Haad extra notes

Arthritis: joint inflammation, all signs of inflammation

Arthralgia: joints pain with no signs of inflammation
Classification of dehydration

H. Pylori treatment
riple-therapy regimens
PPI-based triple therapy regimens for H pylori consist of a PPI, amoxicillin, and
clarithromycin for 7-14 days. A longer duration of treatment (14 d vs 7 d) appears to be more
effective and is currently the recommended treatment. Amoxicillin should be replaced with
metronidazole in penicillin-allergic patients only, because of the high rate of metronidazole
resistance.[43] In patients with complicated ulcers caused by H pylori, treatment with a PPI
beyond the 14-day course of antibiotics and until the confirmation of the eradication of H
pylori is recommended.

PPI-based triple therapies are a 14-day regimen as shown below:

Omeprazole (Prilosec): 20 mg PO bid

or
Lansoprazole (Prevacid): 30 mg PO bid

or

Rabeprazole (Aciphex): 20 mg PO bid

or

Esomeprazole (Nexium): 40 mg PO qd

Plus

Clarithromycin (Biaxin): 500 mg PO bid

and

Amoxicillin (Amoxil): 1 g PO bid

Alternative triple-therapy regimens

The alternative triple therapies, also administered for 14 days, are as follows:

Omeprazole (Prilosec): 20 mg PO bid

or

Lansoprazole (Prevacid): 30 mg PO bid

or

Rabeprazole (Aciphex): 20 mg PO bid

or

Esomeprazole (Nexium): 40 mg PO qd

Plus

Clarithromycin (Biaxin): 500 mg PO bid

and
Metronidazole (Flagyl): 500 mg PO bid

Quadruple therapy
Quadruple therapies for H pylori infection are generally reserved for patients in whom the
standard course of treatment has failed.

Quadruple treatment includes the following drugs, administered for 14 days:

PPI, standard dose, or ranitidine 150 mg, PO bid

Bismuth 525 mg PO qid
Metronidazole 500 mg PO qid
Tetracycline 500 mg PO qid
Consider maintenance therapy with half of the standard doses of H2-receptor antagonists at
bedtime in patients with recurrent, refractory, or complicated ulcers, particularly if cure of H
pylori has not been documented or if an H pylori –negative ulcer is [Link] bowl
syndromes
Rome II criteria for IBS: At least 3 months (consecutive) of abdominal pain with 2 out
of the following 3: Relief with defecation, change in form of stool or change in
frequency of stool. Symptoms that support the diagnosis abnormal stool frequency,
abnormal form, abnormal passage (straining, urgency, sense of incomplete defecation),
passage of mucous and bloating or feeling of distention. Absence of alarming features
which are weight loss, nocturnal defecation, blood or pus in stool, fever, anemia and
abnormal gross findings on flexible sigmoidoscopy.

TOPICS IN MCQS PANEL:

Neuroendocrine tumours
Neuroendocrine tumors Heterogeneous group of neoplasms originating from neuroendocrine
cells (which have traits similar to nerve cells and hormone-producing cells). Most neoplasms
occur in the GI system (eg, carcinoid, gastrinoma), pancreas (eg, insulinoma, glucagonoma),
and lungs (eg, small cell carcinoma). Also in thyroid (eg, medullary carcinoma) and adrenals
(eg, pheochromocytoma). Neuroendocrine cells (eg, pancreatic β cells, enterochromaffin
cells) share a common biologic function through amine precursor uptake decarboxylase
(APUD) despite differences in embryologic origin, anatomic site, and secretory products (eg,
chromogranin A, neuron-specific enolase [NSE], synaptophysin, serotonin, histamine,
calcitonin). Treatment: surgical resection, somatostatin analogue.
Carcinoid tumours
Carcinoid tumors arise from neuroendocrine cells, most commonly in the intestine or lung.
Neuroendocrine cells secrete 5-HT, which undergoes hepatic first-pass metabolism and
enzymatic breakdown by MAO in the lung. If 5-HT reaches the systemic circulation (eg, after
liver metastasis), carcinoid tumor may present with carcinoid syndrome—episodic flushing,
diarrhea, wheezing, right-sided valvular heart disease (eg, tricuspid regurgitation, pulmonic
stenosis), niacin deficiency (pellagra). Histology: prominent rosettes (arrow in A),
chromogranin A ⊕, synaptophysin ⊕. Treatment: surgical resection, somatostatin analog
(eg, octreotide) or tryptophan hydroxylase inhibitor (eg, telotristat) for symptom control.
Rule of thirds: 1/3 metastasize 1/3 present with 2nd malignancy 1/3 are multiple

First-pass metabolism
This is a phenomenon where the concentration of a drug is greatly reduced before it
reaches the systemic circulation due to hepatic metabolism. As a consequence much
larger doses are need orally than if given by other routes. This effect is seen in many
drugs, including: 1) Aspirin 2) Isosorbide dinitrate 3) GTN Glyceryl trinitrate 4) Lignocaine
5) Propranolol 6) Verapamil 7) Isoprenaline 8) Testosterone 9) Hydrocortisone

Sperm
Normal sperm densities range from 15 million to greater than 200 million sperm per milliliter
of semen. You are considered to have a low sperm count if you have fewer than 15 million
sperm per milliliter or less than 39 million sperm total per ejaculate.

Thrombolysis
Thrombolysis should only be given if: It is administered within 4.5 hours of onset of stroke
symptoms (the thrombolytic window) (unless as part of a clinical trial). Haemorrhage has
been definitively excluded (i.e. Imaging has been performed). Alteplase (tPA) is currently
recommended by NICE. Stroke thrombolysis with tPA >> only consider if less than 4.5 hours
and haemorrhage excluded. The National Institute of Neurological Disorders and Stroke
(NINDS) issued a protocol with inclusion and exclusion criteria for tPA: Their inclusion criteria
were: 1) Age over 18 2) Clinical diagnosis of acute ischaemic stroke 3) Known time of onset
4) CT scan consistent with diagnosis, and 5) Treatment can be given within 180 minutes
(though some physicians treat after this period). Their exclusion criteria included: 1)
Intracranial haemorrhage on CT scan 2) Symptoms minor or improving 3) Active bleeding at
any site 4) Gastrointestinal bleed in the last 21 days 5) Major surgery in last 14 days 6)
History of intracranial bleed 7) Serious head injury in last 3 months 8) Pregnancy, or 9)
Active pancreatitis.

Sickle cell anemia

A point mutation in β-globin gene single amino acid substitution (glutamic acid valine).
A point mutation in β-globin gene single amino acid substitution (glutamic acid valine).
Mutant HbA is termed HbS. Causes extravascular and intravascular [Link]:
low O2, high altitude, or acidosis precipitates sickling (deoxygenated HbS polymerizes)
anemia, vaso-occlusive [Link] are initially asymptomatic because of HbF and
[Link] (sickle cell trait) have resistance to [Link] common autosomal
recessive disease in Black [Link] cells are crescent-shaped RBCs A.“Crew cut” on
skull x-ray due to marrow expansion from erythropoiesis (also seen in
thalassemias).Complications in sickle cell disease: Aplastic crisis (transient arrest of
erythropoiesis due to parvovirus B19). Autosplenectomy (Howell-Jolly bodies) risk of
infection by encapsulated organisms (eg, S pneumoniae). Splenic infarct/sequestration
crisis. Salmonella osteomyelitis. Painful vaso-occlusive crises: dactylitis (painful swelling of
hands/feet),priapism, acute chest syndrome (respiratory distress, new pulmonary infiltrates
on CXR, common cause of death), avascular necrosis, stroke. Sickling in renal medulla ( Po2)
renal papillary necrosis [Link] electrophoresis: HbA, HbF, [Link]:
hydroxyurea ( HbF), hydration.

poststreptococcal glomerulonephritis
Acute poststreptococcal glomerulonephritis Nephritic syndrome = inflammatory process.
Most frequently seen in children. ~ 2–4 weeks after group A streptococcal infection of
pharynx or skin. Also called postinfectious glomerulonephritis when caused by non-
streptococcal pathogens. Resolves spontaneously in most children; may progress to renal
insufficiency in adults. Type III hypersensitivity reaction. Presents with peripheral and
periorbital edema, tea or cola-colored urine, HTN. ⊕ strep titers/serologies, complement
levels (C3) due to consumption. LM—glomeruli enlarged and hypercellular A IF—(“starry
sky”) granular appearance (“lumpy-bumpy”) B due to IgG, IgM, and C3 deposition along GBM
and mesangium EM—subepithelial IC hump

Recent poststreptococcal infection is most commonly demonstrated by serologic markers for

elevated antibodies to extracellular streptococcal antigens. The streptozyme test, which
measures 5 different streptococcal antibodies, is positive in more than 95% of patients with
APSGN due to pharyngitis. However, sensitivity drops to 80% if APSGN follows pyoderma.
The streptococcal antibodies measured include the following:
Antistreptolysin (ASO)
Antihyaluronidase (AHase)
Antistreptokinase (ASKase)
Antinicotinamide-adenine dinucleotidase (anti-NAD)
Anti-DNAse B antibodies

Inflammatory bowl disease

Inflammatory bowl disease
= crohn disease and ulcerative colitis

Crohn disease

Location Any portion of the GI tract, usually the terminal ileum and colon. Skip lesions, rectal
sparing.

Gross morphologyTransmural inflammation fistulas. Cobblestone mucosa, creeping fat,

bowel wall thickening (“string sign” on small bowel follow-through A), linear ulcers, fissures

miCrosCoPiC morPHologyNoncaseating granulomas and lymphoid aggregates. Th1

mediated.

ComPliCationsMalabsorption/malnutrition, colorectal cancer ( risk with pancolitis). Fistulas

(eg, enterovesical fistulae, which can cause recurrent UTI and pneumaturia), phlegmon/
abscess, strictures (causing obstruction), perianal disease.

intestinal maniFestationDiarrhea that may or may not be bloody.

eXtraintestinal maniFestationsRash (pyoderma gangrenosum, erythema nodosum), eye

inflammation (episcleritis, uveitis), oral ulcerations (aphthous stomatitis), arthritis
(peripheral, spondylitis). Kidney stones (usually calcium oxalate), gallstones. May be ⊕ for
anti-Saccharomyces cerevisiae antibodies (ASCA).

treatmentCorticosteroids, azathioprine, antibiotics (eg, ciprofloxacin, metronidazole),

biologics (eg, infliximab, adalimumab)

Sweat glands
Sweat glands, also known as sudoriferous or sudoriparous glands, from Latin sudor 'sweat',
are small tubular structures of the skin that produce sweat.
Sweat glands are a type of exocrine gland, which are glands that produce and secrete
substances onto an epithelial surface by way of a duct.
There are two main types of sweat glands that differ in their structure, function, secretory
product, mechanism of excretion, anatomic distribution, and distribution across species

1) Eccrine sweat glands are distributed almost all over the human body, in varying densities,
with the highest density in palms and soles, then on the head, but much less on the trunk and
the extremities. Its water-based secretion represents a primary form of cooling in humans.

2) Apocrine sweat glands are mostly limited to the axillae (armpits) and perineal area in
humans. They are not significant for cooling in humans, but are the sole effective sweat
glands in hoofed animals, such as the camels, donkeys, horses, and cattle.

Eccrine sweat glands are everywhere except the lips, ear canal, prepuce, glans penis, labia
minora, and clitoris.

Hypopituitarism SEcTion
Undersecretion of pituitary hormones due to:

Nonsecreting pituitary adenoma, craniopharyngioma

Sheehan syndrome—ischemic infarct of pituitary following postpartum bleeding; pregnancy-

induced pituitary growth susceptibility to hypoperfusion. Usually presents with failure to
lactate, absent menstruation, cold intolerance

Empty sella syndrome—atrophy or compression of pituitary (which lies in the sella turcica),
often idiopathic, common in obese females; associated with idiopathic intracranial
hypertension

Pituitary apoplexy—sudden hemorrhage of pituitary gland, often in the presence of an

existing pituitary adenoma. Usually presents with sudden onset severe headache, visual
impairment (eg, bitemporal hemianopia, diplopia due to CN III palsy), and features of
hypopituitarism

Brain injury

Radiation

Treatment: hormone replacement therapy (corticosteroids, thyroxine, sex steroids, human

growth hormone)

Cushing syndrome

Etiology: increase cortisol due to a variety of causes:

Exogenous corticosteroids DeCreases ACTH —->bilateral adrenal atrophy. Most common
cause.

Primary adrenal adenoma, hyperplasia, or carcinoma —-> decrease ACTH —>atrophy of

uninvolved adrenal gland.

ACTH-secreting pituitary adenoma (Cushing disease); paraneoplastic ACTH secretion (eg,

small cell lung cancer, bronchial carcinoids) bilateral adrenal hyperplasia. Cushing disease is
responsible for the majority of endogenous cases of Cushing syndrome.

Findings CUSHING Syndrome: raised Cholesterol, raised Urinary free cortisol, Skin changes
(thinning, striae A), Hypertension, Immunosuppression, Neoplasm (a cause, not a finding),
Growth restriction (in children), Sugar (hyperglycemia, insulin resistance). Also,
amenorrhea, moon facies B, buffalo hump, osteoporosis, weight (truncal obesity), hirsutism.

Diagnosis A B Screening tests include:

free cortisol on 24-hr urinalysis,
late night salivary cortisol, and
no suppression with overnight low-dose dexamethasone test.

KOH Test
The KOH Test for Candida albicans, also known as a potassium hydroxide preparation or KOH
prep, is a quick, inexpensive fungal test to differentiate dermatophytes and Candida albicans
symptoms from other skin disorders like psoriasis and eczema.

Autoimmune Polyendocrinopathy / Polyglandular Syndrome (APS)

Addison’s disease (autoimmune hypoadrenalism) is associated with other endocrine

deficiencies in approximately 10% of patients.

There are 2 distinct types of autoimmune polyglandular syndrome (APS

APS type 1
APS type 2

APS type 1:
It is occasionally referred to as Multiple Endocrine Deficiency Autoimmune Candidiasis
(MEDAC).
It is a very rare autosomal recessive disorder caused by mutation of AIRE1 gene on
chromosome 21.
Features of APS type 1 (2 or more of the following):
1) Primary hypoparathyroidism (↓Ca): in 90%
2) Addison's disease: in 60%
3) Chronic mucocutaneous candidiasis (typically first feature as young child).

These 3 major components of APS type 1 tend to present in the following chronological order
of candidiasis, followed by hypoparathyroidism, followed by adrenal insufficiency.

EX: Pt with chronic mucocutaneous candidiasis and you suspect APS type I >>> check serum
Ca and Na & K.

TTT: Antifungals, Vit D, Calcium, Glucocorticoids replacements

APS type 2:

also referred to as Schmidt's syndrome) being much more common.

APS type 2 has a polygenic inheritance and is linked to HLA DR3/DR4.

Patients have:

Addison's disease plus either:

Type 1 DM or
Autoimmune thyroid disease (Hypothyroidism)

N.B: Vitiligo, Myasthenia gravis, primary hypogonadism coeliac disease and pernicious
anaemia can occur in both types of APS.

N.B: Primary hypoparathyroidism (↓Ca) is usually the first endocrine manifestation of type 1
autoimmune polyendocrinopathy syndrome. The contrast to multiple endocrine neoplasia
(MEN), where hyperparathyroidism (↑Ca) is a common finding, should be noted.

So, Primary HYPOparathyroidism is usually the first endocrine manifestation of type I

Autoimmune POLYendocrinopathy syndrome (APS). While, in MEN >>>>>
HYPERparathyroidism is the commonest finding

Thionamides (anti-thyroid) Propylthiouracil, methimazole.

Mechanism :

blocks thyroid peroxidase, inhibiting the oxidation of iodide as well as the organification and
coupling of iodine inhibition of thyroid hormone synthesis.
PTU also blocks 5′-deiodinase Peripheral conversion of T4 to T3.

Clinical Use Hyperthyroidism.

PTU used in Primary (first) trimester of pregnancy (due to methimazole teratogenicity);
methimazole used in second and third trimesters of pregnancy (due to risk of PTU-induced
hepatotoxicity).
Not used to treat Graves ophthalmopathy (treated with corticosteroids).

adverse effects
rash,
agranulocytosis (rare),
aplastic anemia,
hepatotoxicity.
PTU use has been associated with ANCA-positive vasculitis.
Methimazole is a possible teratogen (can cause aplasia cutis).

Pneumothorax

Accumulation of air in pleural space A. Dyspnea, uneven chest expansion. Chest pain, tactile
fremitus, hyperresonance, and diminished breath sounds, all on the affected side.

Primary spontaneous pneumothorax

Due to rupture of apical subpleural bleb or cysts. Occurs most frequently in tall, thin, young
males. Associated with tobacco smoking.

. Secondary spontaneous pneumothorax

Due to diseased lung (eg, bullae in emphysema, Marfan syndrome, infections), mechanical
ventilation with use of high pressures barotrauma.

Traumatic pneumothorax
Caused by blunt (eg, rib fracture), penetrating (eg, gunshot), or iatrogenic (eg, central line
placement, lung biopsy, barotrauma due to mechanical ventilation) trauma.

Tension pneumothorax Can be from any of the above. Air enters pleural space but cannot
exit. Increasing trapped air tension pneumothorax. Trachea deviates away from affected
lung B. May lead to increased intrathoracic pressure mediastinal displacement kinking of
IVC venous return cardiac output, obstructive shock (hypotension, tachycardia), jugular
venous distention. Needs immediate needle decompression and chest tube placement
Syndrome of inappropriate antidiuretic hormone secretion (low ADH)
Characterized by:
Excessive free water retention
Euvolemic hyponatremia with continued urinary Na+ excretion
Urine osmolality > serum osmolality

Body responds to water retention with decrease aldosterone and increase ANP and BNP —
>>urinary Na+ secretion —>>normalization of extracellular fluid volume —>>euvolemic
hyponatremia.
Very low serum Na+ levels can lead to cerebral edema, seizures.

Correct slowly to prevent osmotic demyelination syndrome (formerly called central pontine
myelinolysis).

SIDH CAUSES include (HELD-up water)

H-Head trauma/CNS disorders
E-Ectopic ADH (eg, small cell lung cancer)
L-Lung disease
D-Drugs (eg, SSRIs, carbamazepine, cyclophosphamide)

Treatment:
fluid restriction (first line), salt tablets, IV hypertonic saline, diuretics, ADH antagonists (eg,
conivaptan, tolvaptan, demeclocycline).

Congenital hypothyroidism

More in females
Associated with congenital cardiac abnormalities
If not early treated, leads to permanent neurological damage
Heel prick test in newborn to test TSH and T4
Formerly called cretinism. Most commonly caused by thyroid dysgenesis (abnormal thyroid
gland development; eg, agenesis, hypoplasia, ectopy) or dyshormonogenesis (abnormal
thyroid hormone synthesis; eg, mutations in thyroid peroxidase) in iodine-sufficient regions.

Findings (6 P’s):
pot-bellied, pale,
puffy-faced child E with protruding umbilicus,
protuberant tongue F,
and
poor brain development.
Bladder
Sympathetic >> T10-L2
Parasympathetic —> S2-S4

Cervical spondylosis is a general term for age-related wear and tear affecting the spinal
disks in your neck. As the disks dehydrate and shrink, signs of osteoarthritis develop,
including bony projections along the edges of bones (bone spurs).

Precocious puberty

Appearance of 2° sexual characteristics (eg, adrenarche, thelarche, menarche) before age 8

years in females and 9 years in males.
Raised sex hormone exposure or production > increase linear growth, somatic and skeletal
maturation (eg, premature closure of epiphyseal plates short stature).
Types include:
Central precocious puberty ( GnRH secretion): idiopathic (most common; early activation of
hypothalamic-pituitary gonadal axis), CNS tumors.

Peripheral precocious puberty (GnRH-independent; sex hormone production or exposure to

exogenous sex steroids): congenital adrenal hyperplasia, estrogen-secreting ovarian tumor
(eg, granulosa cell tumor), Leydig cell tumor, McCune-Albright syndrome

Narcolepsy and obstructive sleep apnea (OSA) are both chronic sleep disorders. They have
some symptoms and risk factors in common, and it’s possible to have both conditions at the
same time. But they are two different conditions that require different treatments. That’s why
it’s important to get the right diagnosis if you have one or both conditions.

What Is Narcolepsy?

This is a sleep disorder that causes you to have sudden uncontrollable “sleep attacks” during
the day. It causes you to feel very sleepy and suddenly fall asleep frequently throughout the
day. You fall asleep even if it’s noisy or if there’s activity around you. You find it very difficult
to stay awake. Narcolepsy can cause sudden sleepiness even when you need to stay awake
for your own safety, such as while you drive or cook. You can even keep driving or working
while you’re asleep and not remember what you did or said.
What’s Obstructive Sleep Apnea?

Obstructive sleep apnea (OSA) is a breathing condition. Your airways don’t stay open while
you sleep, so you can’t breathe normally. Your breathing may pause anywhere from a few
times to hundreds of times each night.

OSA can happen when tissue like your adenoid glands, tonsils, or even excess body fat
narrows your throat while you sleep. Your throat muscles may relax as you sleep, so your
tongue rolls back and blocks your throat. You struggle to breathe, and oxygen can’t reach
your lungs.

Like narcolepsy, a common symptom of OSA is excessive daytime sleepiness. You’re tired all
the time, because you can’t get a good night’s sleep.

OSA symptoms include:

Heavy snoring
Quick breathing pauses as you sleep
Frequently waking up to gasp for breath
Dry, sore throat or dry mouth in the morning
Lack of concentration during the day
Headaches in the morning
Night sweats
Mood swings
High blood pressure
Low libido

How Are Narcolepsy and OSA Similar?

The most common symptom of both narcolepsy and OSA is excessive daytime sleepiness.

They also share some of the same risk factors. People with both narcolepsy and OSA are
often overweight or obese. Both conditions may run in families. If any of your relatives have
narcolepsy or OSA, you’re at risk for it, too.

Narcolepsy and OSA may have similar symptoms or effects on your life, too. You may:

Struggle to focus or concentrate during the day.

Nod off for short naps, even at work or in the car.
Have memory lapses.
Struggle to maintain your personal or intimate relationships.
Fall asleep at times when your safety depends on staying awake, like while you drive.
Hallucinate. This are more common in narcolepsy. But it sometimes affects people with OSA,
possibly because you only sleep in very short fragments.

How Are Narcolepsy and OSA Different?

Narcolepsy is somewhat rare. It may affect less than 1% of people in the U.S. OSA is a
common sleep disorder that affects up to 22% of men and 17% of women in the U.S.

Obstructive sleep apnea

Respiratory effort against airway obstruction. Pao2 is usually normal during the day.
Associated with obesity, loud snoring, daytime sleepiness. Usually caused by excess
parapharyngeal/oropharyngeal tissue in adults, adenotonsillar hypertrophy in children.
Treatment: weight loss, CPAP, dental devices, hypoglossal nerve stimulation, upper airway
surgery.

Sleep apnea
Repeated cessation of breathing > 10 seconds during sleep disrupted sleep daytime
somnolence.
Diagnosis confirmed by sleep study.
Nocturnal hypoxia —>systemic and pulmonary hypertension, arrhythmias (atrial fibrillation/
flutter), sudden death. Hypoxia ->EPO release ->erythropoiesis

Schizophrenia
Chronic illness causing profound functional impairment.
Symptom categories include:
Positive—excessive or distorted functioning (eg, hallucinations, delusions, unusual thought
processes, disorganized speech, bizarre behavior)
Negative—diminished functioning (eg, flat or blunted affect, apathy. anhedonia, alogia, social
withdrawal)
Cognitive—reduced ability to understand or make plans, diminished working memory,
inattention

Diagnosis requires ≥ 2 of the following active symptoms, including ≥ 1 from symptoms #1–3

: 1. Delusions
2. Hallucinations, often auditory
3. Disorganized speech
4. Disorganized or catatonic behavior
5. Negative symptoms

Symptom onset ≥ 6 months prior to diagnosis; requires ≥ 1 month of active symptoms over
the past 6 months.

Associated with altered dopaminergic activity, serotonergic activity, and dendritic

branching. Ventriculomegaly on brain imaging. Lifetime prevalence—1.5% (males > females).
Presents earlier in males (late teens to early 20s) than in females (late 20s to early 30s).
suicide risk. Heavy cannabis use in adolescence is associated with incidence and worsened
course of psychotic, mood, and anxiety disorders.

Treatment: atypical antipsychotics (eg, risperidone) are first line. Negative symptoms often
persist after treatment, despite resolution of positive symptoms.

Schizophrenia has three distinct stages: prodromal, active, and residual stage. Each of these
stages is characterized by different symptoms and may indicate the severity of the
individual’s diagnosis. Residual schizophrenia refers to the third stage of schizophrenia in
which the individual experiences fewer or less severe symptoms than those seen in the
active stage. While it is no longer recognized by the Diagnostic and Statistical Manual, Fifth
Edition (DSM-5), the residual phase of schizophrenia is useful for describing and
understanding the symptoms of schizophrenia. Typically, people in the residual stage of
schizophrenia do not experience “positive” symptoms like hallucinations or delusions. Rather
they experience “negative” symptoms like lack of motivation, low energy, or depressed mood

A persecutory delusion is a common type of delusional condition in which the affected

person believes that harm is going to occur to oneself by a persecutor, despite a clear lack of
evidence. The person may believe that they are being targeted by an individual or a group of
people.

The delusion can be found in a multitude of disorders being more usual in psychotic
disorders, such as schizophrenia, schizoaffective disorder and delusional disorder.
Persecutory delusion is at the more severe side of the paranoia spectrum and it often
induces anxiety, depression and sleep disturbance, patients with this delusion have also
been found to have a low self-esteem

Loop diuretics, such as bumetanide and furosemide, inhibit both sodium and calcium
resorption in the thick ascending limb of the loop of Henle. In addition to exerting a diuretic
effect, this mechanism of action produces a hypercalciuric state.
Carbonic anhydrase inhibitors, such as acetazolamide, act in the proximal tubule where they
block resorption of sodium bicarbonate.

Topiramate
Zonisamide
sulfonamide

Ammonium acid urate calculi are more frequent among patients with persistent diarrhea and
have been particularly associated with laxative abuse. In order for these calculi to form, urine
must be supersaturated with both ammonia and uric acid.

Ammonium acid urate calculi are radiolucent unless mixed with calcium.

Silica is a ubiquitously distributed element that is consumed regularly in foods such as

vegetables, whole grains, seafood, and even drinking water. Magnesium trisilicate is a
medication that is available without a prescription for the treatment of symptoms of
gastroesophageal reflux disease.
Indinavir
Lithium

Drug causing hyperthermia

Haloperidol
Lithium

Heat stroke
Condition caused by excessive exposure to high temperatures.
Heat stroke or heatstroke, also known as sun stroke, is a severe heat illness that results in a
body temperature greater than 40.0 °C (104.0 °F), along with red skin, headache, dizziness,
and confusion. Sweating is generally present in exertional heatstroke, but not in classic
heatstroke.

Heatstroke is a life-threatening condition due to the potential for multi-organ dysfunction,

with typical complications including seizures, rhabdomyolysis, or kidney failure.

Osteoarthritis

pathogEnEsis
Mechanical—wear and tear destroys articular cartilage (degenerative joint disorder)
inflammation with inadequate repair. Chondrocytes mediate degradation and inadequate
repair

pREsEntation Pain in weight-bearing joints after use (eg, at the end of the day), improving
with rest. Asymmetric joint involvement. Knee cartilage loss begins medially (“bowlegged”).
No systemic symptoms

. Joint Findings Osteophytes (bone spurs), joint space narrowing, subchondral sclerosis and
cysts. Synovial fluid noninflammatory (WBC < 2000/mm3). Development of Heberden nodes
D (at DIP) and Bouchard nodes E (at PIP), and 1st CMC; not MCP.

tREatmEntActivity modification, acetaminophen, NSAIDs, intra-articular glucocorticoids.

Rheumatoid arthritis
Autoimmune—inflammation C induces formation of pannus (proliferative granulation tissue),
which erodes articular cartilage and bone.

Predisposition Female, HLA-DR4 (4-walled “rheum”), tobacco smoking. ⊕ rheumatoid factor

(IgM antibody that targets IgG Fc region; in 80%), anti-cyclic citrullinated peptide antibody
(more specific).
Presentation Pain, swelling, and morning stiffness lasting > 1 hour, improving with use.
Symmetric joint involvement. Systemic symptoms (fever, fatigue, weight loss). Extraarticular
manifestations common.*
Extraarticular manifestations include rheumatoid nodules (fibrinoid necrosis with palisading
histiocytes) in subcutaneous tissue and lung (+ pneumoconiosis Caplan syndrome),
interstitial lung disease, pleuritis, pericarditis, anemia of chronic disease, neutropenia +
splenomegaly (Felty syndrome), AA amyloidosis, Sjögren syndrome, scleritis, carpal tunnel
syndrome.

Joint findings MCP. Erosions, juxta-articular osteopenia, soft tissue swelling, subchondral
cysts, joint space narrowing. Deformities: cervical subluxation, ulnar finger deviation, swan
neck F, boutonniere G. Involves MCP, PIP, wrist; not DIP or 1st CMC.

Treatment NSAIDs, glucocorticoids, disease-modifying agents (eg, methotrexate,

sulfasalazine), biologic agents (eg, TNF-α inhibitors).

When binding to the pain pathway opioids provide pain relief, however, when binding to the
reward pathway, opioids cause euphoria and release a key neurotransmitter known as
dopamine. Dopamine signals the neurons (brain or nerve cells) of the body to create a
pleasurable feeling or “high
Mania

Mania lasts for a week or more and has a severe negative impact on your ability to do your
usual day-to-day activities – often disrupting or stopping these completely. Severe mania is
very serious, and often needs to be treated in hospital.

Symptoms of mania can include any of the symptoms of hypomania listed above, and can
also include:
How you might feel

You may feel:

happy, euphoric or a sense of wellbeing

uncontrollably excited, like you can't get your words out fast enough
irritable and agitated
increased sexual energy
easily distracted, like your thoughts are racing, or you can't concentrate
very confident or adventurous
like you are untouchable or can't be harmed
like you can perform physical and mental tasks better than normal
like you understand, see or hear things that other people can't.

Hypomania

Hypomania lasts for a few days, and can feel more manageable than mania. It can still have a
disruptive effect on your life and people may notice a change in your mood and behaviour.
But you will usually be able to continue with your daily activities without these being too
badly affected.

Symptoms of hypomania can include:

How you might feel

You may feel:

happy, euphoric or a sense of wellbeing

very excited, like you can't get your words out fast enough
irritable and agitated
increased sexual energy
easily distracted, like your thoughts are racing, or you can't concentrate.
Angiotensin II (Ang II) is not only a vasopressor but also a pro-inflammatory factor that leads
to cardiac hypertrophy, fibrosis and dysfunction

Hypersensitivity pneumonitis Mixed type III/IV hypersensitivity reaction to environmental

antigens. Often seen in farmers and bird-fanciers. Acutely, causes dyspnea, cough, chest
tightness, fever, headache. Often self-limiting if stimulus is removed. Chronically, leads to
irreversible fibrosis with noncaseating granuloma, alveolar septal thickening, traction
bronchiectasis

Polycystic ovarian syndrome A Hyperinsulinemia and/or insulin resistance hypothesized to

alter hypothalamic hormonal feedback response Raised LH:FSH,( high LH and low
fsh)androgens (eg, testosterone) from theca interna cells, rate of follicular maturation
unruptured follicles (cysts) + anovulation. Common cause of fertility in females. Enlarged,
bilateral cystic ovaries A; presents with amenorrhea/oligomenorrhea, hirsutism, acne,
fertility. Associated with obesity, acanthosis nigricans. risk of endometrial cancer 2° to
unopposed estrogen from repeated anovulatory cycles. Treatment: cycle regulation via
weight reduction ( peripheral estrone formation), OCPs (prevent endometrial hyperplasia due
to unopposed estrogen); clomiphene (ovulation induction); spironolactone, finasteride,
flutamide to treat hirsutism

Innate immunity
componentS
Neutrophils, macrophages, monocytes, dendritic cells, natural killer (NK) cells (lymphoid
origin), complement, physical epithelial barriers, secreted enzymes

mechanISm
Germline encoded

reSponSe to pathogenS
Nonspecific Occurs rapidly (minutes to hours) No memory response

Secreted proteInS
Lysozyme, complement, C-reactive protein (CRP), defensins, cytokines

Key FeatureS In pathogen recognItIon

Toll-like receptors (TLRs): pattern recognition receptors that recognize pathogen-associated
molecular patterns (PAMPs) and lead to activation of NF-κB. Examples of PAMPs: LPS (gram
⊖ bacteria), flagellin (bacteria), nucleic acids (viruses)

Adaptive immunity
Component
T cells, B cells, circulating antibodies
Mechanism
Variation through V(D)J recombination during lymphocyte development

Response to pathogens
Highly specific, refined over time Develops over long periods; memory response is faster and
more robust

Secreted protien
Immunoglobulins, cytokines

Key features in pathogen recognition

Memory cells: activated B and T cells; subsequent exposure to a previously encountered
antigen stronger, quicker immune response

Haloperidol
This medicine will often make you sweat less, causing your body temperature to increase.
Use extra care not to become overheated during exercise or hot weather while you are taking
this medicine, since overheating may result in heat stroke. Also, hot baths or saunas may
make you feel dizzy or faint while you are using this medicine

Antipsychotics

Typical (1st-generation) antipsychotics—

haloperidol, pimozide, trifluoperazine, fluphenazine, thioridazine, chlorpromazine.

Atypical (2nd-generation) antipsychotics—aripiprazole, asenapine, clozapine, olanzapine,

quetiapine, iloperidone, paliperidone, risperidone, lurasidone, ziprasidone.

MEchaNisM
Block dopamine D2 receptor ( cAMP).
Atypical antipsychotics also block serotonin 5-HT2 receptor.
Aripiprazole is a D2 partial agonist.

cliNical UsE
Schizophrenia
(typical antipsychotics primarily treat positive symptoms; atypical antipsychotics treat both
positive and negative symptoms), disorders with concomitant psychosis (eg, bipolar
disorder), Tourette syndrome, OCD, Huntington disease.
Clozapine is used for treatment-resistant psychotic disorders or those with persistent
suicidality.

aDVErsE EFFEcts
Antihistaminic (sedation),
anti-α1-adrenergic (orthostatic hypotension),
antimuscarinic (dry mouth, constipation) (anti-HAM).
Use with caution in dementia.
Metabolic: weight gain, hyperglycemia, dyslipidemia.
Highest risk with clozapine and olanzapine (obesity).
Endocrine: hyperprolactinemia galactorrhea, oligomenorrhea, gynecomastia.

Cardiac: QT prolongation.

Neurologic: neuroleptic malignant syndrome.

Ophthalmologic: chlorpromazine—corneal deposits;
thioridazine—retinal deposits.
Clozapine—agranulocytosis (monitor WBCs clozely), seizures (dose related), myocarditis.

Extrapyramidal symptoms—ADAPT: Hours to days:

Acute Dystonia (muscle spasm, stiffness, oculogyric crisis).
Treatment: benztropine, diphenhydramine.

Days to months: Akathisia (restlessness).

Treatment: β-blockers, benztropine, benzodiazepines. Parkinsonism (bradykinesia).
Treatment: benztropine, amantadine.

Months to years: Tardive dyskinesia (chorea, especially orofacial).

Treatment: benzodiazepines, botulinum toxin injections, valbenazine, deutetrabenazine.

Notes
Lipid soluble stored in body fat slow to be removed from body. Typical antipsychotics have
greater affinity for D2 receptor than atypical antipsychotics risk for hyperprolactinemia,
extrapyramidal symptoms, neuroleptic malignant syndrome. High-potency typical
antipsychotics: haloperidol, trifluoperazine, pimozide, fluphenazine (Hal tries pie to fly high)
—more neurologic side effects (eg, extrapyramidal symptoms). Low-potency typical
antipsychotics: chlorpromazine, thioridazine (cheating thieves are low)— more
antihistaminic, anti-α1-adrenergic, antimuscarinic effects.

Adenosine
Increase K+ out of cells hyperpolarizing the cell and decrease ICa, decreasing AV node
conduction.
Drug of choice in diagnosing/terminating certain forms of SVT. Very short acting (~ 15 sec).
Effects blunted by theophylline and caffeine (both are adenosine receptor antagonists).
Adverse effects include flushing, hypotension, chest pain, sense of impending doom,
bronchospasm.

Calcium channel blockers

Amlodipine, clevidipine, nicardipine, nifedipine, nimodipine (dihydropyridines, act on
vascular smooth muscle);
diltiazem, verapamil (nondihydropyridines, act on heart).
MECHANISM
Block voltage-dependent L-type calcium channels of cardiac and smooth muscle decrease
muscle contractility.
Vascular smooth muscle—amlodipine = nifedipine > diltiazem > verapamil.
Heart—verapamil > diltiazem > amlodipine = nifedipine.

ClINICAl uSE
Dihydropyridines (except nimodipine): hypertension, angina (including vasospastic type),
Raynaud phenomeno
. Nimodipine: subarachnoid hemorrhage (prevents cerebral vasospasm).
Nicardipine, clevidipine: hypertensive urgency or emergency. Nondihydropyridines:
hypertension, angina, atrial fibrillation/flutter.

AdvERSE EFFECTS
Gingival hyperplasia. Dihydropyridine: peripheral edema, flushing, dizziness.
Nondihydropyridine: cardiac depression, AV block, hyperprolactinemia (verapamil),
constipation

Lithium
MEchaNisM
Not established; possibly related to inhibition of phosphoinositol cascade.

cliNical UsE Mood stabilizer for bipolar disorder; treats acute manic episodes and prevents
relapse.
aDVErsE EFFEcts Tremor, hypothyroidism, hyperthyroidism, polyuria (causes nephrogenic
diabetes insipidus), teratogenesis (causes Ebstein anomaly). Narrow therapeutic window
requires close monitoring of serum levels. Almost exclusively excreted by kidneys; most is
reabsorbed at PCT via Na+ channels. Thiazides, NSAIDs, and other drugs affecting clearance
are implicated in lithium toxicity.

LiTHIUM:
LiT-Low Thyroid (hypothyroidism)
H-Heart (Ebstein anomaly)
I- Insipidus (nephrogenic diabetes insipidus)
UM- Unwanted Movements (tremor)

MODY 3 (also HNF1A-MODY) is a form of maturity-onset diabetes of the young. It is caused

by mutations of the HNF1-alpha gene, a homeobox gene on human chromosome 12. This is
the most common type of MODY in populations with European ancestry, accounting for about
70% of all cases in Europe. HNF1α is a transcription factor (also known as transcription
factor 1, TCF1) that is thought to control a regulatory network (including, among other genes,
HNF1α) important for differentiation of beta cells. Mutations of this gene lead to reduced
beta cell mass or impaired function

Takotsubo cardiomyopathy: broken heart syndrome—ventricular apical ballooning likely due

to increased sympathetic stimulation (eg, stressful situations).

Kearns-Sayre syndrome (KSS) is characterized by the onset of ophthalmoparesis and

pigmentary retinopathy [1] before age 20 years. Other frequently associated clinical features
include cerebellar ataxia, cardiac conduction block, raised cerebrospinal fluid (CSF) protein
content, and proximal myopathy

. Affected children have short stature and often have multiple endocrinopathies, including
diabetes mellitus, hypoparathyroidism, and Addison disease. [2] Renal tubular acidosis
(proximal or distal) has been described in numerous cases, with occasional progression to
end-stage renal failure.
Bilateral sensorineural hearing loss is almost universal in those who survive into the fourth
decade of life; this may not be fully corrected with hearing aids. No disease-modifying
therapy is available for Kearns-Sayre syndrome.

Erosive osteoarthritis
is a disorder that most often involves the hands of postmenopausal women. It can begin
abruptly with pain, swelling, and tenderness.
Distal interphalangeal joints are involved most frequently, followed by proximal
interphalangeal joints. Occasionally there is metacarpophalangeal, carpal, or large joint
involvement.
Radiologically, the disorder is characterized by central erosions and the "gull wing"
deformity.

A germ cell tumor is a cancer that develops from cells in the reproductive system called germ
cells
In men, germ cells are responsible for producing sperm. Most germ cell tumors in teenage
boys and men start in one of the testicles. There are two different categories of germ cell
tumors: seminoma and non-seminoma. Generally, seminomas grow and spread more slowly
than non-seminomas, but both types of tumors should be treated quickly.

serum tumor markers,

High levels of any one of three tumor markers, called
alpha-fetoprotein (AFP),
beta human chorionic gonadotropin (hCG), and
lactate dehydrogenase (LDH),
may indicate a germ cell tumor.

High AFP levels can also help identify the type of germ cell tumor, by showing whether it is a
pure seminoma or mixed with non-seminoma, since AFP is not made by seminomas.
However, hCG and/or LDH can be higher if a man has a seminoma, non-seminoma, or mixed
tumor. If markers are elevated at diagnosis, changes in their levels can tell your doctor
whether the tumor is responding to treatment.
“Hot T-bone stEAK”:
IL-1: fever (hot).
IL-2: stimulates T cells.
IL-3: stimulates bone marrow.
IL-4: stimulates IgE production.
IL-5: stimulates IgA production.
IL-6: stimulates aKute-phase protein production.

TNF ALPHA
Activates endothelium. Causes WBC recruitment, vascular leak.
Causes cachexia in malignancy.
Maintains granulomas in TB. IL-1, IL-6, TNF-α can mediate fever and sepsis.

Interleukin-12Induces differentiation of T cells into Th1 cells.

Activates NK cells.
Facilitates granuloma formation in TB.
C3b—opsonization.
C3a, C4a, C5a—anaphylaxis.
C5a—neutrophil chemotaxis
. C5b-9 (MAC)—cytolysis.

Albumin in sepsis
Human serum albumin is a small (66kD) globular protein representing over 60 % of the total
plasma protein content.
t is a multifunctional plasma protein ascribed ligand-binding and transport properties as well
as antioxidants and enzymatic functions. It maintains colloid osmotic pressure, modulates
inflammatory response and may influence oxidative damage

Hypoalbuminemia is common in the intensive care unit and may be due to decreased
synthesis by the liver and/or to increased losses or increased proteolysis and clearance

Plummer disease also called TMNG Toxic multinodular goiter (TMNG), also known as
multinodular toxic goiter (MNTG), is an active multinodular goiter associated with
hyperthyroidism.

Toxic multinodular goiter is the second most common cause of hyperthyroidism (after
Graves' disease) in the developed world, whereas iodine deficiency is the most common
cause of hypothyroidism in developing-world countries where the population is iodine-
deficient. Toxic multinodular goiter Focal patches of hyperfunctioning follicular cells
distended with colloid working independently of TSH (due to TSH receptor mutations in 60%
of cases). release of T3 and T4. Hot nodules are rarely malignant.

Sarcomas are cancers that develop from connective tissues in the body, such as muscles,
fat, bones, the linings of joints, or blood vessels. There are many types of sarcomas.
Rhabdomyosarcoma (RMS) is a type of sarcoma made up of cells that normally develop into
skeletal (voluntary) muscles.

Well before birth, cells called rhabdomyoblasts (which will eventually form skeletal muscles)
begin to form. These are the cells that can develop into RMS

Common sites of RMS include:

The head and neck (such as near the eye, inside the nasal sinuses or throat, or near the spine
in the neck)
Urinary and reproductive organs (bladder, prostate gland, or any of the female organs)
Arms and legs
Trunk (chest and abdomen)

Types of rhabdomyosarcoma

There are 2 main types of RMS, along with some less common types.

Embryonal rhabdomyosarcoma (ERMS)

ERMS usually affects children in their first 5 years of life, but it can occur at older ages as
well.

ERMS tends to occur in the head and neck area, bladder, vagina, or in or around the prostate
and testicles.

Two subtypes of ERMS, botryoid and spindle cell rhabdomyosarcomas, tend to have a better
prognosis (outlook) than the more common conventional form of ERMS.

Alveolar rhabdomyosarcoma (ARMS)

ARMS typically affects all age groups equally. It makes up a larger portion of RMS in older
children, teens, and adults than in younger children (because ERMS is less common at older
ages).

ARMS most often occurs in large muscles of the trunk, arms, and legs.

ARMS tends to grow faster than ERMS, and it usually requires more intense treatment.
However, in some cases of ARMS, the cancer cells lack certain gene changes, which makes
these cancers act more like ERMS (and allows doctors to give less intense treatment).

Anaplastic rhabdomyosarcoma and undifferentiated sarcoma

Anaplastic rhabdomyosarcoma (also called pleomorphic rhabdomyosarcoma) is an

uncommon type that occurs mainly in adults and is very rare in children.

Some doctors also group undifferentiated sarcomas with the rhabdomyosarcomas. Using lab
tests, doctors can tell that these cancers are sarcomas, but the cells don’t have any features
that help classify them further.

Both of these uncommon cancers tend to grow quickly and usually require intensive
treatment.
Rhabdomyosarcoma in adults

Most rhabdomyosarcomas develop in children and teens, but they can also occur in adults.
Adults are more likely to have faster-growing types of RMS and to have them in parts of the
body that are harder to treat. Because of this, RMS in adults is often harder to treat
effectively.

Basal cell carcinoma more common above upper lip Squamous cell carcinoma more common
below lower lip Sun exposure strongly predisposes to skin cancer.
Basal cell carcinoma
Most common skin cancer. Found in sun-exposed areas of body (eg, face). Locally invasive,
but rarely metastasizes. Waxy, pink, pearly nodules, commonly with telangiectasias, rolled
borders A, central crusting or ulceration. BCCs also appear as nonhealing ulcers with
infiltrating growth B or as a scaling plaque (superficial BCC) C. Basal cell tumors have
“palisading”

Papillary carcinoma
Most common. Empty-appearing nuclei with central clearing (“Orphan Annie” eyes) A,
psamMoma bodies, nuclear grooves (Papi and Moma adopted Orphan Annie). Increase risk
with RET/ PTC rearrangements and BRAF mutations, childhood irradiation.
Papillary carcinoma: most prevalent, palpable lymph nodes. Good prognosis.

Graves disease
Most common cause of hyperthyroidism.
Thyroid-stimulating immunoglobulin (IgG, can cause transient neonatal hyperthyroidism;
type II hypersensitivity) stimulates TSH receptors on thyroid (hyperthyroidism, diffuse
goiter),
dermal fibroblasts (pretibial myxedema), and orbital fibroblasts

Graves orbitopathy). Activation of T-cells >lymphocytic infiltration of retroorbital space

increase cytokines (eg, TNF-α, IFN-γ) Increase fibroblast secretion of hydrophilic GAGs
increase osmotic muscle swelling, muscle inflammation, and adipocyte count exophthalmos
osmotic A.
Often presents during stress (eg, pregnancy). Associated with HLA-DR3 and HLA-B8.
Histology: tall, crowded follicular epithelial cells; scalloped colloid.
`RESPIRATORY—PhYSIOlOgY Lung volumes and capacities Note: a capacity is a sum of ≥ 2
physiologic volumes.
Tidal volumeAir that moves into lung with each quiet inspiration, typically 500 mL
Inspiratory reserve volume Air that can still be breathed in after normal inspiration

volume Air that can still be breathed out after normal expiration
Residual volumeAir in lung after maximal expiration; RV and any lung capacity that includes
RV cannot be measured by spirometry
Inspiratory capacityIRV + TV Air that can be breathed in after normal exhalation
Functional residual capacity RV + ERV Volume of gas in lungs after normal expiration;
outward pulling force of chest wall is balanced with inward collapsing force of lungs
Total lung capacityIRV + TV + ERV + RV = VC + RV Volume of gas present in lungs after a
maximal inspiration
Vital capacityI RV + TV + ERV Maximum volume of gas that can be expired after a maximal
inspiration

Anagen effluvium
Anagen effluvium is a form of nonscarring alopecia commonly associated with
chemotherapy.
In this disorder, affected anagen hairs suffer a toxic or inflammatory insult, resulting in
fracture of the hair shaft. Anagen effluvium is often referred to as chemotherapy-induced
alopecia, as it can be triggered by antimetabolites, alkylating agents, and mitotic inhibitors
administered as chemotherapeutic therapy. Shedding usually takes place within 14 days of
administration of the offending drug, however, in many instances it is reversible, with hair
regrowth growth upon discontinuation of the offending agen

Telogen Effluvium
Telogen Effluvium more hairs than usual move into the telogen (resting) phase and shed, so
you may notice more hair falling out than usual. Telogen Effluvium is often caused by a
physical or psychological trigger and often resolves itself spontaneously

Hair growth
The hair growth cycle has three phases:
the growing phase, anagen;
the regressing phase, catagen; and
the resting phase, telogen
Bulimia nervosa
Recurring episodes of binge eating with compensatory purging behaviors at least weekly
over the last 3 months.
BMI often normal or slightly overweight (vs anorexia).
Associated with parotid gland hypertrophy (may see raised serum amylase), enamel erosion,
Mallory-Weiss syndrome, electrolyte disturbances (eg, decrease K+, decrease Cl−),
metabolic alkalosis, dorsal hand calluses from induced vomiting (Russell sign).
Treatment: psychotherapy, nutritional rehabilitation, antidepressants (eg, SSRIs). Bupropion
is contraindicated due to seizure risk.

Anorexia nervosa
Intense fear of weight gain, overvaluation of thinness, and body image distortion leading to
calorie restriction and severe weight loss resulting in inappropriately low body weight (BMI <
18.5 kg/m2 for adults).
May present with hypothyroidism, amenorrhea, osteoporosis, lanugo.
Binge-eating/purging type—recurring purging behaviors (eg, laxative or diuretic abuse,
selfinduced vomiting) or binge eating over the last 3 months.

Restricting type—primary disordered behaviors include dieting, fasting, and/or over-

exercising. No recurring purging behaviors or binge eating over the last 3 months.

Refeeding syndrome—often occurs in significantly malnourished patients with sudden

calorie intake Icrease insulin Decrease PO4 3−, decrease K+, decrease Mg2+ cardiac
complications, rhabdomyolysis, seizures.
Treatment: nutritional rehabilitation, psychotherapy, olanzapine.

Left testicular Ca para aortic LN

Right testicular ca pre aortic LN

Manic episode
Distinct period of abnormally and persistently elevated, expansive, or irritable mood and
activity or energy lasting ≥ 1 week.
Diagnosis requires hospitalization or marked functional impairment with ≥ 3 of the following
manics DIG FAST):
Distractibility
Impulsivity/Indiscretion—seeks pleasure without regard to consequences (hedonistic)
Grandiosity—inflated self-esteem
Flight of ideas—racing thoughts
Increasebgoal-directed Activity/psychomotor Agitation
Decrease need for Sleep
Talkativeness or pressured speech

Hypomanic episode

Similar to a manic episode except mood disturbance is not severe enough to cause marked
impairment in social and/or occupational functioning or to necessitate hospitalization.
Abnormally increase activity or energy usually present. No psychotic features. Lasts ≥ 4
consecutive days.

Bipolar disorder

Bipolar I—≥ 1 manic episode +/− a hypomanic or depressive episode (may be separated by
any length of time).
Bipolar II—a hypomanic and a depressive episode (no history of manic episodes). Patient’s
mood and functioning usually normalize between episodes. Use of antidepressants can
destabilize mood. High suicide risk. Treatment: mood stabilizers (eg, lithium, valproic acid,
carbamazepine, lamotrigine), atypical antipsychotics.

Cyclothymic disorder—milder form of bipolar disorder fluctuating between mild depressive

and hypomanic symptoms. Must last ≥ 2 years with symptoms present at least half of the
time, with any remission lasting ≤ 2 months.

The time to reach steady state is defined by the elimination half-life of the drug.
After 1 half-life, you will have reached 50% of steady state.
After 2 half-lives, you will have reached 75% of steady state, and after 3 half-lives you will
have reached 87.5% of steady state.

Ankylosing spondylitis (AS)

Ankylosing spondylitis is a HLA-B27 associated spondyloarthropathy.
Ø It typically presents in males (sex ratio 5:1) aged 20-30 years old.
Ø It has polygenic inheritance

Features:
Typically a young man who presents with chronic lower back pain radiating to his buttocks,
and stiffness of insidious onset. after periods of inactivity and improves with exercise.
· Stiffness is usually worse in the morning more than 30 minutes and worse
· The patient may experience pain at night (waking in the second half of the night) which
improves on getting up. ·
Peripheral arthritis (25%, more common if female) ·
Muscular strain is the commonest cause of back pain in general practice but chronic pain for
more than 3 months may indicate AS and should be investigated
Note The commonest subtype HLA associations are HLA B*2705 (Caucasians), B*2704
(Chinese, Japanese) and B*2702 (Mediterranean). The B*2706 subtype is weakly associated
and commonly found in normal South East Asian individuals.

Clinical examination:
· Reduced lateral flexion
· Reduced forward flexion - Schober's test - a line is drawn 10 cm above and 5 cm below the
back dimples (dimples of Venus). The distance between the two lines should increase by
more than 5 cm when the patient bends as far forward as possible
· Reduced chest expansion
· Sacroiliac joint tenderness
Later (In the advanced stages of AS): loss of lumbar lordosis, buttock atrophy and an
accentuated thoracic kyphosis.

Other features
Apical fibrosis ·
· A nterior uveitis
Aortic regurgitation
Achilles tendonitis
A V node block
A myloidosis
cauda equina syndrome Peripheral Investigation: arthritis ( 25 %, more common if female )

Investigation:
arthritis ( 25 %, more common if female )
Inflammatory markers (ESR, CRP) are typically raised although normal levels do not exclude
ankylosing spondylitis.
HLA-B27: · It is not essential for the diagnosis of AS. · It not used as a screening test for AS. ·
It is of little use in making the diagnosis and as it is positive in:
o 90% of patients with ankylosing spondylitis
o 75% of patient with Reiter's syndrome.
o 10% of normal patients
· Its sensitivity and specificity depend on the racial and ethnic background of the patien
. · Acute anterior uveitis is more common in B27 positive than negative patients.

Ø Plain x-ray of the sacroiliac joints is the most useful investigation in establishing the
diagnosis and monitoring, but changes may not be seen for many years after the onset of
symptoms.
Radiographs may be normal early in disease, later changes include:
· Sacroilitis: sub-chondral erosions, sclerosis
· Squaring of lumbar vertebrae
· 'Bamboo spine' (late & uncommon)
· Syndesmophytes: due to ossification of outer fibers of annulus fibrosus
· Chest x-ray: apical fibrosis

Spirometry may show a restrictive defect due to a combination of pulmonary fibrosis,

kyphosis and ankylosis of the costovertebral joints.

Current British Society for Rheumatology recommendations state that the modified New York
criteria should be used to diagnose ankylosing spondylitis:

Clinical Criteria:
· Low back pain, present for more than 3 months,
improved by exercise but not relieved by rest.
· Limitation of lumbar spine motion in both the sagittal and frontal planes.
· Limitation of chest expansion relative to normal values for age and sex.

Radiological Criteria:
· Sacroiliitis on x ray.

Diagnose: ·
Definite AS if the radiological criterion is present plus at least one clinical criterion.
· Probable AS if 3 clinical criteria are present alone or if the radiological criterion is present
but no clinical criteria are present.

Both HLA-B27 and sacroiliitis on MRI play a major role in the recently proposed Assessment
of Spondyloarthritis International Society (ASAS) diagnostic algorithm. This may replace the
modified New York criteria in the future.

Management:
The following is partly based on the 2010 EULAR guidelines (European League Against
Rheumatism):
The best initial therapy for AS is NSAIDs and physiotherapy.
Ø NSAIDs are the first-line treatment.
Ø Physiotherapy
Ø Encourage regular exercise such as swimming
Ø If symptoms are not controlled additional analgesics (for example, amitriptyline).
Ø Corticosteroid injections or oral corticosteroids can be used.
Ø The DMARDs which are used to treat RA (such as sulphasalazine) are only really useful if
there is peripheral joint involvement as it doesn’t improve spinal mobility.
The 2010 EULAR guidelines suggest: 'Anti-TNF therapy should be given to patients with
persistently high disease activity despite conventional treatments' (severe ankylosing
spondylitis which has failed to respond to NSAIDs.) Ø Research is ongoing to see whether
anti-TNF therapies such as etanercept and adalimumab should be used earlier in the course
of the disease.

Hampton hump refers to a dome-shaped, pleural-based opacification in the lung most

commonly due to pulmonary embolism and lung infarction (it can also result from other
causes of pulmonary infarction (e.g. vascular occlusion due to angioinvasive aspergillosis).

Osteogenesis imperfecta (brittle bone disease)

Osteogenesis imperfecta (more commonly known as brittle bone disease) is a group of

disorders of collagen metabolism resulting in bone fragility and fractures. The most
common, and milder, form of osteogenesis imperfecta is type 1.

Overview:
· Autosomal dominant.
· Abnormality in type 1 collagen due to decreased synthesis of pro-alpha 1 or pro-alpha 2
collagen polypeptides.

Features: · Presents in childhood · Fractures following minor trauma · Blue sclera · Deafness
secondary to otosclerosis · Dental imperfections are common

Treatement and management

Because osteogenesis imperfecta (OI) is a genetic condition, it has no cure.

For many years, surgical correction of deformities, physiotherapy, and the use of orthotic
support and devices to assist mobility (eg, wheelchairs) were the primary means of
treatment

Pharmacological management
Bisphosphonates (eg, pamidronate) are synthetic analogues of pyrophosphate that inhibit
osteoclast-mediated bone resorption on the endosteal surface of bone by binding to
hydroxyapatite. As a result, unopposed osteoblastic new bone formation on the periosteal
surface results in an increase in cortical thickness. Their use in the treatment of OI is on off-
label application.

Adverse effects of pamidronate include an acute febrile reaction, mild hypocalcemia,

leukopenia, a transient increase in bone pain, and scleritis with or without anterior uveitis.
With milder forms of OI, the indications for bisphosphonate therapy have yet to be evaluated.

Growth hormone is known to act on the growth plate and also stimulate osteoblast function,
possibly via insulinlike growth factor (IGF)-1 and IGF-binding protein (IGFBP)-3.

Bone marrow transplantation (BMT) has been advocated as a potential future therapeutic
modality for OI. Transplantation of adult bone marrow in utero has been shown to decrease
perinatal lethality in a murine model of OI.

Carbamazepine and oxcarbazepine are considered first-line therapy in trigeminal neuralgia

Lamotrigine and baclofen are second-line therapy. Osteogenesis imperfecta (brittle bone
disease)

Osteogenesis imperfecta (more commonly known as brittle bone disease) is a group of

disorders of collagen metabolism resulting in bone fragility and fractures. The most
common, and milder, form of osteogenesis imperfecta is type 1.

Overview:
· Autosomal dominant.
· Abnormality in type 1 collagen due to decreased synthesis of pro-alpha 1 or pro-alpha 2
collagen polypeptides.

Features: · Presents in childhood · Fractures following minor trauma · Blue sclera · Deafness
secondary to otosclerosis · Dental imperfections are common

Treatement and management

Because osteogenesis imperfecta (OI) is a genetic condition, it has no cure.

For many years, surgical correction of deformities, physiotherapy, and the use of orthotic
support and devices to assist mobility (eg, wheelchairs) were the primary means of
treatment

Pharmacological management
Bisphosphonates (eg, pamidronate) are synthetic analogues of pyrophosphate that inhibit
osteoclast-mediated bone resorption on the endosteal surface of bone by binding to
hydroxyapatite. As a result, unopposed osteoblastic new bone formation on the periosteal
surface results in an increase in cortical thickness. Their use in the treatment of OI is on off-
label application.

Adverse effects of pamidronate include an acute febrile reaction, mild hypocalcemia,

leukopenia, a transient increase in bone pain, and scleritis with or without anterior uveitis.
With milder forms of OI, the indications for bisphosphonate therapy have yet to be evaluated.

Growth hormone is known to act on the growth plate and also stimulate osteoblast function,
possibly via insulinlike growth factor (IGF)-1 and IGF-binding protein (IGFBP)-3.

Bone marrow transplantation (BMT) has been advocated as a potential future therapeutic
modality for OI. Transplantation of adult bone marrow in utero has been shown to decrease
perinatal lethality in a murine model of OI.

Other treatments are third line and the evidence for their efficacy is scant.

ARDS

PAThOPhYSIOlOg
YAlveolar insult >release of pro-inflammatory cytokines >neutrophil recruitment, activation,
and release of toxic mediators (eg, reactive oxygen species, proteases, etc) >capillary
endothelial damage and increase vessel permeability >leakage of protein-rich fluid into
alveoli formation of intra-alveolar hyaline membranes (arrows in A) and noncardiogenic
pulmonary edema (normal PCWP).

Loss of surfactant also contributes to alveolar collapse.

CAUSES
Sepsis (most common), aspiration, pneumonia, trauma, pancreatitis.

DIAgNOSIS MNEMONIC
Diagnosis of exclusion with the following criteria (ARDS):
Abnormal chest X-ray (bilateral lung opacities) B
Respiratory failure within 1 week of alveolar insult
Decreased Pao2 /Fio2 (ratio < 300, hypoxemia due to intrapulmonary shunting and diffusion
abnormalities)
Symptoms of respiratory failure are not due to HF/fluid overload

CONSEQUENCES
Impaired gas exchange, lung compliance; pulmonary hypertension.

mANAgEmENTTreat the underlying cause. Mechanical ventilation: tidal volume, PEEP (keeps
alveoli open during expiration).
Hypertension

Persistent systolic BP ≥ 130 mm Hg and/or diastolic BP ≥ 80 mm Hg.

RISK FACTORS
age, obesity, diabetes, physical inactivity, high-sodium diet, excess alcohol intake, tobacco
smoking, family history; incidence greatest in Black > White > Asian populations.

FEATuRES
A 90% of hypertension is 1° (essential) and related to increase CO or increase TPR.
Remaining 10% mostly 2° to renal/renovascular diseases such as fibromuscular dysplasia
(characteristic “string of beads” appearance of renal artery A, usually seen in adult females)
and atherosclerotic renal artery stenosis or to 1° hyperaldosteronism.

Hypertensive urgency—severe (≥ 180/≥ 120 mm Hg) hypertension without acute end-organ

damage.

Hypertensive emergency—severe hypertension with evidence of acute end-organ damage

eg, encephalopathy, stroke, retinal hemorrhages and exudates, papilledema, MI, HF, aortic
dissection, kidney injury, microangiopathic hemolytic anemia, eclampsia).

PREdISPOSES TO
CAD, LVH, HF, atrial fibrillation; aortic dissection, aortic aneurysm; stroke; CKD
(hypertensive nephropathy); retinopathy.

Hypertrophic cardiomyopathy

60–70% of cases are familial, autosomal dominant (most commonly due to mutations in
genes encoding sarcomeric proteins, such as myosin binding protein C and β-myosin heavy
chain).

Causes syncope during exercise and may lead to sudden death (eg, in young athletes) due to
ventricular arrhythmia.

Findings: S4, systolic murmur.

May see mitral regurgitation due to impaired mitral valve closure.

Classified as hypertrophic obstructive cardiomyopathy when outflow from LV is obstructed.

Asymmetric septal hypertrophy and systolic anterior motion of mitral valve outflow
obstruction dyspnea, possible syncope.
Other causes of concentric LV hypertrophy: chronic HTN, Friedreich ataxia.
Diastolic dysfunction ensues. Marked ventricular concentric hypertrophy

Treatment: cessation of high-intensity athletics, use of β-blocker or nondihydropyridine

Ca2+ channel blockers (eg, verapamil). ICD if syncope occurs. Avoid drugs that decrease
preload (eg, diuretics, vasodilators)

Atypical anti depressants

Bupropion
Inhibits NE and DA reuptake. Also used for smoking cessation.
Toxicity: stimulant effects (tachycardia, insomnia), headache, seizures in patients with
bulimia and anorexia nervosa. risk of sexual side effects and weight gain compared to other
antidepressants

Cholelithiasis and related pathologies

Increase cholesterol and/or bilirubin,
Decrease bile salts, and gallbladder stasis all cause stones.

2 types of stones:
Cholesterol stones (radiolucent with 10–20% opaque due to calcifications)—80% of stones.
Associated with obesity, Crohn disease, advanced age, estrogen therapy, multiparity, rapid
weight loss, medications (eg, fibrates).

Pigment stones A (black = radiopaque, Ca2+ bilirubinate, hemolysis; brown = radiolucent,

infection). Associated with Crohn disease, chronic hemolysis, alcoholic cirrhosis, advanced
age, biliary infections, total parenteral nutrition (TPN).

Risk factors (4 F’s):

1. Female
2. Fat (obesity)
3. Fertile (multiparity)
4. Forty

Most common complication is cholecystitis; can also cause acute pancreatitis, acute
cholangitis.
Diagnose with ultrasound.

Treat with elective cholecystectomy if symptomatic.

Raynaud phenomenon

Decrease blood flow to skin due to arteriolar (small vessel) vasospasm in response to cold or
stress:
color change from white (ischemia) to blue (hypoxia) to red (reperfusion).

Most often in the fingers A and toes. Called Raynaud disease when 1° (idiopathic),

Raynaud syndrome when 2° to a disease process such as mixed connective tissue disease,
SLE, or CREST syndrome (limited form of systemic sclerosis). Digital ulceration (critical
ischemia) seen in 2° Raynaud syndrome.

Treat with calcium channel blockers.

Amyotrophic lateral sclerosis

Also called Lou Gehrig disease.
Combined UMN (corticobulbar/corticospinal) and LMN (medullary and spinal cord)
degeneration. No sensory or bowel/bladder deficits.
Can be caused by defect in superoxide dismutase 1.
LMN deficits: flaccid limb weakness, fasciculations, atrophy, bulbar palsy (dysarthria,
dysphagia, tongue atrophy).
UMN deficits: spastic limb weakness, hyperreflexia, clonus, pseudobulbar palsy (dysarthria,
dysphagia, emotional lability). Fatal (most often from respiratory failure).
Treatment: “riLouzole”.

Fabry disease
Early: triad of episodic peripheral neuropathy, angiokeratomas B, hypohidrosis.
Late: progressive renal failure, cardiovascular disease.

Enzyme deficient α-galactosidase A.

Accumulation Ceramide trihexoside (globotriaosylceramide).
X link recessive

Lateral epicondylitis (tennis elbow) Repetitive extension (backhand shots) or idiopathic pain
near lateral epicondyle.

Autosomal recessive polycystic kidney disease

Cystic dilation of collecting ducts B. Often presents in infancy. Associated with congenital
hepatic fibrosis. Significant oliguric renal failure in utero can lead to Potter sequence.
Concerns beyond neonatal period include systemic hypertension, progressive renal
insufficiency, and portal hypertension from congenital hepatic fibrosis.

Kearns Sayre syndrome

Kearns-Sayre syndrome (KSS) is characterized by the onset of ophthalmoparesis and
pigmentary retinopathy[1] before age 20 years. Other frequently associated clinical features
include cerebellar ataxia, cardiac conduction block, raised cerebrospinal fluid (CSF) protein
content, and proximal myopathy. Affected children have short stature and often have
multiple endocrinopathies, including diabetes mellitus, hypoparathyroidism, and Addison
disease.[2] Renal tubular acidosis (proximal or distal) has been described in numerous
cases, with occasional progression to end-stage renal failure. Bilateral sensorineural hearing
loss is almost universal in those who survive into the fourth decade of life; this may not be
fully corrected with hearing aids. No disease-modifying therapy is available for Kearns-Sayre
syndrome.[3]

Osteosarcoma (osteogenic sarcoma)

Accounts for 20% of 1° bone cancers. Peak incidence of 1° tumor in males < 20 years. Less
common in elderly; usually 2° to predisposing factors, such as Paget disease of bone, bone
infarcts, radiation, familial retinoblastoma, Li-Fraumeni syndrome.

Location Metaphysis of long bones (often in knee region).

Pleomorphic osteoid-producing cells (malignant osteoblasts). Presents as painful enlarging
mass or pathologic fractures.
Codman triangle D (from elevation of periosteum) or sunburst pattern on x-ray E (think of an
osteocod [bone fish] swimming in the sun). Aggressive. 1° usually responsive to treatment
(surgery, chemotherapy), poor prognosis for 2°.

MODY
Maturity-onset diabetes of the young (MODY) is characterised by the development of type 2
diabetes mellitus in patients < 25 years old. It accounts for 1-2% of diabetes cases, and is an
important diagnosis as the therapy may be different compared with T1DM and T2DM. It is
sometimes called type 1.5 DM. It is typically inherited as an autosomal dominant condition
(i.e. There is usually a strong family history).
Over 6 different genetic mutations have been identified as leading to MODY. Ketosis is not a
feature at presentation. TTT: One third of patients require insulin therapy and around one
third may be controlled with oral hypoglycaemic drugs. Sulphonylureas (SUs) would be the
initial drug of choice, because at least for the first few years, capacity to secrete insulin is
preserved, and use of SUs restores insulin release, avoiding the need for insulin therapy.

MODY >>> Autosomal Dominant

MODY 1:
< 10% ·
Due to defect in HNF-4 alpha gene (Hepatocyte Nuclear Factor).

MODY 2: · 20% of cases. · Due to a defect in the glucokinase gene. · 90% of MODY 2 are
controlled on diet therapy alone.

MODY 3: · 60% of cases (most common). · Due to a defect in the HNF-1 alpha gene

Congenital adrenal hyperplasia (CAH)

CAH is caused by 21-hydroxylase deficiency in around 95% of cases.

This results in cortisol deficiency, aldosterone deficiency and androgen excess.

Due to the enzyme block, cortisol cannot be made effectively and androgens are made
instead.

The classical form has its onset in infancy or childhood.

The non-classical "mild" form are characterised by milder enzyme dysfunction, and
therefore usually only manifest later in adolescence or adulthood. 17-OH progesterone is
elevated because of the enzyme deficiency.

Urinary 17-ketosteroid levels (androgen metabolites) are elevated in the condition.

The clinical presentation may be indistinguishable from (PCO) polycystic ovarian syndrome,
with hirsutism being a dominant feature.

Short Synacthen test (ACTH stimulation test) with measurement of 17-OH progesterone (17-
OHP):
can help to distinguish between PCOS and non-classical CAH:
N-CAH due to 21-hydroxylase deficiency is diagnosed with the ACTHstimulated 17-OHP
levels are more than 30 nmol/L (although this value varies with the assay used). N-CAH is not
characterised by cortisol insufficiency, and as such glucocorticoids are rarely indicated.

TTT:
Ø If the main concern is infertility, ovulation induction is the treatment of choice.
Ø If hirsutism is the presenting problem then anti-androgens (such as flutamide 250 mg cap)
should be used to treat hirsutism, but glucocorticoids are generally not required.
Ø The treatment of CAH is the lowest dose of glucocorticoid (Hydrocortisone) that
suppresses (not totally) adrenal androgens, whilst maintaining normal growth and weight
gain.

Reverse cholesterol transport is a mechanism by which the body removes excess cholesterol
from peripheral tissues and delivers them to the liver, where it will be redistributed to other
tissues or removed from the body by the gallbladder.
The main lipoprotein involved in this process is the HDL-c.

Reactive arthritis is one of the HLA-B27 associated seronegative spondyloarthropathies.

It encompasses Reiter's syndrome, a term which described a classic triad of urethritis,
conjunctivitis and arthritis following a dysenteric illness during the Second World War. Later
studies identified patients who developed symptoms following a sexually transmitted
infection (post-STI, now sometimes referred to as sexually acquire reactive arthritis, SARA).

Reactive arthritis is defined as an arthritis that develops following an infection where the
organism cannot be recovered from the joint. Reactive arthritis is a post-infective
autoimmune condition that is associated with gastrointestinal (Shigella, Salmonella,
Campylobacter) and genitourinary infections (Chlamydia).There will be a recent history of
gastroenteritis or urethritis. Symptoms of reactive arthritis typically appear 1-4 weeks
following the initial infection

Urethritis + arthritis + conjunctivitis = reactive arthritis

Reactive arthritis >>>> the Pt. can’t see, can’t pee, can’t bend the knee
Epidemiology:
· Post-STI form much more common in men (e.g. 10:1)
· Post-dysenteric form equal sex incidence
The table below shows the organisms that are most commonly associated with reactive
arthritis:
Postdysenteric form
Shigella flexneri
Salmonella typhimurium
Salmonella enteritidis
Yersenia enterocolitica
Campylobacter

Post St Form
Chlamydia trachomatis

Features: · Typically develops within 4 weeks of initial infection - symptoms generally last
around 4-6 months
· Arthritis is typically an asymmetrical oligoarthritis of lower limbs, Dactylitis.
· Symptoms of urethritis
· Eye: conjunctivitis (seen in 50%), anterior uveitis
· Skin: o Circinate balanitis (painless vesicles on the coronal margin of the prepuce),
Keratoderma blenorrhagica (palmo-plantar pustulosis) (waxy yellow/brown papules on
palms and soles),
o Psoriasiform skin and o Nail and mucosal lesions

Around 15-50 % of patients with reactive arthritis have recurrent episodes whilst 30 % of
patients develop chronic persistent arthritis or sacroilitis.

Management: First line of TTT of reactive arthritis is oral NSAIDs not antibiotics.

· Symptomatic: analgesia, NSAIDS, intra-articular steroids

· Sulfasalazine and methotrexate are sometimes used for persistent disease
· Symptoms rarely last more than 12 months.
· Antibiotics do not change the course of reactive arthritis, even when an infective cause is
identified. However, some studies show that they may help to reduce the length of arthritis,
particularly if Chlamydia is the triggering infection.
· If Chlamydia infection is suspected/confirmed >>> ttt by Doxycycline. Gonococcal arthritis
is characterized by dermatitis-polyarthritis-tenosynovitis syndrome. It is the most common
cause of septic arthritis in sexually active adults

Multiple myeloma
Multiple myeloma is a neoplasm of the bone marrow plasma cells.
Myeloma is a clonal B-cell malignancy characterized by proliferation of plasma cells that
accumulate mainly in bone marrow and usually secrete paraprotein.

It accounts for 1% of all malignancies and 10% of haematological malignancies.

The peak incidence is patients aged 60-70 years. Multiple myeloma is a relatively common
malignancy that is part of a spectrum of disorders ranging from monoclonal gammopathy of
unknown significance (MGUS) to plasma cell leukaemia.

Gammopathy is a disturbance in the synthesis of immunoglobulins. Monoclonal gammopathy

suggests there is a single neoplastic clone causing an excess of immunoglobulin.
There is overproduction of immunoglobulin (Ig) usually IgG in about 55%, IgA in about 20%:
of these patients, 40% have Bence-Johns proteinuria.
Light chain is found in 20% of patients, while IgD and IgE myeloma account for about 1% of
cases.
Hyperviscosity syndrome: the viscosity is directly proportional to the size of the molecule
causing it; therefore IgM, which is pentameric, is most likely to cause hyperviscosity,
followed by the dimeric IgA, then IgG. An important differential diagnosis is monoclonal
gammopathy of unknown significance (MGUS).

Macroglobulins are plasma globulins of high molecular weight. They are a central feature of
Waldenström macroglobulinaemia, where proliferation of lymphocytes cause an excess of
IgM. This is an important differential diagnosis when multiple myeloma is suspected.
Macroglobulins are not typically a feature of multiple myeloma.

Clinical features:
· Bone disease:
o Bone pain (the commonest presenting symptom, present in 70% of patients at time of
diagnosis),
o Osteoporosis + pathological fractures (in up to 60% of cases) (typically vertebral) and
osteolytic lesions.
· Spinal cord compression can develop due to vertebral compression fractures or vertebral
plasmacytomas >>> Urgent MRI of the spine.
· Lethargy
· Renal failure with proteinuria and normal sized kidneys.
· Other features: AL amyloidosis e.g. Macroglossia, carpal tunnel syndrome; neuropathy;
hyperviscosity
· Acute bacterial Infection (e.g. pneumonia)
· Decreased resistance to infection due to impaired humoral immunity, often compounded by
leukopenia secondary to bone marrow infiltration. Patients therefore have a high prevalence
of infection, especially with encapsulated organisms such as Pneumococcus
Hypercalcaemia and hyperphosphataemia (see below)
· The globulin level is raised (globulin level = total protein – albumin). Normal level should be
below 36 g/L.
· Positive P-ANCA Diagnostic Criteria for myeloma (International Myeloma Working Group
2010):
ALL THREE (3) are required:
1) Monoclonal plasma cells in the bone marrow (involving ˃10% of the bone marrow) and/or
presence of biopsy-proven plasmacytoma.
2) Monoclonal proteins in the serum (Plasma immunoelectrophoresis to look for an M band)
and urine (Lambda light chains secreted in the urine as Bence Jones protein, this is most
accurately detected by urine protein electrophoresis).
3) Myeloma-related organ dysfunction (≥ 1):
1) ↑ Serum Calcium. 2) Renal impairment. 3) Anaemia. 4) Bone lesions on the skeletal
survey: lytic lesions or osteoporosis. Hypercalcaemia in myeloma: 1
) Primary factor: due primarily to increased osteoclastic bone resorption caused by local
cytokines (e.g. IL-1, TNF) released by the myeloma cells. 2) Much less common contributing
factors: impaired renal function, increased renal tubular calcium reabsorption and elevated
PTH-rP levels. The hyperphosphataemia in multiple myeloma: It is due to reduced renal
excretion which may be directly due to renal impairment or interference with excessive
protein load.
Myeloma: prognosis: · B2-microglobulin is a useful marker of prognosis - raised levels of
>3.5 mg/L is strongly imply poor prognosis. L · Low levels of albumin are also associated with
a poor prognosis. L · Hypercalcaemia · Severity of anaemia · Viscosity
· LDH, · Recurrent bacterial infections.

TTT:
Ø Melphalan and prednisolone.
Ø Immunomodulatory drugs such a thalidomide and lenalidomide: significant improvements
in survival may be expected through the addition of it to standard chemotherapeutic
regimes. (SE: Teratogenic, myelosuppression, somnolence, peripheral neuropathy and
constipation) Ø Bortezomib: inhibits the 26 S proteosome, indirectly inhibiting nuclear factor
Kappa and causing apoptosis. Ø Bisphosphonates reduce bony disease in myeloma, lowering
the frequency of pathological fractures. There is also evidence that bisphosphonates
modulate the disease and have some anti-tumour activity. As a result, bisphosphonates
should be given routinely to patients with myeloma, even in the absence of hypercalcaemia.
Ø Plasma exchange.

Koebner phenomenon
The Koebner phenomenon describes skin lesions which appear at the site of injury. It is seen
in: 1) Psoriasis 2) Vitiligo 3) Warts 4) Lichen planus 5) Lichen sclerosus 6) Molluscum
contagiosum

Akathisia is an inability to remain physically still. It's a movement disorder that's linked to
certain types of medications, especially antipsychotic medications. People with akathisia feel
an intense and uncontrollable need to move — mainly, their lower body.

Multiple endocrine neoplasias

All MEN syndromes have autosomal dominant inheritance.
The X-MEN are dominant over villains.

MEN 1
Pituitary tumors (prolactin or GH)
Pancreatic endocrine tumors—ZollingerEllison syndrome, insulinomas, VIPomas,
glucagonomas (rare)
Parathyroid adenomas Associated with mutation of MEN1 (menin, a tumor suppressor,
chromosome 11), angiofibromas, collagenomas, meningiomas

MEN 2A
Parathyroid hyperplasia
Medullary thyroid carcinoma—neoplasm of parafollicular C cells; secretes calcitonin;
prophylactic thyroidectomy required
Pheochromocytoma (secretes catecholamines) Associated with mutation in RET (codes for
receptor tyrosine kinase)

MEN 2B
Medullary thyroid carcinoma
Pheochromocytoma Mucosal neuromas A (oral/intestinal ganglioneuromatosis) Associated
with marfanoid habitus; mutation in RET gene

MEN 1 = 3 P’s: pituitary, parathyroid, and pancreas

MEN 2A = 2 P’s: parathyroid and pheochromocytoma
MEN 2B = 1 P: pheochromocytoma

Extrinsic allergic alveolitis (EAA) (Farmer lung) (HP)

Extrinsic allergic alveolitis (EAA, also known as hypersensitivity pneumonitis) (HP) is a
condition caused by hypersensitivity induced lung damage due to a variety of inhaled organic
particles. It is thought to be largely caused by immune-complex mediated tissue damage
(type III hypersensitivity) especially in acute phase, although delayed hypersensitivity (type
IV) is also thought to play a role, especially in the chronic phase. It is now very rare since the
majority of farmers no longer bale hay in wet conditions. When present, it is most commonly
associated with positive Saccharopolyspora rectivirgula antibodies.

Example
· Pigeon Bird fanciers' lung: avian proteins · Farmers’ lung: spores of Saccharopolyspora
rectivirgula (formerly Micropolyspora faeni) (NB: Contaminated hay / straw is the most
common source of Saccharopolyspora rectivirgula which is responsible for Farmer's lung). ·
Malt workers' lung: Aspergillus clavatus · Mushroom workers' lung: thermophilic
actinomycetes* · Mouldy hay, mushroom compost, house dust, hot/tub steam room and
contaminated water in the humidifiers.

Acute episodes are characterised by neutrophilic infiltration followed by lymphocytic

infiltration and raised levels of interleukins 1 and 8 and TNF-alpha. This results in direct
cellular damage and increased vascular permeability, which results in hypoxia and reduced
lung compliance. Prolonged exposure leads to fibrosis and parenchymal destruction.

Presentation: · Occur 4-8 hrs after exposure, SOB, dry cough, fever. · O/E: Bilateral basal fine
inspiratory crackles

nvestigation:
· CXR: Upper zone fibrosis
· BAL: lymphocytosis
· Blood: NO eosinophilia
· Circulating IgG precipitant: In farmer's lung >>> precipitins to Saccharopolyspora
rectivirgula or Thermoactinomyces vulgaris are found in 75-100% of cases during an acute
episode. Ø Positive serum avian IgG precipitins are not diagnostic of extrinsic allergic
EAA >>> NOT ALLERGY: Ø Ø Ø NO Eosinophilia NO ↑ IgE NO positive skin prick, NO
Antibiotics

Positive serum avian IgG precipitins are not diagnostic of extrinsic allergic alveolitis (EAA),
and only suggest the patient has had old exposure to birds.

TTT:
1) Primary treatment is antigen avoidance (change of job, repainting and ventilation in the
steam room) ,
Then, 2) Systemic corticosteroids (Oral prednisolone). Inhaled corticosteroids (ICS) are not
as effective as oral corticosteroids
. 3) NO role for antibiotic therapy.
Although the aetiology is hypersensitivity to fungal spores, neither amphotericin B nor
fluconazole are effective in the treatment of farmer's lung. *here the terminology is slightly
confusing as thermophilic actinomycetes is an umbrella term covering strains such as
Micropolyspora faeni.

Psittacosis = Chlamydia psittaci pneumonia is endemic in birds including psittacine birds,

canaries, finches, pigeons and poultry. Pet owners, vets and zoo keepers are most at risk.
It is rare in children. Person to person transmission occurs especially in a hospital
environment.
Sputum Gram stain reveals a few leucocytes and no predominant bacteria.
There are few signs and few laboratory/x ray findings.
It is characterized by relative bradycardia with non-specific chest signs, coupled with diffuse
CXR changes like widespread hazy opacities affecting both lower lobes, a low TLC and
abnormal LFTs are consistent with the disease. Positive serology is with complement-fixing
antibodies.
Serum avian precipitins is positive. Tetracyclines are the antibiotics of choice.

Psoriasis

Psoriasis (see pic) Psoriasis is a common (prevalence around 2%) and chronic skin disorder.
It generally presents with red, scaly patches on the skin although it is now recognised that
patients with psoriasis are at increased risk of arthritis and cardiovascular disease.

Pathophysiology:
· Multifactorial and not yet fully understood
· Genetic: associated HLA-B13, -B17, and -Cw6.
Strong concordance (70%) in identical twins.
· Immunological: abnormal T cell activity stimulates keratinocyte proliferation.
There is increasing evidence this may be mediated by a novel group of T helper cells
producing IL-17, designated Th17. These cells seem to be a third T-effector cell subset in
addition to Th1 and Th2. (Psoriasis is mediated by type 1 helper T cells which are involved in
the cell mediated response, rather than type 2 helper T cells).
· Environmental: it is recognised that psoriasis may be worsened (e.g. Skin trauma, stress),
triggered (e.g. Streptococcal infection) or improved (e.g. Sunlight) by environmental factors.

Recognised subtypes of psoriasis:

1) Plaque psoriasis: the most common sub-type resulting in the typical well demarcated red,
scaly patches affecting the extensor surfaces, sacrum and scalp.
Scalp psoriasis may occur in isolation in patients with no history of psoriasis elsewhere.
2) Flexural psoriasis: in contrast to plaque psoriasis the skin is smooth.
3) Guttate psoriasis: transient psoriatic rash frequently triggered by a streptococcal
infection. Multiple red, teardrop lesions appear on the body.
4) Pustular psoriasis: commonly occurs on the palms and soles.
5) Erythrodermic psoriasis:
o May result from progression of chronic disease to an exfoliative phase with plaques
covering most of the body. Associated with mild systemic upset. o More serious form is an
acute deterioration. This may be triggered by a variety of factors such as withdrawal of
systemic steroids.
Patients need to be admitted to hospital for management.

Other features: · Nail signs: pitting, Onycholysis · Arthritis

Complications:
1) Psoriatic arthropathy (around 10%): Psoriatic arthropathy may occur prior to the
development of skin lesions.
2) Increased incidence of metabolic syndrome
3) Increased incidence of cardiovascular disease
4) Increased incidence of venous thromboembolism
5) Psychological distress
Psoriasis: management

NICE released guidelines on the management of psoriasis and psoriatic arthropathy.

Chronic plaque psoriasis: 1) Regular emollients may help to reduce scale loss and reduce
pruritus. 2) First-line: NICE recommend a potent corticosteroid applied once daily plus
vitamin D analogue (Calcipotriol) applied once daily (applied separately, one in the morning
and the other in the evening) for up to 4 weeks as initial treatment. 3) Second-line: if no
improvement after 8 weeks then offer a vitamin D analogue twice daily. 4) Third-line: if no
improvement after 8-12 weeks then offer either: a potent corticosteroid applied twice daily
for up to 4 weeks or a coal tar preparation applied once or twice daily. 5) Short-acting
dithranol can also be used. 1st line ttt of psoriatic plaques is >> Topical steroid + topical
Calcipotriol Scalp psoriasis: · NICE recommend the use of potent topical corticosteroids used
once daily for 4 weeks. · If no improvement after 4 weeks then either use a different
formulation of the potent corticosteroid (for example, a shampoo or mousse) and/or a topical
agents to remove adherent scale (for example, agents containing salicylic acid, emollients
and oils) before application of the potent corticosteroid. Face, flexural and genital psoriasis: ·
NICE recommend offering a mild or moderate potency corticosteroid applied once or twice
daily for a maximum of 2 weeks. · Topical Calcipotriol is usually irritant in flexures. · Mild tar
preparations are an option but may be messy and cumbersome. Flexural psoriasis >>>
topical steroid
Steroids in psoriasis: · Topical steroids are commonly used in flexural psoriasis and there is
also a role for mild steroids in facial psoriasis. · If steroids are ineffective for these
conditions vitamin D analogues or Tacrolimus ointment should be used second line. · Pts.
should have 4 week breaks between courses of topical steroids. · Very potent steroids should
not be used for longer than 4 weeks at a time. Potent steroids can be used for up to 8 weeks
at a time. · The scalp, face and flexures are particularly prone to steroid atrophy so topical
steroids should not be used for more than 1-2 weeks/month Secondary care management: 1)
Phototherapy: · Narrow band ultraviolet B light is now the treatment of choice. If possible this
should be given 3 times a week. · Photo-chemotherapy is also used - Psoralens + Ultraviolet
A light (PUVA). · Adverse effects: skin ageing, squamous cell cancer (NOT melanoma). 2)
Systemic therapy: 1) Oral methotrexate is used first-line. It is particularly useful if there is
associated joint disease. 2) Cyclosporine. 3) Systemic Retinoids. 4) Biological agents:
infliximab, etanercept and adalimumab. 5) Ustekinumab (IL-12 and IL-23 blocker) is showing
promise in early trials. Mechanism of action of commonly used drugs: · Coal tar: probably
inhibit DNA synthesis. It is smelly and messy - most patients would not tolerate facial
application. · Calcipotriol: vitamin D analogue which reduces epidermal proliferation and
restores a normal horny layer. Calcipotriol is not recommended for facial lesions as it may
cause irritation - calcitriol and tacalcitol are alternatives. · Dithranol: inhibits DNA synthesis,
wash off after 30 mins, SE: burning, staining. The following factors may exacerbate
psoriasis: 1) Trauma. 2) Alcohol. 3) Drugs: (Reactions may occur from less than 1 month to 1
year after the medication is initiated): o Beta blockers, o ACEIs, o Lithium, o Antimalarials
(chloroquine and hydroxychloroquine) and o NSAIDs. 4) Withdrawal of systemic steroids.

NB: Precipitation of the rash may take up to a year to develop after initiation of the
medications. NB: It is still difficult to establish the link between anti-malarial and psoriasis
exacerbation. NB: Lithium prescription with ACEI is not recommended due to the problem of
a significant increase in serum Lithium levels. NB: The safest treatment - that which
produces the best clinical effect with minimal side effects >>> Psoralen and ultraviolet light
(PUVA). NB: Oral steroids are contraindicated in psoriasis and although one may see an initial
improvement, a very serious rebound effect may be seen.

Psoriasis: guttate (see pic) Guttate psoriasis is more common in children and adolescents. It
may be precipitated by a streptococcal infection (sore throat/tonsillitis) 2-4 weeks prior to
the lesions appearing. Features: · Tear drop papules on the trunk and limbs which in parts are
covered by a fine scale. Management: · Most cases resolve spontaneously within 2-3 months
· There is no firm evidence to support the use of antibiotics to eradicate streptococcal
infection. · Topical agents as per psoriasis · UVB phototherapy · Tonsillectomy may be
necessary with recurrent episodes

Bronchectasis
Bronchiectasis Bronchiectasis describes a permanent dilatation of the airways secondary to
chronic infection or inflammation.
There are a wide variety of causes are listed below:
Causes:
· Post-infective: tuberculosis, measles, pertussis, pneumonia.
· Cystic fibrosis.
· Bronchial obstruction e.g. lung cancer/foreign body
. · Immune deficiency: selective IgA, hypogammaglobulinaemia.
· Allergic Broncho pulmonary aspergillosis (ABPA).
· Ciliary dyskinetic syndromes: Kartagener's syndrome, Young's syndrome.
· Yellow nail syndrome (associated with pleural effusion – exudates).
NB: Amyloidosis does not cause bronchiectasis per se, but may be seen in bronchiectasis as
a consequence of chronic inflammation and infection.
Most common organisms isolated from patients with bronchiectasis: · Haemophilus
influenzae (most common)
· Pseudomonas aeruginosa · Klebsiella spp. · Streptococcus pneumoniae

Bronchiectasis >>>> most common organism >>>> Haemophilus influenzae

Management:
· Postural drainage: is the cornerstone to treating bronchiectasis and should be undertaken
at least once per day and more frequently during exacerbations.
· Physical training (e.g. inspiratory muscle training) - has a good evidence base for patients
with non-cystic fibrosis bronchiectasis
· Antibiotics for exacerbations + long-term rotating antibiotics in severe cases
Bronchodilators in selected cases · Immunisations
· Surgery in selected cases (e.g. Localised disease) when underlying causes such as primary
ciliary dyskinesia have been excluded.

Inhaled corticosteroids (ICS) should not be used routinely in bronchiectasis until further
evidence of their effect on lung function and exacerbation frequency is available.

Symptom control in non-CF bronchiectasis >>> Inspiratory muscle training + postural

drainage

Claustrophobia is the irrational fear of confined spaces.

But avoiding these places may reinforce the fear. Some people with claustrophobia
experience mild anxiety when in a confined space, while others have severe anxiety or a
panic attack. The most common experience is a feeling or fear of losing control.

Agoraphobia is a fear of being in situations where escape might be difficult or that help
wouldn't be available if things go wrong. Many people assume agoraphobia is simply a fear of
open spaces, but it's actually a more complex condition. Someone with agoraphobia may be
scared of: travelling on public transport.

Arachnophobia is a specific phobia brought about by the irrational fear of spiders and other
arachnids such as scorpions.
Complex regional pain syndrome (CRPS) CRPS is a chronic pain condition that can affect any
area of the body, but often affects an arm or a leg, and occurs after an injury or rarely after a
sudden illness such as a heart attack or stroke. It is the modern, umbrella term for a number
of conditions such as reflex sympathetic dystrophy and causalgia. It describes a number of
neurological and related symptoms which typically occur following surgery or a minor injury.
CRPS is 3 times more common in women. The condition can sometimes appear without
obvious injury to the affected limb. CRPS has two forms: · CRPS I occurs in the absence of a
preceding nerve injury (NO nerve injury) · CRPS II is caused by an injury to the nerve. The key
symptom is pain that: Features: · Allodynia. · Oedema and sweating · Motor dysfunction · Is
intense and burning · Is disproportionate to the original injury · Is worse over time · Spreads
beyond the site of injury and · Is associated with hyperalgesia, hyperpathia or allodynia on
examination. These features do not occur in DVT, osteomyelitis, or cellulitis. · Progressive,
disproportionate symptoms to the original injury/surgery. · Temperature and skin colour
changes · The Budapest Diagnostic Criteria are commonly used in the UK CRPS may have 3
stages (acute, dystrophic, and atrophic), with variable progression from one stage to
another. CRPS is a clinical diagnosis, and various imaging modalities show non-specific
changes which support its diagnosis:

Plain radiographs may show soft tissue swelling, peri-articular osteoporosis, and rarely
erosions. · MRI may also show bone marrow oedema apart from these changes. · 99mTc bone
scan shows hypervascularity in the acute phase, and hypovascularity in the atrophic phase.
In the atrophic phase, imaging may show contractures. Management: · Early physiotherapy is
important. · Neuropathic analgesia in-line with NICE guidelines. · Specialist management
(e.g. Pain team) is required.

EX: A 38-year-old woman comes for review. Six months ago she fractured her left wrist
whilst skiing. The fracture was treated using a cast and repeat x-rays showed that the bone
had healed well. Unfortunately for the past few weeks she has been plagued with ongoing
'shooting pains' in her left hand associated with swelling. On examination the left hand is
extremely tender to even light touch. Her left hand is also slightly swollen compared to the
right. What is the most likely diagnosis? >>>> CRPS.

Charcot joint
In patients with longstanding diabetes and peripheral neuropathy, a red hot swollen foot
should raise suspicion of Charcot neuroarthropathy.
Diagnosis is suggested by severe joint destruction with minimal symptoms and surprisingly
normal joint. First described in 1868 by Charcot in a patient with syphilis, but also seen in
syringomyelia, diabetic neuropathy, spinal cord and peripheral nerve injury, leprosy, multiple
sclerosis and meningeomyelocele. Charcot neuropathy presents as a warm, swollen,
erythematous foot and ankle, and infection is important to exclude. The majority of patients
are in their 50-60s, and they often present in the latter stages of the disease. It can occur in
association with a variety of conditions, including leprosy, poliomyelitis, rheumatoid arthritis,
although today the most common cause is diabetes mellitus. The pathophysiology of Charcot
neuroarthropathy is not completely understood, but is thought to start with peripheral
neuropathy. It is thought to occur due to increased blood flow as a result of neuropathy, this
results in increased osteoclast activity and bone turnover, the foot is then susceptible to
often very minor trauma and destructive changes take place.
The lack of pain sensation may mean that patients subject the foot joints (commonly the mid-
foot at tarsal metatarsal joints) to stress injuries that lead to the Charcot process. It is
important to note however that about half of patients present with pain. Four stages of
Charcot neuropathy are recognised: 1) Stage 0 (inflammation): characterised by erythema
and oedema, but no structural changes. 2) Stage 1 (development): bone resorption,
fragmentation and joint dislocation. Swelling, warmth and erythema persist but there are also
radiographic changes such as debris formation at the articular margins, osseous
fragmentation and joint disruption. 3) Stage 2 (coalescence): bony consolidation,
osteosclerosis and fusion are all seen on plain radiographs. 4) Stage 3 (reconstruction):
osteogenesis, decreased osteosclerosis, and progressive fusion. Healing and new bone
formation occur, and the deformity becomes permanent. Radiographs are an important part
of investigating a patient with possible Charcot arthropathy. All radiographs should be taken
in the weight-bearing position. MRI can demonstrate changes in the earlier stages of the
condition, and is therefore important in allowing treatment to be instigated earlier. Indium-
labelled WBCs scan: although it is not widely available, it is the best way to differentiate
between infective causes of foot and Charcot’s arthropathy. In stages 0 and 1 the treatment
is immediate immobilisation and avoidance of weight-bearing. A total-contact cast is worn
until the redness, swelling and heat subside (generally 8-12 weeks, changed every 1-2 weeks
to minimise skin damage). After this the patient should use a removable brace for a total of 4
to 6 months. D.D: Osteomyelitis. Treatment: Ø First line ttt is total contact plaster and rest
for at least 3 months (immobilisation in a plaster cast for 3-6 months): this allow bone
remodelling/repair to occur. Ø Bisphosphonates can be used, but evidence of clinical benefit
is lacking. Ø Surgery is reserved for severe deformities that are susceptible to ulceration,
and where braces and orthotic devices are difficult to use.

Topical steroid potency

Class I superpotent (clobetasol propionate 0.05%, halobetasol propionate 0.05%,
desoximetasone 0.25%),
Class II: high-potent (betamethasone dipropionate 0.05% cream, halcinonide 0.1%),
Class III: medium-high potency (fluticasone propionate 0.005% ointment),
Class IV medium potency (mometasone furoate 0.1% cream),
Class V: medium potency (betamethasone valerate 0.1% cream, fluocinolone acetonide
0.025% cream),
Class VI: low potency (desonide 0.05% cream, fluocinolone acetonide 0.01% cream), and
Class VII: low potency (hydrocortisone acetate, dexamethasone acetate 0.1%).

Dementia
Dementia is thought to affect over 700,000 people in the UK and accounts for a large amount
of health and social care spending.
The most common cause of dementia in the UK is Alzheimer's disease followed by vascular
and Lewy body dementia.
They may coexist. Features: · Diagnosis can be difficult and is often delayed. · The Mini-
Mental State Examination (MMSE) score is widely used.
A score of ≤ 24 out of 30 suggests dementia.
Management: 1) In primary care a blood screen is usually sent to exclude reversible causes
(e.g. Hypothyroidism).
NICE recommend the following tests: CBC, U&E, LFTs, Ca++, glucose, TFTs, Vit.B12 and
folate levels. Patients are now commonly referred on to old-age psychiatrists (sometimes
working in 'memory clinics'

2) In secondary care neuroimaging is performed* to exclude other reversible conditions (e.g.

Subdural haematoma, normal pressure hydrocephalus) and help provide information on
aetiology to guide prognosis and management

Neuroimaging is required to diagnose dementia

Alzheimer's disease (AD)

Alzheimer's disease is a progressive degenerative disease of the brain accounting for the
majority of dementia seen in the UK. Alzheimer's disease is characterised early in the
disease by short term memory loss.
Genetics: 2) In secondary care neuroimaging is performed* to exclude other reversible
conditions (e.g. Subdural haematoma, normal pressure hydrocephalus) and help provide
information on aetiology to guide prognosis and management. Alzheimer's disease is a
progressive degenerative disease of the brain accounting for the majority of dementia seen
in the UK. Alzheimer's disease is characterised early in the disease by short term memory
loss. · Most cases are sporadic · 5% of cases are inherited as an autosomal dominant trait.
· Mutations in the amyloid precursor protein (chromosome 21), presenilin 1 (chromosome 14)
and presenilin 2 (chromosome 1) genes are thought to cause the inherited form.
· Apoprotein E allele E4 - encodes a cholesterol transport protein.

Pathological changes:
1) Macroscopic = widespread cerebral atrophy, particularly involving the cortex and
hippocampus.
2) Microscopic = intraneuronal neurofibrillary tangles, neuronal plaques, deficiency of
neurons.
3) Biochemical = deposition of type A-Beta-amyloid protein in cortex, deficit of Ach from
damage to an ascending forebrain projection.

Neurofibrillary tangles:
· Paired helical filaments are partly made from a protein called tau
· In AD are tau proteins are excessively phosphorylated
Management:
1) NICE now recommend the three acetyl cholinesterase inhibitors (↑Ach): (Donepezil
(Aricept®), Rivastigmine (Exelon®) and (Galantamine) as options for managing mild to
moderate Alzheimer's disease
. 2) Memantine (Namenda®): (a NMDA receptor antagonist) is reserved for patients with
moderate - severe Alzheimer's. Donepezil → SE: Insomnia, Bradycardia, Heart block and UB
obstruction

The NICE guidelines recommend discontinuation of cholinesterase inhibitors as Donepezil

once the mini mental state examination has fallen below 12/30 and possibly consider
Memantine, which is licensed for use in moderate to severe dementia. So pt. with Dementia
on Donepezil (Aricept®), then ↓ MMSE >>> so withdraw Donepezil and consider Memantine.

Lewy body dementia (LBD)

Lewy body dementia is an increasingly recognised cause of dementia, accounting for up to
20% of cases. It is a mixture of Alzheimer's disease with Parkinson's disease. The
characteristic pathological feature is alpha-synuclein cytoplasmic inclusions (Lewy bodies)
in the substantia nigra, paralimbic and neocortical areas. The relationship between
Parkinson's disease and Lewy body dementia is complicated, particularly as dementia is
often seen in Parkinson's disease.

Also, up to 40% of patients with Alzheimer's have Lewy bodies. Neuroleptics should be
avoided in Lewy body dementia as patients are extremely sensitive and may develop
irreversible Parkinsonism. Questions may give a history of a patient who has deteriorated
following the introduction of an antipsychotic agent (like haloperidol).

EX: A 64-year-old man who is under investigation for parkinsonian symptoms is brought to
the GP by his wife. She is concerned her husband is becoming increasingly agitated. The GP
prescribes haloperidol. One week later the parkinsonian symptoms have deteriorated
markedly. What is the most likely underlying diagnosis? >>> Lewy body dementia.
Features: 1) Progressive cognitive impairment. 2) Parkinsonism. 3) Hallucinations (visual or
non-visual hallucinations, other features such as delusions may also be seen). 4) Symptoms
worsen with neuroleptics/ antipsychotic agent. Diagnosis: · Usually clinical. · Single-photon
emission computed tomography (SPECT) is increasingly used. It is currently commercially
known as a DaTscan (dopamine transporter scan). o Dopaminergic iodine-123-radiolabelled
2-carbomethoxy-3-(4iodophenyl)-N-(3-fluoropropyl) nortropane (123-I FP-CIT) is used as
the radioisotope. o The sensitivity of SPECT in diagnosing Lewy body dementia is around
90% with a specificity of 100%. o Its main drawback is expense. The findings on
conventional imaging such as MRI are generally non-specific. Lewy body dementia has no
specific identifying features on CT or MRI.

Pituitary apoplexy—sudden hemorrhage of pituitary gland, often in the presence of an

existing pituitary adenoma. Usually presents with sudden onset severe headache, visual
impairment (eg, bitemporal hemianopia, diplopia due to CN III palsy), and features of
hypopituitarism

Incretins
Incretins are a group of metabolic hormones that stimulate a decrease in blood glucose
levels. Incretins are released after eating and augment the secretion of insulin released from
pancreatic beta cells of the islets of Langerhans by a blood-glucose–dependent mechanism.
Some incretins (GLP-1) also inhibit glucagon release from the alpha cells of the islets of
Langerhans. In addition, they slow the rate of absorption of nutrients into the blood stream
by reducing gastric emptying and may directly reduce food intake. The two main candidate
molecules that fulfill criteria for an incretin are the intestinal peptides glucagon-like
peptide-1 (GLP-1) and gastric inhibitory peptide (GIP, also known as: glucose-dependent
insulinotropic polypeptide). Both GLP-1 and GIP are rapidly inactivated by the enzyme
dipeptidyl peptidase-4 (DPP-4). Both GLP-1 and GIP are members of the glucagon peptide
superfamily.

Portopulmonary hypertension (PPHTN) refers to pulmonary arterial hypertension that is

associated with portal hypertension; it is a well-recognized complication of portal
hypertension due to chronic liver disease or extrahepatic causes

Richter hernia is a herniation of the anti-mesenteric portion of the intestine through a fascial
defect. Patients often present with symptoms similar to other incarcerated hernias, such as
abdominal discomfort, distention, nausea, and vomiting. The incidence of Richter's hernia
has been increasing with the growing popularity of minimally invasive surgery. Operative
treatment of these hernias depends on the viability of the involved portion of the bowel and
may often require resection in addition to repair of the fascial defect.

Skin infections

Bacterial infections

Impetigo

Skin infection involving superficial epidermis. Usually from S aureus or S pyogenes. Highly
contagious.
Honey-colored crusting A. Bullous impetigo B has bullae and is usually caused by S aureus.

Erysipelas
Infection involving upper dermis and superficial lymphatics, usually from S pyogenes.
Presents with well-defined, raised demarcation between infected and normal skin C.

Cellulitis
Acute, painful, spreading infection of deeper dermis and subcutaneous tissues. Usually from
S pyogenes or S aureus. Often starts with a break in skin from trauma or another infection

Abscess

Collection of pus from a walled-off infection within deeper layers of skin E. Offending
organism is almost always S aureus.

Necrotizing fasciitis
Deeper tissue injury, usually from anaerobic bacteria or S pyogenes. Pain may be out of
proportion to exam findings. Results in crepitus from methane and CO2 production. “Flesh-
eating bacteria.” Causes bullae and skin necrosis violaceous color of bullae, surrounding
skin F. Surgical emergency.

Staphylococcal scalded skin syndrome

Exotoxin destroys keratinocyte attachments in stratum granulosum only (vs toxic epidermal
necrolysis, which destroys epidermal-dermal junction). Characterized by fever and
generalized erythematous rash with sloughing of the upper layers of the epidermis G that
heals completely. ⊕ Nikolsky sign (separation of epidermis upon manual stroking of skin).
Commonly seen in newborns and children/adults with renal insufficiency.
A prion /ˈpriːɒn/ (listen) is a misfolded protein that can transmit its misfolded shape onto
normal variants of the same protein. Prions are the causative agent of several transmissible
and fatal neurodegenerative diseases in humans and other animals.

Creutzfeldt –Jakob Disease (CJD)

Rapidly progressive, severe invariably fatal usually within few months.

Ø Dementia
Ø Cerebellar ataxia.
Ø Diffuse myoclonic jerks: it is typical and progressive, even during the later stage when the
patient is stuporous or comatose.
Ø Ataxia and involuntary movements (for example, myoclonus) usually appear at an interval
of about 6 months after the initial symptoms.
Ø In the majority of the cases the first symptoms are psychiatric (depression, irritability) and
painful sensory symptoms in the LLs.
Ø New variant CJD usually presents in a young person, in their twenties or thirties.
Ø EEG is usually normal in new variant CJD.
Ø Rapid cognitive decline in a young person with myoclonus is strongly suggestive of
Creutzfeldt-Jakob disease (CJD).

Investigations:
Ø EEG: characteristic diffuse non-specific slowing periodic high amplitude sharp wave
complexes PSWCs of 1-2 Hz, but diagnosis relies on either specialized tests for prion protein
in CSF or brain biopsy.
Ø MRI: Pulvinar sign > 90% (bilateral posterior thalamic nuclei high signal abnormalities)
pathological in variant CJD (not sporadic).
Ø CSF:14-3-3 protein
Ø Prion protein in tonsils.
Sporadic CJD: Ø It is a prion disease.
Normal prion proteins are found on cell surfaces all over the body mainly in an alpha helix
structure.
Ø Predominantly affects late mid aged individuals with mean age of death in the late 60s.
Ø Memory impairment and subsequently rapidly progressive dementia from few weeks
duration to less than 2 years.
Ø Commonly accompanying features include cerebellar ataxia, pyramidal and extrapyramidal
signs and myoclonus which are common early features.
Ø A definitive diagnosis can only be made post-mortem.
Ø The median duration of illness is 4 months and about 65% of cases die within 6 months.

EX: Male pt. 60 years with increasing forgetfulness over the last 3 months, he become more
agitated and police brought him home after seeing him wondering in the street, O/E: he has
broad based gait, intention tremor, past pointing, myoclonic jerk, brisk reflexes and bilateral
up-going plantars >>> Sporadic CJD.

Somatotropes (from the Greek sōmat meaning "body" and tropikós meaning "of or
pertaining to a turn or change") are cells in the anterior pituitary that produce growth
hormone
. Gonadotrophs are specialized cell types of the anterior pituitary that synthesize and secrete
LH and FSH.

lactotropic cell is a cell in the anterior pituitary which produces prolactin in response to
hormonal signals including dopamine

Marfan's syndrome
Marfan's syndrome is an autosomal dominant connective tissue disorder, so usually his
parents are also very tall. It is caused by a defect in the fibrillin-1 gene on chromosome 15
and affects around 1 in 3,000 people. Unfortunately DNA testing for fibrillin gene mutations,
whilst helpful, it cannot exclude the diagnosis of Marfan’s because of a number of mutations
exist, at least 130 mutations. Hence diagnosis is based on the major and minor Marfan’s
features. Features: 1) Tall stature with arm span to height ratio > 1.05 and 2) Upper to lower
body ratio is decreased (head to symphysis pubis: symphysis pubis to toes). 3) High-arched
palate 4) Arachnodactyly 5) Pectus excavatum 6) Pes planus 7) Scoliosis of > 20 degrees
>>> Low back pain.
Dural ectasia (ballooning of the dural sac at the lumbosacral level): Dural ectasia affects
around 60% of patients with Marfan's syndrome. It may cause lower back pain associated
with neurological problems such as bladder and bowel dysfunction like incontinence. 9)
Heart: o Dilatation of the aortic sinuses (seen in 90%) which may lead to aortic
regurgitation, aortic aneurysm, aortic dissection, and o Mitral valve prolapse (MVP) (75%):
systolic murmur at mitral area. 10) Lungs: repeated pneumothoraxes 11) Eyes: Upwards lens
dislocation (superotemporal ectopia lentis), blue sclera, retinal detachment and myopia. The
life expectancy of patients used to be around 40-50 years. With the advent of regular
echocardiography monitoring and beta-blocker/ACEinhibitor therapy this has improved
significantly over recent years. Aortic dissection and other cardiovascular problems remain
the leading cause of death however.
Peripheral smear

Howell-Jolly bodies

Functional hyposplenia (eg, sickle cell disease), asplenia

Basophilic nuclear remnants (do not contain iron) Usually removed by splenic macrophages

Basophilic stippling
Sideroblastic anemias, thalassemias
Basophilic ribosomal precipitates (do not contain iron)

Pappenheimer bodies
Sideroblastic anemia
Basophilic granules (contain iron)

Heinz bodies
G6PD deficiency
Denatured and precipitated hemoglobin (contain iron) Phagocytic removal of Heinz bodies
bite cells Requires supravital stain (eg, crystal violet) to be visualized

Diabetes: pathophysiology
Type 1 DM:
· Autoimmune disease.
· Type 1 DM is a primarily T cell mediated disorder. Whilst autoantibodies to beta cell
antigens are measurable in patients with the disease, they are not thought to play direct role
in its pathogenesis
. · Antibodies against beta cells of pancreas.
· Various antibodies such as islet-associated antigen (IAA) antibody and glutamic acid
decarboxylase (GAD) antibody are detected in patients who later go on to develop T 1 DM -
their prognostic significance is not yet clear.
· Anti-IA2 and anti-GAD Abs are measured to support the diagnosis.
· Only 10% of patients have a positive family history.
· Identical twins show a genetic concordance of 40%.
· HLA DR4 > HLA DR3.
· It is inherited in a polygenic fashion.
: · Enteroviruses may play a role in both protection from and susceptibility to T1DM.
· The presence of GAD autoantibodies would signify an autoimmune aetiology and their
presence signifies a 10 fold increased risk of developing IDDM, being found in 70-90% of
type1 diabetics.
This would be a case of latent autoimmune diabetes in adults (LADA) and constitutes
approximately 10% of patients incorrectly labelled as T2DM.
· The most closely associated with the imminent development of DM T1 is loss of first phase
insulin response which is an indicator of significant impending beta cell destruction.

Type 2 DM

· It is thought to be caused by a relative deficiency of insulin and the phenomenon of insulin

resistance. · A reduction in beta cell mass due to amyloid deposition may partly account for
this. · The presence of amyloid polypeptide on pancreatic histology is highly suggestive of
type 2 DM. · Age, obesity and ethnicity are important aetiological factors. · There is almost
100% concordance in identical twins and no HLA associations.

Type 2 DM
Diagnosis

The following is based on the (WHO) 2006 guidelines:

To diagnose Diabetes mellitus:
If the patient is symptomatic plus:
· Fasting glucose ≥ 7.0 mmol/l. (= 125 mg/dl)
· Random glucose ≥ 11.1 mmol/l (= 200 mg/dl) or
· 2 hrs after 75g oral glucose tolerance test OGTT: ≥ 11.1 mmol/l (= 200 mg/dl)

If the patient is asymptomatic the above criteria apply but must be demonstrated on TWO
confirmatory samples on separate occasions.
Diagnosis of DM: symptoms + fasting ≥ 7.0, random ≥ 11.1 - if asymptomatic need two
readings.

The diagnosis of diabetes requires ( · Fasting plasma glucose WHO ≥ 7.0 · · · Random plasma
glucose 75 g OGTT two hour HbA1c >6.5% or 48 ≥ 11.1 guidelines): mmol/l (≥125 mg/dl).
mmol/l (≥200 mg/dl) plasma glucose ≥11.1 mmol/l (≥200 mg/dl). The American Diabetes
Association (ADA) has recently added another criterion: mmol/mol.

In 2011 WHO released supplementary guidance on the use of HbA1c on the diagnosis of
diabetes: · A HbA1c of greater than or equal to 6.5% (48 mmol/mol) is the cut-off point for a
diagnosis of diabetes mellitus. · A HbAlc value of less than 6.5% does not exclude diabetes
(i.e. it is not as sensitive as fasting samples for detecting diabetes). · In patients without
symptoms, the test must be repeated to confirm the diagnosis. · It should be remembered
that misleading HbA1c results can be caused by increased RBCs turnover (as in anaemia,
haemoglobinopathies and pregnancy).
Impaired Glucose Regulation (IGR
Impaired glucose regulation (IGR) may also be referred to as non-diabetic hyperglycaemia
(NDH) or prediabetes. It describes blood glucose levels which are above the normal range
but not high enough for a diagnosis of diabetes mellitus. Diabetes UK estimate that around 1
in 7 adults in the UK have IGR. Many individuals with IGR will progress on to developing
T2DM and they are therefore at greater risk of microvascular and macrovascular
complications. There are two main types of IGR: 1) Impaired fasting glucose (IFG) - due to
hepatic insulin resistance. 2) Impaired glucose tolerance (IGT) - due to muscle insulin
resistance. Patients with IGT are more likely to develop T2DM and cardiovascular disease
than patients with IFG. The absolute risk of progression from IGT to type 2 DM is 33 % over 6
years follow up. This increased to 65% if individuals had both IGT and IFG. Triglycerides is
the strongest independent predictor of cardiovascular death in a Definitions: Management:
patient with impaired glucose tolerance IGT, ahead of other more established risk factors
such as smoking, body weight or blood pressu9re. · Impaired fasting glucose (IFG): A fasting
glucose from 6.1 to 7.0 mmol/l. (= from 110 to 125 mg/dl). · Impaired glucose tolerance (IGT):
A fasting plasma glucose ˂ 7.0 mmol/l and OGTT 2-hour value from 7.8 mmol/l to 11.1 mmol/l
(= from 140 to 200 mg/dl). · The role of HbA1c is diagnosing IGR and diabetes is currently
under review. · People with IFG should then be offered an oral glucose tolerance test (OGTT)
to rule out a diagnosis of diabetes. A result below 11.1 mmol/l but above 7.8 mmol/l indicates
that the person doesn't have diabetes but does have IGT. A 2 hour value of equal to or over
11.1 mmol/L is diagnostic of diabetes. · Diabetes UK suggests using the term 'prediabetes'
when discussing the condition with patients as research has shown that this term has the
most impact and is most easily understood and the term of impaired glucose regulation (IGR)
when talking to other healthcare professionals.
Lifestyle modification: weight loss, increased exercise, change in diet. · Drug therapy is not
currently licensed or recommended for patients with IGR in the UK. · At least yearly follow-up
with blood tests is recommended. EX: Patient with Fasting glucose 6.6 mmol/l >> Impaired
fasting glucose (IFG) >> hepatic insulin resistance.

OGTT
The OGTT has been used for many decades to diagnose diabetes. The test requires: ·
Overnight fast prior to the test. · Normal eating the previous day. · Baseline sample for
glucose using a fluoride tube. · 75 g oral anhydrous glucose usually washed down in 250-300
ml water (if hydrous glucose is used, the same weight represents a lower proportion of
glucose in molar measurement). · Further glucose sample taken at 120 minutes. · Plasma
tubes, such as fluoride oxalate, must be used as the test results have not been validated
using serum samples. · Serum samples without additives allow further metabolism of the
glucose by the red cells and may give a falsely low value. Fluoride oxalate prevents further
metabolism of glucose. The OGTT test has poor reproducibility but is particularly useful in
cases of borderline diabetes or gestational diabetes.
HBA1c

Glycosylated haemoglobin (HbA1c) is the most widely used measure of long-term glycaemic
control in diabetes mellitus. HbA1c is produced by the glycosylation of haemoglobin at a rate
proportional to the glucose concentration. The level of HbA1c therefore is dependant on: 1)
Red blood cell lifespan 2) Average blood glucose concentration A number of conditions can
interfere with accurate HbA1c interpretation:

Lower-than-expected levels of HbA1c (due to reduced RBCs lifespan)

Sickle-cell anaemia. Ø GP6D deficiency. Ø Hereditary spherocytosis. Ø Chronic liver disease.

Ø Splenomegaly Ø Hypertriglyceridemia.

Higher-than-expected levels of HbA1c (due to increased RBCs lifespan)

Ø Iron-deficiency anaemia. Ø Vitamin B12/folic acid def. Ø Alcohol dependence. Ø CRF Ø
Hyperbilirubinaemia. Ø Splenectomy.

HbA1c is generally thought to reflect the blood glucose over the previous '2-3 months’,
although there is some evidence it is weighed more strongly to glucose levels of the past 2-4
weeks. The relationship between HbA1c and average blood glucose is complex but has been
studied by the Diabetes Control and Complications Trial (DCCT). A new internationally
standardised method for reporting HbA1c has been developed by the International
Federation of Clinical Chemistry (IFCC). This will report HbA1c in mmol per mol of
haemoglobin without glucose attached.

N.B: From the above mentioned table we can see that: Average plasma glucose = (2 * HbA1c)
- 4.5

[ NB: Compared with subjects with normoglycaemia, beta cell mass is reduced: - By 50% in
subjects with Impaired Fasting Glucose, - By 65% in subjects with Type 2 diabetes, and -
Over 90% in subjects with type 1 diabetes. The suggestion therefore is one of gradual
insulin deficiency associated with increasing insulin resistance

Diabetes mellitus: management of type 2

NICE updated its guidance on the management of (T2DM): Dietary advice: · Encourage high
fibre, low glycaemic index sources of carbohydrates. · Include low-fat dairy products and oily
fish. · Control the intake of foods containing saturated fats and trans fatty acids. · Limited
substitution of sucrose-containing foods for other carbohydrates is allowable, but care
should be taken to avoid excess energy intake. · Discourage use of foods marketed
specifically at people with diabetes. · Initial target weight loss in an overweight person is
5-10%. HbA1c: · The general target for patients is 48 mmol/mol (DCCT = 6.5%). · HbA1c
levels below 48 mmol/mol (DCCT = 6.5%) should not be pursued. · However, individual
targets should be agreed with patients to encourage motivation. · HbA1c should be checked
every 2-6 months until stable, then 6 monthly. Blood pressure: · Target BP in DM is 135/75
mmHg: Target is < 140/80 mmHg or < 130/80 mmHg if end-organ damage is present. · ACEIs
or ARBs are first-line.

The NICE treatment algorithm has become much more complicated following the introduction
of new therapies for type 2 diabetes. · NICE still suggest a trial of lifestyle interventions first
(many local protocols now recommend starting metformin upon diagnosis). · Usually
metformin is first-line, followed by a sulfonylurea if the HbA1c remains > 6.5%. ·
Sulphonylureas can be used as first-line if the patient is not overweight, metformin is
contraindicated or not tolerated, or a rapid response to therapy is required. · The addition of
either sulphonylureas or insulin at step two. · It does not recommend use of older first
generation sulphonylureas such as chlorpropamide or glibenclamide (Daonil®), instead
recommending use of newer agents such as gliclazide (Diamicron®), glimepiride (Amaryl®)
or glipizide (MiniDiab®). · Glibenclamide (Daonil®) is long-acting SU and likely to increase the
risk of hypoglycaemia and hence “funny turns”. · Maximum daily dose of Diamicron is 160
mg, Amaryl is 6 mg. · If the patient is at risk from hypoglycaemia (or the consequences of)
(e.g. a driver) then a DPP-4 inhibitor or thiazolidinedione (TZD) should be considered rather
than a sulfonylurea. · If patient is intolerant to metformin >>> use TZD (Pioglitazone). ·
Meglitinides e.g. Repaglinide (Novonorm®) (insulin secretagogues): o Like sulfonylureas they
bind to an ATP-dependent K+ (KATP) channel on the cell membrane of pancreatic beta cells.
o Should be considered for patients with an erratic lifestyle. o They are particularly useful
for post-prandial hyperglycaemia. Patients take them shortly before meals. o Adverse effects
include weight gain and hypoglycaemia (but less so than sulfonylureas). · If HbA1c > 7.5%
then consider human insulin. · Metformin treatment should be continued after starting
insulin. · Exenatide should be used only when insulin would otherwise be started, or obesity
is a problem (BMI > 35 kg/m2) and/or the need for high dose insulin is likely. Continue only if
beneficial response occurs and is maintained (> 1.0 %
percentage point HbA1c reduction in 6 months and weight loss > 3% at 6 months). · (I.e. No:
exenatide plus insulin at the same regimen in T2DM. Exenatide should only be used in
combination with metformin, a sulfonylurea or both). Starting insulin: · Usually commenced if
HbA1c > 7.5%. · NICE recommend starting with human NPH insulin (isophane, intermediate
acting) taken at bed-time or twice daily according to need. · The appropriate recommended
starting dose for intermediate acting insulin is 0.2 U/kg or a flat dose of 10 U. · A titration
schedule based on fasting glucose levels is then recommended, with an increase of 2 U of
insulin every 3 days until fasting glucose is in the target range of 3.9-7.2 mmol/L. · If the
fasting plasma glucose is more than 10 mmol/L, then a more aggressive uptitration schedule
of 4 U every 3 days can be considered. · Insulin glargine (Lantus®): is a long acting insulin
analogue, it is an amalgam of Glycine and Arginine: Glycine is at chain A position A21 and two
Arginines are added to B chain position B30. · Glargine and Detemir are insulin analogues, as
such they are considered by NICE to be only suitable in cases: 1) Nocturnal hypoglycaemia is
a problem on isophane (NPH) insulin 2) Morning hyperglycaemia on isophane (NPH) insulin
results in difficult day-time blood glucose control 3) Rapid-acting insulin analogues are used
for meal-time blood glucose control. EX: the most appropriate initial insulin regime for young
patient after being diagnosed with new onset Type1 DM >>> Meal time Actrapid and
insulatard at night. Other risk factor modification: · Current NICE guidelines suggest giving
aspirin to all patients > 50 years and to younger patients with other significant risk factors.
However, recent evidence does not support this approach. The 2010 SIGN guidelines do not
advocate the use of aspirin for primary prevention in diabetics.
The management of blood lipids in T2DM has changed slightly. Previously, all patients with
T2DM > 40-years-old were prescribed statins. Now, patients > 40-years-old who have no
obvious cardiovascular risk (e.g. Non-smoker, not obese, normotensive etc.) and have a 10
years cardiovascular risk < 20% do not need to be given a statin. · If serum cholesterol
target not reach consider increasing simvastatin to 80mg once daily. · If target still not
reached consider using a more effective statin (e.g. Atorvastatin) or adding ezetimibe. ·
Target total cholesterol is < 4.0 mmol/l · High triglycerides and HDL-cholesterol are the
commonest lipid abnormality seen in type 2 DM, and both are associated with increased
cardiovascular risk. · In total, triglycerides above 1.7 are thought to be associated with a 30%
increase in relative cardiovascular risk. The secondary prevention: target of: total cholesterol
to be ˂4 mmol/L, LDL to be <2.0 mmol/L and of triglycerides to the 1.7 mmol/L. [ Cross-
sectional studies across the Caucasian population have suggested that triglyceride/HDL ratio
is most predictive of insulin resistance. As such TG/HDL can be used to stratify both future
risk of the development of CV disease and future risk of DM. Weight loss and exercise
training is seen to impact on TG/HDL ratio; metformin and pioglitazone which impact on
insulin resistance both lead to modest decrease in TG and an increases in HDL in some
patients.

Metformin Metformin is a biguanide used mainly in the treatment of type 2 DM. It has a
number of actions which improves glucose tolerance (see below). It acts to improve insulin
sensitivity through mechanisms that decrease hepatic gluconeogenesis and improved
muscle glucose utilisation, thus some insulin must be produced for it to have an effect.
Unlike sulphonylureas it does not cause hypoglycaemia and weight gain and is therefore
first-line, particularly if the patient is overweight.
Metformin is also used in polycystic ovarian syndrome (PCO) and non-alcoholic fatty liver
disease (NASH). Mechanism of action: 1) Increases insulin sensitivity (is an insulin
sensitizer). 2) Decreases hepatic gluconeogenesis. 3) May also reduce gastrointestinal
absorption of carbohydrates. Adverse effects: 1) Gastrointestinal upsets are common
(nausea, anorexia, diarrhoea), intolerable in 20%. 2) Reduced vitamin B12 absorption - rarely
a clinical problem. 3) Lactic acidosis with severe liver disease or renal failure. High dose (> 2
gm daily) interferes with enterohepatic circulation of the bile salts (Bile salt malabsorption)
>> diarrhoea. [ Long term treatment with metformin increases the risk of vitamin B12
deficiency. The possibility of metformin-associated B12 deficiency should be considered in
patients on metformin who suffer cognitive impairment, peripheral neuropathy, SCD of the
cord or anaemia. Contraindications: · It is contraindicated in subjects with renal failure,
hepatic failure and heart failure due to the association with lactic acidosis. · Chronic kidney
disease (CKD): NICE recommend reviewing metformin if the creatinine is > 130 µmol/l and
stopping metformin if creatinine > 150 µmol/l or the eGFR is less than 30 ml/min/1.73m2. · Do
not use during suspected episodes of tissue hypoxia (e.g. Recent MI, sepsis). · In the BNF,
metform in is listed as contraindicated within 6 weeks of MI. · Alcohol abuse is a relative
contraindication. · Stop 2 days before general anaesthetic, restart when renal function
normal. · Stop prior to IV contrast e.g. angiography, restart when renal function normal. NB:
It is now increasingly recognised that lactic acidosis secondary to metformin is rare,
although it remains important in the context of exams.

NB: Metformin is now sometimes used in pregnancy, for example in women with polycystic
ovarian syndrome. NB: Metformin may be continued (or initiated) with an eGFR less than 60
mL/min/1.73 m2, but renal function should be monitored closely (every 3-6 months). The
drug should be stopped once eGFR falls to less than 30 mL/min/1.73 m2 (creatinine more
than 150 µmol/L). N.B: Gastrointestinal side-effects are more likely to occur if metformin is
not slowly titrated up. The BNF advises leaving at least 1 week before increasing the dose. If
the patient is intolerant to standard metformin, then modified release preparations should be
tried. N.B: The most appropriate prescription is: R/ Metformin 500mg OD with food for 14
days, then metformin 500mg bid for 14 days then review. Sulfonylureas (SU) Sulfonylureas
are oral hypoglycaemic drugs used in the management of T2DM. They work by increasing
pancreatic insulin secretion (insulin secretagogues); and hence are only effective if
functional B-cells are present. On a molecular level they bind to an ATP-dependent K+
(KATP) channel on the cell membrane of pancreatic beta cells. Common adverse effects: 1)
Hypoglycaemic episodes (more common with long acting preparations such as
chlorpropamide) 2) Weight gain. Rarer adverse effects: 1) SIADH (syndrome of inappropriate
ADH secretion). 2) Bone marrow suppression. 3) Liver damage (cholestatic). 4)
Photosensitivity 5) Peripheral neuropathy 6) Sulphonylureas are a class of drugs associated
with increased risk of RBCs oxidation and the absence of G6PD leads to haemolytic anaemia.
7) Sulfonylureas should be avoided in pregnancy and breast feeding
Dr Khaled Magraby MRCP Notes Endocrinology 352 EX: A
62-year-old Caribbean man with new onset type 2 DM presents to the ER. He has increasing
lethargy and tiredness since starting a sulphonylurea a few days earlier. On examination he
has jaundiced sclerae, his BP is 135/72 mmHg, and pulse is 95. His mucous membranes look
a little pale. Lab: Hb=10, Bilirubin = 80 µmol/L (N <17), Heinz bodies in peripheral film. The
most likely diagnosis is Glucose-6-phosphate dehydrogenase (G6PD) deficiency.
[ Thiazolidinediones (TZD) Thiazolidinediones are a new class of agents used in the ttt of
type 2 DM. They are PPAR-gamma receptor agonists and reduce peripheral insulin
resistance. The Peroxisome Proliferator-Activated Receptor Gamma (PPAR-gamma
receptor) is an intracellular nuclear receptor. Its natural ligands are free fatty acids and it is
thought to control adipocyte differentiation and function. i.e it is activated by free fatty acids
and the TZD such as pioglitazone. It is an insulin sensitiser. It upregulates genes for enzymes
which deal with the metabolism of free fatty acids. These lead to increased peripheral insulin
sensitivity, and improve glucose uptake. Pioglitazone is not associated with hypoglycaemia.
It reduces HbA1c by between 1 and 1.3%. Rosiglitazone was withdrawn in 2010 following
concerns about the cardiovascular side-effect profile. Adverse effects: 1) Weight gain. 2)
Fluid retention (in around 10% of patients) - therefore contraindicated in heart failure. The
risk of fluid retention is increased if the patient also takes insulin. 3) Liver impairment:
monitor LFTs. 4) Recent studies have indicated an increased risk of fractures as it decrease
bone mineral density. 5) Bladder cancer: recent studies have showed an increased risk of
bladder cancer in patients taking pioglitazone (hazard ratio 2.64).
NICE guidance on thiazolidinediones: Only continue if there is a reduction of > 0.5
percentage points in HbA1c in 6 months. Diabetes Mellitus: GLP-1 and the new drugs A
number of new drugs to treat diabetes mellitus have become available in recent years. Much
research has focused around the role of glucagon-like peptide-1 (GLP-1), a hormone
released by the small intestine in response to an oral glucose load. Whilst it is well known
that insulin resistance and insufficient B-cell compensation occur other effects are also seen
in (T2DM). In normal physiology an oral glucose load results in a greater release of insulin
than if the same load is given intravenously - this known as the “incretin effect”. This effect is
largely mediated by GLP-1 and is known to be decreased in T2DM. Increasing GLP-1 levels,
either by the administration of an analogue or inhibiting its breakdown, is therefore the target
of two recent classes of drug. Glucagon-like peptide-1 (GLP-1) mimetics (e.g. Exenatide or
Liraglutide): · Increase insulin secretion · Inhibit glucagon secretion by the liver · It
suppresses appetite and slow gastric empting · It does not increase insulin sensitivity ·
licensed for use in T2DM · Must be given by subcutaneous injection within 60 minutes before
the morning and evening meals. It should not be given after a meal. · Patient has no need to
self-monitor his blood glucoses by glucometer. · May be combined with metformin, a
sulfonylurea or a thiazolidinedione. · Typically results in weight loss. · It is a good choice in
patients who are significantly overweight. · Major adverse effect is nausea and vomiting.
NICE guidelines on the use of Exenatide / Liraglutide: · Should be used only when: 1) Insulin
would otherwise be started, 2) Obesity is a problem (BMI > 35 kg/m2) and 3) The need for
high dose insulin is likely. · Continue only if beneficial response occurs and is maintained (>
1.0 % percentage point HbA1c reduction and weight loss > 3% in 6 months). The Medicines
and Healthcare products Regulatory Agency has issued specific warnings on the use of
exenatide: · Increased risk of severe pancreatitis. · Increased risk of renal impairment.
Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. Vildagliptin, Sitagliptin): · Oral preparation. ·
Trials to date show that the drugs are relatively well tolerated with no increased incidence of
hypoglycaemia. · Do not cause weight gain. · SE: GIT disturbance: nausea, flatulence,
diarrhoea and constipation. NICE guidelines on DPP-4 inhibitors: · Continue DPP-4 inhibitor
only if there is a reduction of > 0.5 percentage points in HBA1c in 6 months. · NICE suggest
that a DPP-4 inhibitor might be preferable to a thiazolidinedione if further weight gain would
cause significant problems, a thiazolidinedione is contraindicated or the person has had a
poor response to a thiazolidinedione.

Persistent depressive disorder

Also called dysthymia. Often milder than MDD(major depressive illness; ≥ 2 depressive
symptoms lasting ≥ 2 years (≥ 1 year in children), with any remission lasting ≤ 2 months.

Allopurinol
Sometimes starting allopurinol can trigger a gout attack. This is because some of the
crystals can dislodge into the joint as they get smaller which can cause an attack.

Carcinoid tumors
Carcinoid tumors arise from neuroendocrine cells, most commonly in the intestine or lung.
Neuroendocrine cells secrete 5-HT, which undergoes hepatic first-pass metabolism and
enzymatic breakdown by MAO in the lung. If 5-HT reaches the systemic circulation (eg, after
liver metastasis), carcinoid tumor may present with
carcinoid syndrome—episodic flushing, diarrhea, wheezing, right-sided valvular heart
disease (eg, tricuspid regurgitation, pulmonic stenosis), niacin deficiency (pellagra).
Histology: prominent rosettes (arrow in A), chromogranin A ⊕, synaptophysin ⊕.
Treatment: surgical resection, somatostatin analog (eg, octreotide) or tryptophan
hydroxylase inhibitor (eg, telotristat) for symptom control.

Rule of thirds:
1/3 metastasize
1/3 present with 2nd malignancy
1/3 are multiple

Electroconvulsive therapy (ECT)

Electroconvulsive therapy (ECT) is a useful treatment option for patients with severe
depression refractory to medication or those with psychotic symptoms.

Short-term side-effects: · Headache · Nausea · Short term memory impairment: Memory loss
of events prior to ECT · Cardiac arrhythmia Long-term side-effects: · Some patients report
impaired memory [ · Musculoskeletal injury (Crush fracture of the vertebral bodies) has been
reported after ECT, but with adequate anaesthetisation, this is rare.
Although ECT, by definition, causes a controlled seizure there is NO increased risk of
epilepsy in the long-term. The only absolute contraindications is raised intracranial pressure.

Although ECT has been safely used one month following a stroke, it is advisable to avoid
treatment in the first three months. Most guidelines state that a recent CVA (within 1 to 3
months) is a contraindication. ECT would usually be avoided in a recent cerebrovascular
accident.

Adenosine
Increase K+ out of cells hyperpolarizing the cell and decrease ICa, decreasing AV node
conduction.
Drug of choice in diagnosing/terminating certain forms of SVT. Very short acting (~ 15 sec).
Effects blunted by theophylline and caffeine (both are adenosine receptor antagonists).
Adverse effects include flushing, hypotension, chest pain, sense of impending doom,
bronchospasm.

Calcium channel blockers

Amlodipine, clevidipine, nicardipine, nifedipine, nimodipine (dihydropyridines, act on
vascular smooth muscle);
diltiazem, verapamil (nondihydropyridines, act on heart).
MECHANISM
Block voltage-dependent L-type calcium channels of cardiac and smooth muscle decrease
muscle contractility.
Vascular smooth muscle—amlodipine = nifedipine > diltiazem > verapamil.
Heart—verapamil > diltiazem > amlodipine = nifedipine.
ClINICAl uSE
Dihydropyridines (except nimodipine): hypertension, angina (including vasospastic type),
Raynaud phenomeno
. Nimodipine: subarachnoid hemorrhage (prevents cerebral vasospasm).
Nicardipine, clevidipine: hypertensive urgency or emergency. Nondihydropyridines:
hypertension, angina, atrial fibrillation/flutter.

AdvERSE EFFECTS
Gingival hyperplasia. Dihydropyridine: peripheral edema, flushing, dizziness.
Nondihydropyridine: cardiac depression, AV block, hyperprolactinemia (verapamil),
constipation

Lithium
MEchaNisM
Not established; possibly related to inhibition of phosphoinositol cascade.

cliNical UsE Mood stabilizer for bipolar disorder; treats acute manic episodes and prevents
relapse.

aDVErsE EFFEcts Tremor, hypothyroidism, hyperthyroidism, polyuria (causes nephrogenic

diabetes insipidus), teratogenesis (causes Ebstein anomaly). Narrow therapeutic window
requires close monitoring of serum levels. Almost exclusively excreted by kidneys; most is
reabsorbed at PCT via Na+ channels. Thiazides, NSAIDs, and other drugs affecting clearance
are implicated in lithium toxicity.

LiTHIUM:
LiT-Low Thyroid (hypothyroidism)
H-Heart (Ebstein anomaly)
I- Insipidus (nephrogenic diabetes insipidus)
UM- Unwanted Movements (tremor)

MODY 3 (also HNF1A-MODY) is a form of maturity-onset diabetes of the young. It is caused

by mutations of the HNF1-alpha gene, a homeobox gene on human chromosome 12. This is
the most common type of MODY in populations with European ancestry, accounting for about
70% of all cases in Europe. HNF1α is a transcription factor (also known as transcription
factor 1, TCF1) that is thought to control a regulatory network (including, among other genes,
HNF1α) important for differentiation of beta cells. Mutations of this gene lead to reduced
beta cell mass or impaired function
Takotsubo cardiomyopathy: broken heart syndrome—ventricular apical ballooning likely due
to increased sympathetic stimulation (eg, stressful situations).

Kearns-Sayre syndrome (KSS) is characterized by the onset of ophthalmoparesis and

pigmentary retinopathy [1] before age 20 years. Other frequently associated clinical features
include cerebellar ataxia, cardiac conduction block, raised cerebrospinal fluid (CSF) protein
content, and proximal myopathy

. Affected children have short stature and often have multiple endocrinopathies, including
diabetes mellitus, hypoparathyroidism, and Addison disease. [2] Renal tubular acidosis
(proximal or distal) has been described in numerous cases, with occasional progression to
end-stage renal failure.
Bilateral sensorineural hearing loss is almost universal in those who survive into the fourth
decade of life; this may not be fully corrected with hearing aids. No disease-modifying
therapy is available for Kearns-Sayre syndrome.

Erosive osteoarthritis
is a disorder that most often involves the hands of postmenopausal women. It can begin
abruptly with pain, swelling, and tenderness.
Distal interphalangeal joints are involved most frequently, followed by proximal
interphalangeal joints. Occasionally there is metacarpophalangeal, carpal, or large joint
involvement.
Radiologically, the disorder is characterized by central erosions and the "gull wing"
deformity

A germ cell tumor is a cancer that develops from cells in the reproductive system called germ
cells
In men, germ cells are responsible for producing sperm. Most germ cell tumors in teenage
boys and men start in one of the testicles. There are two different categories of germ cell
tumors: seminoma and non-seminoma. Generally, seminomas grow and spread more slowly
than non-seminomas, but both types of tumors should be treated quickly.

serum tumor markers,

High levels of any one of three tumor markers, called
alpha-fetoprotein (AFP),
beta human chorionic gonadotropin (hCG), and
lactate dehydrogenase (LDH),
may indicate a germ cell tumor.
High AFP levels can also help identify the type of germ cell tumor, by showing whether it is a
pure seminoma or mixed with non-seminoma, since AFP is not made by seminomas.
However, hCG and/or LDH can be higher if a man has a seminoma, non-seminoma, or mixed
tumor. If markers are elevated at diagnosis, changes in their levels can tell your doctor
whether the tumor is responding to treatment.

Hot T-bone stEAK”:

IL-1: fever (hot).
IL-2: stimulates T cells.
IL-3: stimulates bone marrow.
IL-4: stimulates IgE production.
IL-5: stimulates IgA production.
IL-6: stimulates aKute-phase protein production.

TNF ALPHA
Activates endothelium. Causes WBC recruitment, vascular leak.
Causes cachexia in malignancy.
Maintains granulomas in TB. IL-1, IL-6, TNF-α can mediate fever and sepsis.

Interleukin-12Induces differentiation of T cells into Th1 cells.

Activates NK cells.
Facilitates granuloma formation in TB.
C3b—opsonization.
C3a, C4a, C5a—anaphylaxis.
C5a—neutrophil chemotaxis
C5b-9 (MAC)—cytolysis.

Albumin in sepsis
Human serum albumin is a small (66kD) globular protein representing over 60 % of the total
plasma protein content.
t is a multifunctional plasma protein ascribed ligand-binding and transport properties as well
as antioxidants and enzymatic functions. It maintains colloid osmotic pressure, modulates
inflammatory response and may influence oxidative damage

Hypoalbuminemia is common in the intensive care unit and may be due to decreased
synthesis by the liver and/or to increased losses or increased proteolysis and clearance

Plummer disease also called TMNG Toxic multinodular goiter (TMNG), also known as
multinodular toxic goiter (MNTG), is an active multinodular goiter associated with
hyperthyroidism.
Toxic multinodular goiter is the second most common cause of hyperthyroidism (after
Graves' disease) in the developed world, whereas iodine deficiency is the most common
cause of hypothyroidism in developing-world countries where the population is iodine-
deficient. Toxic multinodular goiter Focal patches of hyperfunctioning follicular cells
distended with colloid working independently of TSH (due to TSH receptor mutations in 60%
of cases). release of T3 and T4. Hot nodules are rarely malignant

Sarcomas are cancers that develop from connective tissues in the body, such as muscles,
fat, bones, the linings of joints, or blood vessels. There are many types of sarcomas.
Rhabdomyosarcoma (RMS) is a type of sarcoma made up of cells that normally develop into
skeletal (voluntary) muscles.

Well before birth, cells called rhabdomyoblasts (which will eventually form skeletal muscles)
begin to form. These are the cells that can develop into RMS

Common sites of RMS include:

The head and neck (such as near the eye, inside the nasal sinuses or throat, or near the spine
in the neck)
Urinary and reproductive organs (bladder, prostate gland, or any of the female organs)
Arms and legs
Trunk (chest and abdomen)

Types of rhabdomyosarcoma

There are 2 main types of RMS, along with some less common types.

Embryonal rhabdomyosarcoma (ERMS)

ERMS usually affects children in their first 5 years of life, but it can occur at older ages as
well.

ERMS tends to occur in the head and neck area, bladder, vagina, or in or around the prostate
and testicles.

Two subtypes of ERMS, botryoid and spindle cell rhabdomyosarcomas, tend to have a better
prognosis (outlook) than the more common conventional form of ERMS.

Alveolar rhabdomyosarcoma (ARMS)

ARMS typically affects all age groups equally. It makes up a larger portion of RMS in older
children, teens, and adults than in younger children (because ERMS is less common at older
ages).

ARMS most often occurs in large muscles of the trunk, arms, and legs.

ARMS tends to grow faster than ERMS, and it usually requires more intense treatment.
However, in some cases of ARMS, the cancer cells lack certain gene changes, which makes
these cancers act more like ERMS (and allows doctors to give less intense treatment).

Anaplastic rhabdomyosarcoma and undifferentiated sarcoma

Anaplastic rhabdomyosarcoma (also called pleomorphic rhabdomyosarcoma) is an

uncommon type that occurs mainly in adults and is very rare in children.

Some doctors also group undifferentiated sarcomas with the rhabdomyosarcomas. Using lab
tests, doctors can tell that these cancers are sarcomas, but the cells don’t have any features
that help classify them further.

Both of these uncommon cancers tend to grow quickly and usually require intensive
treatment.

Rhabdomyosarcoma in adults

Most rhabdomyosarcomas develop in children and teens, but they can also occur in adults.
Adults are more likely to have faster-growing types of RMS and to have them in parts of the
body that are harder to treat. Because of this, RMS in adults is often harder to treat
effectively

Basal cell carcinoma more common above upper lip Squamous cell carcinoma more common
below lower lip Sun exposure strongly predisposes to skin cancer.
Basal cell carcinoma
Most common skin cancer. Found in sun-exposed areas of body (eg, face). Locally invasive,
but rarely metastasizes. Waxy, pink, pearly nodules, commonly with telangiectasias, rolled
borders A, central crusting or ulceration. BCCs also appear as nonhealing ulcers with
infiltrating growth B or as a scaling plaque (superficial BCC) C. Basal cell tumors have
“palisading”

Papillary carcinoma
Most common. Empty-appearing nuclei with central clearing (“Orphan Annie” eyes) A,
psamMoma bodies, nuclear grooves (Papi and Moma adopted Orphan Annie). Increase risk
with RET/ PTC rearrangements and BRAF mutations, childhood irradiation.
Papillary carcinoma: most prevalent, palpable lymph nodes. Good prognosis

Graves disease
Most common cause of hyperthyroidism.
Thyroid-stimulating immunoglobulin (IgG, can cause transient neonatal hyperthyroidism;
type II hypersensitivity) stimulates TSH receptors on thyroid (hyperthyroidism, diffuse
goiter),
dermal fibroblasts (pretibial myxedema), and orbital fibroblasts

Graves orbitopathy). Activation of T-cells >lymphocytic infiltration of retroorbital space

increase cytokines (eg, TNF-α, IFN-γ) Increase fibroblast secretion of hydrophilic GAGs
increase osmotic muscle swelling, muscle inflammation, and adipocyte count exophthalmos
osmotic A.
Often presents during stress (eg, pregnancy). Associated with HLA-DR3 and HLA-B8.
Histology: tall, crowded follicular epithelial cells; scalloped colloid

`RESPIRATORY—PhYSIOlOgY Lung volumes and capacities Note: a capacity is a sum of ≥ 2

physiologic volumes.
Tidal volumeAir that moves into lung with each quiet inspiration, typically 500 mL
Inspiratory reserve volume Air that can still be breathed in after normal inspiration

volume Air that can still be breathed out after normal expiration
Residual volumeAir in lung after maximal expiration; RV and any lung capacity that includes
RV cannot be measured by spirometry
Inspiratory capacityIRV + TV Air that can be breathed in after normal exhalation
Functional residual capacity RV + ERV Volume of gas in lungs after normal expiration;
outward pulling force of chest wall is balanced with inward collapsing force of lungs
Total lung capacityIRV + TV + ERV + RV = VC + RV Volume of gas present in lungs after a
maximal inspiration
Vital capacityI RV + TV + ERV Maximum volume of gas that can be expired after a maximal
inspiration

Anagen effluvium
Anagen effluvium is a form of nonscarring alopecia commonly associated with
chemotherapy.
In this disorder, affected anagen hairs suffer a toxic or inflammatory insult, resulting in
fracture of the hair shaft. Anagen effluvium is often referred to as chemotherapy-induced
alopecia, as it can be triggered by antimetabolites, alkylating agents, and mitotic inhibitors
administered as chemotherapeutic therapy. Shedding usually takes place within 14 days of
administration of the offending drug, however, in many instances it is reversible, with hair
regrowth growth upon discontinuation of the offending agen

Telogen Effluvium
Telogen Effluvium more hairs than usual move into the telogen (resting) phase and shed, so
you may notice more hair falling out than usual. Telogen Effluvium is often caused by a
physical or psychological trigger and often resolves itself spontaneously

Hair growth
The hair growth cycle has three phases:
the growing phase, anagen;
the regressing phase, catagen; and
the resting phase, telogen

Bulimia nervosa
Recurring episodes of binge eating with compensatory purging behaviors at least weekly
over the last 3 months.
BMI often normal or slightly overweight (vs anorexia).
Associated with parotid gland hypertrophy (may see raised serum amylase), enamel erosion,
Mallory-Weiss syndrome, electrolyte disturbances (eg, decrease K+, decrease Cl−),
metabolic alkalosis, dorsal hand calluses from induced vomiting (Russell sign).
Treatment: psychotherapy, nutritional rehabilitation, antidepressants (eg, SSRIs). Bupropion
is contraindicated due to seizure risk.

Anorexia nervosa
Intense fear of weight gain, overvaluation of thinness, and body image distortion leading to
calorie restriction and severe weight loss resulting in inappropriately low body weight (BMI <
18.5 kg/m2 for adults).
May present with hypothyroidism, amenorrhea, osteoporosis, lanugo.
Binge-eating/purging type—recurring purging behaviors (eg, laxative or diuretic abuse,
selfinduced vomiting) or binge eating over the last 3 months.

Restricting type—primary disordered behaviors include dieting, fasting, and/or over-

exercising. No recurring purging behaviors or binge eating over the last 3 months.

Refeeding syndrome—often occurs in significantly malnourished patients with sudden

calorie intake Icrease insulin Decrease PO4 3−, decrease K+, decrease Mg2+ cardiac
complications, rhabdomyolysis, seizures.
Treatment: nutritional rehabilitation, psychotherapy, olanzapine.

Left testicular Ca para aortic LN

Right testicular ca pre aortic LN

Manic episode
Distinct period of abnormally and persistently elevated, expansive, or irritable mood and
activity or energy lasting ≥ 1 week.
Diagnosis requires hospitalization or marked functional impairment with ≥ 3 of the following
manics DIG FAST):
Distractibility
Impulsivity/Indiscretion—seeks pleasure without regard to consequences (hedonistic)
Grandiosity—inflated self-esteem
Flight of ideas—racing thoughts
Increasebgoal-directed Activity/psychomotor Agitation
Decrease need for Sleep
Talkativeness or pressured speech

Hypomanic episode

Similar to a manic episode except mood disturbance is not severe enough to cause marked
impairment in social and/or occupational functioning or to necessitate hospitalization.
Abnormally increase activity or energy usually present. No psychotic features. Lasts ≥ 4
consecutive days.

Bipolar disorder

Bipolar I—≥ 1 manic episode +/− a hypomanic or depressive episode (may be separated by
any length of time).
Bipolar II—a hypomanic and a depressive episode (no history of manic episodes). Patient’s
mood and functioning usually normalize between episodes. Use of antidepressants can
destabilize mood. High suicide risk. Treatment: mood stabilizers (eg, lithium, valproic acid,
carbamazepine, lamotrigine), atypical antipsychotics.

Cyclothymic disorder—milder form of bipolar disorder fluctuating between mild depressive

and hypomanic symptoms. Must last ≥ 2 years with symptoms present at least half of the
time, with any remission lasting ≤ 2 months

The time to reach steady state is defined by the elimination half-life of the drug.
After 1 half-life, you will have reached 50% of steady state.
After 2 half-lives, you will have reached 75% of steady state, and after 3 half-lives you will
have reached 87.5% of steady state.

Ankylosing spondylitis (AS)

Ankylosing spondylitis is a HLA-B27 associated spondyloarthropathy.
It typically presents in males (sex ratio 5:1) aged 20-30 years old.
It has polygenic inheritance

Features:
Typically a young man who presents with chronic lower back pain radiating to his buttocks,
and stiffness of insidious onset. after periods of inactivity and improves with exercise.
Stiffness is usually worse in the morning more than 30 minutes and worse
The patient may experience pain at night (waking in the second half of the night) which
improves on getting up.
Peripheral arthritis (25%, more common if female)
Muscular strain is the commonest cause of back pain in general practice but chronic pain for
more than 3 months may indicate AS and should be investigated

Note The commonest subtype HLA associations are HLA B*2705 (Caucasians), B*2704
(Chinese, Japanese) and B*2702 (Mediterranean). The B*2706 subtype is weakly associated
and commonly found in normal South East Asian individuals.

Clinical examination:
Reduced lateral flexion
Reduced forward flexion - Schober's test - a line is drawn 10 cm above and 5 cm below the
back dimples (dimples of Venus). The distance between the two lines should increase by
more than 5 cm when the patient bends as far forward as possible
Reduced chest expansion
Sacroiliac joint tenderness
Later (In the advanced stages of AS): loss of lumbar lordosis, buttock atrophy and an
accentuated thoracic kyphosis.

Other features
Apical fibrosis
A nterior uveitis
Aortic regurgitation
Achilles tendonitis
A V node block
A myloidosis
cauda equina syndrome Peripheral Investigation: arthritis ( 25 %, more common if female )

Investigation:
arthritis ( 25 %, more common if female )
Inflammatory markers (ESR, CRP) are typically raised although normal levels do not exclude
ankylosing spondylitis.
HLA-B27: It is not essential for the diagnosis of AS. It not used as a screening test for
AS. It is of little use in making the diagnosis and as it is positive in:
o 90% of patients with ankylosing spondylitis
o 75% of patient with Reiter's syndrome.
o 10% of normal patients
Its sensitivity and specificity depend on the racial and ethnic background of the patien
. Acute anterior uveitis is more common in B27 positive than negative patients.

Plain x-ray of the sacroiliac joints is the most useful investigation in establishing the
diagnosis and monitoring, but changes may not be seen for many years after the onset of
symptoms.
Radiographs may be normal early in disease, later changes include:
Sacroilitis: sub-chondral erosions, sclerosis
Squaring of lumbar vertebrae
'Bamboo spine' (late & uncommon)
Syndesmophytes: due to ossification of outer fibers of annulus fibrosus
Chest x-ray: apical fibrosis

Spirometry may show a restrictive defect due to a combination of pulmonary fibrosis,

kyphosis and ankylosis of the costovertebral joints.

Current British Society for Rheumatology recommendations state that the modified New York
criteria should be used to diagnose ankylosing spondylitis:

Clinical Criteria:
Low back pain, present for more than 3 months,
improved by exercise but not relieved by rest.
Limitation of lumbar spine motion in both the sagittal and frontal planes.
Limitation of chest expansion relative to normal values for age and sex.

Radiological Criteria:
Sacroiliitis on x ray.

Diagnose:
Definite AS if the radiological criterion is present plus at least one clinical criterion.
Probable AS if 3 clinical criteria are present alone or if the radiological criterion is present
but no clinical criteria are present.

Both HLA-B27 and sacroiliitis on MRI play a major role in the recently proposed Assessment
of Spondyloarthritis International Society (ASAS) diagnostic algorithm. This may replace the
modified New York criteria in the future.

Management:
The following is partly based on the 2010 EULAR guidelines (European League Against
Rheumatism):
The best initial therapy for AS is NSAIDs and physiotherapy.
NSAIDs are the first-line treatment.
Physiotherapy
Encourage regular exercise such as swimming
If symptoms are not controlled additional analgesics (for example, amitriptyline).
Corticosteroid injections or oral corticosteroids can be used.
The DMARDs which are used to treat RA (such as sulphasalazine) are only really useful if
there is peripheral joint involvement as it doesn’t improve spinal mobility.
The 2010 EULAR guidelines suggest: 'Anti-TNF therapy should be given to patients with
persistently high disease activity despite conventional treatments' (severe ankylosing
spondylitis which has failed to respond to NSAIDs.) Research is ongoing to see whether
anti-TNF therapies such as etanercept and adalimumab should be used earlier in the course
of the disease.

Hampton hump refers to a dome-shaped, pleural-based opacification in the lung most

commonly due to pulmonary embolism and lung infarction (it can also result from other
causes of pulmonary infarction (e.g. vascular occlusion due to angioinvasive aspergillosis).

Osteogenesis imperfecta (brittle bone disease)

Osteogenesis imperfecta (more commonly known as brittle bone disease) is a group of

disorders of collagen metabolism resulting in bone fragility and fractures. The most
common, and milder, form of osteogenesis imperfecta is type 1.

Overview:
Autosomal dominant.
Abnormality in type 1 collagen due to decreased synthesis of pro-alpha 1 or pro-alpha 2
collagen polypeptides.

Features: Presents in childhood Fractures following minor trauma Blue sclera

Deafness secondary to otosclerosis Dental imperfections are common

Treatement and management

Because osteogenesis imperfecta (OI) is a genetic condition, it has no cure.
For many years, surgical correction of deformities, physiotherapy, and the use of orthotic
support and devices to assist mobility (eg, wheelchairs) were the primary means of
treatment

Pharmacological management
Bisphosphonates (eg, pamidronate) are synthetic analogues of pyrophosphate that inhibit
osteoclast-mediated bone resorption on the endosteal surface of bone by binding to
hydroxyapatite. As a result, unopposed osteoblastic new bone formation on the periosteal
surface results in an increase in cortical thickness. Their use in the treatment of OI is on off-
label application.

Adverse effects of pamidronate include an acute febrile reaction, mild hypocalcemia,

leukopenia, a transient increase in bone pain, and scleritis with or without anterior uveitis.
With milder forms of OI, the indications for bisphosphonate therapy have yet to be evaluated.

Growth hormone is known to act on the growth plate and also stimulate osteoblast function,
possibly via insulinlike growth factor (IGF)-1 and IGF-binding protein (IGFBP)-3.

Bone marrow transplantation (BMT) has been advocated as a potential future therapeutic
modality for OI. Transplantation of adult bone marrow in utero has been shown to decrease
perinatal lethality in a murine model of OI

Carbamazepine and oxcarbazepine are considered first-line therapy in trigeminal neuralgia

Lamotrigine and baclofen are second-line therapy.
Other treatments are third line and the evidence for their efficacy is scant

ARDS

PAThOPhYSIOlOg
YAlveolar insult >release of pro-inflammatory cytokines >neutrophil recruitment, activation,
and release of toxic mediators (eg, reactive oxygen species, proteases, etc) >capillary
endothelial damage and increase vessel permeability >leakage of protein-rich fluid into
alveoli formation of intra-alveolar hyaline membranes (arrows in A) and noncardiogenic
pulmonary edema (normal PCWP).

Loss of surfactant also contributes to alveolar collapse.

CAUSES
Sepsis (most common), aspiration, pneumonia, trauma, pancreatitis.
DIAgNOSIS MNEMONIC
Diagnosis of exclusion with the following criteria (ARDS):
Abnormal chest X-ray (bilateral lung opacities) B
Respiratory failure within 1 week of alveolar insult
Decreased Pao2 /Fio2 (ratio < 300, hypoxemia due to intrapulmonary shunting and diffusion
abnormalities)
Symptoms of respiratory failure are not due to HF/fluid overload

CONSEQUENCES
Impaired gas exchange, lung compliance; pulmonary hypertension.

mANAgEmENTTreat the underlying cause. Mechanical ventilation: tidal volume, PEEP (keeps
alveoli open during expiration).

Hypertension

Persistent systolic BP ≥ 130 mm Hg and/or diastolic BP ≥ 80 mm Hg.

RISK FACTORS
age, obesity, diabetes, physical inactivity, high-sodium diet, excess alcohol intake, tobacco
smoking, family history; incidence greatest in Black > White > Asian populations.

FEATuRES
A 90% of hypertension is 1° (essential) and related to increase CO or increase TPR.
Remaining 10% mostly 2° to renal/renovascular diseases such as fibromuscular dysplasia
(characteristic “string of beads” appearance of renal artery A, usually seen in adult females)
and atherosclerotic renal artery stenosis or to 1° hyperaldosteronism.

Hypertensive urgency—severe (≥ 180/≥ 120 mm Hg) hypertension without acute end-organ

damage.

Hypertensive emergency—severe hypertension with evidence of acute end-organ damage

eg, encephalopathy, stroke, retinal hemorrhages and exudates, papilledema, MI, HF, aortic
dissection, kidney injury, microangiopathic hemolytic anemia, eclampsia).

PREdISPOSES TO
CAD, LVH, HF, atrial fibrillation; aortic dissection, aortic aneurysm; stroke; CKD
(hypertensive nephropathy); retinopathy
Hypertrophic cardiomyopathy

60–70% of cases are familial, autosomal dominant (most commonly due to mutations in
genes encoding sarcomeric proteins, such as myosin binding protein C and β-myosin heavy
chain).

Causes syncope during exercise and may lead to sudden death (eg, in young athletes) due to
ventricular arrhythmia.

Findings: S4, systolic murmur.

May see mitral regurgitation due to impaired mitral valve closure.

Classified as hypertrophic obstructive cardiomyopathy when outflow from LV is obstructed.

Asymmetric septal hypertrophy and systolic anterior motion of mitral valve outflow
obstruction dyspnea, possible syncope.

Other causes of concentric LV hypertrophy: chronic HTN, Friedreich ataxia.

Diastolic dysfunction ensues. Marked ventricular concentric hypertrophy

Treatment: cessation of high-intensity athletics, use of β-blocker or nondihydropyridine

Ca2+ channel blockers (eg, verapamil). ICD if syncope occurs. Avoid drugs that decrease
preload (eg, diuretics, vasodilators)

Atypical anti depressants

Bupropion
Inhibits NE and DA reuptake. Also used for smoking cessation.
Toxicity: stimulant effects (tachycardia, insomnia), headache, seizures in patients with
bulimia and anorexia nervosa. risk of sexual side effects and weight gain compared to other
antidepressants

Hypersensitivity pneumonitis Mixed type III/IV hypersensitivity reaction to environmental

antigens. Often seen in farmers and bird-fanciers. Acutely, causes dyspnea, cough, chest
tightness, fever, headache. Often self-limiting if stimulus is removed. Chronically, leads to
irreversible fibrosis with noncaseating granuloma, alveolar septal thickening, traction
bronchiectasis.

Polycystic ovarian syndrome A Hyperinsulinemia and/or insulin resistance hypothesized to

alter hypothalamic hormonal feedback response Raised LH:FSH,( high LH and low
fsh)androgens (eg, testosterone) from theca interna cells, rate of follicular maturation
unruptured follicles (cysts) + anovulation. Common cause of fertility in females. Enlarged,
bilateral cystic ovaries A; presents with amenorrhea/oligomenorrhea, hirsutism, acne,
fertility. Associated with obesity, acanthosis nigricans. risk of endometrial cancer 2° to
unopposed estrogen from repeated anovulatory cycles. Treatment: cycle regulation via
weight reduction ( peripheral estrone formation), OCPs (prevent endometrial hyperplasia due
to unopposed estrogen); clomiphene (ovulation induction); spironolactone, finasteride,
flutamide to treat hirsutism

Methotrexate (antidote is leucovorin)

Mechanism

Folic acid analog that competitively inhibits dihydrofolate reductase ResUlting in decrease
dTMP leading to decrease DNA synthesis

Clinical use

Cancers: leukemias (ALL), lymphomas, choriocarcinoma, sarcomas

Nonneoplastic: ectopic pregnancy, medical abortion (with misoprostol), rheumatoid arthritis,
psoriasis, IBD, vasculitis

Adverse effects of methotrexate

Myelosuppression (reversible with leucovorin “rescue”),
hepatotoxicity,
mucositis (eg, mouth ulcers),
pulmonary fibrosis,
folate deficiency (teratogenic),
nephrotoxicity

Cyclophosphamide, ifosfamide
Mechanism :
Cross-link DNARequire
bioactivation by liver

Uses
Solid tumors, leukemia, lymphomas, rheumatic disease (eg, SLE, granulomatosis with
polyangiitis)

Side effects: Myelosuppression, SIADH, Fanconi syndrome (ifosfamide), hemorrhagic cystitis

and bladder cancer (prevent with mesna)

Malabsorption syndrome (celiac disease, lactose intolerance, whipple disease,tropical

sprue)
Celiac disease
Also called gluten-sensitive enteropathy, celiac sprue.
Autoimmune-mediated intolerance of gliadin (gluten protein found in wheat, barley, rye).
Associated with HLA-DQ2, HLA-DQ8, northern European descent.
Primarily affects distal duodenum and/or proximal jejunum malabsorption and steatorrhea
Associated with dermatitis herpetiformis, decrease bone density, increase moderately
risk of malignancy (eg, T-cell lymphoma).

d-xylose test: abnormal.

Serology:
⊕ IgA anti-tissue transglutaminase (IgA tTG),
anti-endomysial,
antideamidated gliadin peptide antibodies.

Histology: villous atrophy, crypt hyperplasia A, intraepithelial lymphocytosis.

Treatment: gluten-free diet.

Tropical sprue
Similar findings as celiac sprue (affects small bowel), but responds to antibiotics. Cause is
unknown, but seen in residents of or recent visitors to tropics.
mucosal absorption affecting duodenum and jejunum but can involve ileum with time.

Associated with megaloblastic anemia due to folate deficiency and, later, B12
deficiency.
Pancreatic insufficiency
Due to chronic pancreatitis, cystic fibrosis, obstructing cancer.
Causes malabsorption of fat and fat-soluble vitamins (A, D, E, K) as well as vitamin B12.

Decrease duodenal bicarbonate (and pH) and fecal elastase.

d-xylose test: normal.

Jaundice
Abnormal yellowing of the skin and/or sclera due to bilirubin deposition.
Hyperbilirubinemia 2° to production or clearance (impaired hepatic uptake, conjugation,
excretion).

HOT Liver—common causes of bilirubin level:

Hemolysis Obstruction Tumor Liver disease

Conjugated (direct) hyperbilirubinemia

Biliary tract obstruction: gallstones, cholangiocarcinoma, pancreatic or liver cancer, liver

fluke.
Biliary tract disease: 1° sclerosing cholangitis 1° biliary cholangitis
Excretion defect: Dubin-Johnson syndrome, Rotor syndrome.

Unconjugated (indirect)hyperbilirubinemia
Hemolytic, physiologic (newborns), Crigler-Najjar, Gilbert syndrome.

Mixed (direct and indirect) hyperbilirubinemia Hepatitis, cirrhosis.