6PD deficiency

aplastic anemia, leukemia, venous thrombosis

Teardrop cells

Myelofibrosis

Diagnosis

Elliptocytes

Hereditary elliptocytosis

1. Hams test (Acidosis in vitro)

Acanthocytes

abetalipoproteinemia

2. sucrose lysis test (sugar water test)

Echinocytes (burr cells)

uremia

Schistocytes (Helmet cells)

HUS, DIC, TTP

Rouleaux

Multiple myeloma

3. flow cytometry: CD55, CD59, much more sensitive and specific

Treatment
1. Glucocorticoids
2. BM transplantation

Summery
RBC
inclusions
Basophilic
stipling

Cytoplasmic remnant
RNA

Lead poisoning

Howell-Jolly
Ho
ell Joll
bodies

Remnants of nuclear
n clear
chromatin

Iron deficienc
deficiency anemia

Other types Anemia

Diseases

1. Diamond-Blackfan Syndrome:
congenital pure RBCs anemia
2. Fanconi anemia (Constitutional)
pencytopenia with abnormal structures

Ring
sideroblasts

Iron trapped
Sideroblastic anemia
abnormally in
mitrochondria forming
a ring around nucleus
Heinz-bodies
G6PD

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Hemostasis
Bleeding
g Disorder

3:1 = M:E (myeloid to erythroid) ratio.

Hasenchecheg Qi MD., Ph.D.

Hemostasis
1. vascular wall
injury

Bleeding

1. bleed
2. transient
vasoconstriction

changes blood flow cause

turbulence and stasis
Reynolds number = (diameter)
(velocity) (density)/viscosity
> 2000 = turbulent flow
< 2000 = laminar flow

3. thrombogenic factors 1. release tissue factor, activate

VII ((extrinsic)
ti i )
2. active factor XII (intrinsic)
due to expose subendothelial
collagen
3. release vWF

Hemostasis

2. transient clotting

platelet clotting

bleeding time 27 min

3. Secondary
clotting

Extrinsic Coagulation
factor

PT: Prothrombin Time 12sec

Intrinsic Coagulation
factor

PTT: Partical Throboplastin

Time 30sec

Platelets

1. platelets
adhesion

Coagulation Factors

1. vWF adheres
to subendothelial
collagen
2. Platelets
adhere to vWF
by glycoprotein Ib

2. platelets
activation

Adhesion

1. platelets
changes shape
and
degranulation

Aggregation

2. synthesis of
TXA2
3. platelets
1. ADP
aggregation clopidogrel,
Ticlopidine

ADP

2. TXA2

Vitamin K

3. GpIIb/IIIa
Abciximab,
Eptifibatide,
Tirofiban

Glutamyl Carboxylase

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10/13/2008

Bleeding Disorder
Platelet

Thrombomodulin (transmembrane protein)

+
Thrombin
(60 hrs)
Protein C

150,000450,000/mm3

bleeding time: 27 min

1. Decrease Platelet
account
2. Abnormal Platelet
function
3. Von Willebrand
Disease (vWD)

C-activated protein

(Half life 14 hrs)

AD/AR, vWF

attributed to Factor 8
deficiency

Protein S

Wafarin:

1. bleeding time prolong

2. ristocetin
3. PTT prolong
Rx: Desmopressin
acetate (DDAVP)

Transient deficiency
of protein C

Inactivates
Factor V leiden:
variant of factor V

Factors Va and VIIIa

4. Bernard-Soulier
Syndrome

Gp Ib deficient

Rx: Platelet

[Link]
Thrombasthenia

Gp IIb/IIIa deficient

Rx:

Thrombocytopenia

Thrombocytosis

Immune
Thrombocytopenia
Purpura

Thrombotic
Thrombosytopenia
Purpura

Hemolytic
Uremic
Syndrome

Disseminated
Intravascular
Coagulation

Thrombocytosis (reactive)

Essential Thrombocythemia (ET)

1. anti-platelet

Fever
Anemia
Thromcytopenia

Diarrhea
Renal failure

1. D-dimers

Cause

Clinical Features

2. Platelet count
decrease

1. Bleeding, hemolysis

1. Increased platelet count

2. Inflammation

2. increased BT

3. Iron deficiency, Stress

3. increased BM megakaryocytes

2. Increase BM
megakaryocyte
3. acute form: child
after viral infection

Renal failure

3. Bleeding time increase

4 chronic: adult
4.
women 20-40 yo

Neuropathy

4 PT and PTT increase

4.

Treatment

Treatment

Treatment

Treatment

1. child self limited in

6mo, or prednisone

plasmapheresis

1. adult:
plasmapheresis

1. supportive

2. child:
self limited

2. FFP
3. Cryoprecipitate
4. treat causes

2. adult
a. prednisone
b. IVIG, anti Rh (D): fast
c. splenoectomy,
Vaccine
d. platelet transfusion

4 postsplenectomy
4.
t l
t
5. Malignancy

Disorder of Coagulation

von Willebrands Disease

Hemophillia A

Hypercoagulation

Hemophillia B

vWF deficiency,

VIII deficiency,

IX deficiency,

1. XII deficiency

Thrombosis, no bleeding

PTT prolong,

AD/AR,

XR,

XR,

2. XIII deficiency

Normal PT and PTT

May have VIII deficiency

vWF normal

Clinical Feature

Clinical Feature

Rare,
newborn bleeding from cut
umbilical cord

1. Cutaneous and mucosal bleeding

1. joint and soft tissue bleeding

3. Antithrombin (AT)
III deficiency

Thrombosis

PTT prolong

4. Antiphospholipid
antibody Syndrome

Thrombosis
Recurrent abortion

PTT prolong

Di
Diagnosis
i

5. Factor V leiden

Leiden variant of factor V,

(Activated protein C
resistance)

recurrent DVT

6. Protein C
Deficiency

Active Factors Va and VIIIa

1. dermal vascular thrombosis

2. skin necrosis

2. Menorrhagia,

2. Hemarthrosis: m.c.

3. GI bleeding

3. Intracranial bleeding: 2nd m.c.

Di
Diagnosis
i

Di
Diagnosis
i

1. BT increase, may with increase PTT

1. PTT increase

1. PTT increase

Treatment

Treatment

Treatment

Do not give Aspirin/NSAIDs

1. DDAVP (desmopressin)

1. factor VIII

2. Factor VIII concentrations,

give all Pt with vWD after major trauma
or during surgery

2. FPP not recommended because virus infections

(reduced ristocetin-induced platelet

aggregation)

1. factor IX

Dx. Clot solubility test in 5M

urea, positive

Rx: life-along anticoagulation

(Warfarin)

7. Protein S
Deficiency

Treatment of Acute hemarthrosis

1. Analgesia, (Codeine)
2. Immobilization
3. Synovectomy (arthroscopic) or radiosynovectomy
for severe and recurrent hemarthrosis

2
245

10/13/2008

Streptokinase

Urokinase
Alteplase (tPA)
Reteplase (rPA)

Plasma: no cells from blood

Anistreplase

Serum: no coagulation factor from plasma.

include all the ion and antibodies, immunoglobulin.

Heparin

Thrombolytics

Anticoagulation Medications
LMWH

Warfarin

Low-Molecular Weight Heparin

VIt K antagonist

Inhibit IIa and Xa

Mostly inhibit Xa

Inhibit II, VII, IX, X, and protein C and S

Half-lift time

Half-lift time

Half-lift time

1 hour

3-24 hours

4 days

Administration

Administration

Administration

1. therapeutic dose:
IV heparin, monitor PTT

1. subcutaneously
PTT monitor not necessary

1. orally: monitor PTT, Monitor INR (2-3)

SE and Advantage

2. prophylactic dose:
SC low-dose
low dose heparin
heparin,
PTT monitor not necessary
SE and Advantage

SE and Advantage

1. Bleeding

1. easer use out Pt

1. Hemorrhage

2. Heparin-induced
thrombocytopenia (HIT)

2. no HIT or osteoporosis

2. skin necrosis ( decrease protein C)

3. Osteoporosis

4. no osteoporosis

3. Teratogenic during pregnacy

4. Transient alopecia

5. more expensive

5. rebound hypercoagulability
d/t depression of ATIII
SE Treatment

SE Treatment

1. stop medication, 2. Give PPF, 3. Warferin over dose may also give Vit K

3
246

10/13/2008

4
247

10/13/2008

Lymphoma
&
L k i
Leukemia

3:1 = M:E (myeloid to erythroid) ratio.

Hasenchecheg Qi M.D.; PH.D.

Lymphoma

Lymphoma

Non-Hodgkin Disease
Precursor
B-Cell

Precursor
T-Cell

ALL

T-ALL

< 15 year old

Thymoma

Positive TdT

< 25 years old

Mature
B cell

HD

Plasma Cell
Neoplasma

Mature
T cell

1. Multiple myeloma
2 MGUS (Monoclonal Gammopathy
2.
undetermined significance)

Non-Hodgkin Disease

Not B-cell
Not T-cell

1. L1
2. L2
3. L3

1. not infections

chronic lymphocytic leukemia, or

small lymphocytic lymphoma

2. owl-eye

2. Hairy cell leukkemia

1. Follicular
Lymphoma

1. m.c. non
non-HD
HD
2. t (14, 18)

2. Diffuse large Bcell lymphoma

1. EBV
2. HHV-8

3. Samll noncleaved
lymphoma (Burkitt
lymphoma)

1. starry-sky
2. t (8, 14)

4. Mantle Cell
Lymphoma

T (11, 14)

Dx: TRAP +

3. R-S cell

Rx: 2CDA

1. ATLL

Tartrate-resistant acid
phosphatase

2. MF and Sezary S.
1. NS: m.c. Lacunar cell

Acute Lymphoblastic Leukemia

Mature B cell

1. CLL: m.c.

3. Waldenstrom macroglobulinemia
Terminal Deoxynucleotide
transferase

HD

If > 65 years old

2chlorodeoxyadenosine

2. LP: popcorn cell

3. LD: most RS cell
4. Mixed: eosinophils, IL-5

5. MALToma
(Marginal zone
Lymphoma)

18: bcl
bcl-2:
2: inhibits
apoptosis by blocking the
bax channel

8: c-myc

11: bcl-1 (cyclin D)

Treat as [Link]

Leukemia
AML
BM blast > 30%

MDS
BM blast <30%

Myeloproliferative Syndrome

CML

P. vera

ET

MF

1. M0M4: myelo-, WBC

2 M3:
2.
M3 t (15
(15, 17)
15: PML
17: retinoic acid receptor -gene
(RAR- )

1 t (9
1.
(9, 22)
9: c-abl

1. Dry tap
2. Teardrop RBC

22: bcr
2. LAP low

3. M5: monoblasts
4. M6: erythroblasts
5. M7: megakaryocytes

1
248

Biochemistry:
Week Three

249261

250262

Three sources of energy

Proteins
Fats
Sugars

BIOCHEMISTRY
AMINO ACIDS

AMINO ACIDS

Proteins
The main intracellular buffers

An Acid

A Base

Pka is less than 7

Pka is greater than 7

1
251263

An Acid

A Base

Dissociates early
Likes to give up hydrogen ions (protons)
Pka is less than 7
Strong acid: Pka 1 to 3
Weak acid: Pka 4 to 7

Dissociates later
Likes to accept hydrogen ions (protons)
Pka greater than 7
Weak base: Pka 7 to 9
Strong base: Pka greater than 9

Three Easy Words That are Hard

To Understand
Dissociate: to lose a hydrogen (proton)
Soluble: charged or polar
Bioavailable: neutral

Pka 4 to 9
Can be a weak acid or a weak
base

Dissociation

Dissociation
To Lose A Hydrogen

2
252264

Soluble

Soluble
Charged Or Polar

Soluble

Bioavailable

Water Soluble

Bioavailable

Bioavailable

Neutral

Fat Soluble

3
253265

As an acid dissociates

AMINO ACIDS

It gains a negative charge

It gains solubility
It loses bioavailability

As a base dissociates

Henderson-Hasselback Equation

It loses its positive charge

It loses solubility
It gains bioavailability

ACIDS

Henderson-Hasselback Equation

IF you want to absorb more

Add more Acid

IF you dont want to absorb it

Add base

4
254266

Base

Acids you need to know

IF you want to absorb more

Add more base

IF you dont want to absorb it

Add acid

Aspirin
Barbiturates
Myoglobin
TCAs

Bases you need to know

Amphetamines

The main acid used in

medicine
NH4CL

Now we look at the ISOELECTRIC

POINT

The main base used in

medicine
HCO3

5
255267

Isoelectric Point
NO NET charge on the molecule
Also called a zwitterion
Will NOT migrate towards anode or
cathode

Cathode

Anode

Where CATIONS go: the

negative electrode

Where ANIONS go: the positive

electrode

6
256268

To further categorize the

amino acids

PHE, TRP, TYR

Glycine
Smallest amino acid
NO chiral carbon
Inhibitory neurotransmitter for the spinal
cord

Aromatic amino acids

Recognized by chymotrypsin

LYS, ARG

Asp, Glu

Basic amino acids

Have a positive charge
Recognized by trypsin

Acidic amino acids

7
257269

Asp

Cys, Met

The only excitatory amino acid in the brain

( NMDA pathway)

Contain sulphur
Make disulphide bonds

Asparagine, Glutamine

Serine, Threonine, Tyrosine

Involved in N- bonds

Involved in O- bonds

Leu, Iso, Val

Tyr

Branched chain amino acids

Used to make catecholamines

Used to make melanin

8
258270

Trp

Ketogenic Amino Acids

Used to make serotonin

Lysine
Arginine

Glucogenic Amino Acids

Both glucogenic and ketogenic

PHE
ISO
THR
TRP

ALL OTHERS

Essential Amino Acids

Essential Amino Acids

You get them ONLY from the diet

NO cycle in YOUR body can make these
A deficiency will ALWAYS lead to a
disease
Deficiencies put the body into a starvation
state

9
259271

How does the body utilize energy

during starvation?

Energy Utilization

Notables

(1) plasma glucose: lasts 2 to 4 hours

(2) liver glycogen: lasts 24 to 28 hours
(3) proteolysis for gluconeogenesis
(4) lipolysis
(5) ketogenesis

Phenylketonuria

PHE used to make TYR

Phenylalanine hydroxylase is deficient

Unable to make tyrosine

TYR becomes essential if PHE is deficient

Unable to make DA and NE and EPI

MET used to make CYS

Unable to make melanin without tyrosine

Blonde hair; blue eyes; fair skin

CYS becomes essential if MET is deficient

Phenylacetate and phenylpyruvate build

up
Musty odor

PKU

Newborn Screening

Must screen all newborns at 48 hours

Must avoid aspartame (nutrisweet)
Pregnant mother must be on restricted diet
especially during first 8 weeks while brain
is developing
Rainbow colored wheel on food products
would warn these patients against
aspartame

PKU ( Guthrie test)

Hypothyroidism (TSH)
CAH
Biotinidase def
Galactosemia

10
260272

Albinism

Vitiligo

Tyrosinase deficiency
Predisposed to skin cancer

Autoimmune antibodies against

melanocytes
Loss of pigmentation
Predisposed to skin cancer

Alcaptonuria (ochronosis)

Maple Syrup Urine Disease

Homogentisic acid oxidase deficiency

Tyrosine builds up
Urine turns black when exposed to air

Involves branched chain amino acids

Defective renal transport of these amino
acids
LEUCINE
ISOLEUCINE
VALINE

Cystinuria
Defective renal transport of amino acids
Hexagonal, envelope shaped, or coffin lid
shaped crystals in the urine
CYSTIENE
ORNITHINE
LYSINE
ARGININE

THE END
TO BE CONTINUED

11
261273

Protein Structure

Protein Structure
and Function
Putting the Amino Acids
Together

Protein Structure

Primary
Secondary
Tertiary
Quarternary

Primary Structure

Primary
Secondary
Tertiary
Quarternary

The amino acid sequence

Involves peptide bonds
Restriction enzymes are used to sequence
proteins

Peptide Bond

Peptide Bond
Planar
Restricted mobility
R-groups are in trans-configuration

1
262274

Sequencing
Before we understand the
present
We need first visit the past!

Acid Hydrolysis

The history of sequencing

Acid hydrolysis
Gel electrophoresis
Ninhydrin reaction
Edmans degredation
Restriction peptidases

Denatures the protein

Does NOT actually sequence the protein
Turns asparagine into aspartate (acidic
form) and glutamine into glutamate (acidic
form)

Gel electrophoresis

Gel Electrophoresis

Uses agarose gel to separate proteins by

size first, charge second
Smaller proteins migrate further
Larger proteins stay closer to the start site
Does NOT sequence the proteins

2
263275

Ninhydrin Reaction

Edmans degredation
Uses phenylIsoThioCyanate (PITC)
Reacts with ANY amino acid starting on
the amino terminal
Amino acids are identified by
spectrophotometry (light transmission)

Reacts with all amino acids creating a

purple color
Proline reaction creates a yellow color
Good ONLY for counting prolines

Procedure is accurate ONLY up to 100

amino acids

Restriction Peptidases

Restriction Peptidases

Restricted by what amino acids they can

recognize
Used to actually sequence proteins

Trypsin: cuts to the right of LYS and ARG

Chymotrypsin: cuts to the right of the
aromatic amino acids, PHE, TRP, TYR
Elastase: cuts to the right of GLY, ALA,
SER
CNBr: cuts to the right of MET
Aminopeptidase: cuts to the right of the
amino terminal amino acid

Restriction Peptidases, cont

An Example

Carboxypeptidase: cuts to the left of any

amino acid on the carboxyl terminal
Mercaptoethanol: breaks up disulfide bonds

3
264276

Secondary structure

Alpha helix

Alpha helix
Beta pleated sheet

Beta pleated sheet

Serum proteins
Functional
Acute phase reactants

Too many proteins in your plasma

Elevated ESR or CRP

TOO many acute phase

proteins

Indicates nonspecific inflammation

Falsely high ESR: anemia

Falsely low ESR: sickle cell anemia;
polycythemia
Acute phase reactants caused by IL-6

Leads to AMYLOIDOSIS

4
265277

AMYLOIDOSIS

Secondary Amyloidosis

Primary: autosomal dominant

Massive intracerebral hemorrhage in a young

person with no prior h/o HTN

Secondary: due to any chronic

inflammatory disease

AA: chronic inflammatory disease

AB: Alzhiemers disease
AB-2: Chronic renal failure
AE and AF: MEN-II
AL: Multiple myeloma

Congo red stain

Apple green birefringence

Tertiary Structure

Quarternary Structure

3-D structure
Most important factor is hydrophobic and
hydrophilic interactions
Covalent bonds now form

Two or more proteins are interacting

Cooperativity
Allosterism: refers to enzymes
Allosteric enzyme means the slowest enzyme;
means rate-limiting enzyme; means the
kinetic curve is sigmoidally shaped

Hemoglobin
Type A: 2 alpha 2 beta chains

Hemoglobin

Type A-2: 2 alpha 2 delta chains

The first quarternary protein

discovered

Type F: 2 alpha 2 gamma chains

5
266278

Hemoglobin F

Hemoglobin F

Found in the fetus

Disappears by 6 months of age
Has a low affinity for 2,3, DPG
Has a high affinity for oxygen

Erythropoiesis

Heme Synthesis

Begins: in yolk sac at 4 months gestation

6 mo gestation: moves into the liver,
spleen, and flat bones
8 mo gestation: moves into the long bones
1 year of age: liver, spleen, and flat bones
close
If you lose the long bones after 1 year, the
spleen can reopen causing massive
splenomegaly

Iron deficiency anemia

Lead Poisoning

Most common cause of microcytic

hypochromic anemia
In children: Mcc is inadequate intake
In young adults: Mcc is still inadequate
intake
20 to 40: IBD
> age 40: mucasal bleeding
Tx: ferrous sulphate

Lead inhibits delta ALA dehydratase as

well as ferrochetolase
Mcc: eating peeling paint from old
buildings
Classic clue: basophilic stippling; elevated
FEP (free erythrocyte protoporphrins)

6
267279

Heme Synthesis

Lead levels to know

Normal: < 10
If above 10: notify PHD; treat with succimer
If above 30: notify PHD; hospitalize; do a
Ca-EDTA challenge; treat with
penicillamine and dimercaprol (BAL) if
urinary lead is high
If above 50: do as above; skip EDTA
challenge

Drug induced lupus

Antihistone antibodies

Lead used to be the most

common cause of mental
retardation

Hydralazine
INH
Procainamide
Penicillamine
Phenytoin
Ethusuximide

But NOT ANY MORE!

Mental retardation

Porphyrias

Fetal alcohol syndrome

Fragile X syndrome
Downs syndrome

A group of enzyme deficiencies

Synthesize too many porphyrin rings or
inadequate metabolism are the problems
Porphyrin rings in the urine make it red
Two types are most important

7
268280

Erythrocytic Protoporphyria and

Porphyria Cutanea Tarda

Acute Intermittent Porphyria

Enzyme dificiency
A build up of porhyrin rings
Porphyrin rings are deposited in visceral
organs and around nerves
Recurrent severe abdominal pain and
neuropathy
Tx:

Enzyme dificiency
Porphyrin rings are deposited underneath
the skin
Light reacts with the rings causing a
release of heat which leads to burns
Mcc of death: skin infections
Tx: protect them from light

Opiates

Opiates

CNS depressants
Muscle relaxants
Analgesics
Receptors:
Mu ( CNS)
Kappa: Spinal cord

Hemoglobinopathies

Heroin
Methadone
Morphine
Meperidine
Codone
Oxycodone
Codiene
Dextromethorphan

Loperimide
Diphenoxylate
Fentanyl
Pentazocine

Hemoglobin S disease

Hemoglobin S disease
Hemoglobin C disease

Autosomal recessive
High prevalence in Africa ( natural
selection)
Substitution of valine for glutamate at
position 6 of beta chain
Hypoxia causes cells to sickle leading to
vaso-occlusion

8
269281

Vaso-occlusive crises

Aplastic crisis

CVA
PULMONARY INFARCTION
SPLENIC SEQUESTRATION
PRIAPISM

Complete bone marrow suppression

Always check the reticulocyte count
Mcc: parvovirus B-19

Tx: exchange transfusion; oxygen

Hemoglobin C disease

A Few Points to Remember

Functional asplenia by age 6 due to
infarcts

Autosomal recessive
Substitution of LYS for GLU at position 6
of beta chain
NO sickling occurs since both amino acids
are hydrophilic

Susceptible to encapsulated organisms

Give pneumovax anytime after age 2

Infections are mcc reason for crises

Hydroxyurea increases HgF, decreasing
chance for hypoxia
Use opiates for pain
Transfuse when anemic and symptomatic

Thallesemias

Hemoglobins

Represent gene deletions

Autosomal recessive
Common in Mediterainian people
Minor: at least one gene remaining
Major: no genes remaining

9
270282

Alpha Thalessemia

Baseline labs
RBC Mass: 3.5 to 4.5 million
Hemoglobin/Hematocrit: 15/45%

Alpha Minor

Alpha Thalessemia Major

One gene missing

Asymptomatic ( HG 12) 75%

Two genes missing

IF sedentary: asymptomatic
IF active: symptomatic (HG 7.5) 50%

Three genes missing

NO genes remaining
Unable to make any hemoglobin at all
Hydrops Fetalis
Hemoglobin Bart ( 4 gamma chains)
Hemoglobin H ( 4 beta chains)

Symptomatic in ALL (HG 4 to 5)

Beta Thalessemia: 2 genes

Beta minor (Hg 7.5)
One gene missing
If sedentary:
asymptomatic
If active: symptomatic
Increased Hg A-2 and
Hg F
Ineffective
erythropoiesis

Blood Transfusions
Done ONLY when patient is symptomatic
One unit of PRBCs

Beta major
Both genes missing
Able to make only Hg
A-2 and Hg F
Asymptomatic until 6
months of age
Transfusion dependent

Raises Hg by 1 to 2 grams ( 3 to 6 HCT)

Delivers 3.4 grams of iron

10
271283

Iron Overload

Hemochromatosis

Hemosiderosis: bone marrow is

overwhelmed by iron
Hemochromatosis: iron overload has
involved other organs

Primary

Secondary

Autosomal recessive
Too much iron
absorption from
duodenum
HLA A3 on
chromosome 6

Skin: bronze pigmentation

Liver: bronze cirrhosis
Pancreas: bronze diabetes
Heart: restrictive cardiomyopathy

Transfusion Related INFECTIONS

Too many transfusions

Mcc of death in first 10
years: transfusion
related infections
Mcc of death after 10
years: CHF

Transfusion related infections

HIV
Hepatitis B
Hepaitis C
Hepatitis D
EBV
CMV
Hemorrhagic viruses

Bacterial infections
Malaria
Babesiosis
Syphilis

COLLAGEN

Hemoglobin Saturation Curve

11
272284

4 Types of collagen

More than a quarternary

structure

Type 1: Skin
Type 2: Connective tissue
Type 3: Arteries
Type 4: Basement membrane

Its a TRIPLE HELIX

To synthesize collagen

Protein synthesis for packaging

Glycine: every third amino acid

Lysine
Proline
OH-Proline
OH-Lysine

Protein synthesis for packaging

Protein synthesis for packaging

12
273285

Who makes collagen?

Protein synthesis for packaging

Fibroblasts: simple scarring

Myofibroblasts: if you need wound
contraction

When collagen synthesis goes

wrong
DESMOPLASIA
COLLAGENOUS REACTION
SURROUNDING A TUMOR

COLLAGEN PROFILE
KELOID
TOO MUCH COLLAGEN
DEPOSITION

13
274286

Collagen diseases

ALL YOU NEED NOW IS A CLUE

Ehlers Danlos
Marfans
homocystienuria
Scurvy
Osteogenesis imperfecta
Minkys kinky hair syndrome

Secondary collagen diseases

Collagen Vascular Diseases

Ankylosing spondylitis
Fragile X syndrome
Syphilis
Takayasus disease

CREST
Scleroderma
Progressive systemic
sclerosis
Rheumatoid arthritis

SLE
MCTD

Feltys syndrome
Becets syndrome
Sjogrens syndrome

ELASTIN

Elastin

Has many GLYCINES

Has PROLINES
Has LYSINES
Has OH-PROLINES
NO hydroxylysines

14
275287

Elastin

Elastase

Provides COMPLIANCE
Provides ELASTICITY
Has DESMOSINE

Whos afraid of staph aureus and

pseudomonas?

Emphysema
Destruction of elastin
Loss of recoil

Destroys elastin
Cuts to the right of GLY, ALA, and SER
Alpha-one antitrypsin inhibits elastase
Found in neutrophils and bacteria
Smoke inhibits alpha-one antitrypsin
Decreased alpha-one antitrypsin with
aging

Panacinar: alpha-one antitrypsin deficiency

Centroacinar: smoking
Disto-acinar: aging
Bullous: staph aureus and pseudomonas

Neutropenic
Burn patients
Cystic fibrosis
Diabetics

If any fever, cover staph aureus with one

antibiotic and cover pseudomonas with
two antibiotics

Keratin
Made for tensile strength
Contains a lot of CYSTEINES

THE END
ONLY FOR NOW

15
276288

ENZYMES

IF asked whether a reaction is

possible

THE MOST IMPORTANT

PROTEINS IN YOUR BODY

THE answer is always YES!

A Reaction

ANYTHING, as we know
IS

POSSIBLE!!

An Enzyme

An ENZYME has

Brings substrates together in space and

time
Lowers the free Energy of activation
Stabilizes the hi energy intermediate
Is not consumed in the reaction

1
277289

Competitive inhibition

Noncompetitive inhibition

Inhibitor is similar to the substrate

The inhibitor is competing for the active
site
Affinity I decreased
Km increases
Vmax remains the same ( just add more
substrate)
reversible

What makes a reaction favorable

and spontaneous

NOT similar to the substrate

Does NOT bind active site
Binds to regulatory site
Turns off the enzyme
Km remains the same
Vmax decreases
irreversible

Effects of temperature on a
reaction

E
You want it to be negative
When negative: has electrons
to give
When positive: wants to accept
electrons

E
REDOX POTENTIAL

2
278290

Reducing agent

Oxidizing agent

Has a negative delta E

Wants to give away electrons
Gets oxidized after the reaction

Has a positive delta E

Wants to accept electrons
Gets reduced after the reaction

Electron Transport System

Inhibitors and Uncouplers

3
279291

Inhibitors

Uncouplers
DNP
ASPIRIN
FREE FATTY ACIDS

How to name enzymes

FIRST NAME of an enzyme
IS the name of the SUBSTRATE

LAST NAMES of enzymes

LAST NAME of an enzyme

Is what you did to the substrate

Kinase
Phosphorylase
Isomerase
Epimerase
Mutase
Transferase
Lyase
Carboxylase

Synthase
Synthetase
Dehydrogenase
Hydrolase

4
280292

Coming to a screen near

you

THE PATHWAYS

5
281293

Anabolic Pathways:

As soon as you eat

Putting it all back together

You replenish your plasma glucose

After glucose returns to

the liver

After you turn off

gluconeogenesis

You turn off gluconeogenesis

You turn on glycogen synthesis

Glycogen Synthesis

282294

Pentose Pathway

NADPH is used for

X-linked Recessive Enzymes

Fatty acid synthesis

DNA synthesis
RBC repair ( used by glutathione)

G6PD
More common in Meditteranians ( protects
them from malaria)
Mcc of hemolytic crisis: ( 1) infection (2)
drugs
Drugs that oxidize RBCs: sulfa drugs;
antimalarials; metronidazole; INH

283295

G6PD
Fabrys ( alpha galactosidase)
Hunters ( Iduronidase)
CGD ( NADPH Oxidase)
Lesch-Nyhan ( HGPRT)
Pyruvate Dehydrogenase
Adrenoleukodystrophy ( CAT-1)

Fatty Acid Synthesis

Amino Acid Synthesis

Palmitic Acid
The main fatty acid that we make every
day
Saturated FA: NO double bonds
Unsaturated FA: has double bonds
Omega FA: counting carbons from the right
side
Omega 3 FA: Lowers serum cholesterol
Pocosanol

Rules for Fatty Acids

Essential Fatty Acids

We do NOT go beyond C-16

Double bonds have to be at least 3
carbons apart
NO double bonds after C-10

284296

Linolinic
Linoleic ( used to make arachadonic acid)
Come ONLY from the diet
Your body can not make these

Irreversible Cyclo-Oxygenase
Inhibitor

Arachadonic Acid

Aspirin

Reversible Cyclo-Oxygenase
inhibitors

Steroids

NSAIDs

Antiinflammatory
actions

Indomethacin
Phenylbutazone
Ibuprofen
Naproxen
Baclofen
Ketorelac
cyclobenzaprine

Inhibit PLP-A
Kills T-cells and
eosinophils
Inhibits macrophage
migration
Stabilizes mast cells
Stabilizes endothelium

Steroids

Prednisone
Methylprednisalone
Triamcinalone
Beclamethasone
Betamethasone
Hydrocortisone
Dexamethasone
fludrocortisone

Physiologic actions
Proteolysis
gluconeogenesis

Mast Cell Stabilizers

Cromolyn
Nedacromyl

Cypropterone
Megestrol
Fluticasone
Mometasone
Danazol

285297

LRBs

Triglyceride Synthesis

Triglyceride Transport

Sphyngolipids

Zifurlekast
Montelekast
Zileutin

Chilomicrons
VLDL
IDL
Signs:
Xanthelesma
Pancreatitis

Lysosomal Storage Diseases

Gaucher: glucocerebrosidase
Fabrys: alpha galactosidase
Krabbes: beta galactocerebrosidase
Tay Sacks: hexoseaminidase A
Sandhoffs: hexoseaminidase A & B
Nieman Pick: sphyngomylinase
Metachromatic leukodystrophy: arylsulphatase
Hurlers: iduronidase
Hunters: iduronidase sulphatase

And Now
The final anabolic
process

286298

Cholesterol Synthesis

NUCLEOTIDES

NUCLEOTIDES

PURINES
Adenine
Guanine

RNA
DNA
ENERGY
CARRIERS ( UDP & CDP)
METHYL GROUP CARRIER ( S-AM)
SECOND MESSENGERS

PYRIMIDINES

NUCLEOTIDES

Thymidine
Cytidine
Uracil

287299

THE BLOTS

Southern blot: DNA

Northern blot: RNA
Western blot: PROTEIN
PCR: amplifies DNA or RNA
ELIZA

EUCHROMATIN
Loose DNA; has more A and T

PURINES
HETEROCHROMATIN
Tight DNA; has more G and C

PYRIMIDINES

RIBONUCLEOTIDE REDUCTASE

288300

The DNA Helix

SCID
Adenosine deaminase def
Unable to make DNA
Affects all rapidly dividing cells, especially
bone marrow
Bone marrow transplant is now current
therapy

HISTONES

Anti-Histone Antibody

Help bind DNA helix

H-1
H-2a
H-2b
H-3
H-4
Basic

CELLULAR CYCLE

Hydralazine
INH
Procainamide
Penicillamine
Phenytoin
Ethusuximide

DNA REPLICATION

289301

TRANSCRIPTION

TRANSLATION

DIFFERENCES

MUTATIONS

DNA Replication

Translation

DNA POL alpha

DNA POL beta
DNA POL gamma
DNA POL delta
DNA POL epsilon
Replication forks

Frameshift mutations
Point mutations

Fmet vs met

Transition mutations
Transversion mutations
Silent mutations
Missence mutations
Nonsence mutations

Transcription
Monocistronic
polycistronic

IT IS THE END
CAN IT BE ?
YES, IT IS!!!

290302

OR IS IT.

291303

Sources of Energy

Catabolic Pathways
Breaking it all down

Glucose ( 40% of diet)

Proteins ( 30% of diet)
Fats ( 30% of diet)
Ketones ( last resort)

Breaking Down Sugars First

Breaking Down Sugars

Begins With Glycolysis

RBC Connection
RBCs use ONLY glucose for energy
Hypoglycemia will ALWAYS affect RBCs
first, causing a hemolytic anemia
The only other pathway RBCs have is the
pentose pathway for making NADPH to
maintain the membrane

292304

Glycolysis

Glycolysis
The most active pathway in your body
CATABOLIC in all cells except the liver
where it is ANABOLIC

How to use energy

CATABOLIC STATE
Is controlled by the sympathetic system
Second messenger is C-amp
Is controlled hormonally by epinephrine
and glucagon

293305

DHAP
Used in the glycerol 3 phosphate shuttle
Used in triglyceride synthesis

Glyceraldehyde 3 phosphate
dehydrogenase

Mercury Toxicity

Has sulphur in the active site

Is blocked by mercury poisoning

Mcc: (1) Tuna (2) a child biting into a

thermometer
Blocks glyceraldehyde 3 phosphate
dehydrogenase
LOW ENERGY STATE
RBCs affected first
Brain affected the most

Pallegra
Niacin deficiency
The 4 Ds
Dermatitis
Diarrhea
Dimentia
Death

Hartnups: presents just like pallegra.

Defective renal transport of tryptophan

294306

Flouride Poisoning
Blocks the enzyme ENOLASE
Caused in the past by eating rocks of
flouride
Rare today since flouride added to water
and toothpaste
Clue: extra white teeth and bones

Gluconeogenesis

Gluconeogenesis
Controlled by epinephrine and glucagon
Second messenger is C-amp
Occurs only in the liver (90%) and the
adrenal cortex (10%)
Occurs while other tissues are running
glycolysis
Occurs in the mitochondria and cytoplasm

295307

Galactose Metabolism

To reverse glycolysis

Pyruvate carboxylase ( rate limiting)

PEP Carboxykinase
F16DPase
G6Pase

Detecting Sugars
In the urine: CLINITEST
In the stool: positive REDUCING SUBSTANCES

Galactosuria

Galactokinase deficiency
Hexokinase fills in for galactokinase
Galactose in the urine ( clinitest positive)
Symptoms: polyuria; polydypsia; UTIs

296308

Fructose Metabolism

Galactosemia
Galactose 1 phosphate uridyltransferase
deficiency
Galactose 1 phosphate builds up in the
cells
RBCs affected first
Brain affected the most
LOW ENERGY STATE

Fructosuria

Fructokinase is missing
Hexokinase fills in
Fructose in the urine ( clinitest positive)
Polyuria
Polydypsia
UTIs

Fructosemia
Aldolase B is missing
Fructose 1 phosphate is trapped within the
cells and can not leave
RBCs affected first
Brain affected the most
LOW ENERGY STATE

Before you enter the KREB CYCLE

YOU NEED TO
KNOW

297309

THE FIVE FATES OF

PYRUVATE

5 FATES OF PYRUVATE

Pyruvate Dehydrogenase

KREB CYCLE

Malate-Aspartate Shuttle

Glycerol 3 Phosphate Shuttle

298310

Fatty Acid Catabolism

Amino Acid Catabolism

Palmitic acid: C-16 the main fatty acid we

make daily
Three formulas to know:
( C/2 1) : the number of rounds it takes to
break down a fatty acid chain or the number
of rounds it took to make a fatty acid chain
( C/2 1) 2 : the number of NADPHs it cost to
make a fatty acid chain
( C - 1): the number of ATPs it cost to make it

Fatty Acid Catabolism

Adrenoleukodystrophy
Defective carnitine shuttle
Long chain free fatty acids accumulate in
the cytoplasm, unable to enter
mitochondria
X-linked recessive
Adrenal gland failure
Early white matter involvement

Beta - Oxidation

X-linked Recessive Enzymes

G6PD
Pyruvate dehydrogenase
NADPH-Oxidase
HGPRT (Lesch-Nyhan)
Alpha-Galactosidase ( Fabrys)
Iduronidase ( Hunters)
CAT-1 (Adrenoleukodystrophy)

299311

Odd numbered carbon fatty acid

metabolism

Ketogenesis

IDDM ( TYPE 1 DIABETES)

Reasons NEVER to give bicarbonate

in treatment of DKA

Autoimmune
2 weeks after a viral
(Cocksackie B) infection
Anti-islet cell antibody
Sx begin after 90% of
islet cells are destroyed
Remaining 10% will
undergo hyperplasia
( honeymoon period)
Signs and sx: LOW
ENERGY STATE

DKA

It merely corrects a number without

correcting the actual problem
Decreased cardiac output
Causes hypokalemia
Shifts hemoglobin dissociation curve to the
left
Bicarbonate ion does NOT cross the blood
brain barrier ( CSF pH falls paradoxically)

Hypovolemia
Lack of insulin
Low body potassium
Hyperkalemia
Hypophosphatemia
Pseudohyponatremia
Correcting sodium
Visceral pain
False high creatinine
Correcting glucose
Correcting acidosis

NIDDM ( Type II Diabetes)

Genetic
Connected to obesity
Downregulation of
insulin receptors
Hyperinsulinemia
Nonketotic
Hyperglycemic,
nonketotic coma

Sulfonylureas
Chlorpropamide
Tolbutamide
Tolezalide

Complications

Vasculitis
Clots
Bleeds
Nephropathy
Neuropathy
IDM
Tx: weight loss

Glipizide
Glyburide

Meds
insulin

300312

Insulins

Other Oral Hypoglycemics

Ascarbose
Miglitol
Metformin

Piaglitazone
Rotiglitazone
Repaglinide
Troglitazone

Dawn effect

Somoji effect

Increase in blood sugar each morning

caused by the normal increase in
epinephrine, glucagon and cortisol that
occurs each morning

Actually caused by HYPOGLYCEMIA that

occurred in the early morning ( 2 to 3 am)
leading to reactive HYPERGLYCEMIA in
the late morning ( 6 to 7 am)

Tx: increase morning regular insulin

Tx: decrease evening NPH insulin

Glycogen: Synthesis / Catabolism

Glycogen: Synthesis / Catabolism

301313

Glycogen: Synthesis / Catabolism

Glycogen: Synthesis / Catabolism

Glycogen: Synthesis / Catabolism

Glycogen Storage Diseases

Glycogen Storage Diseases

Von Gierkes: glucose 6 phosphatase

Andersons: branching enzyme
Corys: debranching enzyme
Hers: liver phosphorylase
Mcardles: muscle phosphorylase
Pompes: cardiac alpha 1,4 glucosidase

The End of CATABOLISM

The Beginning of ANABOLIC
PATHWAYS

302314

Forgiveness
Through Gods love, you always have
infinite forgiveness
Unfortunately, you dont always have
infinite time

The Physiology of CANCERS

CELLS OUT OF CONTROL

Anaplasia

Metaplasia

Cells revert back to their mesenchymal

origin
NO MATURATION TIME NEEDED
The most aggressive type of cancer
Divides rapidly
Metastasizes early and aggressively
SENSITIVE to radiation or chemo

Replacement of one adult cell type for

another
The new cell can better handle the stress

1
303315

Desmoplasia
A collagenous reaction surrounding a
tumor

Dysplasia

Loss of cell to cell contact inhibition

Cells begin to crawl on top of each other
This is the FIRST STAGE OF CANCER
Also known as carcinoma in situ ( CIN)
Any cancer that is caught at this stage has
a good prognosis if removed ( 90% 5 year
survival)
ALL screening is done to find cancer at
this stage

NEOPLASIA
BENIGN

Well circumscribed
Freely mobile
Encapsulated
Does not outgrow
capsule
Does not outgrow
blood supply
NO METS
Obeys physio

Malignant Neoplasia

MALIGNANT

Angiogenin
Endostatin

Not circumscribed
Adherent
Not encapsulated
Outgrows capsule
Outgrows blood supply
METS
Does NOT obey
physio

2
304316

When you have one BILLION

cells

How long does it take for ONE

BILLION cells to reassemble?

You can SEE the cancer with the naked

eyes
You can PALPATE it on exam
Chemo must kill at least one billion cells to
be considered effective

If a cancer outgrows its blood

supply, go to the

To Name a Tumor

BRAIN
LUNGS
BONE
LIVER
ADRENAL
PERICARDIUM

First name: the most common cell type

Last name: add - oma at the end

To Name a Cancer

TRICKY - OMAs

First name: most common cell type being

stressed
Prefix for every glandular tissue is ADENO
Last name: carcinoma if it originates from
epithelium

Hamartoma: abnormal growth of normal

tissue
Choristoma: abnormal location of normal
tissue

Sarcoma if it originates from connective tissue

3
305317

Cancers that lost their proper

endings

Let us now beginone organ at a

time

Hepatoma
Seminoma
Lymphoma
Teratoma
Mesothelioma
Retinoblastoma
Neuroblastoma
Nephroblastoma ( Wilms tumor)

BRAIN

Psammoma Bodies

Most common INTRACRANIAL tumor:

MENINGIOMA

Displaces the brain

Psammoma bodies ( calcifications)

BRAIN, cont

Papillary carcinoma of thyroid

Serous
Adenocarcinoma of the ovaries
Meningioma
Mesothelioma

Neurocutaneous Syndromes

Most common primary brain tumor:

ASTROCYTOMA

ALL have mental retardation, seizures and

cerebral calcifications in common
All have tumors or cancers associated with
them
All have different cutaneous findings

GLIOMA
OLIGODENDRIGLIOMA
EPENDYMOMA

4
306318

Neurofibromatosis

Sturge Weber syndrome

Caf au lait spots ( hyperpigmented

macules)
Associated with chromosome 17/22
Neuromas

Port wine stain on forehead

Angiomas of retina and brain

Peripheral neuromas: chromosome 17(type 1)

Central neuromas: chromosome 22(type 2)

fibromas

BRAIN, cont

Pituitary

Most common primary brain cancer:

astrocytoma grade IV or GLIOBLASTOMA
MULTIFORME

Most common tumor: pituitary ADENOMA

Cell types:

Most common cancer: METASTASES

Usually found at the grey-white matter
junction

Chromophobes ( nonfunctional) 95%

Acidophils (produce PRL and GH)
Basophils ( produce ACTH, TSH, FSH and LH)
Most common FUNCTIONAL tumor:
PROLACTINOMA

Most common cancer:

ADENOCARCINOMA (rare)

Pineal

Posterior Fossa Tumors

Present with early morning vomitting
Common in children

Most common tumor: pineal adenoma

( PINEALOMA)
CN VI palsy (esotropia)
Precocious puberty

MEDULLOBLASTOMA
Cerebellar origin; it sits on top of the medulla

Most common cancer:

ADENOCARCINOMA (rare)

CRANIOPHARYNGIOMA

Develops from Rathkes pouch

Has a motor oil appearance
Has some calcifications
May damage anterior or posterior pituitary

5
307319

Mediastinum

Posterior Mediastinum

Anterior
Middle
Posterior

Mostly ganglia located there

Most common tumor: NEUROMA
Most common cancer:
NEUROBLASTOMA

Neural Crest Cancers

NEUROBLASTOMA
Most common
abdominal mass in
children
Hypsarrythmia
Opsoclonus
Highest spontaneous
regression rate (2%)

Neural Crest Cancers

Paroxysmal palpitations, HTN, headache
and diaphoresis
Unable to differentiate benign from
malignant histologically
Must remove ALL of them
Dx: check urinary VMA, metanephrines, or
HVA

PHEOchromocytoma
Located in adrenal
medulla
10% in children
10% bilateral
10% metastatic
10% familial
10% malignant

Phentolamine
Phenoxybenzamine

Anterior Mediastinum

Thymus

Thymus
Thyroid
T-cell leukemias/lymphomas
Teratomas

Most common tumor: THYMOMA

Associated with ALL autoimmune diseases
except Graves disease
These cells are pleuripotent;
Thymus is immunopreviledged

Most common cancer:

ADENECARCINOMA (rare)

6
308320

Thyroid

Thyroid Masses
CYSTIC

Most common mass: cyst( throglossal)

Most common tumor: follicular adenoma
Most common cancer: papillary
carcinoma

SOLID

Thyroglossal cyst is
most common
Do ultrasound to verify
Do FNA: diagnostic
and therapeutic

Local metastases only

Psammoma bodies
Risk factor: previous irradiation to the neck

First do a thyroid scan

cold nodule and h/o
previous irradiation to
the neck: lobectomy
If hot nodule: treat
hyperthyroidism
Cold nodule w/o h/o
previous irradiation:
biopsy
Do lobectomy only if
malignant

Parathyroid

MEN Syndromes

Located behind the thyroid glands

Most common tumor: parathyroid adenoma

MEN I: pituitary, pancreatic, and

parathyroid tumors ( Wermer Syndrome)
MEN II: medullary carcinoma of thyroid,
pheochromocytoma, plus or minus
parathyroid adenomas ( Sipple
Syndrome)
MEN III: MEN II plus neuroma or
ganglioneuroma but w/o PTH adenomas

Most common cause of isolated

hypercalcemia in adults

Most common cancer:adenocarcinoma

Men Syndromes

Parafollicular Gland

Middle Mediastinum

Also found behind the thyroid glands

Most common tumor: adenoma
Most common cancer: medullary
carcinoma of thyroid (produces calcitonin)

Contains the heart

Heart has three layers: endocardium,
myocardium, and epicardium. Pericardium
encases the heart

7
309321

Endocardium

Myocardium

Most common tumor: myxoma

Related to skeletal muscle

Most common tumor: rhabdomyoma
Most common cancer: rhabdomyosarcoma

Usually seen in left atrium

Diastolic plop
Middle aged female who passes out, only to
recover a few seconds later
Estrogen connection

Most common cancer: angiosarcoma (rare)

Epicardium

Pericardium
Most common tumor: fibroma
Most common cancer: metastases

Hardly ever involved in neoplasia

Lungs

Lung Cancers

Most common mass in children:

hamartoma
Most common mass in adults: granulomas
Most common tumor: adenoma
Most common cancer: metastases
Most common intrathoracic cancer:
squamous cell carcinoma
Most common primary cancer:
bronchogenic adenocarcinoma

CENTRAL: squamous cell carcinoma

( produces PTH)
Small cell carcinoma ( produces ACTH, ADH,
PTH and TSH)

8
310322

Lung Cancers, cont

Lung Cancers, cont

Peripheral: bronchogenic adenocarcinoma

and bronchoalveolar adenocarcinoma

RISK FACTORS: primary smoker risk

increases with amount and duration
Radon
Second hand smoke

Bronchoalveolar adenocarcinoma is the

only primary lung cancer NOT related to
smoking

Sidestream smoke
Mainstream smoke

Pneumoconioses: all of them increase risk of

cancer except anthracosis

Pneumoconioses

Treatment of Lung Cancer

Anthracosis
Asbestosis
Silicosis
Bissinosis
berryliosis

Poor prognosis
Surgery done only if lesion smaller than
2cm in size and localized, and if there is a
V/Q mismatch
Chemo or radiation is effective against
small cell carcinomas

Pleural Cavity

Nasopharynx

Most common tumor: mesothelioma

Most common cancer: mesothelioma

Most common mass: polyp

Aspirin sensitive asthma: avoid aspirin or
NSAIDS

Ferrugenous bodies
Psammoma bodies
Pleural thickening

Most common tumor: fibroma

most common cancer: nasopharyngeal
carcinoma
Commonly seen in Chinese women
EBV association

9
311323

Oral Cavity

Esophagus
Most common tumor: leiomyoma
Most common cancer: squamous cell
carcinoma
Most common cancer in lower 1/3rd of
esophagus: adenocarcinoma

Most common tumor: fibroma

Most common cancer: squamous cell
carinoma
Floor of mouth
Lower lip
Tip of tongue

Risk factor: Barretts esophagus

Almost always ulcerates
Odynophagia
Poor prognosis ( < 5% 5 year survival)

Stomach

Risk Factors for UGI Cancers

Most common tumor: leiomyoma

Most common cancer: adenocarcinoma

Virchows nodes
Leather water bottle appearance
Linnitis plastica
Signet ring cells
Kruckenberg tumor
Severe weight loss ( due to stomach
distention)

Small Intestine

Smoking
Alcohol
Nitrites
Japanese

Appendix

Most common tumor: leiomyoma

Most common cancer: adenocarcinoma
Most common cancer of the ileum:
lymphoma

Most common tumor: leiomyoma

Most common cancer: carcinoid
Does NOT metastasize
Carcinoid syndrome usually originates from
the (1) pancreas and (2) ileum

Early UGI obstruction

Napkin ring lesion
70% of lymphoid tissue is located in the ileum

Puts out large amounts of serotonin (check urinary

5-HIAA

10
312324

Colon

Colon cancer risk factors

Most common tumor: leiomyoma

Most common cancer: adenocarcinoma

Napkin ring lesion

Eaten apple core lesion
Pencil thin stool
Melena
Third most common cancer, and most
common cause of cancer deaths in both
sexes

Polyps

Low fiber diet

High fat diet
Polyps
Ulcerative colitis

Liver

Hepatic Adenoma

Most common mass: cyst

Most common tumor: adenoma and AVMs
Most common cancer: metastases
Most common primary cancer:
hepatocellular adenocarcinoma

AVMs

Associated with estrogen use or injected

steroids
Tends to rupture if abdominal pressure
rises significantly
Rupture can lead to acute life threatening
hemorrhage

Connect arteries to veins

Increased venous oxygen
Decreased AVO2 difference
Risk:
Burst and bleed
Sequester platelets and cause bleeding
Sequester blood, leading to high output heart
failure

11
313325

Risk Factors for Hepatocellular

Carcinoma

AVM Syndromes

Osler Weber Rondu: multiple AVMs in

the pulmonary circulation
Von Hipple Landau: multiple AVMs in the
abdomen and brain
Has an increased incidence of renal cell
carcinoma
Associated with chromosome 3p

Gallbladder

Smoking
Alcohol
Hepatitis B
Hepatitis C
Shistosomiasis
Analene dyes
Aflatoxin
Vinyl Chloride ( Angiosarcoma)
Benzene

Biliary Tract

Most common tumor: leiomyoma

Most common cancer: adenocarcinoma

Most common mass: choledochal cyst

Most common tumor: cholangioma
Most common cancer: cholangiosarcoma
Risk increase with chronic scarring

Poor prognosis because its hidden

beneath the liver
Thickened calcified gallbladder

PRIMARY BILIARY CIRRHOSIS

Antimitochondrial antibodies

SCLEROSING CHOLANGITIS
Seen in ulcerative colitis

Pancreas

Pancreatic Adenomas

Most common mass: cyst

Most common tumor: adenoma
Most common cancer: Adenocarcinoma

Glucagonoma: elevated glucose, lipids,

and ketones
Insulinoma (or nessidioblastosis): high
insulin and high C-peptide
Somatostatinoma: severe constipation
Vipoma: watery diarrhea
Gastrinoma (Z-E syndrome) elevated
gastrin levels all the time

Cholestatic jaundice: blocks biliary tract

High direct ( conjugated) bilirubin
Trousseau syndrome: migratory
thromphlebitis
Most common mucinous cancer

12
314326

Ovary

Other Ovarian Tumors

Most common mass: follicular cyst

Most common tumor: serous cystadenoma
Most common cancer: serous
cystadenocarcinoma

Fibroma: associated with pleural effusion or

ascites ( Meigs syndrome)
Granulosa cell tumor: high estrogen
Yolk sack cancer: high AFP
Choriocarcinoma: high HCG
Sertoli-Leydig cell tumor: masculinization
Mucinous cystadenocarcinoma: very mucinous
(pseudomyxoma peritonei)
Teratoma: struma ovarii

Highly malignant
Most mucinous cancer in women

Uterus

Uterine Polyp

Most common mass: polyp

Most common tumor: leiyomyoma
Most common concer: adenocarcinoma

Presents with passing of blood clots

Tx: surgery

Fibroids

Endometrial adenocarcinoma

Submucosal (90%): presents with

menorhagia
Subserosal: presents with pelvic pain or
pressure
Dependent on estrogen
Focal thickening; firm mass
Tx: OCPs; Leuprolide; surgery

Dependent on estrogen
Presents with metrorrhagia
Metrorrhagia after age 35 requires
endometrial biopsy
Tx: surgery

13
315327

Cervix

Warts

Most common mass: warts

Most common tumor: fibromas
Most common cancer: squamous cell
carcinoma

Condyloma lata: secondary to syphilis

Fleshy appearance

Condyloma accuminatum: secondary to

HPV
Verrucous or mushroom like warts
Tx: podophyllin drops; cryosurgery

Cervical cancer

Vagina

Squamous cell carcinoma

Risk factors: HPV; other STDs
Tx: hysterectomy

Most common mass: warts; Bartholin cyst

Most common tumor: fibroma
Most common cancer:
Upper half: squamous cell carcinoma from the
cervix
Lower half: skeletal muscle
Tumor: rhabdomyoma
Cancer: rhabdomyosarcoma (sarcoma botyroides)

Warts

Bartholin cyst

Condyloma lata: secondary to syphilis

Congenital
Fluctuant mass behind the labia majora
Complication: infections/ abscess
formation
After first infection: treat with antibiotics
After second infection: surgery
(marsupialization)

Fleshy appearance

Condyloma accuminatum: secondary to

HPV
Verrucous or mushroom like warts
Tx: podophyllin drops; cryosurgery

14
316328

Rhabdomyoma/
Rhabdomyosarcoma

Kidney

90% of rhabdomyosarcomas occur under

age 3 years
Increased incidence in Tuberous Sclerosis
Sarcoma botyroides: looks like a ball of
grapes when removed

Most common mass: cyst

Most common tumor: adenoma
Most common cancer:
In children: Wilms tumor
In adults: renal cell adenocarcinoma

Wilms tumor

Renal Cancer

90% occur on superior pole of kidney

Presentation: painless hematuria; flank mass
Most vascular cancer
Produces erythropoietin
Metastasizes via retroperitoneum
Favorite metastatic site: lungs (cannon ball
metastases
20% contralateral recurrence

Renal cancer in children

Classic clues: aniridia and
hemihypertrophy

Renal Cancer, cont

Adrenal Gland

Risk factors: smoking; Von Hippel Landau;

Tuberous Sclerosis
Evaluation: UA; sonogram;IVP; CT scan;
angiogram;
Tx: surgery
Annual CT scans after surgery to detect
contralateral recurrence

Most common mass: cyst

Most common tumor: adenoma
Most common cancer: adenocarcinoma

15
317329

Adrenal adenomas

Bladder

Glucagonoma
Insulinoma
Somatostatinoma
Pheochromocytoma

Most common mass: diverticulum

Most common tumor: leiomyoma
Most common cancer (including ureters):
transitional cell adenocarcinoma

Bladder diverticulum

Bladder Cancer
Transitional cell adenocarcinoma

Complications: UTIs and kidney stones

Tx: surgery

Multiple primaries
Presents with painless hematuria
Tx: surgery; radiation
Risk factors: smoking; anilene dyes; benzene;
aflatoxin; cyclophosphamide

Squamous cell carcinoma

Schistosoma hematobium

Prostate

BPH

Most common tumor: BPH

Most common cancer: adenocarcinoma

Presentation: strains to urinate; weak

stream; dribbling after urination; frequency
and urgency
Tx: terazicin/doxazocin; tamsulocin;
fenesteride; TURP

16
318330

Prostate Cancer

Prostate cancer screening

Most common cancer in men

Second to lung cancer for cancer deaths
in men
Tx: surgery; hormonal therapy or radiation
after surgery

Age 35: baseline rectal/prostate exam

After age 40: annual rectal/prostate exams
Annual sigmoidoscopy begins after age 40
After 2 normal annual sigmoidoscopies,
repeat in 3 to 5 years

Colonoscopy every 3 to 5 years begin at

age 50
Full colonoscopy should follow any abnormal
sigmoidoscopy

Testicles

Testicular exams

Most common mass:

Begin in adolescence
ANY firm testicular mass: perform an
orchiectomy

In newborns: hydrocele
In children and adults: hematoma
In older adults: varicicele

Most common tumor: adenoma

Most common cancer:
In first year of life: yolk sak cancer
In teens to adults: seminoma

Skin

Skin Tags

Most common mass:

Very common
Tx: shave it off

Skin tag (acrochordon)

hemangioma

Most common tumor: fibroma

Most common cancer: basal cell
carcinoma
Most common malignancy: squamous cell
carcinoma

17
319331

Hemangiomas

fibromas

Found anywhere on the body

An enlarged flat blood vessel
Tx: observation for 18 months; inject with
steroids; laser surgery

Very common
Easy to remove if you need to do so
Many of them seen in neurofibromatosis

All Neurocutaneous Diseases

have

Neurocutaneous Diseases
Neurofibromatosis
Sturge Weber
Tuberous Sclerosis

Mental retardation
Cerebral calcifications
Seizures

Neurofibromatosis

Sturge - Weber syndrome

Caf au lait spots (at least 3 with 1.5 cm

diameter minimum); hyperpigmented
macules
Neuromas
Fibromas
Chromosome 17/22 involved

Port wine stain on face ( V-1)

Angiomas of retina and brain associated

Type 1: chromosome 17; peripheral

neuromas
Type 2: chromosome 22; central neuromas

18
320332

Tuberous Sclerosis

Basal cell carcinoma

Ashen leaf spots (hypopigmented

macules)
Tubors: primary brain tumors
Rhabdomyomas and rhabdomyosarcomas
of the heart
Renal cell carcinoma

Most common skin cancer; but, it does

NOT behave malignantly
Usually found on the face from sun
exposure
Wide resection is curative

Squamous cell carcinoma

melanoma

Behaves malignantly
Ulcerates
Main risk factor: sun exposure (use SPF
15 )
Predisposing skin diseases: actinic
keratosis; Bowens disease
Diseases with increased risk: albinism;
vitiligo; porphyria cutanea tarda; PKU;
Wiscott-Aldridge; Jobs syndrome

The MOST malignant skin cancer

Melanotic nevi are risk factors
Malignant risk:

Bone neoplasia

Area
Borders
Color
Depth of invasion (worst prognostic factor)

Epiphysis
Made of cartilage
Most common tumor: chondroma
Most common cancer:chondrosarcoma

19
321333

Diaphysis

Metaphyseal osteosarcoma

Made of osteocytes
Most common tumor: osteoma
Most common cancer: metastases
Most common primary cancer:
osteosarcoma

Seen mainly in adults

Codmans triangle
Star burst effect on the cortex

Diaphysis

Ewings osteosarcoma

Made of osteocytes
Most common tumor: osteoma
Most common cancer: metastases
Most common primary cancer:

Primary bone cancer in children

Onion skinning seen in bone
T(11/22)

In children: Ewings osteosarcoma

In adults: plasmacytoma or multiple myeloma

Multiple myeloma

Breasts

Plasmacytoma: when single lesion

Multiple myeloma: MULTIPLE osteolytic
lesions

Most common mass: cyst

Most common tumor:
< 25y/o: fibroadenoma
>25y/o: fibrocystic disease

IG-g: most common heavy chain

Kappa: most common light chain
Hypercalcemia
Ruleaux formation

Most common cancer: intraductal

adenocarcinoma

20
322334

Fibroadenomas

Fibrocystic disease

Estrogen dependent
Enlarges in first two weeks of menstrual
cycle

Progesterone dependent
Enlarges in the two weeks preceeding
menses
Has greenish fluid on aspiration

Intraductal adenocarcinoma

Other breast neoplasms

Intraductal papilloma: nipple bleeding
Lobular adenocarcinoma: contralateral primary;
cells lined up in single file
Comedocarcinoma: focal areas of necrosis
Inflammatory adenocarcinoma: peau dorange
(infiltrates lymphatics); the most malignant
cancer
Cystsarcoma phylloides: a sarcoma; explodes out
of the breast, then stops growing; wide resection
is adequate

Estrogen dependent
Top locations: upper outer quadrant;
nipple
Usually presents with a dimple
Metastases can be osteolytic or
osteoblastic

Breast cancer screening

Cystic breast mass

Baseline exam: age 35

Age 40 to 50: annual breast exam by
doctor; monthly SBE
Age 50 to 79: add annual mammogram
Family h/o breast cancer: begin
mammography 5 years before the age of
the index case

History
Physical
Ultrasound
Fine needle aspiration: diagnostic and
therapeutic

21
323335

Firm breast mass

Benign firm breast mass

History
Physical
Mammogram
Lumpectomy
Send to pathologist for definitive
identificaton

After lumpectomy, we are done

Malignant firm breast mass

Tamoxifin / Roloxifene

After lumpectomy, perform a modified

radical mastectomy
Nodal dissection
Check for estrogen and progesterone
receptor positivity
Tamoxifin or Roloxifene for estrogen
positive cases
Chemotherapy for premenopausal women
and radiation for postmenopausal cases

Anti-estrogen at the breast and pituitary

Proestrogen at the bone, liver, and the
uterus (Tamoxifin only)

Cancer Profile

Cancer Antigens

Signs and symptoms: low energy state

Cancer more common in males: under age
30 and after age 50
Cancer more common in women: age 30
to 50
Most common cause of death: infections,
except for uterine and cervical cancers
(renal failure)

Prior to surgery: associated with

After surgery: if it rises again, there is a
95% chance you have recurrence or
metastases

22
324336

Cancer Antigens

PSA
CEA
S-100
AFP
HCG
C-MYC
L-MYC
N-MYC

Cancer Markers

Desmin
Vimentin
Ca-125
Ca-19
BCL-2
RET
RB

T(9/22)
T(8/14)
T(14/18)
T(11/22)
T(15/17)
ERB
HER 2 NEU
BRCA
P53

THE END

23
325337

326338

Microbiology & Immunology:

Week Four

327339

328340

Immunology

Immunology

LISCENCED TO KILL

Study of the immune system

Antigen
HAPTEN

IMMUNOGEN

Less than 6000D

Too small to set off the
immune system by
itself

The most important factor that

determines Immunogenicity is

Greater than 6000D

Large enough to set
off the immune system
by itself

Antigen
HAPTEN
Less than 6000D
Too small to set off the
immune system by
itself

IMMUNOGEN
Greater than 6000D
Large enough to set
off the immune system
by itself

1
329341

Carrier Effect

Making use of the carrier effect

What macrophages do for a living

Ingest
Phagosome formation
Digest
Present
MHC II complex
V-beta region
Invariant chain is displaced
IL-1 is released

IL-1
Fever
Nonspecific symptoms of illness
Recruits T-helper cells

Fever

Infections that cause heart block

Def: one degree above normal body temp

Raises heart rate 10bpm for each degree
rise above normal
Allows immune cells to come around
faster
Causes secretion of Ig-A

Legionella
Lyme disease
Chagas disease
Diptheria
Typhoid fever

2
330342

Fever

Antigen
HAPTEN

Means that IL-1 showed up

By itself can NOT tell you the cause
The pattern of fever can be diagnostic
Causes discomfort at about 101 degrees F

IMMUNOGEN

Less than 6000D

Too small to set off the
immune system by
itself

How do you make an Immunogen

less immunogenic?

Greater than 6000D

Large enough to set
off the immune system
by itself

Detergent
Disrupts the ADHESION of pathogens by
disrupting membrane forces

Antiseptic/Disinfectant

Sterilization

Phenol is most common

Iodine is most common in the hospital
These chemicals DESTROY the
membrane and INACTIVATE endotoxin
These chemicals actually KILL 99% of
germs

For spores
A dormant form of a bacteria
CAN NOT replicate in this form
CAN still release toxin, especially when
exposed to heat
Bacillus and Clostridium

Done at 121* C with VAPORIZED heat

3
331343

The two arms of the Immune

system

Most immunogenic bacteria

SHIGELLA
Only 8 to 10 microbes required to get a full
infection

HUMORAL
BLOOD

The two arms of the Immune

system
HUMORAL
BLOOD
B-CELLS
NEUTROPHILS

TISSUE

MACROPHAGES

CELL MEDIATED
TISSUE
T-CELLS
MACROPHAGES

Microglia: brain
Type-1 pneumocytes: lungs
Kuffler cells: liver
RES cells: spleen
Dendritic cells: lymph nodes
Osteoclasts: bone
Mesangial cells: kidneys
M cells: Peyers patches
Langerhans cells: skin
Monocytes: blood
Connective tissue: epitheloid cells; giant cells; histiocytes

The two arms of the Immune

system
HUMORAL

BLOOD
B-CELLS
NEUTROPHILS
BACTERIA

All Else

CELL MEDIATED

CELL MEDIATED

TISSUE
T-CELLS
MACROPHAGES
ALL ELSE!!!

Virus
Fungus
Mycobacteria
Protozoa
Parasite
Neoplasm

4
332344

Inflammation

Acute Inflammation
Look for SWELLING or NEUTROPHILS

Chronic Inflammation

Can it really be this easy?

Cellular infiltrate: T-cells and macrophages

What you see on biopsy: fibrosis
What you see on x-ray: calcifications

THE END

Can it really be this easy?

YES!

5
333345

Or Maybe Not.

Let The Leukocytes Loose!

6
334346

Humoral Immune Sytem

Protect the blood

Immunodeficiencies
LACKING A LITTLE

Humoral Immune Sytem

Humoral Immune Sytem

Protect the blood

B cells

Protect the blood

B cells
Neutrophils

Humoral Immune Sytem

Cell mediated Immune System

Protect the tissues

Protect the blood

B cells
Neutrophils
Bacterial infections

1
335347

Cell mediated Immune System

Cell mediated Immune System

Protect the tissues

T-cells

Protect the tissues

T-cells
Macrophages

Cell mediated Immune System

Cell mediated Immune System

Protect the tissues
T-cells
Macrophages

Protect the tissues

T-cells
Macrophages
Nonbacterial infections

Nonbacterial infections

DiGeorge syndrome

T-cell immunedeficiencies

Virus
Fungus
Mycobacterium
Protozoa
Parasite
neoplasm

DiGeorge syndrome
Chronic mucocutaneous candidiasis
Steroids
Cyclosporine
Hairy cell leukemia
SCID
Wiscott-Aldridge syndrome
HIV

Third pharyngeal pouch is missing

Inferior parathyroids glands are missing
The only immunodeficiency with
hypocalcemia

2
336348

Chronic Mucocutaneous
Candidiasis

Steroids
Anti-inflammatory actions

A T-cell defect at a submolecular level

T-cells can fight everything else under all
else except candida
Candida infections on skin and mucous
membranes
Causes chronic fatigue syndrome

Physiologic actions (catabolic)

Proteolysis
Gluconeogenesis
Upregulates all receptors during stress ( permissive)

Steroids

Prednisone
Hydrocortisone
Methylprednisalone
Triamcinalone
Beclamethasone
Betamethasone
Fluticasone
Mometasone

Kills T-cells and eosinophils

Inhibits macrophage migration
Stabilizes mast cell membranes
Stabilizes endothelium
Inhibits phospholipase A

Cyclosporine

Fludrocortisone
Danazole
Cypropterone
Megesterol
Dexamethasone

Revolutionized transplantations in America

Prolongs the longevity of transplanted
organs
Inhibits calcineurin which is needed to
produce the interleukins
Causes gingival hyperplasia and
hirsutism

Tacrilimus

Hairy Cell Leukemia

Now used in place of cyclosporin due to

much fewer side effects

Most commonly a B-cell leukemia (75%)

More frequently a T-cell leukemia (25%)
Has hairy cell membrane projections
Tartrate Resistant Acid Phosphatase (TRAP)

3
337349

T-cell Lymphomas

SCID

Mycosis Fungoides ( cutaneous)

Sezary syndrome ( present in the blood)
T-cells have characteristic indented cell
membrane

Wiscott-Aldridge syndrome

Involves adenosine deaminase deficiency

DNA synthesis is disrupted
Affects all rapidly dividing cells
Affects T and B-cells
Bone marrow transplant is now the
standard of care

B-cell Immunodeficiencies

Involves T-cell interaction with B-cells

X-linked recessive
Fair-skinned
Eczema
Thrombocytopenia
Normal Ig-A and Ig-E levels
Increased incidence of lymphoma

Brutons agammaglobulinemia
CVID
Leukemias
Lymphomas
Plasmacytoma
Multiple myeloma
Heavy Chain disease
Selective Ig-A def
Selective Ig-G2 def
Jobs syndrome
SCID
Wiscott-Aldridge syndrome

Brutons Agammaglobulinemia

CVID

X-linked recessive
Cell signalling is defective
B-cell count is normal; function is lacking
Early onset

Late onset Brutons ( after first year of life)

B-cell count is also normal; B-cell function
is lacking
Cell signalling is defective

4
338350

Leukemias

Lymphomas

98 B-cells for every T-cell in periphery

98 B-cells for every T-cell in periphery

Plasma Cell Cancer

Heavy Chain Disease

Plasmacytoma: only ONE lesion

Multiple Myeloma: MULTIPLE osteolytic
lesions

Ig-A Multiple Myeloma of the bowel wall

Ig-A plasma cells visible on biopsy
Causes malabsorption

Ruleaux formation
Hypercalcemia
Ig-G is most common M-spike
Kappa light chains are most common Bence
Jones protienuria

Selective Ig-A def

Selective Ig-G2 def

Many mucosal infections

Runs with selective Ig-G2 def 95% of time
Anaphylaxis during a transfusion

Runs with selective Ig-A def

Ig-G is main opsin ( coats encapsulated
organisms)
Recurrent encapsulated organism
infections

Must use a filter for all subsequent

transfusions or use blood from another Ig-A
def patient

5
339351

Encapsulated Organisms
Gram positive

Jobs syndrome

Gram negatives

Streptococcus
pneumonia

Salmonella
Klebsiella
H. Influenza B
Pseudomonas
Nisseria
citrobacter

The Final Two

Cell signalling defect

Increased Ig-E
Fair-skinned
Red-haired female

Neutrophil Defects

SCID
WISCOTT-ALDRIDGE

Myeloperoxidase def
NADPH-oxidase def (CGD)
Absolute neutropenia

Chronic Granulomatous Disease

(CGD) NADPH-oxidase def

Myeloperoxidase def
Recurrent gram positive infections

X-linked recessive
Negative NBT test ( detects nadph-oxidase)

6
340352

At Risk for Staph and Pseudomonas

Infections

Absolute Neutropenia
ANC = ( % Neutrophils + % bands) WBC

< 2500
<1500
<1000

At risk for staph aureus and pseudomonas

infections
If any fever: cover staph aureus with one
antibiotic and pseudomonas with two
antibiotics

Macrophage Defects

Absolute neutropenia
Cystic Fibrosis
Burn patients
Diabetics

Chediak-Higashi syndrome

NADPH-Oxidase def ( CGD)

Chediak-Higashi

Lysosomes are slow in fusing with

ingested pathogen
Lysosomal inclusions
Albinism

HIV

Where CD-4 receptors are found

The two populations with the highest

incidence are heterosexual Black women
and the elderly
Lowest risk population: prepubertal female
HIV likes acidic medium, mucosae, and
CD-4 receptors

Female cervix
Blood vessels
Macrophages
T-helper cells
CNS
Testes
HIV is only virus that does NOT penetrate
the cells; it injects its RNA into the cells

7
341353

Cancers Common in HIV

HIV Infection

Cervical cancer
Kaposi sarcoma ( helped by Herpes 8)
CNS and testicular lymphomas

Attaches to CD-4 receptor using GP120

GP 41 has no known function
Injects the RNA inside
POLymerase protein is used to integrate
the RNA into host genome
Reverse transcriptase is used for
transcription
P17 and P24 used for assembly

Screening for HIV

To Prevent Attachment of HIV

CCR5
CCR4

Screening for HIV, cont

ELIZA ( Ig-G antibody test)

Western blot ( detects protein)
Northern blot ( detects RNA)
Southern blot ( detects DNA)
PCR ( amplifies RNA or DNA)

PCR
MORE sensitive than Southern blot or
Northern blot
Used for screening only in the first 18
months of life ( moms Ig-G interferes with
ELIZA)

8
342354

T-helper cell Counts

HIV Treatment

Normal: 800 to 1200

normal in newborns: 1500
Begin treatment: CD4 counts < 500

START with two nucleoside inhibitors and

one protease inhibitor
AZT
3TC
4DT
DDI or DDC
Rotenovir; Indinavir; Sequinavir

Pediatrics: < 50% ( 750)

Begin PCP prophylaxis

CD4 count < 200
Pediatrics: < 20%

Begin MAI prophylaxis

CD4 count < 100
Pediatrics: <10%

Mycobacterium Avium
Intracellulare ( MAI)

PCP Prophylaxis
Trimethoprim/Sulfamethoxazole
Pentamidine aerosole

Clarithromycin
Azithromycin

HIV: THE END

THE MOST COMMON CAUSE OF DEATH FROM AGE
19 TO 44 !!!

9
343355

Leukocytes

NORMAL: 4 to 12K
Leukopenia: < 4K
Leukocytosis: > 12K
Your leukocyte count accounts for only
10% of total leukocytes
90% of leukocytes are marginated

LEUKOCYTES
Shoot when you see the WHITES of
their eyes

When Leukocytes are needed

Leukopenia

Demargination: caused by epinephrine and

cortisol
Pavementing:

Most common causes: acute viral infection

and drugs

Selectrins
Integrins

Margination
Diapedesis
Migration

Drugs that suppress the

bone marrow

Viruses that commonly suppress

leukocytes
Any virus can do it; but, the most common
are
Parvovirus B19
Hepatitis E
Hepatitis C

Vinblastine
AZT
Chloramphenicol
benzene

1
344356

Leukocytosis

Drugs that cause agranulocytosis

Carbamezapine
Ticlopidine
Clozapine

Leukocytosis

Stress demargination
Infections
Leukemoid reaction
Leukemia
Myelodysplastic syndromes

Leukemoid Reaction
Extreme demargination
Looks like leukemia because WBCs so
high
Increased leukocyte alkaline phosphatase
( LAP)
Extreme stress

Leukemia

Lymphomas
Cancer of the lymph nodes
Involves the lymphocytes

Too many white cells in the periphery

A cancer
Acute: cancer began in the bone marrow
Chronic: cancer began in the periphery

2
345357

Leukemias

Myelodysplastic syndromes
Cancer that involves the ENTIRE bone
marrow
All cell lines are involved

Lymphomas

Lymphomas, cont

Hodgkins lymphoma: 20 to 40 y/o

Nonhodgkins lymphoma

Characterized by the Reed-Sternberg cells

which have the CD 30 marker
Commonly begins as a swollen lymph node
Most malignant lymph nodes

Usually occurs in immunocompromised

persons
Presents as an abdominal mass in America,
or a jaw mass in poor countries
Most common type: follicular lymphoma

Supraclavicular
Epitrochlear
inguinal

BCL-2
T( 14/18)

Burkitts Lymphoma

Lymphomas

BCL-2
C-myc
T( 8/14)
EBV
Starry sky appearance

3
346358

Lymphomas

Lymphoma: Staging
Stage 1: one group of lymph nodes involved
Stage 2: two groups of lymph nodes on
same side of diaphragm involved
Stage 3: two or more groups of lymph
nodes on both sides of diaphragm
involved
Stage 4: metastases

Lymphoma Treatment

Lymphoma Treatment, cont

Nodular Sclerosis

Lymphocyte Predominance

More common in women

The fewest Reed-Sternberg cells
Intermediate prognosis

Best prognosis

4
347359

Lymphocyte Depleted

Mixed Lymphocytic/Histiocytic

Worst prognosis
A paucity of lymphocytes

Intermediate prognosis
Has the most Reed-Sternberg cells
(lacunar cells)

Myelodysplastic Syndromes

Myelodysplastic syndromes
Hyperproliferative:
Polycythemia Rubra Vera
Essential thrombocythemia

Hypoproliferative:
Aplastic Anemia
Myelophistic Anemia ( myelifibrosis;
agnogenic myeloid dysplasia)

Polycythemia Rubra Vera

Essential Thrombocythemia

ALL cell lines are elevated; RBCs elevated

the most
HCT> 60%
Itching after a hot bath
Uric acid stones
Increased gout
Splenemegaly
Increased LAP

ALL cell lines are increased; platelets are

increased the most
Platelet count > 600K

5
348360

Aplastic Anemia

Aplastic Anemia: Viruses

ALL cell lines are depleted

Bone marrow usually suppressed by virus
or drugs
Bone marrow usually replaced by fatty
infiltration
Low reticulocyte count

Parvovirus B-19: 90%

Hepatitis E : pregnant women
Hepatitis C : occassional

Aplastic Anemia: Drugs

Myelofibrosis

Chloramphenicol
AZT
Benzene
Vinblastine

Bone marrow is destroyed by cancer and

replaced by scarring
Tear drop cells
Low reticulocyte count

The End

Or Is It??

6
349361

Aint No Groove Like A Granulocyte

Groove

7
350362

Lymphocytes
The ultimate control

B-Lymphocytes

B-Lymphocyte Differentiation

Develop in the bone marrow

Mature : Bursa of Fabricus equivalent ??
Differentiate : germinal centers of lymphoid
tissue

B-Lymphocyte Differentiation

Macrophage ingests antigen

Macrophage forms a phagosome
Lysosome digests the antigen
Macrophage presents the antigen
Antigen binds to MHC-II complex
IL-1
IL2
IL-3

Stages of B cell development

IL-4
1L-5
IL-6
IL-10
IL-12
T cells talk to B cells via the CD-40 ligand
B cells display CD-19 and CD-20

1
351363

To stimulate B cells

Primary Response
IG-M:

Endotoxin
Pokeweed mitogen

Arrives in 3 days
Peaks in 2 weeks
Lasts for 2 months

Then add labelled thymidine

IG-G:
Arrives in 2 weeks
Peaks in 2 months
Lasts for 1 year

Vaccines Schedule

Memory

Memory Response

Memory Response

(Anamnestic)
Develops beginning at 12 months; fully
developed by 15 months
Involves ONLY IG-G
IG-G has highest affinity
Arrives in 3 days
Peaks at 5 years
Lasts for 10 years

2
352364

Live Vaccines

Antibody Structure/Function

MMR
BCG
OPV ( Sabin)
Varicella
Rotavirus
Smallpox
Yellow fever

Vaccine changes at age 6

Pertussis no longer needed
HIB no longer needed
Only half dose diptheria needed (D
becomes d)

Isotype
Antibody Class: Gamma;
Alpha; Mu; Delta; Epsilon

Idiotype

Allotype

The actual antigen binding

site

Differences between two

members of same species

3
353365

Applied to Transplants
Xenotype or Heterotype
Differences between two
members of different
species

Isograft or Syngraft

Allografts

Twin to Twin transplants

Transplants between
members of same species

Autografts

Xenograft or Heterograft

Self to Self transplants

Transplant between
members of different
species

4
354366

T cell
maturation/differentiation

T cell differentiation

T cell differentiation

Macrophage ingests antigen

Macrophage forms a phagosome
Lysosome digests the antigen
Macrophage presents the antigen
Antigen binds to MHC-II complex
IL-1
IL2
IL-3

IL-4
1L-5
IL-6
IL-10
IL-12
T cells talk to B cells via the CD-40 ligand
T cells talk to macrophages via B-7 molecule (on
T cell) connecting with the CD-4 receptor
causing the formation of the CD-28 molecule

T Lymphocytes

At the thymus

Develop in the bone marrow

ALL T cells have CD3
ALL have CD4 and CD8 labels when they
leave the bone marrow
They have to go to the thymus to
differentiate
Express the MHC II complex
One T cell controls many B cells

T cells enter undifferentiated

They must go through NEGATIVE
selection followed by POSITIVE selection
Thymosin and Thymopoietin control clonal
deletion
Thymus is one of four immunopriviledged
sites in the body
Have no lymphatics; express NO antigens

5
355367

Immunopriviledged sites

CD 8 CELLS

Brain
Thymus
Cornea
Testicle

First cells to make it through clonal

deletion
Express MHC I complex; respond to MHC I
antigens (self antigens)
T suppressors: keep infection from
spreading
T cytotoxic: destroy infected cells

T Helper cells

CD 4 CELLS

T Helper 1: respond to cell mediated

T Helper 2: respond to humoral
Secrete every interleukin except IL-I
Produce interferon gamma and TNF
gamma
Control B cells and macrophages

The second set of lymphocytes to make it

through clonal deletion
Express MHC II complex; responds to
foreign antigens
Speaks to B cells via CD 40 ligand;
speaks to macrophages via B7 / CD28
molecule
T Helper cells

NK Cells
Develop WITH the T cells in the thymus
Do NOT go through clonal deletion
Express MHC I complex and actually
COUNT MHC I antigens
Express CD 16 and CD 56
Responsible for immunosurveillance
Can detect cancer at the one cell stage

Levamisole
Enhances NK cells ability

6
356368

Once a T cell processes

an antigen
It is considered differentiated

THE ENDFOR NOW

GREED
A MAN SPENDS HIS HEALTH CHASING
GREAT WEALTH
THEN HE SPENDS HIS WEALTH TRYING
TO GET BACK HIS HEALTH

7
357369

Granulocytes

Granulocytes
What do they do for a living?

Granulocytes

Granulocytes

Gram stain
Step 1: add crystal violet ( binds to
exposed peptidoglycan)
Step 2: add iodine ( seals blue color into
wall)
Step 3: wash with alcohol ( washes off
excess crystal violet)
Step 4: add saffrin ( colors outer
membranes)

1
358370

Acid fast stain

Neutrophils

Also called Ziel Neilson stain

The pathogen stains pink;ALL other cells
stain blue
Completely acid fast: mycobacterium
Partially acid fast: Nocardia ( gram
positive) and Cryptosporidium ( protozoa)

The most abundant granulocytes

60% of WBCs
First line of defence
Show up at 24 hours; peak at day 3
10% are circulating; 90% are marginated
Contain myeloperoxidase and NADPHOxidase

Catalase positive bacteria

Staph Aureus
Pseudomonas
Nisseria

2
359371

Free Radicals

Abscesses

Day 1 to 3: staph aureus

Day 3 to 7: strep pyogenes
After day 7: anaerobes
Abscesses are anaerobic by nature
Occurs most commonly in: the brain
( liquefactive necrosis)
Occurs least commonly in: the lungs (most
oxygen)

Begin coming into the area at 3 hours

Oxygen burst ( peak free radical formation)
occurs at day 7
Hi energy free radicals transfer their
energy to anything in the way
Area becomes anaerobic once oxygen
burst occurs
Now you have an abscess

Clues to anaerobic infections

Malodorous smells
Gas formation

Absolute Neutropenia

Neutropenia

ANC = (% neutrophils + % bands) WBC

< 2500
< 1500
< 1000
ANY FEVER: cover staph aureus w/ one
antibiotic and cover pseudomonas with
two antibiotics; and if fever persists after 48
hours, then cover for fungus

Most common causes: viral infection and

drugs

3
360372

Monocytes

Macrophages in the

A macrophage in circulation
They change names after they enter
tissues
Interferon mediates their transformations
after they enter different tissues
Contain ONLY nadph-oxidase for killing
since free radicals can kill anything

Monocytosis

Brain
Lungs
Liver
Kidneys
Spleen
Lymph nodes
Skin
Bone

Peyers patches
Connective tissue

Granulocytes

Mcc: viral infection ( cell mediated)

Extreme monocytosis: monocytes > 15%

Salmonella typhi
Tuberculosis
EBV
Lysteria
Syphilis

Understanding Allergies
MAST CELLS

Primary response to allergens

First contact: asymptomatic

EOSINOPHILS

Allergen was ingested

Phagasome formed
Digested
Presented to T-lymphocytes
T-cells bind to B-cells by CD-40 ligand
T-cells produced IL-4
B-cells produced Ig-E

4
361373

Understanding Allergies

Secondary response to allergens

Symptomatic
When allergen re-enters the system, Ig-E
now binds the allergen
Ig-E buries the F-c portion into a mast cell
Mast cell degranulates

MAST CELLS
Histamine (immediate)
SRS-A ( 4 to 8 hrs later)
ECF-A

EOSINOPHILS
Histaminase
Arylsulphatase
heparin

Slow Reacting Substance of

Anaphylaxis (SRS-A)

Histamine

The most potent bronchoconstricter that

we know
This is responsible for late symptoms of
allergies
Produced 4 to 8 hours after initial
symptoms
Responsible for killing many asthmatics
before we understood it

Responsible for all of the acute symptoms

of allergies
Redness and flushing
Wheezing
Itching
Warmth
Swelling (nasal congestion; rhinitis;
conjunctivitis; wheal and flare; urticaria)

Eosinophil Chemotactic Factor of

Anaphylaxis ( ECF-A)

Eosinophils

Chemoattractant for eosinophils

Responsible for the eosinophilia seen in
allergic reactions

Are counter-regulatory
Make sure mast cells do NOT get out of
hand

In other words

5
362374

Eosinophils

Eosinophils

Histaminase: breaks down histamine

Histaminase: breaks down histamine

Arylsulphatase: breaks down SRS-A

Eosinophils

Heparin

Histaminase: breaks down histamine

Arylsulphatase: breaks down SRS-A
Heparin : breaks down any clots that might
have formed

Acts as a cofactor for antithrombin III

Blocks thrombin as well as clotting factors
IX,X,XI and XII ( the intrinsic clotting
cascade)
Follow the PTT
INR should be 2 to 3 times normal
If INR too high, reverse it with protamine
sulphate

Heparin, cont

Low Molecular Weight Heparins

If patient acutely bleeding then give FFP to

correct immediately
Side effects:

Well standardized to minimize physician

errors
BENEFITS:
NO need to do daily PTTs (saves on
nursing and hospital costs)
Fewer bleeding complications
Lower incidence of heparin induced
thrombocytopenia

Bleeding
Hyperlipidemia ( activates hormone-sensitive
lipase)
Heparin induced thrombocytopenia ( acts as a
hapten, inducing autoimmune antibodies)

6
363375

Eosinophilia

Eosinophilia

N
A
A
C
P

Neoplasia, especially lymphomas

A
A
C
P

Allergic Rashes: type 1

Eosinophilia

hypersensitivity

Neoplasia
Allergies and Addisons disease
Allergic rhinitis and conjunctivitis

A
C
P

Allergic Rashes: type IV

Urticaria
Erythema multiforme
Stevens-Johnson syndrome
Toxic Epidermal Necrolysis

Eosinophilia, cont

hypersensitivity
Atopic dermatitis
Contact dermatitis
Eczema

Spongiotic
nummular

Neoplasia
Allergies and Addisons disease
Asthma
C
P

7
364376

Asthma

Eosinophilia, cont

Intrinsic asthma: you are born with it; colds

and cold air set it off
Extrinsic asthma: caused by environmental
factors

Dust mites
Roach droppings
Pet dander

Eosinophilia, cont

Neoplasia
Allergies and Addisons disease
Asthma
Collagen Vascular Disease
P

Bands

Neoplasia
Allergies and Addisons disease
Asthma
Collagen Vascular disease
Parasites

Immature neutrophils with maximum germ

fighting ability
Have myeloperoxidase and NADPHOxidase enzyme systems
Come straight out of the bone marrow
without margination
Increased numbers = a left shift

Basophils

To Be Continued

Said to be precursors to mast cells

They have similar granules to mast cells

8
365377

TYPE I
Immediate hypersensitivity
Involves mast cells and eosinophils
NO COMPLEMENT involved

THE FOUR HYPERSENSITIVITIES

PUTTING IT ALL
TOGETHER

TYPE II

TYPE III

Cytotoxic
A deliberate attack on self
Complement comes in after the attack

Immune complex deposition

NOT a deliberate attack on the tissue
Tissue is damaged due to inflammation
So much COMPLEMENT used that it
measures LOW

Complement System

TYPE IV
CELL MEDIATED
T cells
Macrophages

366378

Angioedema

ACE Inhibitors and ARBs

Due to C-1 esterase inhibitor deficiency

Too much C5-A produced
Causes recurrent facial swelling and
abdominal pains
Mcc of death: suffocation due to airway
swelling
Caused by ACE inhibitors and ARBs

Losartan
Vosartan

ANTIBODIES

Antimicrosomal
Antithyroglobulin
Anti-TSH receptor
Anti-ACH receptor
Anti-myelin
Anti-parietal cell
Anti-mitochondrial
Anti-melanocyte
Anti-IgG

Captopril
Enalopril
Lisenpril
Rinilopril

Antibodies

Anti-rho, La, SSA

Anti-SM
Anticardiolipin
Anti-DS DNA
Anticentromere
Anti-smooth muscle
Antihistone
Anti-Scl 70
Anti-RNP

Anti-topoisomerase
P-anca
C-anca
Anti-GBM
Anti-anchoring
proteins
Antiplatelet
Anti-RBC

ABO

TRANSPLANT IMMUNOLOGY

367379

CROSSMATCH

MIXED LYMPHOCYTE REACTION

HLA TYPING

Rejection

Hyperacute
Acute
Chronic
Graft vs host

Now it is time for the BUGS !!!

Just when you thought it was over

368380

4/29/2008

Gram + Cocci: Semisynthetic PCNs

More efficacious than Vancomycin

Beta-lactamase resistant PCN
MRSA tx- Vancomycin (linezoid)

Antibiotics

Streptococci:

Oxacillin
Cloxacillin
Dicloxacillin
Nafcillin

pyogenes
viridans
pneumonia

Ampicillin + Amoxicillin:
can be used for Strep infections
when combined with beta-lactamase
inhibitor:
- Sulbactam
- Amoxacillin+clavulanate
A
illi + l
l
t

Penicillin G
Penicillin
P i illi VK
Ampicillin
Amoxicillin

Effective against: Enterococci

Listeria

Cephalosporins:

Cephalosporins:

1st Generation: Cefazolin 2nd Generation: Cefoxitin

Cefadroxil
Cefotetan
Cephalexin
Cefuroxime
Cefprozil
Loracarbef

3rd Generation:Ceftazidime 4th Generation: Cefepime

Cefotaxime
Ceftraxone
Cefotaxime

generation: Staph
p and Strep
p
1st g
Some gram negatives (E. coli, Moraxella)

O l C
Only
Ceftazidime
ft idi
&C
Cefepime
f i
cover P
Pseudomonas
d

3rd Generation: not good for Staph (especially

Ceftazidine)

2nd generation: Moraxella, E. coli, Haemophilus,

Klebsiella, Citrobacter, Proteus Vulgaris

4th Generation: Cefipime (never pick Stap/Strep)

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Allergic cross reactivity with penicillins:

Allergic cross reactivity with penicillins:

Genuine allergy to PCN has less than 5% cross

reactivity with Cephalosporins

If anaphylaxis to PCN, never pick a Cephalosporin as

an answer

Seldom anaphylactic reaction will occur

Minor infectioninfection Macrolide (Clarithromycin, Azithro)

New fluoroquinolones : (Levofloxacin, goti, moxi)

Patients usually just get a rash, so you can still use

cephalosporins

Serious infections: life threatening

- Vancomycin, Linezolid

Quinolones:

Aminoglycosides:
-Gentamicin
-Tobramycin
-Amikacin

Ciprofloxacin
Levofloxacin
Gatifloxacin
Moxifloxacin
Ofloxacin
Good for. E. coli
Proteus
Enterobacter
Haemophilius

Monobactams:
-Aztreonam

Moraxella
Citrobacter
Serratia
Kelbsiella

For the test, think of these as exclusively

Gram negative agents

Ciprofloxacin is good for pseudomonas

New fluoroquinolones- first line in pneumonias
because it covers, Mycoplasma, Chlamydia,
Legionella

Aminoglycosides have a synergistic effect

with PCN

Anaerobes:

Carbapenems:

Metronidazole (Flagyl)- most active against

anaerobes

- Imipenem
- Meropenem

Clindamycin- less active against anaerobic

gram negative bacteria in the bowel
(Bacteroides fragilis, Clostridium difficle)

g
infections:
Best use for Gram negative
- Pseudomonas
- Enterobacteraceas

Carbapenems have the same efficacy as

Metronidazole

Excellent staph and anarobic coverage

2
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4/29/2008

If a bacteria normally lives on

a part of your body, normally
exposed to OXYGEN

Microbiology:
Normal Flora
What is bugging you !!!

Call it a GRAM POSITIVE

If a bacteria lives on a part

of your body NOT normally
exposed to oxygen.

Skin flora
Staphylococcus aureus
Staphylococcus pyogenes
Staphylococcus epidermitis
Staphylococcus saprophyticus
Propionobacterium acne

Call it a GRAM NEGATIVE

Strep pyogenes is # 1
Lymphangitis
Impetigo
Necrotizing fascitis
Erysipelas
Scarlet fever

Skin Infections

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4/29/2008

Skin Infections

Skin Infections

Cellulitis: flat, red, blanches

Mastitis: cellulitis around the breast

Skin Infections

Skin Infections
Balanitis: infection at the head of the penis

Panniculitis- cellulitis around abdomen

Skin Infections

Skin Infections

Periorbital cellulitis: infants, trauma

Staph aureus

Orbital cellulitis: proptosis, older patient

Strep pneumonia

2
372

4/29/2008

Skin Infection

Skin Infections
Carbuncle: nodular induration w/ infection

Furuncle: hair follicle in middle of

carbuncle, No pus

Skin Infections

Skin Infection

Carbunculosis: deep skin infection

Staph aureus

Furunculosis: many infections of hair shafts

Skin Infection

Skin Infection
Fasciitis: inflammation of fascia
Plantar or Necrotizing

Folliculitis: infection of hair shaft

3
373

4/29/2008

Skin Infection

Mouth Flora

Blepharitis: infection of eye lid

Strep pyogenes
Strep pneumonia
H. Influenza
Nisseria catarrhalis
N. gonorrhea
N. meningitidis

Stomach Flora

Mouth Flora cont.

Peptococcus
Peptostreptococcus
Fusobacterium
Actinomyces
Strep viridans

Helicobacter pylori

S. mutans
S. sanguis
S. salivarius

Curved Rods

Urease Positive Bugs

Vibrio
Camphlobacter
Lysteria
H. pylori

Proteus
Pseudomonias
Ureoplasma
Nocardia
Cryptococcus
H. Pylori
Staph. Saprophyticus
Brucellosis

4
374

4/29/2008

Small Intestinal Flora

Small Intestinal Infections

Cholecystitis
Ascending cholangitis
Appendicitis
pp
Spontaneous bacterial peritonitis
Abdominal abscess

95% E. coli

E. Coli makes

E. Coli helps you absorb..

90% of your vitamin K

Biotin
Folate
Panthotenic acid

Vitamin B12

Big MaMa anerobes

Distal ileum and colonic flora

Proteus
Klebsiella
Serratia marscencens
Acenetobacter
Citrobacter
E. coli

Bacteroides fragilis
Strep bovis
Clostridium melanogosepticus
Clostridum difficile

5
375

4/29/2008

GET READY FOR THE

RIDE..

Rectal flora
Group B Strep
E. Coli
Lysteria
L t i monocytogenes
t

It allll buzz
Its
b
words
d from
f
here on !!!!

STAPHLOCOCCUS

Gram
Positives
GRAM POSITIVE
COCCI IN CLUSTERS

Staphylococcus aureus enzymes:

Catalase + : breaks down H2O2
-lactamase : breaks through lactam
containing drugs
Coagulase & Staphlokinase- eats
through clots
MCC of Acute Endocarditis- eats
through valves
MCC of death in burn patients in the first week

6
376

4/29/2008

Enzymes continued::

Staphylococcus aureus toxins:

Lipase: breaks down fat

Panniculitis
Folliculitis
Mastitis

Staph Scalded Skin Syndrome:

Exfoliating (Nikolski sign)
Red rash all over the body
Palms and Soles

Elastase: breaks elastin

Bullous
B ll
Emphysema
E h
(Pneumatocelle)
(P
t
ll )

Toxic Shock Syndrome:

Triad: high fever, hypotension (shock), rash (P & S)
Retained tampon

Collagenase: skin & bone (breaks peptide bonds)

MCC of osteomyolitis (2nd Salmonella)

Type IV (basement membrane)
Type III (endothelium- arteries affected)
Type II (connective tissue)

Erythrodermic Toxin:
Scarlet fever [Strep]
Sand paper rash, palms and soles, strawberry tongue

Staphylococcus aureus toxins:

Staph epidermidis:

Lecithinase: causes skin infections

subcutaneous fat

Enterotoxin:
i causes food
f d poisoning
dairy products- gastroenteritis
Fast 2-6 hours

Catalase +
White pigment
Resides under the skin
MCC of shunt infections and central line
infections

Tx: Vancomycin
Linezolid- for Vancomycin resistance
Keep patient is a negative pressure room

Staph saphrophyticus:

STREPTOCOCCUS

Catalase +
No Pigment
Frequent cause of UTIs:
Age 5-10- play with themselves
Age 18-24: post coital UTI,
no circumcision
(E. coli- MCC of UTIs)

Gram positive
cocci in chains

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377

4/29/2008

Streptococcus
Streptococcus

Streptokinase- responsible for

hemolysis- clear zone

Groups: A, B, C, D

Breaks clots converts plasminogen to

plasmin

Types of hemolysis:
hemolysis
hemolysis- partial (green zone)
hemolysis- complete (clear zone)
hemolysis- no hemolysis (red zone)

If recent Strep infectioninfection it will not

work, use tPA
- Converts plasminogen to plasminbreaks clots
- Binds fibrinogen- will not clot again

Strep pneumoniae
(Pneumococcus)

Thrombolytics
Urokinase- opens fistulas and grafts

Gram + diplococci
hemolysis (green zone)
80 strains

Streptokinase- hemolytic- acute MI

Tissue plasminogen activator (tPA)acute MI, acute stroke (within 3 hrs)

Pneumococcal vaccine (pneumovax)

Covers 23 strains (98%) coverage

Antidote: aminocaproic acid

(for all three)

: on it
Who should be

Group A: Strep pyogenes

> 65 y/0

-hemolytic (clear zone)

70 Strains

> 2 y/o with Sickle cell (spleen- encapsulated

organisms)
End organ failure

Most common cause for throat infectionscan lead to Rheumatic fever

PSGN (skin and throat can cause this)

strain 12

2nd most common cause of skin

infections

8
378

4/29/2008

Group D: Strep viridians

(mutans, saguis, salivarius)

Group B: Strep agalactaciae

Most common cause of Neonatal Sepsis

hemolytic (green zone)

- hemolytic (clear zone)

# 1 cause of Subacute Bacterial

Endocarditis
Previous damage to heart valve
predispose to SBE
Tx: Amoxicillin

Group D: Strep viridians

(mutans, saguis, salivarius)

Enterococcus
(Faecalis, Faeceum)

# 1 cause of Subacute Bacterial Endocarditis

Septic emboli to brain

Roth spots- emboli to retina
Osler nodes- emboli to fingers (painful)
Splinter hemorrhages- emboli to nail beds
Janeway lesions- emboli to toes

Anaerobic
hemolytic (red zone)
Likes immunocompromised patients
Nitrite Negative UTI
Tx: Vancomycin

Vancomycin treatment:

Vancomycin:

1. MRSA

MOA: cell wall inhibitor

Inhibits phospholipid carrier (irreversible)
Tx for all gram +

2 Staph epidermidis
2.

Toxicity:
Red man syndrome
Intense histamine release (not allergic)
Ototoxicity
Nephrotoxicity

3. Enterococcus

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379

4/29/2008

Cornybacterium Diptheria

Meningitis

Chinese letters

0 to 2 mo:
Group B strep: Strep agalactaciae
E. Coli
Lysteria

Toxin that ADP-ribosylates EF-2

(affects translocation of protein synthesis)

2 mo to 10 years:
Strep pneumonia
Nisseria M.

Intracellular pathogen

10 years to 21 years:
Cells die, slough off, and mix with
mucus, forming a grey membrane in
posterior pharynx
Do NOT scrape: will hemorrhage profusely

Nisseria M.
Strep pneumonia

> 21 years:
Strep pneumonia

Cornybacterium Diptheria,
cont.

ADP-Ribosylators

Toxin may also cause heart block

DPT: 2m, 4m, 6m, 18m, 5-6y

Gs: Vibrio cholera, ETEC

Gi: Bordatella pertussus
p

Tx: antitoxin first; antibiotic (toxin is

hurting the patient, not the bug)

EF2: C. diptheria, pseudomonas

Cause heart block

Lyme disease
Legionella
Typhoid
yp
fever
Diptheria
Chagas disease

SPORE FORMERS

BACILLUS &
CLOSTRIDIUM

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4/29/2008

A SPORE

Bacillus

Made of Ca-dipocholinate

Has poly D-Glutamate membrane

(we have L-amino acids)

Dormant form of the bacteria

B. Anthrax
Has a toxin:

C
Can NOT replicate
li t but
b t CAN release
l
toxin
t i
especially when exposed to heat
(MAD!!!)

(1) lethal factor kills cell

(2) edema factor
(3) protective factor- mediates entry

Cutaneous Anthrax: malignant pustule

(skin necroses)

Is destroyed ONLY by sterilization process

Pulmonary Anthrax: wool sorters disease

(hot desert) mediastinal hemorrhagic
lymphadenitis

121 degrees centigrade vaporized heat

Clostridium

Bacillus

C. difficile: gastroenteritis associated with

antibiotic use

B. Cereus:
Fried / Reheated rice (hot wok)

Antibiotics destroy E. coli

Two toxins:
Emetic toxin- (from the rice) fast (1-6 hrs)
diarrhea, vomiting

Pseudomembranous colitis
colitis- gray membrane
with yellow plaques on colon

Diarrheal toxin (meats, sauces):

18 hrs- increases cAMP- watery diarrhea

Current treatment is metronidazole

(promotes production of free radical)

Most effective drug - vancomycin;

Side effect: dysguzia, disulfiram reaction

Clostridium

Clostridium

C. perfringens:

C. perfringens: food poisoning

Gas gangrene

Gastroenteriti
associated with holiday ham or turkey

Known to attack extremities in diabetics

Dry gangrene- necrotic skin

Enterotoxin

Wet gangrene- blood to the area

(risk of gas emboli)

Immediate symptoms- diarrhea

Tx: Immediate amputation

(hyperbaric chamber) ?????

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Clostridium

Clostridium
C. tetani

C. melanogosepticus

Associated with dirty wound

Associated with colon cancer

( along with strep bovis )

Give anti-immunoglobulin
g
to bind toxin
(into the wound)

Produces a black pigment

Toxin:
inhibits release of glycine (inhibitory)
in the spinal cord- increasing contractionrespiratory failure
Lock jaw

Clostridium
C. botulinum: - botulism
Toxin- inhibits presynaptic release of
Ach- flaccid p
paralysis
y (floppy
( ppy baby)
y)
Muscle wont work- die of respiratory
failure

Propionobacterium Acne

C. botulinum: - botulism
:

Progesterone stimulates propionic acid or

sebum

Children- honey, molasses

Do not give children honey until 6 mo of age
(normal flora will appear)

Acne more severe in women and adolescent

boys

Adults- ingest spores via canned foods

Tx: antitoxin first, antibiotic second

Refer to a dermatologist when its nodular

or nodulocystic
Gram positive anaerobe; hides in the
hair follicles

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4/29/2008

Propionobacterium Acne,
cont.

Retinoic acid

White comedones: clear vesicles

Black comedones: sebum has been
oxidized; turns black

Pre vitamin A
Cause proliferation of skin cells, pushing the
pathogen to the surface (hypersensitivity)

Tx: oxy-5 or oxy-10; benzoyl peroxide

or abrasive pads; antibiotics
( minocycline, clindamycin, or
erythromycin ); retinoic acid

Main side effects:

hyperlipidemia (fat soluble);

hyperparathyroidism;
pseudotumor cerebri;
teratogenic (must do pregnancy test)

Monocytosis

Lysteria monocytogenes

Syphilis
Tuberculosis
EBV
Lysteria monocytogenes
Salmonella typhi

The only gram positive with endotoxin

(kills quickly)
Causes monocytosis
monocytosis- granulomatous
inflammation
Attack placentas, causing abortions

STELS

Requires iron to grow; high incidence in

patients with hemochromatosis

Lysteria monocytogenes

Curved rods

Causes neonatal sepsis

Vibrio
Campylobacter
Lysteria
H. Pylori

Causes gastroenteritis associated with

migrant workers, raw cabbage, spoiled
milk,
ilk hot
h t dogs
d
Curved rod, tumbling motility
Intracellular, Cold growth
Tx: Ampicillin, Macrolide, Vancomycin

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383

4/29/2008

Listeria cont.

Gram Negatives

Listeria meningitis:
Is
Is the most common cause of
meningitis in
Renal transplant patients
Adults with cancer

Hemophilus

Hemophilus

Gram negative pleomorphic rod

80% are not encapsulated and

therefore cause noninvasive
respiratory diseases
(
(non-typeable)
bl )

Has IgA protease (cuts IgA)

Part of normal flora for the posterior
pharynx

20% are encapsulated

( poly D-glutamic acid) causes
the systemic form (H. inf. B)

Hemophilus

Hemophilus

Influenza:

Influenza, type B: #1 ONLY for epiglottitis

thumb print sign
drooling
g
fever
stridor

2nd MCC of sinusitis,, otitis media,,

bronchitis and pneumonia
Strep pneumoniae # 1

Tx: intubate immediately

14
384

4/29/2008

Thumb Print Sign

Hemophilus
Aegyptus: Pink eye (not viral conjunuctivitis)

Painful genital lesions

Hemophilus

Chancroid ( H. Ducreyi)- Most common ulceration

with central necrotic area. Tx: Ceftriaxone

Ducreyi: MCC of chancroid, the most common

painful genital lesion (LN unilateral)

Herpes ( Herpes Simplex II)- small vesicular rash

Acyclovir 5x day
Pancyclovir 3x day
Valcyclovir (Valtrex) 2x day- more compliant

Remember: does not cure- dec. symptomatic days

dec. viral shedding
dec. recurrence
Pregnancy- symptomatic within 2 weeks of
planned deliver- you must do a C-section

Painful genital lesions

HiB Vaccine

Lymphogranuloma venereum (

Has cut HiB infections down by 90%

Chlamydia trachomatis- ulcerative LN drain

(bilateral)
Tx: Doxycycline

Given at 2m, 4m, 6m, 18m;

Last dose (at 5y) no longer needed

Granuloma Inguinale

( Calymmatobacterium Donovini)
Donovini bodies macrophages with the
bug in it

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385

4/29/2008

Nisseria

Nisseria

Meningitidis: ferments maltose + glucose

The only gram negative diplococci

Presents with DIC (uses up clotting factors)

D-dimer and Fibrin split products

Has IgA protease

Waterhouse-Fredrickson syndrome-hemorrage into

adrenal gland

Part of normal throat flora

MCC of meningitis from 10 to 21y/o

Encapsulated (Has the largest capsule)

Give Dexamethasone BEFORE antibiotic

to prevent hearing loss from inflammatory
neurological damage

The ONLY gram negative that releases

endotoxin during the log phase

Give Rifampin to close contacts (>25 hrs wk)

Nisseria

Nisseria
Gonorrhea: ferments glucose

Gonorrhea, cont

Has pili that naturally transform each year

( phase variation)

Fitz-Hugh-Curtis syndrome: purulent

abscess right underneath the liver

#1 for causes of purulent STDs

#2 for causes of STDs (1# Chylamidia)

Gonococcal arthritis: it loves tendons and

ligaments (i.e. tenosynovitis)

In men: 90% of cases are symptomatic

In women: 50% are symptomatic

When cultures positive, cover for

chlamydia as well ( but not vice-versa)

Uses the pili to walk up the uroepithelium

to gain access to the blood

One dose therapy for GC

and Chlamydia

Nisseria

Azythromycin: 1gm or 2gm

Catarrhalis : does not ferment sugar

Ceftriaxone: 250mg I.M.

Cefixime: 400mg po
Cefoxitin: 250mg I.M.

Most common strain in the back of the throat

Ciprofloxacin: 500mg po
Gatifloxacin: 400mg po
Ofloxacin: 400mg po

#3 for respiratory tract infections

( sinusitis; otitis media; bronchitis;
pneumonia)

Loves mucus

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386

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Helicobacter Pylori

H. Pylori

Curved rod, Urease positive

Silver stain GI tissue
CLO test
Associated: duodenal ulcers (95%) and
gastric
t i ulcers
l
(70%)

Treatment: Amoxicillin, Bismuth, H-2

blocker or PPI
Bismuth- suffocates
3 drugs for 2 weeks (98%
eradication)
MCC- bad water (sewer system)

Treat ALL positive gastric cultures

Hydrogen breath test is most
diagnostic if available for eradication

Urease positive bugs

E. Coli

Protease
Pseudomonas
Ureoplasma Urolyticum
Nocardia
Cryptococcus
H. Pylori
Staph Saprophyticus
Brucellosis

Makes:

Makes up 95% of small intestinal normal flora

Small intestinal infections:

E. Coli

Acute cholecystitis- + murphy sign, colic pain

Ascending cholangitis- inc. alk phos
Acute appendicitis
Abdominal abscess
Acute spontaneous bacterial peritonitis

ETEC (Enterotoxogenic E. coli)

90% of vitamin K
Biotin
Folate
Panthotenic acid

Major cause of diarrhea in

developing areas
Travelers diarrhea (rice water)

Helps absorb:
Vitamin B-12

Severe watery diarrhea

( > 20 L day)

Dorsal column
Cortical spinal tract
USA- pernicious anemia
Antiparietal cell Ab

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EPEC (Enteropathognic E. coli)

EIEC (Enteroinvasive E. coli)

Plasmid shared by Shigella

Young children and infants

Invades intestinal mucosa

Causes loss of microvilli

Produces shiga like toxin (verotoxin)

Diarrhea from malabsorption

Bloody, purulent diarrhea

EHEC (Enterohemorrhagic E. coli)

Proteus Mirabilis

O157:H7 (out break- epidemic)

#2 for UTIs (1# E. coli)

Cattle, sheep, goats

Urease positive

Ingestion
I
ti off contaminated
t i t d ffood
d

Associated with high urine pH,

struvite stones, staghorn calculus,
high ammonia in the urine

Bloody diarrhea, endemic HUS

(renal failure)

Tx: Quinolones

Anemia, thrombocytopenia, renal failure

Klebsiella Pneumonia

Like Immunocompromised
people

#3 for UTIs
Likes to attack alcoholics and homeless
people

Serratia Marscesens
Citrobacter
Pseudomonas auregenosa

In lungs: curant ( blood mixed with

mucus) jelly sputum; likes to attack
fissures
Encapsulated

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388

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Citrobacter

Serratia Marscesens

Produces citric acid

Produces a red pigment

Encapsulated
Likes to attack 0 to 2m/o (babies)
Causes multiple cerebral abscesses

Pseudomonas Auregenosa

Pseudomonas Auregenosa

Same enzymes as Staph aureus

Causes: whirlpool folliculitis:

Tennis shoe folliculitis- nail through shoe

Likes to attack diabetics, burn patients,

neutropenics, and cystic fibrosis

Malignant otitis externa- mastoid (coagulase)

Gold
G ld pigment
i
l k staph
like
h aureus
Mcc of death in second week after a burn
Also produces a green pigment
Recurrent pulmonary infections in CF

Has a fruity grape smell when plated

Likes plastic ( endotracheal tubes; bladder
catheters)

ICHTHYMA GANGRENOSUM- blood form

(black bulla on the skin)

Shigella

Salmonella

Causes gastroenteritis associated with daycare

outbreaks

Encapsulated
Loves to attack people with sickle cell
anemia ( causes osteomyelitis)
Causes gastroenteritis associated with
raw chicken or raw eggs
Runs and hides in the gallbladder if
you treat it with antibiotics

Most immunogenic bacteria

Has an exotoxin ( shigatoxin) which causes
seizures
S. Sonneii: common in the US

Can precipitate cholecystitis

S. Dysentery: common outside the US

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Salmonella Typhi

Salmonella, cont

The cause of typhoid fever

Causes monocytosis

Triad: (1) Fever (2) Rose spots (3)

Intestinal fire

S. Enteritidis:
d most common strain
in US

Causes heart block

Associated with contaminated water

S. Dysentery: common outside the

US

Treat with ciprofloxacin

Bordatella, cont

Bordatella Pertussis

Causes extreme lymphocytosis (? PMNs)

Causes whooping cough

Prodromal stage- fever, runny nose
Catarrhal stage- increase mucus
Paroxysmal stage- cough

Mcc of death was suffocation

Vaccination

Has an exotoxin that ADP-ribosylates Gi

subunit of the G-protein

Diagnosis: do ELIZA on nasopharyngeal

washings

Exotoxin is intracellular; kills cells

Treatment: erythromycin; also treat

close contacts with erythromycin

High cAMP increases mucus in the lungs

Pasturella Multocida

Brucella

Causes cellulitis associated with an

infected cat or dog bite.

Causes undulating fever (5 to 7 fever

spikes per day)

Found in the saliva of cats and dogs

Seen primarily in vetrinarians and

farmers who deliver animals

Tx: Amoxacillin

Attaches to placenta

20
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Bartonella Henselae

Francisella Tularensis
Causes tularemia or oculo-glandular
fever

Silver stains
Causes cat scratch disease

Transmitted by rabbits (90%) and

deer (10%)

Carried by kittens

Treatment: Streptomycin

Vibrio

Miscellaneous
Gram Negatives

CHOLERA
Curved rod
Has an exotoxin that ADP ribosylates Gs and elevates
cAMP
Rice water diarrhea (also ETEC)

PARAHEMOLYTICUS
Diarrhea associated with raw fish

VULNIFICUS
Diarrhea associated with raw oysters

Campylobacter Jejunii

Yersinia

A curved rod

Likes the Southwest

Attacks the jejunum, causing a

p
bloody
y diarrhea
copious

PESTIS

Causes diarrhea associated with raw

chickens or raw eggs

Enterocolitica

Bubonic plague
Pneumonic plague

Likes to attack the ileum, causing ileitis

or mesenteric adenitis (mimic append)
Causes Reiters syndrome

Treat with erythromycin

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HLA-B27 DISEASES

Atypicals

Reiters Syndrome- any post infection

arthritis
Ankylosing Spondilytis- Shoeberg
test, bamboo spine
Psoriasis- silver plaque on extensor
surfaces
Psoriasis w/o arthritis- HLA B13

Atypicals

Chlamydia

Have NO cell wall

Parasites: depend on host for ATP

Granulomatous inflammation

Eosinophilia

Covered by Quinalones, Macrolides and

Tetracyclines

Has two forms:

elementary body (infectious)
reticulate body ( dormant form)

Causes interstitial pneumonia

Symptoms out of proportion to physical
findings

Granulomatous inflammation

Chlamydia Trachomatis

Chlamydia Trachomatis

Causes trachoma: Mcc of neonatal blindness

in the world

Do ELIZA with all pap smears

Trachoma: destruction of cornea from scarring

Prevention: apply erythromycin to eyes

One-dose treatment: azithromycin

1gm

Mcc of lymphogranuloma venereum

Mcc of STDs ( 90% are asymptomatic)

Old treatment: doxicycline

for 7 days

Mcc of infertility in WOMEN

Mcc of ectopic pregnancy ( from scarring)

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Chlamydia Pneumonia

Chlamydia Psitacii

Mcc of atypical pneumonia (0 to 2 mo)

Associated with parrots and

parakeets

Eosinophilia
Interstitial pneumonia

Causes interstitial pneumonia or

nonbacterial endocarditis

Symptoms out of proportion to physical findings

Steccato coughing
Found to be connected to alzheimers
disease and coronary artery disease

Mycoplasma Pneumonia

Mycoplasma
NO cell wall

Mcc of atypical pneumonia from age

10 to 30

NO epithelial lining

Cold agglutinins
gg
(cryoglobulinemia)
( y g
)

Look like jellyfish

Causes walking pneumonia

Interstitial pneumonia with symptoms
out of proportion to physical findings

Legionella Pneumophila

Mycoplasma Hominis

An occassional cause of vaginitis

Mcc of atypical pneumonia age 40yr

Interstitial pneumonia
silver stains
Grows on CYAE
Likes standing water on heating and air
conditioning systems

Causes high rise building syndrome

or hotel/motel syndrome

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Heart Blocks

Legionella Pneumophila

First degree: fixed prolonged PR

interval

Pontiac Fever: fever and nonspecific

symptoms

Second degree:

Legionnaires
g
disease: full blown
pneumonia

Mobitz 1: progressively prolonged PR

interval until a QRS complex is dropped
Mobitz 2: normal PR interval; erratic
dropping of QRS complexes

Granulomatous inflammation

Third degree: NO relationship

between P waves and QRS complexes

Causes heart block

Infections that cause heart

blocks

Ureoplasma Urolyticum
An occasional cause of vaginitis

Legionella
Lyme
Diptheria
Chagas
Typhoid fever

Has NO cell wall or epithelial lining

like mycoplasma
Urease positive

Urease Positive

Fungi

Proteus
Pseudomonas
Ureoplasma
Nocardia
Cryptococcus
H. Pylori
Staph saprophyticus
Brucellosis

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Antifungals

FUNGI

Bind to ergestrol

Like warmth and moisture

(skin folds, groin, axilla, vagina)

Amphotericin B- IV for systemic fungal infections

Gets confused with cholesterol
Pokes holes in your cells- releasing K+

Like to eat sugar- in diabetics

To prevent fungal infections, keep cool

and dry
Have a unique lipid in their
membrane called ergesterol

Nystatin
Mycostatin
Miconazole
Clotrimazole
Tolnaftate
Terbenafine

Flucytosine (5FC) inhibits mitosis

(acts like pyramadine)

Superficial Fungi

Antifungals
Inhibits ergesterol synthesis

Piedre black balls on the hair

shaft

Fluconazole- best CNS penetration

Itraconazole
Ketoconazole- inhibits P450s, blocks 5
reductase

Tx: cut hair

Microsporum Beigeii- white

balls on hair shaft

Inhibits microtubules
- Griseofulvin

Tx: cut hair

Cutaneous Fungi

Cutaneous Fungi

General (4 classes):

Tinea
Capitus - scalp
Versicolor- v on back
Corporus- body ring worm
Manis between fingers
Nigra palms life lines get dark
Intertrigo- skin to skin
Cruris- jock itch - groin
Pedis between the toes
Unguum under nail beds (one nail
affected)

Dermatophyton skin
Trichophyton- hair follicle
Epidermaphyton- epidermis
Microsporum- (Wood lamp +)

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Vaginitis

Deep Fungi

Candida: curdy white discharge; pruritic

Candida part of normal flora and lactobacili keep
it in check (antibiotics will destroy lactobacilli)
Tx: Fluconazle

Onychomycosis- fungus of nails

Candidiasis most common
cause of vaginitis

Gardnerella:
G d
ll fishy
fi h odor;
d
clue
l cells
ll
Tx: Metronidazole

Trichamonas : frothy green discharge

Protozoa: flagella
Tx: Metronidazole and remember to treat
partner (STD)

Systemic Fungi

Systemic Fungi

Histoplasmosis (Midwest) pigions, bats

Sporothrix- rose gardner, skin-potassium

iodine; Amph B and Fluconazole if systemic

Blastomycosis (North east) pigon,

broad base budding

Cryptococcus- AIDS patient with

meningitis indian ink stain
meningitis,

Coccidiomycosis ( South west) Broad

base budding

Aspergillus-Moldy hay or moldy

basement (mimics asthma)

Paracoccidiomycosis (South America)

shipwheel

Rhizor/ Mucor nose of diabetic

patients

Pulmonary Infiltrate with

Eosinophilia

Symptoms from the

Southwest

Allergic Bronchopulmonary Dysplasia

Coccidiomycosis- fungus

Loefflers Syndrome

HantavirusH t i
virus
i
(hemorrhagic)
(h
h i )

Yersinia Pestis- bacteria

Necator Americanus
Anclystoma Duodenale
Strongyloides
Shistosomiasis
Ascaria Lumbricoides

Churg-Strauss

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PARASITES

PARASITES

Cause gastroenteritis
T-cells, Macrophages, Eosinophils
LOW VOLUME STATE

FARTENPOOPIN

Chronic infections lead to iron

deficiency anemia

Liver Flukes

Liver Flukes

Toxacara : cat or dog poop

Carti- cat larvae

Cani- dog larvae
Cutaneus larva migrans- burrowing under
skin

Schistosomiasis : walking barefoot thru a

swamp

S mansoni: liver cancer

S. hematobium: causes squamous cell carcinoma
of the bladder (chronic irritation)

Ecchnococcus : messing with sheep; raw

lamb; dog food
Causes solitary ( hydatid) cyst of the liver

Liver Flukes

Hookworms
Hooks into the intestinal/bowel wall
Severe cramps and diarrhea

Clinorchis ( or opthorchis)
Sinensis: seen in Chinese; likes the
p
)
biliaryy tract ((Alkaline Phosphatase)

NEAT
NEAT AS
AS
Necator americanus
Enterobius Vermiculris- pin worm

TX for all liver flukes:

Parziquantel

Pruritis ani (eggs)

Scotch tape test- female comes out at night
Worm lives in the cecum

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Hookworms

Hookworms

NEAT AS
Anclystoma Duodenale

Treatment:
Mobendazole- paralyzes microtubules
(cant hook on to tissue)

Duodenal obstruction

Trichuris Trichurium
Trichurium- Whip worm

Pyrantel pamaoate- specific treatment

for pin worm

Anchors into rectum

Rectal prolapse

Ascaris lumbricoides
Strongyloides

Thiobendazole- tx for Strongyloides

NASSA

Flat Worms

NASSA- parasites associated with

loffler syndrome (endocarditis
and pneumonitis)

Will curl around the intestine:

D. Latum- like to eat B12
Tanea Saginatum- raw beef
Tanea Solium- raw pork, swims in
aqueous
q
humor of the eye
y
Trichinella Spiralis- raw bear meat,
tunnel under skin causing myoisitis

Necator americanus
Anclystoma duodenale
Schistosomiasis
Strongyloides
Ascaris lumbricoides

Tx: Hyclosamine
Niclosamine
Inhibit oxidative phosphorylation decreasing ATP

Protozoa
Brain:

Protozoa

Naeglaria Fowleri
Swimming through swamp- cribiform plate
Fulminant meningo encephalitis
Toxoplasmosis
Cat litter (feces)
Parietal lobe ring enhanced lesion
Tx: Pyremethamine/ Sulfadiazine
Trypanosoma Rhodienses
Carried by Tsetse fly
African sleeping disease

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Protozoa

Protozoa

Cornea:
Acanthomoeba

Erlichiosis
Dog licking face (in saliva)
Penetrates side of eye

Contact lenses
Will eat through cornea

Protozoa

Protozoa

Heart
Trypanasoma Cruzi

Lung:
Pneumocystic Corinii

Chagas disease
Eats g
ganglia
g and causes heart block
South America
Reduuvid bug

Silver stain (also Legionella)

CD4 count < 200
Tx: Bactrim (SMX-TMP)

Protozoa

Protozoa

GI

GI

Giardia- gastroenteritis

Microsporidium

Loves fresh water/well water

Hiking in the mountains
Tx: IV Metronidazole

MCC of diarrhea in AIDS patients

Cryptosporidium
E. histolyticum

Watery diarrhea
Partially acid fast
Tx: Ciprofloxacin

Multiple liver abscesses

(never do surgery)
Tx: Metronidazole (8 weeks)

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Protozoa

Protozoa
Skin
Leschmaniasis (RASH)

GU
Trichimonas

Gulf War syndrome

Sand fly

3rd MCC of Vaginitis

Tx: Metronidazole 2gm
g x1
Also treat partner

Leschmania Donivini (face eaten away)

Attacks skin and nostrils

Leschmania Rhodiensis (organ)

Systemic (attacks organs)-Kala Azar
Tx: Stibogluconate

Protozoa

Protozoa

Lymphatics
Wucheria Bacrofti

Blood

Elephantitis
No treatment

Babesiosis
East coast
Looks different on a smear
Tx: anti-malarial
Ixodes tick
(same for Lyme disease)

Blood

Protozoa

Protozoa
Blood- Plasmodium
Symptoms

Plasmodium Malaria
- MC strain world wide (fever every 3rd
day)
Falciparum
Falciparum- most fatal (hemolize
RBCs)

Malaria- fever every 3rd day

Falciparum, vivax, ovale- fever every 2
days

Treatment:

Black water fever- urine turn black

Vivax- go to the liver (chronic malaria)

Likes reticulocytes (young RBCs)

Ovale- go to the liver (chronic malaria)

Likes mature RBCs

Quinine
Chloraquine- mostly RBCs
Mefloquine- good liver penetration
Primaquine- best liver penetration
(vivax and ovale)

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4/29/2008

Mycobacterium,
Spirochetes ,
Rickettsia

Mycobacterium
NOT a true bacterium
Has bacterium in its name because
it has a peptidoglycan wall
Atypical due to MYCOLIC ACID in
its membrane
Cell mediated inflammation
If you destroy mycolic acid, you
destroy mycobacterium

Mycolic Acid

Isoniazid ( INH)

A special lipid found in the wall of

mycobacterium

INH works by inhibiting mycolic acid

synthesis

Inhibits the synthesis of mycolic acid

Fat soluble
Pulls vitamin B6 out of the system
Must give vitamin B6 with this drug to
prevent neuropathy

Side effects: myositis; hepatitis;

hepatic necrosis ( especially after
age 35 years); neuropathy;
oxidizes RBCs: blocks P450

Primary response to
Mycobacterium

Primary Tuberculosis

Asymptomatic
Ghon focus: naked tubercle on
respiratory epithelium
Virulence
Vi l
factor:
f
CHORD FACTOR
Ghon complex: tubercle ingested by
macrophages and taken to the
lymph nodes
Granuloma: macrophages now
surrounded by T cells

Usually lands in the RLL in terminal

bronchioles
Once GRANULOMA is formed:
Interferon
Tumor Necrosis Factor
1 hydroxylase

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4/29/2008

Infliximab

As long as your T cells and

macrophages stay healthy

An antibody against TNF

Useful in patients with RA

You have nothing

g to worryy
about.
.

Decreases joint destruction

But if cell mediated immunity is

ever impaired

Secondary Tuberculosis
Fever, night sweats, weight loss,
and hemoptysis
RLD profile
Cavitary lesion visible in upper
lobes on the Xray

Mycobacterium is still alive within

macrophages
Mycobacterium explodes out of the
macrophages
h
and
d into
i t the
th airways
i
Hemoptisis occurs
Mycobacterium works its way to
the upper lobe and sets up a
cavitary lesion
Patient now very symptomatic

Tx: first isolate patient when

TB is suspected; get sputum
sample for culture

Disseminated Tuberculosis
After TB replicates inside of the cavity,
it then disseminates

Mycobacterium now has full access

to the entire body.

In GI: causes ileum obstruction

Bone: Potts Disease
Lymph Nodes: diffuse lymphadenopathy
Skin: Erythema Nodosum
Along Psoas Muscle: cold abscess
CNS: posterior fossa
Neuropathies
Hydrocephalus
Meningitis

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Disseminated Tuberculosis
Renal: sterile pyuria
Adrenal gland: insufficiency
In pregnant woman: treat as in
anyone else
Most people dont know they
have ever come in contact
with TB unless

TB Treatment

TB Treatment

Four drugs for 4 months for everyone

At the end of twelve months of treatment, then

culture the sputum again

If strain of TB is sensitive to both INH

and RIFAMPIN, then finish 8 more
months with just these two drugs

Sputum cultures are repeated monthly

Stop treatment when there are three
consecutive negative sputum samples

If strain of TB is NOT sensitive to both

of these drugs, complete 8 more
months with four drugs

Patient may take drugs every day; or he

may opt to take it every other day but
witnessed by a healthcare professional

Substitute other drugs if any bad

side effects

TB Prophylaxis

Mycobacterium Family

INH plus vitamin B6 for 9 to 12

months

M.
M.
M.
M.
M.
M.
M.

In pregnant women, you must still

give
i prophylaxis
h l i
In patients with history of BCG
vaccine, ignore the history, and
merely follow the algorhythm

TB
Leprae ( Hansons Disease)
Avium Intracellulare
Scrofulaceum
f l
Marinum
Ulcerans
Kansasii

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Dapsone

Spirochetes

Indicated for the treatment of dermatitis

herpetiformis, Pneumocystis carinii in HIV
patients, and for leprosy

So named due to their spiral shape

For leprosy: use with clofazimine and

p for 6 to 24 months
rifampin

Have axial filaments at their two

ends

Mimics PABA like sulfa drugs

Use a lateral tumbling motion

Side effects: megaloblastic anemia;

oxidizes RBCs; coombs positive hemolytic
anemia; inhibits P450 system

Cell mediated response

Treponema Pallidum

Tertiary Syphilis

Causes syphilis
The most common cause of painless
genital ulcer

Tabes Dorsales
Shooting, lancinating, stabbing neuropathy

Primary syphilis- non tender chancre

( contagious )

Syphilitic aortitis
Argyle Robertson pupil

Secondary syphilis- 1 to 3 mo
( rash P & S )

Syphilis loves to attack bones

( saber shins)

Tertiary syphilis *

Toxoplasmosis

TORCH infections

Multiple ring enhancing lesions in the parietal

lobes
Caused by cat urine
Asymptomatic in healthy people (walled off
in a granuloma)
Symptomatic
S
t
ti iin pregnantt women d
due tto
suppressed immune system
Pregnant women should NOT change a litter
box
Treat with pyremethamine/sulfadiazine
combo

They attack in the first trimester

( except herpes)
They cause severe neurological
damage
All cause IUGR, microcephaly,
hypotonia and developmental
impairment
How do you separate them ?

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Rubella

Syphilis

Blueberry muffin rash

Cataracts
PDA
Hearing loss
l
Autism

Loves to attack bones

Flat forehead
Saddle nose
Sniffles
Micrognathia
Rhagades
Hutchinsons teeth
Sabre shins

Autistic

Autism

AUTISM- below normal intelligence, difficulty

forming relationships

Four features:
Inability to bond
Impaired language development
Automatism- no control of there actions
Overreacts to small disturbances

Asperger syndrome: milder form, normal

intelligence and lack social skills
Pervasive developmental disorder of childhood

Brain is found on autopsy to be

arrested in development

Retts syndrome- girls only, starts by

age 4, hand wringing

MMR controversy

Herpesvirus

Cytomegalovirus

Attacks newborn on the way through the

vagina

Loves to attack the retina

Loves to attack the temporal lobe, causing

temporal lobe hemorrhagic encephalitis

Mcc of Congenital blindness

Causes central calcifications

If pregnant mother has an outbreak of

lesions within two weeks of delivery, do a
C-section

Attacks the midline

Give pregnant mother acyclovir in last

month to prevent outbreaks

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Syphilis

Treponema Family

Treatment:

Treponema Pallidum

Primary syphilis: 1.2 million units of long

acting penicillin (Procaine or Benzathine)
Secondary syphilis: 2.4 million units, half in
each
h buttock
b tt k
Tertiary syphilis: 2.4 million units once
weekly for 3 weeks
Neonatal syphilis: 50,000 units per
Kg per day in divided doses

Treponema Pallidum variant: Bijel

Treponema Pertenue: Yawstropical form
Treponema Carateum: Pinta

Borellia Borgdorferi

Borellia Borgdorferi

Lyme Disease
Primary stage- bulls eye rash (resolve
in 1 month)
Secondaryy stageg flu like symptoms
y p
,
organ involvement
Tertiary stage- arthritis

Treatment:
Penicillin
Doxycycline
If a pregnant woman is bitten by a tick,
treat with IV ceftriaxone
Any patient with heart block,
hospitalize and treat with
IV ceftriaxone

Dx: history of Erythema Chronicum

Migrans;
Do IgM and IgG titers

Leptospira Interrogans

Borellia Recurrentis

Causes leptospirosis

Causes Relapsing Fever

Seen primarily in sewage workers

Fever occurs once weekly

Transmitted by rat urine

Organism hides in lymph nodes and

mutates slightly each week

Weils Disease: attacks the liver

(hepatitis) and the kidney (nephritis)

Treat with penicillin or doxicycline

Causes Fort Braggs Fever

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Rickettsia

Rickettsia

Rickettsia Rickettsia: RMSF: tick borne

Treatment: Doxicycline or
Chloramphenicol

Rickettsia Typhi: endemic typhus: flea borne

Rickettsia Prowzekii: epidemic typhus: louse
borne
Rickettsia Akari: rickettsial pox: mite borne
Rickettsia Tsutsugamushi- scrub typhus;
chiggers

We both wish you the best

of luck on your exam !!!!

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407

6/25/2008

What all viruses do

And NOWThe final topic!

VIRUSES

To prevent uncoating

Invasion
Adhesion
Penetration
Uncoating
Replication
Assembly
Lysogeny

To prevent replication

Amantidine
Rimantidine

Acyclovir
Pencyclovir
Demcyclovir
Valcyclovir
Famcyclovir
Gancyclovir
Ribavarin

Detectives

The 90%
DNA Viruses

Southern blot
Northern blot
Western blot
Southwestern blot
ELIZA
PCR

Double stranded ( ex
parvovirus and
hepadnovirus
Replicate
p
in nucleus ( ex
poxvirus)
Assemble on nuclear
membrane
Naked ( ex herpesvirus)

RNA Viruses
Single stranded ( ex
orthomyxovirus and
renovirus
Replicate
p
in cytoplasm
y p
(ex retrovirus)
Assemble on cell
membrane
Enveloped (ex
cocksackievirus)
+-strand vs -strand

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408

6/25/2008

Encephalitis
Presents with headache and ataxia

Most Common causes of

viral infections
infections

Causes:
Arbovirus
Herpesvirus

From head to toe

Common Cold

Meningitis
AKA aseptic meningitis
Presentation: mild headache; photophobia;
Kernigs and Brudzinskis signs
CSF
CS results
l
Causes: enteroviruses

Childhood Rashes

Common Childhood infections

Mumps
Rubeola
Rubella
Varicella
Varicella-Zoster
Fifths disease
Roseola
Pityriasis Rosea
Rosacea

Rhinovirus
Coronavirus vs Adenovirus
Herpesvirus
Influenzavirus
Parainfluenzavirus

Hand-Foot-Mouth
disease
Kawasaki disease
Molluscum
contagiosum
i

Seborrheic dermatitis diaper dermatitis

Erythema toxicum
Pediculosis pubis
Milia
Mongolian spots
Nevus Flemmeus
Caf au lait spots
Port wine stain

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409

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Croup

The four itchiest rashes

Stridor and barking cough

Steeple sign on neck film
Cause:

Urticaria
Scabies
Dermatitis herpetiformis
Lichen planus

Parainfluenzavirus 80% mild

RSV 15% severe
Adenovirus
Influenzavirus

Bronchiolitis

Myocarditis

All the signs and symptoms of asthma

Under 2 years of age
Caueses:

Leads to loss of contractility

Diffuse ST wave depression on EKG
Cause:

Parainfluenzavirus 80% mild

RSV 15% severe
Adenovirus
Influenzavirus

Cocksackie B Virus

Pericarditis

Gastroenteritis
In adults: Adenovirus
In children: Rotavirus
Travel: Norwalk agent

Causes a friction or tri-phasic rub

May lead to tamponade
Diffuse ST wave elevation
Cause:
Cocksackie B Virus

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410

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Cystitis

Hepatitis

Urgency and frequency

Cause: Adenovirus

Hepatitis

Chronic Active Hepatitis

Active inflammation on biopsy

Fibrosis present
May progress to liver cancer
Will lead to cirrhosis
Due to Hepatitis B: Tx with interferon and
lamuvidine
Due to hepatitis C: Tx with interferon and
ribavarin

Chronic Carrier

Chronic Persistent Hepatitis

Elevated liver enzymes or persistent
symptoms after 6 months
No active inflammation or fibrosis on liver
biopsy

Still has positive HbSag after 6 months

No active inflammation or fibrosis on biopsy
Still pose a threat to others
Can NOT be blood donors or organ donors

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411

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THE END

5
412

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4/29/2008

G5 P4 Ab1
G: Gravita: number of
pregnancies
P: Para: > 20 Weeks

Obstetrics and
Gynecology

Ab: Abortive: abortions

G6 P0 Ab5

Ultrasound (Utz.)

Prenatal
Diagnostic
g
Testing

Non-invasive imaging
No adverse effects on the fetus
18-20 weeks of gestational
anatomical anomalies
Accuracy for gestational age:
At 12 weeks +/- 5 days
At 18 weeks +/- 7 days

Chorionic Villous Sampling

(CVS)

Nucal Translucency
10- 14 weeks via Utz.

Aspiration of placenta
tissue (9-12 wks)
Sono guided
Karyotyping

Thick area you should think of

cystic hydroma Downs Syndrome

Pregnancy loss rate 0.7%

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Percutaneous Umbilical Blood

Sampling (PUBS)

Amniocentesis
Transabdominal needle to withdraw
amniotic fluid under sono (15-20 wks)

Fetal blood from umbilical vein

(> 20 weeks)

Looking at DNA from fetal cells

Fetal karyotyping

Not enough fluid prior to 15 weeks

IgM antibody

Pregnancy loss rate (0.5%)

Blood typing

24 weeks- Rh isoimmunization
(bilirubin levels)

Intrauterine Blood Transfusion

34 weeks- Lecithin-sphingomyelin

Pregnancy loss rate 1-2%

Fetoscopy

Fetal Development

Experimental (18-20 weeks)

1 week for Implantation

Fetal tissue biopsy

Ichthyosis
y

Genetic skin condition

(fish scales)

Folic acid
1mg
4mg

Coagulation in twin-twin
transfusion

Week 2-3 post conception

Weeks 4-8 Post Conception

Bilaminar germ disk:

Major organs forming

Teratogenic risk

- Epiblast
- Ectoderm
- Hypoblast
- Mesoderm
Cytotrophoblast
- Endoderm
Synchotrophoblast
Must have all 3 in order to a
teratogen to cause problems

Primitive streak

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Female vs Male cells

Teratogenesis Stages

Theca
Granulosa

Conception to end of first week

Weeks 3-8

Leydig
L
di
Sertoli
5 alpha reductase DHT (external
genitalia)

Post week 9

Teratogens

Teratogenic Syndromes

Ionizing radiation

Alcohol: fetal alcohol syndrome

Chemotherapy
Long philtrum
T b
Tobacco
ETOH

Midfacial hypoplasia

Cocaine
Short palpebral fissure

Teratogenic Syndromes

Teratogenic Syndromes

Diethylstilbestrol (DES)

Isotretinoin (Accutane)

T-shaped uterus

Congenital deafness
Congenital heart defects

Vaginal adenosisadenosis clear cell

carcinoma

iPLEDGE

Incompetent cervix

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Teratogenic Syndromes

Teratogenic Syndromes

Lithium:

Streptomycin

Ebstein anomaly (R heart defect)

CN 8 damage- hearing

Tricuspid lower
Very large right atrium

Teratogenic Syndromes

Teratogenic Syndromes
Thalidomide: drug for N/V

Tetracycline
Competes with Ca2+

Phocomelia (days 42-48)

Teeth discoloration after 4 months

Pyloric and duodenal stenosis

Teratogenic Syndromes

Teratogenic Syndromes
Warfarin (Coumadin)

Valproic acid (Depakote)

Chondrodysplasia: stippled
epiphysis

Neural tube defect

Mgt: Migrans and Bipolar

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Human Chorionic Gonadotropin

Pregnancy
Hormones

Syncytrophoblast
In blood by day 10
Alpha subunit
Beta subunit (specific)

Human Placental Lactogen

(HPL)

High levels of hCG

Twins
Hydatiform moles
Choriocarcinoma

Increased through pregnancy

Antagonizes
tago
es insulin
su

LOW levels:
Ectopic
Threatened abortion
Missed abortion

Skin

Organ
system
changes in
pregnancy

Line nigra
Chloasma
Chadwick sign
Stria gravidarum
Spider angiomata/palmer erythema

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Heart

Murmurs

Blood pressure

Systolic murmur:

Plasma volume

Diastolic murmur:

Femoral venous pressure

CO
Peripheral vascular resistance (PVR)

GI

Blood

Stomach:

RBCs
Plasma volume

Large bowel

WBCs
Platelets
Coagulation

Renal

Pulmonary
Tidal Volume

Increase in size:

Minute volume

Gl
Glucosuria:
i

Respiratory volume

Proteinuria:

Blood gases

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Endocrine

Fetal Circulation
3 in utero shunts:

Pituitary

Ductus venosus

Thyroid

Foramen ovale
Ductus arteriosus

Fetal Hart Tone (FHT)

Fetal
Testing

Doppler stethoscope: 10-12 wks

Auscultation 18-20 wks

Quickening: 16-18 weeks

(primigravida 18-20)

Ultrasound Dating

Pregnancy 1st trimester

1st trimester:

< 13 weeks
N/V

2nd trimester and 3rd

S tti / bl
Spotting/
bleeding
di

Biparietal diameter
Head circumference
Abd. Circumference
Femur length

Wt gain 5-8 lbs

Complication: spontaneous
abortion

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Pregnancy 2nd trimester

Pregnancy 3rd Trimester

13 26 weeks

Decreased libido, back pain, urinary

frequency

Round ligament pain

Lightening

Braxton-Hicks contractions

Bloody show

Quickening

Wt gain 1 lb/week

Wt gain 1 lb/wk

Complication: PROM

Complication: incompetent cervix

Mean Corpuscular Volume

Prenatal
Lab
Test

Hb/Hct- low due to dilution

MCV most reliable

< 80
> 100

Rubella IgG antibody

Hepatitis B Virus

Antibodies present

HBV surface antibody: successful

vaccination
HBV surface antigen:

Absence puts patient at risk

E antigen:

Immunization:

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STD screening

Urine Screening

Cervical cultures:

Urinalysis:
Proteinuria
Ketones
Glucose
Bacteria

Syphilis:
VDRL
RPR
MHA-TP
FTA

Culture: asymptomatic bacteruria

(ASB)

Mgt. Penicillin

Tuberculosis Screening

HIV screening

PPD or Tine test:

Recommended for all pregnant

women

Positive skin test

Opt out: informed refusal

CXR negative

Opt in: informed consent

CXT positive

Elisa test

Alpha Fetal Protein

Detectable HIV antibodies

True causes of increased AFP:

Babies born to an HIV + mothers

MCC dating
MCCd ti
errors

Western Blot
Zidovudine

9
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Triple Marker Screening

Triple marker screening

MS-AFP
hCG
Estriol

Trisomy 21
Downs

Trisomy 18
Edwards

MS-AFP

Accurate dating is important

hCG
Estriol

Do karyotype for both

Third Trimester Lab Test

Antenatal
Fetal
Testing

Diabetic Test:

1hr (50 gm) oral glucose

3hr (100 gm) oral glucose

Normal: FBS: < 95, 1hr <180, 2hr < 155,

3hr < 140

Nonstress Test (NST)

Fetal Monitor Tracing

Check frequency of fetal movement

External fetal HR monitor
Accelerations

Base line FHR: 110-160

< 110 Bradycardia

Meds: beta adrenergic blockers, anesthetics

Fetal arrhythmiaarrhythmia congenital heart block (lupus)

< 32 wks: > 10 or more BPM,

lasting >10 sec

>160 Tachycardia

Meds: beat adrenergic agonist (terbutaline,

ritodrine)
Fever
Fetal repetive movements

> 32 wks: > 15 or more BPM,

lasting > 15 sec

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Early Deceleration:

Variable Decelerationcord compression

head compression

Late Decelerations- uteroplacental

insufficiency ( fetal acidosis)

Biophysical profile (BPP)

5 components of fetal well

being:
1.
2.
3.
4.
5.

NST: scores 0-2 for each

Amniotic fluid volume
Fetal g
gross body
y movement
Fetal extremity tone
Fetal breathing movements

2-5 assessed through Utz.

BPP scoring

Contraction stress test (CTS)

8-10 = reassuring (weekly BPP)

Testing fetus response to tolerate

transitory decreases in blood flow

4-6 = worrisome

Presence or absence of late

deceleration

> 36 wks- deliver

< 36 wksk BPP every 12-24
12 24 h
hours

Induce with IV oxytocin

0-2 = fetal hypoxia (deliver ASAP)

Negative test is good- no late Dcells

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Umbilical Artery Doppler

Measures ratio of Systolic and
Diastolic blood flow in umbilical
artery

Infections

Increased throughout
g
pregnancy,
p g
y,
since diastolic pressure falls more

Group B beta hemolytic Strep

Treat for Group B Strep if

Normal GI tract flora

Positive urine culture GBBS

30% of women are asymptomatic carriers

Previous baby had GBBS

Vertical transmission

Screening by vaginal cultures:

Early onset

3rd trimester
If + then prophylaxis IV PCN

Late onset

Preterm or Membrane rupture > 18hrs,

or maternal fever Mgt.
Prophylaxis IV PCN

Mgt: IV penicillin: if allergic- Clindamycin

and Erythromycin

Toxoplasma Gondii

Varicella
Chicken Pox
Herpes Zoster
Spread via respiratory droplets
ZIG ZAG skin lesion
Maternal varicella pneumonia

Parasite associated with cat feces

Raw goat milk
Under cooked infected meat
Vertical transmission
Lethal if first trimester
Third trimester- asymptomatic
Intracranial calcification

Mgt: administer VZIG to suspected

gravid within 96 hrs of exposure

Mgt: Pyrimethamine Sulfadiazine

12
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Rubella

Cytomegalovirus (CMV)

RNA virus spread through

respiratory droplets
Transmission only if primary
infection
Fetus= VSD
Neonate= congenital deafness
Prevention: rubella IgG antibody
screening

Spread via body secretions

Life long latency, so fetus can get
it on reactivation
Periventricular calcification
MCC of congenital deafness

Live attenuated virus- avoid

pregnancy for 1 month after
immunization

Mgt: Ganciclovir

Herpes Simplex Virus (HSV)

Human Immunodeficiency Virus

Multinucleated Giant Cells

Maternal genital lesion is MC route
for fetal infection

HIV + mothers take zidovudine

starting at 14 wks until delivery

Dx: + culture from ruptured vesicle

Prevention: C-section
C section

C-section for delivery

Breast feeding contraindicated

If membrane already ruptured and it

has been >8-12 hours- too late to
do a C-section

Neonate gets AZT for 6 wks, then

check again

Mgt: Acyclovir

Maternal Syphilis infection

Bleeding
g late
during
pregnancy

Primary- painless ulcer with rolled up

edges (chancre)- gone in 2-3 wks
Secondary- 2-3 months after contact,
maculopapular skin rash and
condyloma lata
Tertiary- organs affected

Heart- aortitis
Dorsal column- tabes dorsalis
CSF +

Mgt: Vaginal delivery: Benzathine PCN and if allergic

desensitization to PCN

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Bleeding

Abruptio Placenta

Painful bleeding

Initial evaluation:
Maternal : check vitals
Fetus: FHT

Overt (external)

Concealed (internal)

Mgt: large bore IV NS

Foley- monitor output
If fetal jeopardy is present or +/- 36
wks- deliver

Types of Abruption

Mgt. of Abruptio

Mild- no fetal abnormality

Emergency Cesarean if mother or

fetal jeopardy

Moderate- 25 50% surface

separation

Vaginal delivery if bleeding is

controlled or > 36 wks

Monitor
o to for
o late
ate D-cells
ce s

Severe- abrupt, knife like uterine

pain

Conservative (in hospital)

> 50% placental separation

DIC may occur
Severe late D-cells

Stable and remote from term

Confirm placental location on sono
Replace fluids

Placenta Previa

Mgt. for Placenta Previa

Painless bleeding

Emergency Cesarean if mother or

fetal jeopardy

Placenta is implanted in lower

uterine segment

Vaginal delivery- lower placental

edge must be > 2cm of os

Common early in pregnancy

(migration)

Scheduled C-section
Fetal lung maturity by amniocentesis

3 types:
Total, complete or central- covers os
Partial- partial cover of os
Marginal, low lying- near os

Conservative (in hospital)

Bed rest, preterm, confirm placental
location

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Complications of Placenta Previa

Vasa Previa
Fetal vessels transverse the internal OS

Villi may invade uterine tissue

Bleeding from fetoplacental circulation

Endometrium

Myometrium

Serosa

Rapid fetal exsanguination

Placenta
accreta 75%

Due to amniotomy (AROM)

Placenta Increta
20%

Triad:

ROM
Painless vaginal bleeding
Fetal bradycardia

Placenta
percreta 5%

Mgt: immediate C-section

Bladder

Uterine Rupture
Triad:

Obstetrical
Complications
p

Painful bleed
Loss of FHT
Head floating

MCC- classical incision

MCC
Myomectomy
Excessive oxytocin
Mgt: surgical

Abortion vs fetal demise

Fetal demise (>20 wks)

Fetal death prior to 20 weeks:

Abortion

Most serious consequence

Missed
Threatened
Inevitable
Incomplete
Complete

DIC (disseminated intravascular

coagulation)
Usually takes 3-4 wks to occur
Release of thromboplastin from
deteriorating fetal organs

After 20 weeks: fetal demise

Must report to the state

Do not deliver until mom is ready as

long as there is no DIC

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Twin Delivery
Vaginal

Rho GAM

C-section

Pooled anti-D IgG

Passive antibodies (IM)

B

B
A

Both
Cephalic

A- breech
B- cephalic

IIgG
G antibodies
tib di
attach
tt h to
t the
th
foreign RBC and lysis occurs
before mom can produce an
immune response

A- cephalic
B- breech

RhoGAM given at

Kleihauer Betke Test

Give to Rh(D) negative mothers at

28 weeks

Quantitates fetal RBCs in moms

blood

Within 72 hours of

Looks at a peripheral smear

Chorionic villus sampling

Amniocentesis
Rh+ delivery
D&C

Will access if more than one vial is

needed

Give 300 micrograms (1 vial)

Premature Rupture of Membrane

(PROM)

Diagnosis PROM
Sterile speculum

Risk of ascending infection

Pooling clear fluid in posterior

vaginal fornix

History of sudden gush of copious

vaginal fluids

Nitrazine p
positive ((turns p
paper
p blue))

Oligohydramnios on Utz.

Fern test- on microslide

Chorioamnionitis:

Maternal fever
Uterine tenderness
Confirmed PROM

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Management PROM

Preterm Labor
3 criteria:
Between 20 and 37 weeks

Uterine contractions present

(dont use tocolysis)

Uterine contractions (3 in 30 min.)

Chorioamnionitis IV antibiotics,
Chorioamnionitisdelivery

Cervical changes
(dilation changes > 2cm)

No infection
< 24 wks- dismal outcome
>24- bed rest, IM betamethasone, 7 day
prophylaxis of ampicillin and
erythromycin

Tocolytic Agents

Types of Tocolytics

Prolong pregnancy for up to 72 hrs

MgSO4- blocks Ca2+

Monitor: DTR
Antidote: IV calcium gluconate
Contraindications: renal insufficiency, MG

IM betamethasone to work
Transport mother/fetus to neonatal
intensive care

Beta adrenergic agonist- terbutaline,

ritodrine

Given parenteral

Ca2+ blockers- Nifedipine, Procardia

PG inhibitors- Indomethacin

Post Date Pregnancy

HTN during
p g
pregnancy
y

Worried about placental breakdown

Fetus not getting the O2 it needs
Meconium risk
42 wks maximum time in uterus
Shoulder dystocia

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Preeclampsia:
Mild

Eclampsia
Unexplained grand mal seizures
with

Severe

HTN
Proteinuria
> 20 wks gestation

B/P
Proteinuria

Severe diffuse cerebral

vasospasms

Gestation
Mgt.

Mgt. of Eclampsia

HELLP Syndrome
5-10% of preeclamptic patients
H- hemolysis
EL- elevated liver enzymes
LP- low platelets

First protect the mothers airway

IV MgSO4, with IV bolus of 5g to stop
seizure

Mgt. prompt delivery at any age

Maintenance dose 2g/hr

Deliver at any gestational age
Lower diastolic B/P to 90-100mmHg

Fetal Presentation

Station in delivery

Cephalic- head presents first

Breech- feet or buttock first

Frank (vaginal delivery)- sucking on
toes
Complete
Footling

Compound- more than one body part

present

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Overview of Labor

Cardinal Movement in Labor

Engagement
Descent
Flexion
Internal rotation
Extension
External rotation
Expulsion

Uterine changes:
Contraction of upper uterine segment
Exerting expelling forces

Cervical effacement:
Thinning due to oxytocin and PGE2
breaking disulfide bonds in collagen
fibers

Normal cervix: 2cm long/ 2cm wide

Stages of Labor
Stage 1: onset of uterine contraction
and ends with complete dilation

Abnormal
L b
Labor

Latent- cervical dilation up to 20 hrs (3-4 cm)

Active rapid cervical dilation (1.2 cm/hr)

Stage 2: complete cervical dilation to

delivery (2 hrs)
Stage 3: delivery to placental expulsion
(30 min)
Stage 4: observation of mother for
preeclampsia and post partum
hemorrhage

Prolonged Latent Phase

Prolonged Active Phase or Arrest

Cervical dilation > 3cm
Prolonged dilation < 1.2 cm for > 2h

Cervical dilation <3cm for

> 20hrs primipara
> 14 hrs multipara

Passenger problem: size or

orientation

MCC iinjudicious
j di i
analgesia
l
i

Power problem: inadequate uterine

contraction

Mgt. Therapeutic rest

Hypotonic muscle- IV oxytocin

Contraction normal- go to C-section

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Prolonged 3rd stage

Prolapsed Umbilical Cord

Obstetric emergency

Placenta has not delivered within 30

min

Cord gets compressed affecting

fetal oxygenation

If it does not remove with IV

oxytocin,
y
, then think accreta ((etc.))

Occult- head and uterine wall

Partial- head and cervical os
Complete- protruding into vagina

Mgt. manual removal or

Hysterectomy

Mgt. Knee-chest position

Elevate presenting part
Immediate C-section

Shoulder Dystocia

Cesarean Section
Maternal mortality and morbidity is
higher than vaginal delivery

Delivery of fetal shoulder is

delayed after delivery of head

Hemorrhage : > 1000 ml

Impacted of pubic symphysis

Infection

Mgt. suprapubic pressure

McRoberts maneuver- thigh flexed
Woods corkscrew- internal rotation
Manual delivery of posterior arm

Visceral injury: bowel, bladder

Thrombosis- DVT

Cervical Ceretage

Uterine Incisions

Pts with incompetent cervix

Lower segment transverse
(pull bladder down)

Shirodkar- beneath cervical

mucosa- left in place with deliver
of C-section

Fetus must be in longitudinal lie

Cut non-contractile portion of uterus

McDonald- removed by 36 wks for

vaginal delivery

Can still have VBAC

(vaginal birth after c-section)

Placed at 14 wks, before cervical

dilation and effacement occur

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Post Partum Fever

Gynecologic
Neoplasia
and Cancer

PP day 0: Atelectasis
PP day 1-2: UTI
PP day 2-3: Endometritis
PP day 4-5: Wound infection
(antibiotics and drain)
PP day 5-6: Septic thrombophlebitis
(IV heparin 7-10 days)
PP day 7-21: Infectious mastitis
(oral cloxacillin and continue
breast feeding)

Human Papilloma Virus (HPV)

PAP test

Screening for premalignant lesions

Transformation zone (T-zone)
squamous/columnar

16, 18, 31, 33 and 35

Premalignant
Cancerous

3 years after onset of sexual

activity
act
ty o
or 21 y/o

6,11
6
11
Benign condyloma acuminata

Discontinued >70 with 3 negative

paps
< 30 y/o annually (2 yrs liquid based)
> 30 every 2-3 yrs after 3 (-) paps

Bethesda System

Diagnostic Approach

Negative- no malignancy

Accelerated repeat PAP: ASC-US

ASC- atypical squamous cells

HPV-DNA testing: ASC-US

LSIL low grade squamous intraepithelial

LSILlesion (HPV or CIN I)

Colposcopy abnormal pap

Colposcopy(acetic acid)

HSIL high grade squamous intraepithelial

lesion ( CIN 2,3, moderate dysplasia)

Endocervical curettage (ECC)- r/o

endocervical lesion [not in pregnancy]

Cancer- invasive

Cone biopsy- PAP worse than histological

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4/29/2008

Mgt. according to histology

Invasive Cervical CA

Observation: CIN I, repeat pap 6-12

months

Penetrated through basement

membrane

Ablative: CIN 1, 2, 3: Cryotherapy

Postcoital vaginal bleeding

Excisional: CIN 1, 2, 3: LEEP (loop

electrosurgical excision), cold
knife

Dx. Cervical biopsy- sq. cell CA

Mgt. Hysterectomy

Hysterectomy- recurrent CIN 1,2,3

Cervical Neoplasia in
Pregnancy

Post Menopausal Bleeding

Menopause- after 3mo or cessation
of menses

Pregnancy does not change

progression

Endometrial carcinoma (MCC)

p g
Test female same as non-pregnant
Skip ECC- cervix more vascular

Unopposed estrogen

Invasive CA:
<24 wks: hysterectomy
> 24 wks: wait until 32-33 wks, then
C-section and hysterectomy

Dx: Endometrial sampling

Mgt: Positive histology: TAH & BSO

Enlarged Uterus

Enlarged Uterus

Leiomyoma:
Benign smooth muscle of the
myometrium

Adenomyosis:
Ectopic endometrial glands and stroma
located within the myometrium of the
uterine wall

More common in black females

Tender uterus in absence of pregnancy

p g
y

Mgt. Observation

Dx. Utz or MRI

Presurgical shrinkage 3-6 mo GnRH analog

Myomectomy
Embolization
Hysterectomy

Mgt. Levonorgestrel intrauterine system

Definitive : Hysterectomy

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Premenopausal Adnexal Mass

Ovarian
Neoplasia

Simple Cyst- luteal or follicular

Complex cyst- dermoid (germ layers)
Dx. hCG levels to rule out pregnancy:
Sonogram
Mgt.
Simple cyst- observation, OCPs,
(>7cm laparoscopic)
Complex cyst- surgical removal

Adnexal Mass With Pain

Prepubertal Adnexal Mass

Sudden onset of severe lower

abdominal pain in presence of
adnexal [Link] torsion

Functional ovarian cyst not

possible because ovarian
follicles are not functioning

Mgt. untwist

p
of neoplasm
p
Suspicious

Observation to assure revitalization

Routine exam annually

Dx. Tumor markers

LDH- dysgerminoma
Beta HCG- Choriocarcinoma
Alpha fetal protein- endodermal sinus
tumor

Postmenopausal Adnexal Mass

Classifications

Ovaries should be atrophic

Epithelial tumor (80%)- post menopausal

MC serous

Any enlargement, should draw

suspicion of ovarian cancer

Germ Cell tumor (15%)- teenagers

MC dysgerminoma

BRCA-1

Stromal tumor (5%)

Granulosa cell tumor- increased estrogen

Metastatic tumor- Krukenberg

stomach to ovary

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Vulvar Intraepithelial Neoplasia

(VIN)

Vulvar Neoplasia
Vulvar lesion with pruritus
Vulvar itching

Squamous dysplasia

Squamous hyperplasia
((whitish focal area))

Mgt. surgical excision

Mgt. corticosteroids

Lichen Sclerosis
(bluish-white papule)
Parchment like
Mgt. testosterone cream

The
End

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Trauma" refers to a serious

or critical bodily injury,
wound, or shock, as from
violence or accident.

477

Immediately lifethreatening injuries

Potentially lifethreatening injuries

Airway obstruction

Simple
pneumo/haemothorax

Tension pneumothorax

Aortic rupture

Open pneumothorax

Blunt cardiac injury

Massive haemothorax

Pulmonary contusion

Flail chest

Tracheobronchial rupture

Cardiac tamponade

Diaphragmatic rupture

10/13/2008

SIGNS & SYMPTOMS: (Your CLUES)

1. No, weak, noisy, labored or gurgled respiration
2. Pale, cool, clammy skin; delayed capillary refill
3. Irregular/unstable vital signs
4. Contusion, abrasion, laceration, hematoma
5. Pain, tenderness, guarding, numbness/tingling
6. Bruising, swelling, deformity, false/limited motion
7. Muscle weakness/paralysis, loss of sensation
8. Altered mental status
9. Asymmetric pupils, JVD, incontinence

OBTAIN HISTORY OF:

1. PMH/Meds/Allergies
2. Mechanism of injury/weapon description
3. Use of protective devices: helmets, seatbelts,
airbags, padding
4. Substance abuse
5. Estimated blood loss at scene
6. Time of injury
7. Loss of consciousness

UNSTABLE

STABLE or UNSTABLE

The Famous A B Cs
- Airway
- Breathing
- Circulation

The Famous A B Cs
In the vignette:
- GET RID OF DISTRACTORS!
- Look for Pt. Stability and
decide:

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10/13/2008

The Famous A B Cs
In the vignette:

Case:
25 y/o man falls from a tree. At the moment
he is unconscious. His breathing is difficult
and his mouth is full of blood. His arm has an
unusual angle and theres laceration in his
forehead and chest. What is the best next
step?

- GET RID OF DISTRACTORS!

- Look for Pt. Stability and
decide:

Case:
25 y/o man falls from a tree. At the moment
he is unconscious. His breathing is difficult
and his mouth is full of blood. His arm has an
unusual angle and theres laceration in his
forehead and chest. What is the best next
step?

AIRWAY:
What to check?
-No, weak, noisy, labored or gurgled respiration
-Abnormal, silent or low voice or uncompleted
sentences while talking
- Unconsciousness

AIRWAY:
Then: Administer air ANYHOW!

AIRWAY:
Then: Administer air ANYHOW!

- Mask w/ 100% O2
- Orotracheal intubation
- Cricothyroidotomy

- Mask w/ 100% O2

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10/13/2008

AIRWAY:
Then: Administer air ANYHOW!

AIRWAY:
Then: Administer air ANYHOW!

- Orotracheal intubation

- Cricothyroidotomy

AIRWAY:
Then: Administer air ANYHOW!
How to choose?
Rules:
1.-Use less invasive first
2.-Follow the order if the patient
has been started but
oxygenation didnt succeed
(Check PULSE OX. <90)

AIRWAY:
Possible causes: (If diagnose is asked)
- Foreign object
- Body fluids (blood, vomit)
- Swelling of trachea, epiglottis,
tongue, uvula, etc
- Disruption of airway (direct trauma)
- Anesthesia, drugs
- Head trauma

Case:
25 y/o man falls from a tree. At the moment
he is unconscious. His breathing is difficult
and his mouth is full of blood. His arm has an
unusual angle and theres laceration in his
forehead and chest. In the ambulance the
patient is intubated successfully. Physical
Examination: Loud blow sound in the left
when ambu is compressed. What is the best
next step?

Case:
25 y/o man falls from a tree. At the moment
he is unconscious. His breathing is difficult
and his mouth is full of blood. His arm has an
unusual angle and theres laceration in his
forehead and chest. In the ambulance the
patient is intubated successfully. Physical
Examination: Loud blow sound in the left
when ambu is compressed. What is the best
next step?

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BREATHING:
What to check?
-Symmetry of air flow
-Is air going to lungs actually?
-Breath automatism
-OVERVENTILATION
-Crepitus in peri respiratory system

BREATHING:
Then: CORRECT (Depends in vignette)
One side airflow
- Re-direct tube
Crepitus peri resp. - Other way of ventilat.
Pulse Ox. Low
- Other way of ventilat.
Air outside lungs - Re-diagnose

BREATHING:
Possible causes:
- Bad technique
- Flail chest
- Cardiac tamponade
- Rupture of airway, thorax,
diaphragm or arthery (hemo,
pneumo thorax)
- Under ventilation

Case:
19 y/o unmarried, at term pregnant woman
has a MVA 30 minutes ago. She is able to
answer the anamnesis and is lucid. At the
moment she is crying, and seeks for
companion, she is very worried about the
baby because she doesnt feel movements
anymore and ask for the mother to be called.
Temperature is 37C, Pulse 102m, BP 60 over
40. Fetal signs negative. What is the best next
step?

Case:
19 y/o unmarried, at term pregnant woman
has a MVA 30 minutes ago. She is able to
answer the anamnesis and is lucid. At the
moment she is crying, and seeks for
companion, she is very worried about the
baby because she doesnt feel movements
anymore and ask for the mother to be called.
Temperature is 37C, Pulse 102m, BP 60 over
40. Fetal signs negative. What is the best next
step?

CIRCULATION:
What to check?
-History of profuse bleeding
-Hypotension
-Pale, cool, clammy skin
-Delayed capillary refill

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CIRCULATION:
What to check?
-History of profuse bleeding
-Hypotension
-Pale, cool, clammy skin
- Dry mucosas (Tounge, no tears)
- Depresed fontanelles (children)
-Delayed capillary refill

CIRCULATION:
Then: Restore volume ASAP
[Link] IV lines (16-Gauge)
2. Plenty liquids:
Ringer lactate
Normal saline
Blood
3. If not enough, third line in
saphenous vein
4. Children <4y/o Intraosseus in tibia
or frontal

CIRCULATION:
Possible causes:
- Trauma in abdomen or thorax (not in
cranium, not enough space to cause
shock)
- Bleeding (obstetric, big wounds)
- Dehydration (deprivation)
- Hyper urination (DI, diuretic overuse)

CIRCULATION:
Then: Control of hemorrhage
- Direct pressure
- Clamping artery
- Curettage if obstetric

GENERAL:

SHOCK
SEPTIC

DUE TO

SKIN

BACT.
TOXIN

WARM

CO

SVO2

SVR PCWP

HIGH

HIGH

LOW

LOW

VOLUME BLEEDING PALE

LOW

LOW

HIGH

LOW

CARDIO HYPO

PALE
MOTILITY COLD

LOW

LOW

HIGH

HIGH

VAGAL
REFLEX

LOW

LOW

LOW

LOW

LIQ. DEP

NEURO

COLD

WARM

1) All Trauma Patients: CS, Chest, Pelvic XR

2) If unstable, proceed to laparotomy
3) If abdomen cannot be examined: CT scan
of abdomen and pelvis w/ oral and IV
Contrast
4) Gunshot in abdomen: Laparotomy

CO: Cardiac Output

SVR: Sistemic Vascular Resistance
SVO2: Systemic Venous Oxigen
PCWP: Pulmonary Capilary Wedge Pressure

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BEST WAY ORGANIZATION:

From HEAD TO TOES

EPIDURAL HEMATOMA:
- Bleeding between skull bone and
dura mater
- Rupture of Middle Meningeal Artery
- PROGRESSION:
- Unconciusness
- Lucid interval
- Coma

EPIDURAL HEMATOMA:
- Anisocoria
- Bi-concave hematoma
- Tx:
1. After trauma, only image
w/o symptoms at all: OBSERVATION
2. Symptoms & Immage:
EMERGENCY SURGERY

EPIDURAL HEMATOMA:

SUBDURAL HEMATOMA:
-Bleeding between dura mater and
arachnoides
- Rupture of veins crossing subdural
space Bridging veins
- Image: Concave hematoma

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SUBDURAL HEMATOMA:
- SEEN TYPICALLY IN:
Elderly, demented, alcoholics

SUBDURAL HEMATOMA:

- Tx: [Link] small and no symptoms:

OBSERVATION
2. Affect mental status:
SURGERY

SUBARACHNOID HEMORRHAGE:
- Bleeding between arachnoides and
pia mater.
- MCC: TRAUMA followed by Ruptured
Berry Aneurism (HTN)
- Blood is seen in ventricles and
around brain (NOT IN BRAIN)

SUBARACHNOID HEMORRHAGE:
- MOST SEVERE EVER headache.
- Leaves sequelae like epilepsy,
blindness
- IF VIGNETTE LOOKS FOR Dg:
NEVER USE CONTRAST

SUBARACHNOID HEMORRHAGE:

SUBARACHNOID HEMORRHAGE:

Tx: If due to anaeurism or AV

malformation, SURGERY
Otherwise: Support, observation or
anti-convulsivats if needed.

-No mases
-No ventricules
-Deviation

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INTRACEREBRAL HEMORRHAGE
-Bleeding into brain parenchima
typically in basal ganglia.
-Due to Trauma, HTN, tumor.
- IF VIGNETTE LOOKS FOR Dg:
NEVER USE CONTRAST

INTRACEREBRAL HEMORRHAGE
- Tx: Surgery is reserved for large
bleedings if they are accesible.

WHEN DO WE DECIDE FOR

SURGERY IN ANY CASE?

INTRACEREBRAL HEMORRHAGE

WHEN CT scan OR MRI SHOW

DEVIATION OF MIDDLE
LINE

DIRECT HEAD TRAUMA:

CONSECUENCE:
CONSECUENCE:

- Open or close head injury

- Increased Intracranial Pressure
- Reversible or Irreversible neuronal
damage
- DEAD

2
3

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What to do next?
- After ABCs finish PE w/ Glasgow
scale
- Look for signs of Intracranial
Hypertension:
- Decrease in the comma scale
- Anisocoria
- Signs of decerebration

What to do next?
- Elevate head
- Intubate and hyperoxigenate
- Lower CO2
- Mannitol
- Sedation

After stabilization:

DIFUSE AXONAL INJURY

- High speed injury with stretching or
shearing of brain tissue
- Immage shows petechial hemorrhages in
white matter tracts
- Associated with immediate deep coma,
cerebral edema and elevation of ICP
- High mortality

- CT scan
- XR of skull (look for fractures)
- If Open Wound (clean and close)

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DIVIDED IN TWO:

WHAT TO DO IN BLUNT TRAUMA:

- BLUNT TRAUMA

- PENETRATING TRAUMA

WHAT TO DO IN BLUNT TRAUMA:

-

If UNSTABLE: -EXPLORE
Respiratory compromise
Hematoma
Shock

WHAT TO DO IN PENETRATING TRAUMA

If STABLE: -Look for other symptoms

If patient OK then
REASURANCE

- Decide which ZONE is compromised

IF ZONE I & III

UNSTABLE:
1)A, B, C always first!
2) Surgical exploration

Necks base to mandibles angle III

Mandibles angle to Cricoid II
Cricoid to Clavicle I

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IF ZONE I & III

IF ZONE II

STABLE:
1) Endoscopy of: Respiratory tract
Esophago/Gastro
Artheries
2) Reassurance if nothing found

UNSTABLE:
1)A, B, C always first!
2) Surgical exploration
Always explore if
musculocutaneus platysma is
affected

IF ZONE II
UNSTABLE:

IF ZONE I & III

STABLE:
1) Endoscopy if hoarseness/hematoma:
Respiratory tract
Esophago/Gastro
Artheries
2) Reassurance if nothing found

Musculocutaneus
Platysma

488

PROBLEM

MISCELANEUS

SYMPTOM (CLUES)

TEST

TREATMENT

Rib Fracture

MCC of injury
Elderly
Fall

History
Pain w/ resp.
Hematoma/open
wound
Costochondral
junction middle
and lower ribs

CXR

Pain medication

Flail Chest

4 or more ribs
fractured in 2
places

Major trauma
Caves during
respiration and
bulges in
expiration

CXR

Anesthesia and rib

blockage, positive
ventilation and high
oxygen (avoid
barotrauma) surgical
stability not required

Cardiac
tamponade

Liquid between
heart and
pericardium, CA

Trauma, URI
Tachycardia
Hypotension
Pulsus paradoxus
JVD

Echocardiogram

Pericardiocentesis,
pericardial window

12

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PROBLEM

MISCELANEUS

SYMPTOM (CLUES)

TEST

TREATMENT

Pericarditis

Inflammation of
pericardium

URI
Friction rub

CXR,
echocardiogram,
EKG, CK MB (rule
out MI), ESR very
high

Treat cause, NSAIDS,

pericardiocentesis,
pericardiostomia

Pleuritis
(Pleuresy)

Inflammation of
pleura

URI, CA, LES, RA,

Irritants (asbestos),
Drugs
Stabbing pain
during inspiration

CBC,
thoracocentesis,
CXR, Chest echo

Treat cause, NSAIDS

Tracheal/
Bronchial
rupture

Violent trauma

Trauma, gunshot,
infection, object
Cough w/blood
Gas under need
skin of neck, chest

X-rays, CT scan

Object: rigid fiber optic

bronchoscopy to
retrieve object
Others: Surgery
if big plus chest tube w/
suction

PROBLEM

MISCELANEUS

SYMPTOM (CLUES)

TEST

TREATMENT

Hemothorax

Trauma, CA,
thorax surgery

Respiratory failure
TachycardiaAnxiet
y

CXR
Thoracocentesis
Analysis of fluid

Treat the cause

Stabilize, Stop bleeding,
Thoracic tube,

Trauma
(spontaneus)

Sudden sharp pain

on respiration,
Tachycardia,
cianosis, nasal
flaring, no air
movement

CXR, ABG

Treat the cause, drain

gas w/ needle if
emergency and later w/
thoracic tube

Sounds of bowel in
thorax (left) or no
air in left lung

CXR, Barium
swallow

Pneumothorax

Diaphragmatic
rupture

Trauma, only in
left side

Surgery

PROBLEM

MISCELANEUS

SYMPTOM (CLUES)

TEST

TREATMENT

Aortic rupture

Violent trauma,
deacceleration

Look for wide

mediastinum in
CRX

If CRX not
conclusive and
suspicious is
high, CT scan or
transesophageal
echo

Surgery

Pulmonary
contusion

Violent trauma

With flail chest or

rib fracture, but
crackles

CT scan, look for

atelectasia

Fluid restriction and

oxygen. Prolonged
symptoms possible
ARDS

Cardiac
contusion

Violent trauma,
CPR

Abnormalities in
ventricle to
contract
EKG right bundle
branch block)
Sinus tachycardia
Ventricular
dysrhythmia

EKG
Echocardiogram

Supportive
EKG monitorization

Trachea

Expansion

Breath Sounds

Percussion

Tension
Pneumothorax

Away

Decreased.
Chest may be fixed
in hyper-expansion

Diminshed or
absent

Hyper-resonant

Simple
Pneumothorax

Midline

Decreased

May be diminished

May be hyperresonant. Usually

normal

Haemothorax

Midline

Decreased

Diminished if large.
Normal if small

Dull, especially
posteriorly

Pulmonary
Contusion

Midline

Normal

Normal. May have

crackles

Normal

Lung collapse

Towards

Decreased

May be reduced

Normal

CARDIAC TAMPONADE

PNEUMOTHORAX

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AORTIC DISECTION

BRONCHIAL RUPTURE

INSPIRATION

DIAPHRAGMATIC RUPTURE

EXPIRATION

FLAIL CHEST

ACUTE ABDOMEN: Sudden, severe

abdominal pain that is less than 24
hours in duration

490

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IMPORTANT POINTS: ALWAYS

1)
2)
3)
4)
5)

LOOK FOR CLUES:

PROBLEM

MISCELANEUS

SYMPTOM (CLUES)

TEST

TREATMENT

Appendiscitis

Inflamation of
apendix, young
people.
Causes:
Inflamation
Fecalith
Parasite
Trauma
Complication:
peritonitis

First periumbilical
and then iliac
fossa (migration)
Tender Mc.
Burneys point,
Rovsings sign,
Obturator sign,
Psoas sign, fever,
anorexia and
vomit

CBC (infection)
Normally clinical,
and only atypical
cases CT scan or
ultrasound to rule
out ectopic
pregnancy or
pregnant ladies

Laparoscopy,
laparotomy

Due lith in
cystic duct
leading to stasis

Famous FFFs
Pain after fatty
meals radiate to
shoulder

ALK Phos.
Elevation, CBC,
Ultrasound. Best
diagnosis is CT
scan. HIDA if
suspect and
negative US

If acute: surgery
If septic shock:
percutaneus
drainage
If not acute:
elective surgery

Cholecystitis

PROBLEM

MISCELANEUS

SYMPTOM
(CLUES)

TEST

TREATMENT

Pancreatitis

Peptic ulcer perforation

Alcohol
Neoplasm
Cholelithiasis, CF
Renal Dz
ERCP
Anorexia
Trauma
Infection
Toxins: Prils, HIV, ASA
Incinerations
Scorpion bite

Epigastric pain
radiating to the
back (belt)
Cullens sign:
Periumbilical
Turners sign:
Flanks

High Sens:
Amylase
High Spec:
Lipase
CT Scan

If cyst> 5Cm
Dranaige
If due to
obstruction: ERCP
Pancreatic CA:
Surgery bad prog

Due to Shock, Atrial fib.

Hypercoagulable state
Watershed area SMA and
IMA pancreatic flexure

Bowel
distention, and
bloody diarrhea,
bowel sounds
will be absent

Intestinal
Ischemia

1)
2)
3)
4)
5)
6)

NPO to reduce risk of aspiration

NG tube to decompress abdomen
IV hydration/ secure via
Analgesia (meperidine)
Abdominal X-RAY

Neutrophilic
leucocitosis (left)
increase amylase.
CT scan Air in
bowel and
inflamation of
watershed area

How and why of pain, how often

Time of iniciation (cronic or acute)
Localization and Progresion
Irradiation
Scale of pain and type
AGE, GENDER

DIFFERENTIAL DIAGNOSIS
PROBLEM

Surgery

491

SYMPTOM (CLUE)

TEST

Biliary colic

Cystic duct blocked. Sharp and constant pain

without fever. Negative Murphy's sign.

LFT WNL. Ultrasound

Cholecystitis

Cystic duct blocked with infection. Colicky

brief pain at first, then constant pain in RUQ
with fever caused by E coli, klebsiella,
pseudomonas, B fragilis, enterococcus.
Murphy's sign positive.

Increased AST, ALT, AP,

WBC.
Ultrasound

Choledocholithiasis

Common bile duct blocked. Colicky pain.

Jaundice.

Increased bilirubin.
Cholangiogram, ERCP

Cholangitis

Infection of entire biliary tract. Charcot's triad.

Jaundice and fever

Increased AST, ALT, AP,

bilirubin. Cholangiogram

PROBLEM

MISCELANEUS

SYMPTOM (CLUES)

TEST

TREATMENT

Diverticuliti
s

Older people w/
diverticulosis becames
inflamed and
perforated(bulging of
colon walldue to
weakness) low fiber diet,
family history.

Left Lowe Q pain,

leucocitosis, fever

CT scan, No
enemas or
contrast

First episode: IV
fluids and
antibiotics
Subsequent:
Surgery

Ectopic
Pregnancy

Prior PID

Acute L R or L Q
pain, acute,
maybe shock
(rupture)
localized in area.
Vaginal bleeding,
cullen sign

Positive pregnancy
test, Ultrasound
for evidence

laparoscopy and
laparotomy

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PROBLEM

MISCELANEUS

SYMPTOM
(CLUES)

TEST

TREATMENT

Peritonitis

Inflamation of peritoneum
due to perforation

Pain, tenderness
and guarding,
rebound
Complication of
rupture of
viscera

CBC leucocitosis
Plain AXR,
edematous
vicerae, air. Lavage
if doubt

Stabilization with
IV liquids, correct
acidosis and
electrolite
imbalance,
Surgery,
antibiotics broad
spectrum

Volvulus

Malrotation of midgut,

Bowel
obstruction and
distension and
vomitus. No
passage of
gases, intestinal
silence.

Abdominal X-ray,
upper GI series

Surgery, correct
rotation, if
necrosis resection
of portion.

PANCREATITIS

APPENDISCITIS

CHOLECYSTITIS

PELVIC FRACTURE:

PERITONITIS

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PELVIC FRACTURE:
1)
2)
3)
4)

HAND

Stabilize patient
Military Antishock Trousers
Fixate externally
If blood loss, Embolize

HAND:

HAND:

Sacaphids: Avascular necrosis

Hamate: Rupture of hook, nerve damage
(Ulnar)

BOXERS FRACTURE
Tx:
Mild: Immobilize
Severe: Surgery w/ pins

ARM:

ARM:

Tx:

- Alignement
- Analgesia
- Close reduction: No complication, no skin break
- Open reduction: Intra-articular fracture is displaced
ORIF
Closed reduction was ineffective
Fracture traverses a cancerous lesion
When prolonged immobility
- Surgery: If artery damage is suspected

493

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- COMPARMENT SYNDROME:

- COMPARMENT SYNDROME:

Due to inflamation of tissues

underneed the skin or fascia
Nerve and circulation compression
OPEN THE AREA!

- GANGRENE:
Infection due to deep entrance of
bacteria to body (diabetic foot, nail)

- GANGRENE:

AMPUTATION!

- OPEN FRACTURES:
Clean the area w/ saline and
pressure
2) Verify if nerves or circulations are
intact
3) If < 6 hours, SUTURE AND REDUCT
IN OR

- OPEN FRACTURES:

1)

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- DISLOCATION OF HIP: Shorten leg,

un-anatomical position.

- DISLOCATION OF HIP:

1) Correct position
2) Emergency Reduction

FEVER:
DAYS

Famous W

LUIDA

NEUROLOGICAL:
-Hypoxia
ARDS
Post- anesthesia
-Delirium Tremens
-Water intoxication: HypoNA
HyperNA

CAUSE

DAY 1

WIND

LUNGS

Pneumonia,
Atelectasis

DAY 3

WATER

URINE

UTI

DAY 5

WOUND

INFECTION

S. Aureus

DAY 7

WALK

DVT

DAY 10

WONDER WHY

Abscess

NEPHROGENIC:
-Post Surgery Urinary Retention
-Hypovolemia
-Clamping of ureter

ABDOMINAL:
- Paralysis of intestine (Ogilvie Synd)
- Adhesions
- Paralytic Ileus due to Anesthesia

495

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INFECTION:

Do you understand that ABCs always

is first?
Can you do differential diagnosis?
Do you know what to do first?
Do you have a sequence of thinking?
Do you know basically the treatment?
Are you consistent with your thought
process?

1)Find the cause with multiple culture

2) Antibiotic Therapy

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ANTIBIOTICS
What is an antibiotic?
An agent that inhibits the growth or multiplication
of, or kills, a living organism; usually used in
reference to bacteria or other microorganisms.

Who invented them?

Alexander Fleming, in 1928 is the one who
purified PENICILLIN.

THE CAT?
PURE LUCK?

Who is the genius?

Of course not
OR

1
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BASIC PRINCIPLES
FOR
PHARMACOTHERAPIE

TYPES OF
ANTIBIOTICS
Cell Wall Inhibitors
P
Protein
i Synthesis
S h i IInhibitors
hibi
Metabolite Inhibitors
Special Function Inhibitors

Learn MOA
Learn SIDE EFFECTS

Dont kill a mosquito with a gun

Cost Benefits law

CELL WALL INHIBITORS

Where do you get the molds?

1.-- Penicillin
1.
- Oxa,
Oxa, cloxa dicloxa,
dicloxa, nafi
nafi-- CILLIN
- Ticarcillin
- Aztreonam
2.-- Cephalosporins
2.
3.-- Carbipenems
3.
4.-- Vancomycin
4.

1.--PENICILLINE
1.

1.--PENICILLINE
1.

2
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1.--PENICILLIN
1.

1.--PENICILLINE
1.

1.
1.-- Binds to PBP

1.
1.-- Binds to PBP

2 - Disrupt cell wall

2.2.
3.
3.-- Provoke apoptosis

1.-- PENICILLIN
1.

1.--PENICILLIN
1.
2.
2.-- Disrupt cell wall
3.
3.-- Provoke apoptosis

1.--PENICILLINE
1.

1.--PENICILLIN
1.

What does it
kill?
Staph. Aureus
Staph. Epidirmidis
Staph. Saprophiticus
Strep. Pneumoniae
Strep. Pyogenes
Strep. Sanguis
Strep. Mutans
Strep. Agalactiae

Bacillus
Clostridium
Klebsiella
Neisseria
Citrobacter
P. Auroginosa
H. Influenza B
Actinomyces israelii

3
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1.--PENICILLIN
1.

1.-- PENICILLIN
1.

Or, if you dont remember:

Side effects:
1.- Typical: Anemia, Vomiting,
[Link] Alopecia
Diarrhea,
Alopecia, Photosensitivity
Photosensitivity.

GRAM +
Capsulated bacteria

2.-- Special: Allergie

2.

1.-- PENICILLIN
1.

1.-- PENICILLIN
1.
Resistance:
- Mutate PBP, so drug cannot bind
- Thicker
Thi k membranes,
b
so ddrug
cannot get in
- Mutate or destroy the drug with an
enzyme

Typical side effects:

D to d
Due
destruction
i off R
Rapidly
idl
dividing cells

1.-- PENICILLIN
1.

1.-- PENICILLIN
1.
Oxa, Cloxa,
Oxa,
Cloxa, Dicloxa
Dicloxa,, Nafi CILLIN
1.-- MOA Same as penicillin
1.
2.-- BULKIER - R - Ring
2.

4
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1.-- PENICILLIN
1.

1.-- PENICILLIN
1.

What does it mean?

- Penicillinase cant bind to
the R group for being huge
so the antibiotic wont get
deactivated and will attach
PBP

What do you kill with them?

- Staph.
S h Aureus
A

1.-- PENICILLIN
1.

1.-- PENICILLIN
1.

Can you kill OTHER gram

positives and capsulated
bacteria?

WHY?
You could use simple
penicillin for that
that

YES !
Do you kill them w/ Naficillin
Naficillin??
NO !

Dont kill a Mosquito with a gun!

1.-- PENICILLIN
1.

1.-- PENICILLIN
1.

AMPICILLIN Vs. AMOXICILLIN

AMPICILLIN Vs. AMOXICILLIN

5
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1.-- PENICILLIN
1.

1.-- PENICILLIN
1.

AMPICILLIN Vs. AMOXICILLIN

Ampicillin
- 80% off d
drug deactivated
d
i
d with
ihP
P--450
Amoxicillin
- Gets ACTIVATED with PP-450

AMPICILLIN Vs. AMOXICILLIN

- Ampicillin
Ampicillin:: Adults

1.-- PENICILLIN
1.

1.-- PENICILLIN
1.

AMPICILLIN Vs. AMOXICILLIN

AMPICILLIN Vs. AMOXICILLIN

A
Amoxicillin
i illi + Cl
Clavulanic
l i ac.:
To inhibit B
B--Lactamase

Amoxicillin: Children
Liver failure

MOA SAME
MOA:
SIDE EFFECTS: SAME

1.-- PENICILLIN
1.

1.-- PENICILLIN
1.

AMPICILLIN Vs. AMOXICILLIN

Bugs to kill:
G
Gram
+
Capsulated bacteria
E. Coli?

Ticarcillin::
Ticarcillin
T kill PSEUDOMONA
To
PSEUDOMONA

6
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1.-- PENICILLIN
1.

1.-- PENICILLIN
1.

Ticarcillin:
Ticarcillin:
WHY?

Ticarcillin:
Ticarcillin:
WHY?

1.-- PENICILLIN
1.

1.-- PENICILLIN
1.

Ticarcillin::
Ticarcillin

AZTREONAM:
For GRAM
S
Same
principle:
i i l If you would
ld kill
a Gram+, then use a smaller
weapon
SIDE EFFECTS: SAME

Pseudomona
P d
i li
is
lion attacking,
ki
so you need a big riffle to kill it
SIDE EFFECS: SAME

2.-- CEPHALOSPORINS
2.

2.-- CEPHALOSPORINS
2.

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2.-- CEPHALOSPORINS
2.
1st gen

2de ggen

3th gen

4th gen

2.-- CEPHALOSPORINS
2.

Cephalexin, cefazolin

MOA: SAME AS PNC

SIDE EFFECTS
EFFECTS: SAME

Cefuroxime, cefotetan

Ceftriaxone, cefotaxime

Cefepime

2.-- CEPHALOSPORINS
2.

2.-- CEPHALOSPORINS
2.

3.-- CARBAPENEMS
3.

4.-- VANCOMYCIN
4.

THIS IS A BAZOOKA FOR

TERRORISTS
IMIPENEM/CILASTATIN
- To inhibit renal dihidropeptidase
MOA: SAME
SIDE EFFECTS: SAME
$ 450 a vial QUID X 10 days

Inhibits cell wall of ALL GRAM+

MOA: Inhibit cell wall
mucopeptide formation gen
D-ala D-ala
Resistance: mut.
mut. DD-ala to DD-lac

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PROTEIN SYNTHESIS
INHIBITORS

4.-- VANCOMYCIN
4.
RED MAN SYNDROME:
- Pretreat w/ antihistaminics
-LOWER INFUSSION

A good business:
BUY
A
30s
T

C
E
50s
L
L

PROTEIN SYNTHESIS
INHIBITORS

PROTEIN SYNTHESIS
INHIBITORS

PROTEIN SYNTHESIS
INHIBITORS

PROTEIN SYNTHESIS
INHIBITORS

OR

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PROTEIN SYNTHESIS
INHIBITORS

PROTEIN SYNTHESIS
INHIBITORS

A good business: Chloramphenichol

BUY
Erithomycin
Aminoglucosides
(Macrolides
Macrolides))
Tetracyclins
cLindamycin

Aminoglucosides:
Aminoglucosides:
-Gentamicin,
Gentamicin, amikacin,
amikacin, streptomycin
-MOA: Inhibit Initiation complex
-Bactericidal
-Potentiation w/
w/ampicillin
ampicillin

Linezolid

PROTEIN SYNTHESIS
INHIBITORS

PROTEIN SYNTHESIS
INHIBITORS
Tetracyclins:
Tetracyclins:
-Doxicycycline:
Doxicycycline: Lyme, Tularemia,
Francicella (Fecally excreted)
-Minocycline:
Minocycline: Propionebacterium Acne
(Not even excreted)
-Demeclocycline:
Demeclocycline: SIADH ((Neprotox
Neprotox))

Aminoglucosides: (CONT.)
Aminoglucosides:
- SIDE EFFECTS: SAME
- PLUS: Ototox and Nephrotox

PROTEIN SYNTHESIS
INHIBITORS

PROTEIN SYNTHESIS
INHIBITORS

Tetracyclins:: (CONT.)
Tetracyclins

Tetracyclins::
Tetracyclins

-MOA:
MOA Inhibiting
I hibi i the
h binding
bi di off
aminoacyl--tRNA to the mRNA
aminoacyl
mRNA-ribosome complex.
-Bacteriostatic

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PROTEIN YNTHESIS
INHIBITORS

PROTEIN SYNTHESIS
INHIBITORS

Tetracyclins::
Tetracyclins

Chloramphenichol:
Chloramphenichol:
- MOA: Inhibit peptide bond at 50s
- I
Inhibit
hibi P
P--450
- NOT IN USA
- SIDE EFFECTS: SAME
Plus: BM Sup. A. Anemia, GBSynd.
GBSynd.

SIDE EFFECT:
EFFECT
[Link]: Ototox Nephrotox

PROTEIN SYNTHESIS
INHIBITORS

PROTEIN SYNTHESIS
INHIBITORS

Erithromycin: MACROLIDES
Erithromycin:
- Clarithrmomycin
Clarithrmomycin,, azithromycin
- Inhibit
I hibi translocation
l
i by
b reversibly
ibl
binding to 23s portion of 50s.
- Bacteriostatic

Erithromycin: MACROLIDES (CONT.)

Erithromycin:
- Tx for: Atypical pneumonia
(Mycoplasma
Mycoplasma)),
Mycoplasma),
) Chlamydia 2g,
2g N.
N
Gonorhea 1g. ((azithromycin
azithromycin))

PROTEIN SYNTHESIS
INHIBITORS

PROTEIN SYNTHESIS
INHIBITORS

cLindamycin:
cLindamycin:
- MOA: Inhibit elongation factor of
50s
- Uses: Anaerobes above diapragm
- SIDE EFFECTS: SAME
Plus: (before) No1. for Pseudo. Colitis

Linezolid:
Linezolid:
- MOA: Inhibit initiation of 50s AND
30s
- MRSA w/ resistance to Vanco
- DONT USE IT...Like pressing the
RED BUTTON

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PROTEIN SYNTHESIS
INHIBITORS

METABOLITE
INHIBITORS

cLindamycin:
cLindamycin:
- MOA: Inhibit elongation factor of
50s
- Uses: Anaerobes above diapragm
- SIDE EFFECTS: SAME
Plus: (before) No1. for U. Colitis.

To destroy nucleotides:

To destroy nucleotides:
What is a nucleotide?

To destroy nucleotides:

To destroy nucleotides:

S-ADENOSYLADENOSYL-METHIONINE (SAM)
Methilate or differentiate the nucleotides
All of them.
Except: T (thimidine
(thimidine),
thimidine)),
) who is methilated
by Folic Acid

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METABOLITE
INHIBITORS

To destroy nucleotides:
5-FU

dUMP

TRIMETHOPRIM
MOA: Inhibit DHF
Works?....Not at allAlone

Thymidylate synthase

dTMP
CH2-THF

DHF
THF

DHF reductase
TMX/SMX
OR MTX

METABOLITE
INHIBITORS

METABOLITE
INHIBITORS

SULFONAMIDES
MOA: Inhibit Dihydropteroato
synthetase
Works?....Not at allAlone

BUT:TMX + SMX
Good for: UTI, Prof and tx of
Pneumocystis Carinii
Carinii,, Shigella
and Salmonella.

METABOLITE
INHIBITORS

METABOLITE
INHIBITORS
SIDE EFFECTS: SAME
The same as B9 defficiancy
- Neural pores non
non--fusion
- Megaloblastic anemia
- Kernikterus in neonates

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SPECIAL FUNCTION
INHIBITORS

SPECIAL FUNCTION
INHIBITORS

QUINOLONES:
MOA:Antitopoisomerase II
Inhibit WindingWinding- unwinding

Topoisomerase

SPECIAL FUNCTION
INHIBITORS

SPECIAL FUNCTION
INHIBITORS

NAMES:
Cipro
Levo
Levo
FLOXACIN
Gati
Nor

SIDE EFFECT:
Besides typical:
- Tendonitis
T d i i or tendon
d rupture
- Myalgia in kids

SPECIAL FUNCTION
INHIBITORS

SPECIAL FUNCTION
INHIBITORS

METRONIDAZOLE:

METRONIDAZOLE:
C
Covers:
M
Monocelular
l l parasites:
i
G. Lamblia
Lamblia,, E. Hystolitica,
Hystolitica, G.
Vaginalis,, anaerobes below
Vaginalis
diapragm.. T. Terapie H. Pylori.
diapragm

MOA: Free radicals and toxic

metabolites formation.

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ANTI TB DRUGS

ANTI TB DRUGS

RIFAMPIN: MOA:Inhibit

RIFAMPIN:

DNA dependent RNA

pol merase Crosses BBB.
polymerase,
BBB
PROF. TB and N. Menigitidis
SIDE EFFECT: Hepatotoxic
(Frecuent LFT)

Enhances PP-450
Orange body fluids.

ANTI TB DRUGS

ANTI TB DRUGS

Ethanbutol:
thanbutol: MOA: Obstructs

Ethanbutol:
thanbutol:

cell wall formation by disrupting

arabinogalactan ssynthesis,
nthesis
increases permeability of cell
wall.

SIDE EFFECT:
-Optic neuritis
-Red
Red--green color blindness
-Peripheral neuropathy
-Arthtalgia

ANTI TB DRUGS

ANTI TB DRUGS

Streptomycin: Aminoglucoside

Pyrazinamide
yrazinamide:: MOA: Stops TB
growth by, in acid media,
media,
ihibiting enzime fatt
fatty acid
synthetase..
synthetase
SIDE EFFECTS: Arthralgia
Arthralgia,,
hepatotoxicity..
hepatotoxicity

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10/13/2008

ANTIFUNGAL
THERAPY

ANTI TB DRUGS

Amphotericine B:
MOA : Binds to ergostyerol and
pokes the cell wall provoking
leakage of electrolites.
electrolites.

Isoniazid
soniazid:: MOA: Inhibit
synthesis of mycolic acid.
Enhances
h
PP-4450.
0
SIDE EFFECTS: Hemolys in
G6PD pts, hepatotoxicity
hepatotoxicity,,
neurotoxicity that can be
prevented w/ B6.

ANTIFUNGAL
THERAPY

ANTIFUNGAL
THERAPY

Amphotericine B:
Used in systemic mycosis
SIDE EFFECTS
EFFECTS: H
Hypotension,
i
fever and chills, flebitis if IV

ANTIFUNGAL
THERAPY

ANTIFUNGAL
THERAPY

Nystatin:: Same as Amphotericine B

Nystatin

Nystatin: SWISH AND SWALOW

Nystatin:
For oral candidiasis.
candidiasis.

SIDE EFFECTS
EFFECTS: O
Only
l used
d topycall
for being very toxic.

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512

10/13/2008

ANTIFUNGAL
THERAPY

ANTIFUNGAL
THERAPY

Caspofungin: Disturb integrity of

Caspofungin:
Cell Wall Disruption.
Indication: Aparagillosis
Side effects: Increase Crea
Crea,,
hypokalemia,, hypersensitivity
hypokalemia

Azoles:

Caspofungin::
Caspofungin

ANTIFUNGAL
THERAPY

ANTIFUNGAL
THERAPY

AzoLE
AzoLEss:
MOA: Prevent conversion of
Lanosterol to Ergosterol by
inhibiting fungal P
P--450.
FUNGISTATIC!

-Flucon
-Ketocon
K
-Itracon

ANTIFUNGAL
THERAPY

ANTIFUNGAL
THERAPY

Terbinafine:
Terbinafine:
MOA: Inhibit Squalen epoxidase
USES Onicomycosis
USES:
O i
i
Bad cases: ORAL

AZOLES AND TERBINAFINE

Azoles

Terbinafine

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513

10/13/2008

ANTIFUNGAL
THERAPY

ANTIFUNGAL
THERAPY

Flucytosine
Flucytosine::
MOA: 1) Inhibit microtubules
2) Inhibit 55--FU
Consequence: Inhibit DNA Synt

Flucytosine
Flucytosine::
Side effecs
effecs:: Typical very strong
Plus: Hallucinations, psycosis,
psycosis,
peripheral neuropathie
neuropathie..

ANTIFUNGAL
THERAPY

IN ONE GRAPH:

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514

10/13/2008

Objective

Biochemistry
Glycolysis, Gluconeogenesis
&TCA
Mong-Khanh Le, M.D.

Focus

Why Glycolysis?

Most used pathway in body

Turn food into energy
Start w/ Glu, Lactose, Fructose
Simple Vs Complex Carbo
Substrate = Glu and production = pyruvate
In cytosol (what does not have Mito will
depend solely on it for ATP!!!!)
Organ effected: RBC, B>>H>>K

Naming enzymes
Where it happens: cytosol vs mitochondria
energy usage and production
Regulations
Clinical significant Dzs
Connections!!!! AS ALWAYS

What is in our diet

USDA

Name Enzymes Review

% in Diet Converting Pathways

in Calorie

Carbohydrate 55%
P t i
Protein
15%
Lipid
30%(<10
% sat)
Alc
??????

4Kcal/g
4K l/
4Kcal/g
9Kcal/g
7Kcal/g

Glycolysis
Sucrose metabolism
Lactose metabolism
Gluconeogenesis
TriCarboxylic Acid Cycle (TCA)

Substrate=1st name

Glycolysis
TCA Urea
TCA,
U
FAsyn, Boxidation
TCA,
Lactate

What was done to substrate= 2nd part or

l t name
last

1
515

10/13/2008

Name Enz (cont)- Move around

Name Enz (cont)-Add stuff

Kinase= use ATP to add P, Mg cofactor.
Phosphorylase=Use free P adding to
substrate.
Carboxylase
Carboxylase= uses CO2 to add C,
C uses
ATP and Biotin.
Synthase= 2 substrates consumed in
reaction, named after product.
Synthetase= 2 substrates consumed.
Need ATP

Isomerase= create isomer, think Fructose

and Glucose
Epimerase= make epimer, differs around 1
chiral C (glu galactose)
Mutase= move P fr one C to another C
Transferase= move sidechain fr 1
substrate to another (interchain)

Name Enz (cont)-remove stuff

B-compx

Dehydrogenase= take out H+ with

coFactor (ie. Tender Loving Care For
Nancy).
Phosphatase= breaks phosphate bond
Hydrolase= break a bond with H2O
Lyase= cut C-C bond with cofactor
Thio= breaks S bond

Tender Loving Care For Nancy.

PLAN F.
Dzs.

Glycolysis

Glu Transport

Substrates=Glu and end products of

Sucrose and Lactose pathways (also fr
glycerol)
Final product: Pyruvate
9 steps
3 irrversible steps= Exclusive glycolysis
Triangle at mid way (4th reaction)

GLU 1 & 3: basal uptake most cells.

GLU 2: Storage (liver); Glucose sensor (Bislet)
GLU-4:
GLU 4 increase
i
by
b INSULIN iin ffatt and
d
muscle. Increase in exercising skeletal
muscle. (Fat, skeletal and heart)

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10/13/2008

Glycolysis

Glycolysis Regulations
HK: Most Tissues, low Km= works both in
fed and fast. Inhibited by its own product,
G-6-P.
GK: Liver only, High Km=works during fed
only. +++ by insulin
Why Glu has to be phospholation?

PFK-1

PKF-2

Rate Limiting Step

Stimulated by: AMP, F-2,6-BP, Insulin

(FIA)
Inhibited by: Citrate, ATP, PEP, Glucagon,
Acidosis (the GA CAP).

PK

Fruct-6-P to F-2,6BP fed state

F-2,6BP to Fruct-6-P fast state
Increases glycolysis
Decreases gluconeogenesis
Stimulated by Insulin
Inhibited by Glucagon

Glycolysis Regulations Recap

Enzymes Stimulated Inhibited

Stimulated by: F1,6-P, Insulin (FI)

HK

Inhibited by: Glucagon,

Glucagon Alanine,
Alanine
cAMP, ATP, AcetylCoA (GA AAA)

Comments

G6P

PFK-1

*AMP
*F-2,6-P
*Insulin

Citrate, ATP
PEP, Glucagon,
lowPH

Pyruvate
Kinase

*F1,6-P(feed
forward
pos=only
one in
Biochem)
*Insulin

Alanine,
Glucagon,
cAMP, ATP,
AcetylCoA

RLS

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10/13/2008

Glycolysis Dz: MODY

Glycolysis Dz=Chronic Hemolysis

Chronic Hemolysis dt RBC lacks of energy fr
glycolysis.
PK Def. leads to elev 1,3BPG, which can
convert to 2,3BPG.

O
Oxygen
curve shift
hift to
t R (incr
(i
Km,
K decr
d
Affinity).

Also elevate other glycolytic intermediates in

RBC (inhibition to many steps)

No Heinz bodies

AR

Mature Onset Diabetes of the Young:

Liver (= GK)
Glucokinase mutations leads slow down
glycolysis.
l
l i Pl
Plasma Gl
Glu iincreased.
d

Other Glycolysis Dz

Other Glycolysis Dz

Arsenate inhibits Glyceraldehyde-3-P

dehydrogenase

Phosphoglycerate kinase inhibited:

increase 1,3-BPG, which converted to 2,3BPG by RBC mutase decrease Hb
affinitive for O2 (shift to R,
R incre Km)

Fl
Fluoride
id inhibits
i hibit E
Enolase:
l
Shiny
Shi white
hit
teeth

Other Glycolysis Dz

Other Glycolysis Dz

Glyceraldehyde-3-P: has disulfide bonds

which can be disrupted by Alc.
Also Mercury can inhibit sulfur group of
enzyme (brain,
(b i llung, kid
kidney))

ANY glycolysis enz def= HEMOLYSIS

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10/13/2008

Glycolysis Connections

Sucrose/Fructose Metabolism

In anaerobic state, production of lactate

and NADH reoxidized back to NAD+.
In RBC (no mitochrondria) turns to LDH
solution Lactate pathway.
pathway
What are 3 enz exclusively from
glycolysis?
Net fr 1 Glu= 2 pyruvate + 2ATP +2NADH

Fructose

Fruits
3 reactions
End products: Glu, DHAP, GA3P
Continues with Glycolysis after trio Rx

Fructosuria
Essential Fructosuria: FructoKinase Defpolydipsia, polyuria, and UTI. BENIGN.
Fructose Intolerance: Aldolase B def.
[Link], liver and proximal renal tubular
disorder.
When Fruc-1-P accumulated, it inhibits Glu
production causing severe Hypoglycemia.

Point Upon Wonder

Lactose/Galactose

Why Fructose Intolerant Pt has

hypoglycemia when we give them
fructose?
Why DM can eat fruit without increase
their plasma Glu?
Why diet people can eat lots of fruit w/o
gain wt?

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519

10/13/2008

Galactose Recap

Lactose Intolerant

End with: Glu-1-P and Glu. Both feed into

Glycolysis
Uses 1ATP
4 reactions
ti
Enzymes: lactase, GK, G-1-P UT

Type 1 Galactosuria

Latase Defieciency
Osmotic diarrhea
Bloated, pain
Rx: Avoid Soy milk or Latase added
milk.

Type 2 Galactosemia
Type 2 (Classical) Galactosemia
Gal-1-P Uridyl transferase Def.
Increase Gal-1-P will inhibits P-Glu Mutase,
which interferes with glycogen syn and
d
degradation
d ti
H
Hypoglycemic.
l
i
Excess converted to Galactitol via aldose
reductase causes cataract.
More severe addition to above. Vomit/diarrhea/
liver/ lethragy/ MR.
Rx: avoid

Type 1 (Non Classical)

Galactokinase def.
Galactosemia<< galactosuria (polydip &
polyuria
l i with
ith UTI!!!!)
UTI!!!!).
Excess converted to Galactitol via aldose
reductase causes cataract.
Rx: avoid

Clinic Test

Galactose Connections

Glu has OH which can be reduced for a

positive test in cases of excess Glu
Galactosuria and Fructosuria are urine pos
test
If stool pos test = malasorption, osmotic
diarrhea or inflammation
Also called reducing substance

Babies need a lot of milk (rich lactose)

because of baby uncoupling its ECT.
UDP-Gal can reenter the pathways
If lactose intolerant: Soy milk

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520

10/13/2008

Point upon wonder

Gluconeogenesis
A de novo synthesis of Glu from 3C and
4C precusors.
4 irreversible steps
In both Mitochondria and Cytoplasm
Cytoplasm.
Occur during fasting state, glycogen
depleted.
Mainly in Liver, Kindney, Adrenal Cortex
and intestinal epithelilium.
Provide Glu to brain and RBC.

Why galactosemia Type 2 pt has

hypoglycemia when we give them lactose?
C
Comparing
i G
Galactose,
l t
why
h F
Fructose
t
can
be given to baby at 6 months?

Gluconeogenesis

Regulation of Glyconeo.

Substrates are:
glucogenic aa (protein fr muscle)
Lactate (fr RBC and anaerobic exercise)
Glycerol 3 P (fr adipose tissue/
triacylglycerol)

Pyruvate carboxylase
=RLS*******

+ Acetyl CoA

*Anapleurotic enz.
*Biotin
*mitochodria

PEPCK

+ Glucagon
+ Cortisol

*GTP
*cytosol

F 1,6- BisPtase

+ ATP
- AMP
- F-2,6-BP (fr PFK2)

*Cytosol
* inhibited by insulin,
stim by glucagon.

Product: Glu

G6Ptase

Gluconeogenesis

*In ER; liver only.

(other tissue Glu with P
grp prevent Glu exit cell)

Von Gierke: G6Ptase deficiency

severe fasting hypoglycemia

Lactic acidosis
HyperLipidemia
Hyperuremia
short stature

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521

10/13/2008

Malate shuttle

Malate shuttle

To bring NADH (product fr glycolysis) into

mitochondria/ETC
T
To bring
bi
OAA (f
(fr pyruvate
t
OAA) into
i t
cytosol for gluconeogenesis

Viral Hepatitis vs. Alc Hepatitis

Pyruvate D.H. Complex

Viral = lyses/ effects cell membrane

AST to ALT is 1:1

Pyruvate
complex)

Acetyl CoA (Pyr D.H./ B

Alc = Lyses/effects cell mb and

mitochondria mb

AST to ALT is 2:1

P
Pyruvate
t
OAA (PC is
i in
i mitochondria
it h d i
matrix, not in muscle)
Inhibited by: ATP, NADH, Acetyl CoA

B complex=PLAN F

Why TCA???
Intermediates in fasting/ liver

B1= TTP- decarboxylase

B5=Lipoic acid- accepts acetyl grp
B4=CoA- final acetyl aceptor
B3=NAD- oxidizes FADH2 NADH
B2=FAD- oxidizes Lipoic acid FADH2

Intermediates in fed

Glu

Fatty Acid

Intermediates also use for syn AA or

converting one AA to another

DZs!!!!!!

Potentiate ATP product per Glu eat in!!!

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522

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TCA

TCA

In mitochondria
Cindy Is Kind So She Feeds Many
O h
Orphans
4 irreversible steps

TCA Regulation
Enzymes Stimulated Inhibited by
by

Link to other pathways

Comments

Citrate
Synthase

ATP

Isocitrate ADP
D.H.

ATP
NADH

Major RLS

Alpha KG
D.H.

Succinyl CoA
ATP
NADH

B complex
RLS

Malate Gluconeogenesis
Citrate FA synthesis
Oxaloacetate and Alpha-KG AA
synthesis
th i (Glutamate/GABA!!!!)
(Gl t
t /GABA!!!!)
Succinyl CoA Heme Synthesis
Fumarate urea cycle
Alpha KG all transaminases AST & ALT

TCA Recap

TCA Connections

In mitochondria= aerobic

No specific Dzs
Problem with TCA is a major low energy
state
No
N ATP

No Glu, AA, FA
No intermediates to other linked
pathways

Substrate: 1 Acetyl CoA + 3NAD + FAD

+GDP
GDP + Pi
Product: 2 CO2 + 3NADH + FADH2 +GTP
+ CoA
Net of 1 cycle of 1 Acetyl CoA= 12 ATPs

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523

10/13/2008

Summary 5 pathways

10
524

525

526

527

528