INTRODUCTIO

TO
INTERNAL
MEDICIN
-~ APPROACH TO PATIENTS IN INTERNAL MEDICINE

1. History Taking

2. Physical Examination

0 ROTATING IN THE WARDS

1. Writing the Problem List

2. Making Daily Rounds

3. The "S-O-A-P" Format

4. Writing the Diagnostic & Management Plan

5. Presenting the Case

INTRODUCTION
SECTION
APPROACH TO PATIENTS IN INtERNAL MEDIGINE
ONE

Internal Medicine (IM) can be quite overwhelming because of the complexity of cases and
•
long work hours. Despite these inherent toxicities, it remains one of the most rewarding fields
in Medicine. Students and practitioners alike enjoy the intellectual stimulation and experience
of translating theoretical knowledge into direct patient care. As basic IM principles cannot be
dissociated from the cases we encounter, it is imperative for every practitioner to acquire the core
competencies and skills of an internist. The approach to patient encounter and chart writing are
discussed in the succeeding parts.

HISTORY TAKING
Good history-taking is central to good patient care
• The steps to performing a complete history are outlined below

I. COMPONENTS OF A PATIENT'S HISTORY

Chief complaint • The main reason for the patient's consult or admission

History of • Includes details of the patient's chief complaint

present illness • Problems are elicited from the patient in chronological order

Review of • Runs through all organ systems for symptoms the patient may have
systems failed to mention
• Probes further into the patient's other medical conditions, including
Past medical
present medications, other co-morbidities, past surgeries, and any
history
food/drug allergies
• Looks for the presence of diseases in the family such as hypertension
Family medical
(HPN), diabetes mellitus (DM), heart disease, early cardiac death,
history
atopy, and autoimmune disease

Personal and • Includes the patient's dietary habits, smoking history, alcohol intake,
social history illicit drug use, travel history, and if relevant, sexual history

Obstetric and • Female patients should be asked about details on menstruation and
gynecologic pregnancy

II. ATTRIBUTES OF A SYMPTOM: PQRST

• PQRST is an acronym, usually for the assessment of"pain" or "discomfort"
• Pain is one of the most commons atients to seek consult

Provocation/ • What provokes the symptom? What makes the pain worse?
palliation • What palliates or relieves the symptom?
Quality • Description of the pain (e.g., dull, aching, sharp, heavy, tingling, burning)
, Radiating pain: spreads from the source of the pain (e.g.,in sciatica, pain
Radiation or is felt shooting down the leg as far as the toes)
Referred • Referred pain: felt in a location different from the actual cause of the pain
(e.g., cholecystitis may cause right shoulder pain)
• An accurate way to measure severity is to score the pain on a scale of I to
Severity
10 (with JO points being the worst pain)
• When did the pain start? When does it happen? Is it constant or
Timing
intermittent (comes and goes)?
3
PHYSICAL EXAMINATION
History-taking is followed by a physical examination (PE). Permission should always be asked
from the patient before doing any maneuver, especially the more intrusive ones. A systematic PE
starts with a general survey of the patient followed by measurement of the patient's vital signs
and anthropometrics. Special focus is then given to certain body parts pertinent to the identified
problems of the patient. Specific details on PE findings per organ system are discussed in each of
the succeeding subspecialty chapters.

• Check the patient's level of consciousness and general state of nutrition,

General survey and look for any signs of distress
• Inspect the patient's skin and hair

Vital signs • Take patient's pulse rate, respiratory rate, blood pressure, & temperature
Anthropometrics • Take patient's weight and height, and compute for the BM!
• Check the sclerae, conjunctivae, pupillary light reflex, and extraocular
muscles (tests for visual acuity, tonometry, and fundoscopy may be
needed for patients with ophthalmologic complaints)
• Grossly examine the outer ear, nose, and oral cavity (otoscopy, runing
Head and neck fork tests, and rhinoscopy may be needed for patients with complaints
specific to these organs)
• Check for neck vein engorgement & measure jugular venous pressure
• Auscultate for bruits over the carotid artery and thyroid gland
• Palpate neck for presence of goiters, enlarged lymph nodes, & masses

• Inspect the chest for deformities, retractions, and masses

• Palpate for areas of tenderness, respiratory excursion, tactile fremiti, and
crepitations
Chest and lungs • Percuss in proper sequence & listen for differences in percussion sounds
• Auscultate both the anterior and posterior chest, noting the character of
breath sounds as well as for adventitious breath sounds; auscultate for
vocal fremiti as well

• Inspect the precordial area for bulging and identify the point of maximal
impulse (PM!)
Cardiovascular • Palpate for the apex beat as well as for any heaves and thrills
system • Auscultate using both the bell and diaphragm and note the cardiac rate
and rhythm, the character of St and S2, the presence of S3 or S4, and the
character of any murmurs present
• Inspect the abdomen's shape and contour, as well as for any visible
masses, scars, pulsations, and discolorations
• Auscultate for the character and frequency of bowel sounds, as well as
Abdomen for bruits and succussion splash
• Palpate the abdomen using both light and deep palpation, noting the
presence of tenderness, guarding, organomegaly, and masses
• Percuss for the liver span, Traube's space, and shifting dullness

• Inspect for the presence of cyanosis, clubbing, edema, and tremors

• Palpate and characterize arterial pulses on both sides
Extremities
• Check for joint swelling, erythema, warmth, tenderness, and limitation
of motion

• Neurological exam for patients with altered sensorium or those with

complaints involving the neurologic system
Others • Mental status exam for psychiatric patients
• Gynecologic exam for pregnant patients or female patients with
complaints involving the urogenital system

4
 SECTION TWO
ROTATING IN liME . :ARDS
WRITING THE PROBLEM LIST
The problem list is a list that presents a current, concise picture of all of a patient's
medical problems and significant health factors
Gives the medical care team a quick yet comprehensive overview of the patient's health
care needs, thus enabling better follow up of the patient's case
Provides a readily accessible database from which epidemiologic data can be drawn
I. CHARACTERISTICS OF A GOOD PROBLEM LIST
Complete
Prioritized
Specific without being overly redundant
Dynamic (once a problem resolves it should be removed)

II. TIPS ON HOW TO MAKE A GOOD PROBLEM LIST

• First perform a thorough history & physical examination, and review all labs available
• List all problems identified & process into accurate terminologies guided by:
• Use terms that best define and encompass each problem.
• Use modifiers to better characterize each problem in terms of the following: severity (mild,
moderate, severe); duration (acute, chronic); and cause (primary, secondary)
• If unsure of a particular diagnosis or problem, labels such as "suspected" or "probable" may be
used. A "rule out" (R/0) designation is rarely needed but may denote a competing diagnosis that
is still a possibility pending the results of work-up.
• For each problem, place a corresponding date and ICD code if possible.
• Symptoms may be rarely used if it is not currently possible to describe the problem at a
higher diagnostic level.
• Group common/related problems. There could be an umbrella problem, and a list of sub-
problems under that.
• Classify problems into active or inactive (usually prior, resolved medical/surgical conditions
that are still important to be remembered).
• Arrange problem list in order of priority, with the most active problems first. The topmost line
usually reflects the problem that brought the patient in for consult (i.e., the chief complaint).
• Review the problem list regularly. As the patient's diagnosis and labs are being updated
regularly, update the problem list as well to reflect that.

MAKING DAILY ROUNDS

Given the limited time and the multitude of patients in the hospital, making daily rounds efficiently
and effectively is an important internist skill. Here are a few tips on how to do daily rounds like a pro:
Start with a quick review of the patient's past problems, which includes reviewing the
1.
previous day's chart entries.
2. Identify present problems at bedside.
3. Check the chart for entries of co-managing services, nursing staff, and pharmacists.
4. Write the day's chart entries in "S-0-A-P" format.

"S-O-A-P" Format
A short, structured note that provides clinicians a quick cognitive framework for clinical reasoning to
assess, diagnose, and treat a patient based on the presented information. Shows at a glance the essential
parts of a patient's health status, enabling quicker communication between health professionals.

"S" (Subjective) • State pertinent positives and negatives in the review of systems

"O" (Objective) • State the [Link] ex<!Jlllllationfindings

"A"(Assessment) • State the present assessment in the form of a problem list

"P" (Plan) • State the diagn_e>sti~ t~erapeuti~ managem~nt plan for the day

5
WRITING THE DIAGNOSTIC AND MANAGEMENT PLAN
With the information obtained from the history and PE, a prioritized problem list is then
created, with the most urgent conditions listed first. Based on the problem list (see above), the
management plan is then outlined.
Admission • Decide where the patient will be admitted (e.g., general ward, ICU)

• Dietary preparations (e.g., general liquids, soft diet, full diet) and specific
Diet
dietary prescriptions (e.g., low-salt, low-fat, low-purine, low-protein)

Fluids& • Main IV lines (e.g., plain saline, D5-containing fluids) and side drips (e.g.,
drips vasopressors, electrolyte solutions)

• Blood pressure, heart rate, respiratory rate, temperature, peripheral oxygen

Monitoring saturation, neurologic vitals, intake and output (I/0)
• Frequency by which these parameters are checked (e.g., q4 hours, qshift)
• Prioritized list of diagnostic procedures such as imaging, blood tests and
Diagnostics
special procedures
• Medications with corresponding doses, frequency of dosing, duration and
Therapeutics side effects to watch out for
• Goals of treatment may be written as a side note
• Type of blood products, the amount to be transfused, rate of transfusion and
interval between transfusions
Transfusions • Pre-medications and side effects to watch out for
• Anticipatory measures: diuretics for possible congestion, anti-pyretics for
febrile transfusion reactions

• 0, delivery system to be used (e.g., nasal cannula, face mask) and the
Oxygen(02) amount of 0, to be delivered (in liters per minute)
support • Specify target 0, saturation for the patient (i.e., keep 0, sats >95%)
• If on mechanical ventilation, the ventilator settings are included
• Nursing care (e.g., bed turning, wound dressing, catheter care)
Others
• Referrals to different specialties and reason for referral

PRESENTING THE CASE

Goodendorsements& presentationsform an integralpart of [Link],
in turn, translatesto excellentcontinuityof carefor [Link] the steps to a goodcasepresentation:
• Begin with the patient's name or initials, followed by the age, sex,
General data
chief complaint, reason for admission, & date of admission or referral

• State pertinent details in the history of present illness, review of

History
systems, past medical, family medical, and personal/social histories
• State significant diagnostic results and their interpretations, including
Diagnostic results pertinent normal findings to rule out differentials being considered by
the healthcare team

• Emphasize the developments or important events that happened to

Hospital course
the patient .,
Case summary • Summarize the case in two to three sentences
Assessment • State your assessment in the form of a prioritized problem list

• State your management plan based on the assessment; this should be

Management plan
detailed and specifically tailored to the patient
Clarifications and
• Entertain clarifications or questions from the audience
open forum

6
BASIC
DIAGNOST
__ -,....B
....
~;,c;..SI_G,_T..,.·E
.....
R....
M.....
IN_..©.-L""'O...,G.,..IE
...S..,.1..,.N..,.D...,IA_G
__
N_O_S_l_lC_t
__
E_S_T
__
IN.....
G____ _
OVERVIEW OF LABORATORY MEDICINE
Clinical science devoted to quantitative or qualitative assays of biological substances for
medical or research purposes
Raw data is translated into actionable information for patient care improvement
I. DEFINITION OF TERMS
TERM I DEFINITION
Reference • Derived from a sample of a healthy population
ranges • Reflects results of 95% of disease-free individuals
Accuracy • [Link] how close the values are to the true value
Precision • Refers to reproducibility of a value during repeated testing of a sample
• Ability of a test to detect a true abnormality
• Very sensitive tests are helpful for screening (rules out a diagnosis or
Sensitivity disease when result is negative)
• Example: An ANA titer <I:40 has a sensitivity of 98%; arid thus a negative
result (titer <I:40) is useful for ruling out SLE
• Ability of test to detect a normal result if the abnormality is not present
• Very specific tests are useful for confirmation (rules in a diagnosis or
Specificity disease when result is positive)
• Example: HbA1c 2:6.5%has 99% specificity for diagnosis of diabetes; &
thus a positive test is useful to confirm the diagnosis
• Positive predictive value: probability that subjects with a positive
Predictive screening test truly have the disease
value • Negative predictive value: probability tl;iat subjects with a negative
screening test truly do not have the disease

II. BRANCHES OF LABORATORY MEDICINE

BRANCH I DEFINITION I EXAMPLES OF TESTS
• Complete blood count
• Microscopic and laboratory
• Coagulation parameters
Hematology examination of blood and its
• Hemoglobin electrophoresis
properties including coagulation
• Flow cytometry
• Detection and quantification of • Fasting blood sugar, lipid profile
Clinical
compounds of interest (analytes) in • Serum electrolytes
chemistry
blood and other bodily fluids • Drug testing
Clinical • Microscopic examination of bodily • Urinalysis
microscopy fluids (including feces) other than blood • Fecalysis
• Detection & identification of micro- • Gram stain
Microbiology
organisms in tissues, [Link], other fluids • Culture and sensitivity
• Detection/quantification of compounds • Dengue duo test
Immunology of interest (analytes) in blood & other • COVID-19antigen/antibody assays
fluids that assess immune function • Antinuclear antibody (ANA)
• Blood typing
Blood • Collection, storage, and dispensing of
• Crossmat~hing
banking blood products
, Antibody screening/identification
• Real-time PCR
Molecular • Specialized field that deals with
•LAMP
pathology nucleic acid-based techniques
• FISH
9
CONVERSION FACTORS OF ROUTINE LABORATORY TESTS
General Formula
• To convert a value from conventional unit to SI unit, multiply by the conversion factor
(e.g., an albumin of2 g/dL x 10 = 20 g/L)
To convert from SI unit to conventional unit, divide by the conversion factor (e.g., an
LDL of 3.2 mmol / 0.0259 = 124mg/dL)

Convert Conventional unit to SI unit = Conventional unit x Conversion factor

SI unit
Convert SI unit to Conventional unit=
Conversion factor

Conversion Factors
I CONVENTIONAL I CONVERSION
LABORATORY
UNIT FACTOR I SI UNIT

Albumin g/dL 10 g/L

Bicarbonate mEq/L 1.0 mmol/L
Calcium (total) mg/dL 0.25 mmol/L
Calcium (ionized) mEq/L 0.50 mmol/L
Carbon dioxide mEq/L 1.0 mmol/L
Chloride mEq/L 1.0 mmol/L
Cholesterol mg/dL 0.0259 mmol/L
Creatinine mg/dL 88.4 umol/L
Glucose mg/dL 0.0555 mmol/L
Hemoglobin g/dL 10 g/L
HDL-Cholesterol mg/dL 0.0259 mmol/L
Lactic acid mg/dL 0.111 mmol/L
LDL-Cholesterol mg/dL 0.0259 mmol/L
Magnesium mg/dL 0.411 mmol/L
Phosphorus mg/dL 0.323 mmol/L
Potassium mEq/L 1.0 mmol/L
Sodium mEq/L 1.0 mmol/L
FreeT4 ng/dL 12.87 pmol/L
Free T3 pg/dL 0.0154 pmol/L
Triglycerides mg/dL 0.0113 mmol/L
Troponin I ng/mL 1.0 ug/L
Uric acid mg/dL 59.48 umol/L
VitaminD ng/mL 0.0738 pmol/L

HbA1C I PLASMA GLUCOSE

6% • 7.0 mmol/L(126mg/dl) 9% • 11.8mmol/L(212mg/dl)
7% • 8.6 mmol/L(154mg/dl) 10% • 13.4mmol/L(240mg/dl)
8% • 10.2mmol/L(183mg/dl) 11% • 14.9mmol/L(269mg/dl)
10
 . . .
SECTION
NORMALLABORATORYVALUES
TWO
. . •.
The values in this chapter are only generalizationsfor most [Link] laboratory .. ;
I
has its own specificreferenceranges.

COMPLETE BLOOD COUNT (CBC)

I. FISHBONE DIAGRAM OF COMPLETE BLOOD COUNT
Neutrophil Monocyte

Hemoglobin

Hematocrit
Lymphocyte Eosinophil
Basophil

Reference
rangesfor completebloodcountvaryfromlaboratoryto laboratory.
Alwayscorrelateclinically.

II. COMPONENTS OF A CBC

I
PARAMETER REFERENCE I REMARKS
• Definition of anemia (WHO):
Hemoglobin 12 0-16.0g/dl
0<I3.o g/dL in men
(Hgb) (120-160g/L)
0<12.0g/dL in women
Hematocrit • Refers to proportion of the volume of a blood sample
0.38-0.47
(Hct) that is occupied by red cells
• Automated analyzers more accurately count red cell
numbers
Red blood • Mentzer index= (MCV/RBC count) x 100
4.2-5.4x10'/mm3
cell count
(4.2-5.4x1012/L)
0 If <13:microcytic hypochromic anemia most likely
(RBC) from thalassemia
0 If >13:microcytic hypochromic anemia most likely
from iron deficiency
• Measures the average volume of red blood cells
• Used in classification ofred cell disorders:
Mean cell
0 MCV >IO0:macrocytosis
volume 80-100fl
0 MCV <80: microcytosis
(MCV)
• Falsely elevated MCV: red cell agglutination, severe
hyperglycemia causing osmotic swelling
, Measures the average Hgb content per red cell
• Reflects the hemoglobin mass
Mean cell
27-31pg • Adjunct in classification of red cell disorders
hemoglobin
0 MCH <27:hypochromia
(MCH)
° Falsely elevated MCH: hyperlipidemia
• More important in laboratory quality control
• Measures the average hemoglobin concentration in a
Mean cell given red cell volume
hemoglobin • Differentials for increased MCHC: hereditary
320-360.g/L
concentration spherocytosis,,homozygous sickle cell disease,
(MCHC) hemoglobin C disease
• More important in laboratory quaiity control
11
PARAMETER I REFERENCE I REMARKS
• Quantitates cellular volume heterogeneity
(reflects range of red cell sizes within a sample)
Red cell • Very useful in classification of anemia (especially
distribution 11-16% in microcytic anemia)
width
(ROW) • Also increasingly being used as a prognostic tool
in various inflammatory, cardiac, autoimmune,
and malignant conditions
White blood 4,500-11,000/mm 3
cell (WBC) • Number of white blood cells per mm' of blood
(4.5-11x109/L)
count
• Relative percentage or absolute number of
neutrophils in peripheral blood
50-70% • Neutropenia defined as absolute neutrophil count
Neutrophil
ANC':1,500-8,000/mm' (ANC) <2 SD below mean of normal population
• Neutrophilia defined as increase in ANC >2 SD
above normal population mean
1l • Relative percentage or absolute number of
lymphocytes in peripheral blood
20-50% • Lymphopenia defined as absolute lymphocyte
Lymphocyte
ALC*:1,000-4,000/mm' count (ALC) <!,ooo/mm 3 (typically reflects
depletion ofT-cells)
• Lymphocytosis defined as ALC >4,000/mm'
0-6% • Relative percentage or absolute number of
Eosinophil
AEC': 50-500/mm' eosinophils in peripheral blood
0-2% • Relative percentage or absolute number of
Basophil ABC': 25-100/mm' basophils in peripheral blood
• Relative percentage or absolute number of
2-9% monocytes in peripheral blood
Monocyte
AMC': 100-700/mm • Monocytosis defined as increase in absolute
3

monocyte count (AMC) >800/mm'

• Number of platelets per mm 3 ofblood
Platelet 150,000-450,000/mm'• Falsely low levels: platelet activation in
count (150-450x109/L) disseminated intravascular coagulation (DIC)
and acute leukemia
• Reticulocytes are immature, non-nucleated RBCs
that still retain ribosomal RNA
Reticulocyte 0.005-0.015
count 0.5%to 1.5% • Used to calculate for reticulocyte production
index which is helpful in pathophysiologic
classification of red cell disorders
•Absolutecounts(AC)arecalculated
by multiplying
theWBCcountby 1000and% of cellof interest

12
COAGULATION TESTS
I. PROTHROMBIN,
I
PARAMETER REFERENCE
Prothrombin
time(PT)
PARTIAL THROMBOPLASTIN,

9-12 sec
I
AND THROMBIN TIME
USES
• Assess deficiencies/inhibitors of extrinsic & common pathways
• PT percent activity has no proven clinical utility
I
International
• Developed to standardize PT to allow for monitoring of
normalized 0.8-1.1
oral vitamin K antagonist (e.g., warfarin) therapy
ratio (INR)
Partial • Assess deficiencies/inhibitors of extrinsic & common pathways
thromboplastin 25-40 sec • Used to monitor response to anticoagulation (e.g.,
time(PTT) unfractionated heparin)
• Assesses deficiencies/dysfunction of fibrinogen or the
Thrombin
14-16sec presence of an inhibitor of thrombin (i.e., factor Ila)
time(TT)
• Most common cause of prolonged TT: anticoagulants

MixingStudies:
• Used to determine if prolonged PT or PTT is due to a factor deficiencyor an inhibitor
• ProlongedPT/PTTbecomes normalafter initialmix& stays normalafter 2 hrs: suggests factordeficiency
• ProlongedPTTbecomesnormalafterinitialmixbutprolongsafter2 hrs:indicatesfactorVIII(orfactorV) inhibitor
• Prolonged PT or PTT remains prolonged after mixing:suggests presence of inhibitor(e.g., lupus
anticoagulant or anticoagulation)

II. INTERPRETING ABNORMAL PT AND PTT

PT/INR
I PTT

• Factor VII deficiency (congenital & acquired from early warfarin

Prolonged Normal therapy/vitamin K deficiency, early liver disease)
• Factor VII inhibitors
• Deficiency of factors VIII, IX, • Non-specific inhibitors:
XI or contact factors (usually heparin, lupus anticoagulants,
Normal Prolonged single factor deficiency only) direct thrombin inhibitors
• Contact factor deficiencieselevate • Specific inhibitors: usually
PTT, but do not cause bleeding factor VIII inhibitors
• Non-specific inhibitors:
0 Drugs (direct Xa inhibitors, direct

thrombin inhibitors, heparin)

0 Lupus anticoagulants

• Congenital deficiency of • Specific factor inhibitors

factors X, V, II, or fibrinogen • Severe vitamin K deficiency
Prolonged Prolonged
(usually single factor • Severe liver disease
deficiency) •DIC
• Isolated factor X deficiency
(usually with amyloidosis)
• Severe fibrinogen depletion
• Hemodilution
• Drugs (e.g., heparin, direct
thrombin inhibitors)
• Inhibitors to factor II or fibrinogen
Normal • Congenital deficiency of
•DIC
(but prolonged TT) fibrinogen
• Acquired hypofibrinogenemia:
liver disease, systemic
fibrinolysis, massive hemorrhage
13
III. OTHER COAGULATION TESTS
I
PARAMETER REFERENCE I REMARKS
• Detects primary hemostatic disorders
Bleeding <5 mins
time(BT) • Prolonged BT in asymptomatic patients do not predict
risk of abnormal bleeding during invasive procedures
• Plasma protein broken down by thrombin into fibrin
175-400 mg/dl • Assesses fibrinogen activity (critical value is <IOOmg/dL)
Fibrinogen
([Link]/L) • Used in evaluating DIC and assessment of various
bleeding conditions
• Terminal product of fibrinolysis generated by action of
plasmin on cross-linked fibrin
D-dimer <500 ng/ml
• Used in excluding diagnosis of venous
thromboembolism (VTE) and in the diagnosis of DIC
• Designed to measure plasma levels of anticoagulants
Anti-Xa Laboratory- • Usually used to monitor response to therapy with
levels dependent LMWH (and other newer anticoagulants) or when the
P1T cannot be reliably used for UFH

SERUM CHEMISTRY AND RELATED TESTS

I. FISHBONE DIAGRAM FOR SERUM CHEMISTRY AND RELATED TESTS

Na Cl BUN Ca TP AST LDH

CO2
K Crea Alb ALT AP

II. COMPONENTS OF SERUM CHEMISTRY AND DESCRIPTION

PARAMETER I
SI UNITI CONV I REMARKS
• Possible critical value: >3x ULN
25-125 25-125
Amylase IU/L U/L • Sensitive (but not specific) test for pancreatic
disorders
• Found in the liver (predominantly), kidneys,
Alanine heart, and skeletal muscle
5-35 5-35
Aminotransferase IU/L mU/L • Specific & sensitive for hepatocellular disease
(ALT/SGPT) • Liver parenchymal injury releases this enzyme
to the bloodstream
• Makes up -60% of total body protein
35-50 3.5-5.0
Albumin g/L • Synthesized in liver (thus a measure ofliver function)
g/dl
• Also a prognostic tool in many conditions

Alkaline • Highest concentrations in liver, biliary tract

0.5-2.0 30-120
Phosphatase uKat/L U/L epithelium, and bone
(ALP) • Used in evaluation ofliver and bone disorders
• Used to evaluate hepatocellular disease, but not
Aspartate very specific
7-40 7-40
Aminotransferase IU/L • AST/ALT ratio usually >LOin alcoholic cirrhosis,
mU/L
(AST/SGOT) chronic passive congestion, or metastatic tumors
to the liver
SI units: International System of Units Conv: Conventional Units
14
 ISI UNIT I CONV I
I
PARAMETER REMARKS

, Byproduct of protein catabolism

6-47 10-80
Ammonia umol/L mcg/dL , Used to support diagnosis of severe liver
disease & follow-up of hepatic encephalopathy
• Possible critical value: >12mg/dL
Total Bilirubin 5.1-17 0.3-1.0
(TB) umol/L mg/dL • Sum of direct and indirect bilirubin
• JaundiGe presents with total bilirubin >2.5mg/dL'
• Conjugated form ofbilirubin
• Elevation usually associated with extrahepatic
biliary obstruction
Direct 1.7-5.1 0.1-0.3
• Conjugated hyperbilirubinemia (>50%
Bilirubin (DB) umol/L mg/dL
ofbilirubin is conjugated) usually from
gallstones, tumors, inflammation, scarring, or
obstruction of extrahepatic ducts
• Unconjugated form ofbilirubin
Indirect 3.4-12.0 0.2-0.8 • Unconjugated hyperbilirubinemia (when <15-
Bilirubin (IB) umol/L mg/dL 20% of total bilirubin is conjugated): usually
·from RBC hemolysis, hepatitis, or sepsis
• Possible critical value: >IOOmg/dL
Blood Urea 2.9-8.2 8-23 • Measures amount of urea nitrogen in blood
Nitrogen (BUN) mmol/L mg/dL • Related to hepatic metabolic function and
renal excretory function
• Possible critical values: <6 or >13mg/dL
2.10-2.50 8.4-10.6 • Directly measures calcium in blood
Calcium .mmol/L mg/dL • To evaluate parathyroid disease, renal disease,
malignancies, & other systemic conditions
• Possible critical values: <2.2or >7mg/dL
Calcium, 1.15-1.35 4.6-5.1
• Roughly 50% of total calcium in blood exists
Ionized mmol/L mg/dL
in its free (ionized) form
• Non-specific acute-phase reactant to evaluate
bacterial infections and inflammatory conditions
• Produced by the liver during acute inflammation
C-Reactive <10.0 <1.0 • More sensitive and rapidly responding indicator
Protein mg/L mg/dL than erythrocyte sedimentation rate (ESR)
• High-sensitivity CRP (hs-CRP):enables accurate
assays even at low levels (independent prognostic
marker for cardiovascular conditions)
• Measurement of the rate at which RBCs settle in
Erythrocyte 0-15 0-15 saline or plasma over a specified time period
sedimentation mm/h mm/h
rate (ESR) • Non-specific marker of inflammation to monitor
treatment of inflammatory/autoimmune conditions

• Possible critical values: <80 or >ll5 mEq/L

96-106 96-106 , Measurement can give an indication of the
Chloride mmol/L mEq/L acid-base balance and hydration status of
patients (tested alongside other electrolytes)
, Excreted entirely by the kidneys & is therefore
50-110 0.6-1.2 directly proportional to renal function
Creatinine umol/L mg/dL • Used to estimate renal function
, Affected by protein intake and muscle mass

15
 I
PARAMETER SI UNIT I CONV I REMARKS
• Used to assess folate availability in the
work up of anemia and pregnancy
11-57 5-12 , If folic acid is low, tissue folate is measured
FolicAcid nmol/L ng/ml by determining content of folate in RBCs
(RBC folate: 360-1400 nmol/L)
• Done in conjunction with vitamin B12assays
" • Globulin represents all non-albumin protein
• May be used as measure of nutrition
• Normal albumin/globulin ratio: >I.0
23-34 2.3-3.4
Globulin g/L g/dl • Lesser ratios seen in liver disease,
autoimmune conditions, paraproteinemia
• Very high globulin levels should make
you suspect paraproteinemia
Glucose 3.9-6.1 70-110 • Possible critical values: <40-50 & >400 mg/dL
(fasting) mmol/L mg/dl • Should be evaluated in relation to meal-time
• Good indicator of body iron stores
• Assess iron deficiency & overload states
20-200 20-200
Ferritin ug/L ng/ml • Acute-phase reactant & may rise in
conditions not reflecting iron stores (e.g.,
inflammation, infection, cancer)
• -70% of iron is bound to hemoglobin
• Iron is bound to transferrin: when iron is
Iron low, transferrin levels increase (& vice versa)
Male 13-31umol/L 75-175mcg/dl
Female 5-29umol/L 28-162mcg/dl • Serum iron determination is a
measurement of the quantity of iron bound
to transferrin
• Measurement of all proteins available for
:, binding mobile iron (transferrin accounts
for a majority of these)
• Increased in iron deficiency (mostly)
,, • Since transferrin is a negative acute
' phase reactant, TIBC will be decreased
Total Iron- in inflammatory states (e.g., malignancy,
Binding 45-73 250-410 liver disease, or connective tissue disease)
Capacity umol/L mcg/dl • TIBC is more reflective of hepatic
(TIBC) function rather than iron metabolism
• Serum iron & TIBC used to compute for
transferrin saturation (TSAT): useful to
assess iron status (reference: 20-50%)
0 TSA T = [Serum iron/TIBC] xroo%

0 TSA T <20%: suggests iron deficiency

0 TSAT >50%: suggests iron overload

Lactic Acid • Used to document presence of tissue

Arterialblood 0.3-0.8mmol/L 3-7 mg/dl hypoxia, determine its severity, and
Venousblood 0.6-2.2mmol/L 5-20 mg/dl monitor effect of therapy
Lactate • Used in a multitude of inflammatory
Dehydrogenase
states, myocardial injury, red cell
(LOH)
Adult 45-90 IU/L 45-90 U/L hemolysis, infections, and malignancy as
>60yrsold 55-100IU/L 55-100U/L marker of tumor burden

16
PARAMETER I SI UNIT I CONV I REMARKS
• Enzyme secreted by pancreas to break
down triglycerides into fatty acids
0-160 0-160
Lipase units/L units/L • May rise in renal failure, intestinal
obstruction, or imestinal perforation
• Values >3x: seen in acute pancreatitis

• Possible critical values: <0.5 or >3 mg/dL

0.65-1.05 1.3-2.1
Magnesium mmol/L mg/dl • Intracellular cation essential in most organs
(especially in cardiovascular system)

• Critical values: <120 or >160 mEq/L

135-145 135-145
Sodium mmol/L • Major cation in extracellular space
mEq/L
• Major determinant of extracellular osmolality
• Critical values: <I mg/dL
1.0-1.5 3.0-4.5 • Phosphorus in the body exists as phosphate
Phosphate mmol/L mg/dl • Measures inorganic phosphate, most of
which is intracellular
3.5-5.1 3.5-5.1 • Critical values: <2.5 or >6.5 mEq/L
Potassium mEq/L
mmol/L • Major intracellular cation
Total protein 60-80 g/L 6.0-8.0 g/dl • Sum of measured serum albumin & globulin

• Critical value: >12 mg/dL

120-420 2 0-7 0 • Byproduct of purine catabolism
Uric Acid umol/L mg/dl • Majority is excreted by kidney (smaller
proportion excreted by GI tract)

Total <5.2 <200 • Lipid associated with atherosclerotic disease

Cholesterol mmol/L mg/dl • Done as part of lipid profile testing
0.45-1.71 40-150 • Possible critical value: >400 mg/dL
Triglycerides mmol/L mg/dl • Act as energy storage source
• Associated with decreased cardiovascular risk
>0.91 >35
HDL-C mmol/L mg/dl
• HDL removes cholesterol from peripheral
tissues & transports them to liver for excretion
• Associated with increased cardiovascular risk
<3.4 <130
LDL-C • Carries cholesterol that can be deposited
mmol/L mg/dl
into linings of blood vessels
• Major form circulating in the blood (it
is the inactive precursor to the active
hormone 1,25-dihydroxyvitamin D)
25-hydroxy- 62.5-200 25-80 • Used to assess vitamin D deficiency and
vitamin-D nmol/L ng/ml monitor treatment response
• Also tested at baseline prior to starting
osteoporosis treatment
• Vitamin D deficiency: defined as <20 ng/mL

• Active hormone tested in some conditions:

0 Renal disease
1,25-dihydroxy- 0 Enzyme abnormalities (that
vitamin-D
45-159 pmol/L 18-64 pg/ml convert 25-hydroxyvitamin D to
Male
45-194 pmol/L 18-78 pg/ml 1,25-dihydroxyvitamin D)
Female
0 Hypercalcemic states from
hyperproduction of1,25-dihydroxyviramin
D (e.g.1 sarcoidosis, some lymphomas)

SI units: International System of Units Conven: Conventional Units

17
HORMONES AND BIOMARKERS
PARAMETER I SI UNIT I CONV I REMARKS
• Screening serum marker for fetal body
Alpha wall defects (e.g., neural tube defects)
<40 <40
Fetoprotein • Also used in the evaluation and follow-
mcg/l ng/ml
(AFP) up of hepatocellular carcinoma, germ cell
tumors/yolk sac tumors and other cancers

Adreno- • Assesses anterior pituitary gland

corticotropin function
(ACTH)
7-69 pg/ml 7-69 pg/ml • Used in the evaluation of
Male
Female 6-58 pg/ml 6-58 pg/ml hypercortisolism and hypocortisolism

Cancer Antigen 0-35 0-35 • Used in the evaluation and follow-up

(CA) 125 kU/l U/ml of ovarian cancer (CA)

0-37 0-37 • Used in evaluation & follow-up of

CA19-9
kU/l U/ml pancreatic, biliary, & stomach cancers

Calcitonin • Used in evaluation and follow-up of

Male <13.8 ng/l <13.8pg/ml medullary thyroid cancer
Female <6.4 ng/l <6.4 ng/l • Also high in lung, breast, pancreatic CA

Carcinoembryonic
• Used in the evaluation and follow-up
antigen (CEA)
of colon (and other gastrointestinal
Nonsmoker 0-3 mcg/l 0-3 ng/ml
0-5 mcg/l 0-5 ng/ml tumors) and breast cancers
Smoker

Cortisol • Important in assessing adrenal function

AM 170-635 nmol/L 6-23 mcgldl • Demonstrates diurnal variation: peak in
PM 82-413 nmol/L 3-15 mcg/dl the morning and nadir around midnight

Creatine Kinase • Elevated in conditions with injury to

(CK)-Total
cardiac muscle, skeletal muscle, brain
Male 20-215 lU/L 20-215 U/l
Female 20-160 lU/L 20-160 U/L • Isoenzymes: CK-MM, CK-MB, CK-BB

CK-MB 0-16 U/L 0-16 U/L • CK isoenzyme specific for myocardium

• Makes up almost all of circulating CK

CK-MM 8-97 Ull 8-97 U/L
• Elevations in skeletal muscle injury
Follicle-stimulating
• Produced in anterior pituitary gland
hormone (FSH)
• For evaluation of infertility
Male 1-10 lU/l 1-10 mU/ml
• For assessment of anterior pituitary
F (premenopausal) 20-50 IU/L 20-50mU/mL
F (postmenopausal) 40-250 lU/l 40-250mUml gland function

Luteinizing
hormone (LH) • Produced in anterior pituitary
Males 1-9 IU/l 1-9 lU/l • Evaluation of infertility & assessment
Female (follicular) 2-10 lU/l 2-10 lU/l of anterior pituitary gland function
Female(mid-cycle) 15-65 lU/l 15-65 lU/l • Also used to determine whether
Female (luteal) 1-12 IU/l 1-12 lU/l ovulation has occurred
F (postmenopausal) 12-65 IU/l 12-65 IU/l

• Produced in anterior pituitary

Growth
• Evaluation of short stature, delayed
hormone 0-10 mcg/l 0-10 ng/ml
sexual maturity, growth deficiencies,
(hGH), fasting
or ectopic production from neoplasms

18
 PARAMETER I SIUNIT I CONV I REMARKS
• Used to document wherher ovulation
has occurred (ro evaluare inferrility)
Progesterone
• To moniror placental srarus in high-
Male 0-1.3nmol/L 0-0.4 ng/ml
risk pregnancies
Female (follicular) 0.3-4.8 nmol/L 0.1-1.5ng/ml
• To monitor progesterone supplementation
Female (luteal) 8.0-89 nmol/L 2.5-28ng/ml
in inadeguare !urea! phase (ro
mainrain an early pregnancy)
• Secreted in anterior pituitary gland
Prolactin
• To monitor activity of prolactinomas
Male 1-20 mcg/l 1-20 ng/ml
• Also elevated in some paraneoplastic
Female 1-25 mcg/l 1-25 ng/ml
syndromes (e.g., lung cancer)
• To evaluate ambiguous sex characteristics,
Testosterone
precocious puberty, virilizing syndromes
Male 9.5-30 nmol/l 275-875ng/dl
among females, and male infertiliry
Female 0.8-2.6 nmol/l 23-75 ng/dl
• Tun1or n1arker for rare ovarian/
Pregnant 1.3-6.6 nmol/l 38-190ng/dl
resticular rumors
Prostate Specific • Elevated in prostate diseases,
Antigen (PSA) especially in prostate cancer
<40years old 0-2.0 mcg/l 0-2.0 ng/ml • Free (unbound) PSA: more accurate
~40 years old 0-4.0 mcg/l 0-4.0 ng/ml for screening
• To evaluare hyperparathyroidism & in
Parathyroid 1.4-6.8 13.2-64
disringuishing non-pararhyroid from
Hormone pmol/l pg/ml
pararhyroid causes of hypercalcemia
• Peptide precursor of calcitonin
• Biomarker which is specific in
identifying sepsis and can be used in
the diagnosis of bacterial infections
• Mildly elevated (0.15-2 ng/mL) in:
0 Localized mild-to-moderate infection
<0.15 <0.15 0 Noninfectious systemic
Procalcitonin
ng/ml ng/ml inflammatory response
0 Untreated end-stage renal disease
• Significantly elevated (>2 ng/mL) in:
0 Bacterial sepsis
0 Severe localized infection
0 Severe noninfectious inflammation
0 Medullary thyroid carcinoma
• Identifies lgM directed against the Fe
fragment oflgG
• Marker for rheumatoid arthriris
Rheumatoid <60 <60
• May be posirive in other
Factor IU/ml U/ml
autoimmune disorders (e.g., SLE,
Sjogren's syndrome) and orher
diseases (e.g., TB, chronic hepatitis)
13-27 1.0-2.1 • Measures unbound active thyroxine
FreeT4
pmol/l ng/dl (more accurate than total T 4)
3.5-6.5 2.4-5.0 • Less stable than T 4; comprise -7-10%
Free T3 pg/ml
pmol/l of thyroid hormones
Thyroid 0.4-4.8 0.4-4.8 • Used to differentiate primary from
Stimulating
mlU/l ulU/ml secondary thyroid disorders
Hormone (TSH)
19
 I
PARAMETERSI UNIT CONV I I REMARKS
0-0 09 0-0.09 • To evaluate suspected acute coronary syndromes
Troponin I • In cardiac injury, troponin becomes elevated
ng/ml mcg/L
sooner & remain elevated longer than CK-MB
• Measures cardiac troponin 5- to 100-fold lower
High
<14.4 <14.4 than early conventional assays
Sensitivity • Allows lower limits of detection, earlier detection
ng/L ng/L
Troponin I of myocardial injury, detection of smaller areas of
injury, & reduced time to diagnosis
SI units: InternationalSystem of Units Conv: ConventionalUnits

URINE STUDIES
I. ROUTINE URINALYSIS
Provides significant information about the urinary system
Ideally a midstream catch specimen after cleaning external genitalia is preferred especially if
primary indication for doing urinalysis is suspected urinary tract infection (UT!)
If with indwelling catheter, fresh specimen should be submitted (avoid samples that
have been stagnant in the catheter tubing or bag)
Sample must be analyzed within 2-4 hours from collection to prevent cellular lysis and
precipitation of solutes
Yellowishcolor from urochrome: intensity depends on urine concentration & specific gravity
PARAMETER
NORMAL I I REMARKS
• Determined by chemical content, concentration and pH
• Color changes can indicate presence of a disease process,
metabolic abnormality, or ingested food/drug
Yellow
° Colorless: if high output and with low osmolality
Urine color
0 Dark-yellow: concentrated urine during limited fluid
intake or excess bilirubin
0 Red: hemoglobin from RBCs
0 Brown: myoglobin from rhabdomyolysis or methemoglobin
• Precipitation of solutes dissolved in urine (amorphous urates
& phosphates) can cause normal urine to appear cloudy
Urine clarity Clear ° Cloudy: leukocytes, bacteria, crystals, lipids, contaminants
0 Turbid: mucus, pus, semen or prostatic fluid,

radiocontrast media (RCM) or contaminants

• Relative density of urine compared to density of pure water
• Most accurate when urine pH is 7.0-7.5 (acidic urine causes
falsely high SG, while alkaline urine causes falsely low SG)
Specific 1.010to • Indirectly measured when using reagent strips
gravity (SG) 1.025 0 High SG (hypersthenuria) or concentrated urine: dehydration,

AKI with oliguria, CHF, SIADH, glucosuria, proteinuria

0 Low SG (hyposthenuria) or dilute urine: diabetes
insipidus, CKD, ingestion of large amounts of water, aging
• Useful in diagnosing systemic acid-base disorders:
0 Alkaline urine (pH >7.0): infection with urea-splitting

organisms (Proteus sp.), prolonged storage of urine,

vomiting, gastric suction, diuretic & alkali therapy,
4.5 to 8 metabolic & respiratory alkalosis, and in those on
pH
Average: 6 vegetarian, citrus fruit, and low carbohydrate diets
0 Acidic urine (pH <5.0): metabolic & respiratory acidosis,
uremia, & infection with acid-producing bacteria(£. coli)
• Urine pH >5.0 in the setting of metabolic acidosis may
indicate possible renal tubular acidosis
20
 I
PARAMETER NORMAL I REMARKS

• Glucosuria from hyperglycemia may occur at blood glucose

levels >IO mmol/L (>180 mg/dL)
Glucose Negative • Glucosuria can also occur in cases of proximal tubular
disorders (Fanconi syndrome), pregnancy, hormonal
disorders, liver disease, & drug intake (e.g., thiazides, steroids)

• Screening measure using a reagent strip for presence of

proteins in urine (most especially sensitive to albumin)
• Insensitive to other proteins (globulins, hemoglobin, light chains)
• Scored from trace to 4+ based on concentration of protein
Protein 0-8 mg/dl Negative: <15mg/dL 2+: wo-300 mg/dL
Trace: 15-30 mg/dL 3+: 300-IO00 mg/dL
1+: 30-IOo mg/dL 4+: >IOoo mg/dL
• If proteinuria is detected by dipstick, it is best quantified
either by 24-hour urine testing, or spot urine PCR or ACR
• Leukocyte esterase is released from lysed urine leukocytes
Leukocyte
Negative • Positive leukocyte est erase: reflect presence of pyuria, even in
esterase
the absence ofleukocytes (indicates infection or inflammation)

• Positive nitrite test: presence of nitrate-reducing bacteria

Nitrites Negative
(e.g., [Link], Proteussp., Enterobactersp., Klebsiellasp.)

• Detected if in the form of acetoacetate & acetone

• May appear in urine during prolonged starvation or
Ketones Negative fasting, alcoholic or diabetic ketoacidosis
• Note that beta-hydroxy butyrate (80% of total ketones) is
not normally detected

• Various crystals can be seen, most commonly calcium

Crystals Negative oxalate, uric acid, calcium phosphate, triple phosphate
(struvite), cholesterol and cystine crystals

• Cylindrical bodies unique to the kidneys, formed from

aggregation ofTamm-Horsfall glycoprotein (uromodulin)
Casts Negative
• May be hyaline, granular, waxy, fatty, RBC, WBC, or
tubular epithelial cell/muddy brown cast

• Hematuria is defined as ~3 RBCs/hpf

• Transient hematuria may be from strenuous exercise
RBC 0-2/hpf • Persistent microscopic hematuria on 3 repeated samples warrants
investigation of glomerular lesions or non-glomerular hematuria
• Macroscopic hemaniria: malignancy, bleeding diathesis, calculi
• Most commonly in the form ofneutrophils (indicates
infection or contamination)
WBC 0-4/hpf • Eosinophils detected by Hansel or Wright stain can
indicate drug-induced hypersensitivity, renal cholesterol
embolism, RPGN, and prostatitis

• Can be squamous, transitional, or renal tubular epithelial

None
Epithelial • Squamous epithelial cells rarely have diagnostic value
to very
cells and their presence indicates that urine specimen was not
minimal
midstream clean catch (contaminated)

Bacteria Negative • Presence indicates contamination or infection

Mucus Small • Commonly in urine sediments & has no clinical

thread amounts significance
21
II. 24-HOUR URINE CHEMISTRY
Timed urine collection used in the metabolic evaluation of renal stone disease, proteinuria,
estimation of renal function using creatinine clearance, or estimation of residual kidney
function in ESRD using urea and creatinine clearance
Requires collection of all urine within a 24-hour period (unlike random urine sampling)
The completeness of a 24-hour urine collection is important, especially in evaluating
proreinuria (measured in g/day), and completeness is assessed by urinary creatinine excretion
(not by urine volume)
The 24-hour urinary creatinine excretion reflects muscle mass and excretion is relatively
constant over time in each person
Unlike crearinine excretion, protein excretion varies throughout the day, hence a random urine
sample will be inaccurate in measuring proteinuria, unless corrected for creatinine excretion

PARAMETER I NORMAL
I REMARKS

• Indicative of daily fluid intake (minus insensible losses);

diminishes with low fluid intake, sweating, and diarrhea
Total 1000-2000 • Target >2500 ml/day
Volume ml/day • Decreased urine volume is a major risk factor for stone
disease as concentrated urine raises the supersaturation
of all stone-forming salts

Creatinine 20-25 mg/kg

Male (0.15-0.22mmol/kg) • Used for assessment of completeness of collection
• Valid only in steady state of constant serum creatinine
Female 15-20 mg/kg concentration ,vith time
(0.13-0.15mmol/kg)

Total Protein • Normal or mildly increased: <150 mg/day

At rest 50-80 mg/day • Moderately increased: 150-500 mg/day
Exercise <250 mg/day • Severely increased: >500 mg/day
• Nephrotic range: >3500 mg/day

• Ar <30 mg/day, nonnoalbuminuria

• A2 30-300 mg/day, microalbuminuria
Albumin <30 mg/day
• A3 >300 mg/day, macroalbuminuria
• Nephrotic range >2200 mg/day

Glucose 50-300 mg/day • See discussion above

• <5.5:increases risk of uric acid precipitation
pH 4.5 to 8.0 • >6.7: increases risk of calcium phosphate precipitation
• >7.0-7.5:indicates UT! from urease-producing bacteria

• Reflects dietary sodium intake (minus extrarenal loss)

100 mEq/day • Much lower than dietary intake in diarrhea and with
Sodium
(100 mmol/day) excessive sweating
• High sodium intake is a major cause of hypercalciuria

• Reflects dietary potassium intake (minus extrarenal loss)

• Most useful in monitoring compliance of treatments
40-60 mEq/day such as potassium citrate
Potassium (40-60 mmol/day) • Much lower than dietary intake in diarrhea states
• Measure of dietary alkali intake because most dietary
potassium is accompanied by organic anions
100 mEq/day
Chloride • Chloride varies with sodium intake
(100 mmol/day)

• Hyperuricosuria: encountered with overproduction of

600-800 mg/day endogenous uric acid or overindulgence of purine-rich food
Uric acid
(3.57-4.76mrrdJday) • Risk factor for Ca" oxalate stones when urine pH is >5.5
• Risk factor for uric acid stone when urine pH <5-5

22
 I I

•
PARAMETER NORMAL REMARKS I
, A higher value is expected in males
• Urine calcium is dependent on dietary calcium,
$250-300mg/day
Calcium
mmol/day) sodium intake, and protein intake
(6.24-7.49
• Rule out secondary causes before making the
diagnosis of idiopathic hypercalciuria I
• Low urinary magnesium detected with low
30-120mg/day magnesium intake, intestinal malabsorption (small
Magnesium
mmoVday) bowel disease), and following bariatric surgery
(1.23-4.94
• Low magnesium may increase risk of calcium stones
• Indicative of dietary organic and inorganic
$1100mg/day phosphorus intake and absorption
Phosphorus
($35.5mmol/day) • Higher excretion may increase the risk of calcium
phosphate stone formation
• Commonly encountered in intestinal disease with
$45 mg/day fat malabsorption (e.g., inflammatory b_oweldisease)
Oxalate
($0.51mmol/day) and following bariatric surgery
• Values >IOO mg/day (1.14 mmol/day) suggest
primary hypernxaluria (PH)
• Potent inhibitor of calcium salt crystallization
• Hypocitraturia: risk factor for stone disease (found
;;:320mg/day
Citrate
(<!1.67mmol/day) in up to a third of calcium stone formers)
• Low urinary citrate: can be idiopathic or from other
factors (e.g., diet, metabolic acidosis, hypokalemia)

STOOL ANALYSIS
I. TESTS FOR OCCULT GI BLEEDING
SPECIMEN &
TEST
I INDICATIONS I REMARKS

• Detects heme part of Hgb from blood in stool

• Fresh stool (heme, however, is common to blood from all
Fecal sample in sources & thus is not specific for GI bleeding)
occult a sterile • Specific restrictions apply prior to testing:
blood test container avoidance of intake of red meat, avoidance of dental
(FOBT) • Used to detect procedures, avoidance of vitamin C
conditions • Test relies on a chemical reaction to produce a color
that can cause change
bleeding
within the GI • Specifically detects globin part of human
tract hemoglobin (will not detect globin from non-human
Fecal blood) from blood in stool
immuno- • Used as a
screening test • Less sensitive for upper GI bleeds as hemoglobin is
chemical
for colorectal broken down before it reaches the lower GI tract
test (FIT)
cancer • No specific restriction prior to testing
• Test uses antibodies to detect human globin

23
II. ROUTINE FECALYSIS
Test done on a stool sample for differential diagnosis of certain diseases of the GIT
• It can be divided into: physical+ chemical+ microscopic examination
PARAMETER I NORMAL
I REMARKS

Ph,]ISICQ 1Ex_qminat1'1!'
'
• Black: bleeding in GIT, intake of iron, bismuth, charcoal
Yellow,
• Red: bleeding, usually in lower GIT
Color/ brown,green
• Green: biliverdin/oral antibiotics, green vegetables
appearance (depends on
• Clay/acholic: biliary obstruction or residual barium sulfate
food intake)
• Mucus: colitis (infectious/inflammatory), neoplasm
Well-formed • Semi-solid or watery: dysentery & other gastroenteritis
Consistency (solidto semi- , Fatty: maldigestion, vitamin deficiency, pancreatic disorders
solid) • Frothy: pancreatic disorders
. .
Cb~mical Ex".imi~ai1,en ;;;_
"''
Neutralto • Acidic stools (<5.5pH): may be used to determine
pH
alkaline(7.0-7.5) lactose intolerance
• Detects hemoglobin in stool
Occult
Negative • Associated with any bleeding (e.g., hemorrhoids,
blood
neoplasm, ulcers, inflammatory bowel disease, infections)
• 2:60stained droplets of neutral fats/HPF: steatorrhea
<6 gramsof
Fat (pancreatitis or exocrine pancreatic insufficiency), celiac
fat/24hrs
disease, intake of castor oil or mineral oil, cystic fibrosis
Nitrogen <2.5g/24hrs , >2.5 g/24 hrs may indicate chronic progressive pancreatitis
.. fr

Micros~opic ExamiJStion "

• >50 leukocytes/HPF: shigellosis
Leukocytes 0-1/HPF • <20 leukocytes/HPF: salmonellosis, invasive [Link]
, <5 leukocytes/HPF: cholera, EPEC, ETEC, viral diarrhea
• Detects intact RBCs in stool (unlike occult blood)
RBCs None • Suggests infection (parasitic, bacterial, viral), inflammatory
bowel disease, neoplasm, ulcers, hemorrhoids
Bacteria Normalfiora • Pathogenic bacteria: Campylobacter,Salmonella,Shigella
Amoebas, • Pathogenic cysts & trophozoites: Entamoeba histolytica,
None
flagellates Giardialamblia, Trichomonas vagina/is
Eggs of None • Pathogenic eggs: roundworm, hookworm, Taenia
parasite
• May be present in small quantities in skin, mouth, intestine
Yeasts Noneto rare • Presence of moderate/heavy yeast seen in potential
yeast overgrowth or non-viable, dietary-derived yeast
• Charcot-Leyden crystals:parasitic infections (e.g.,amoebiasis)
Crystals None • Triple phosphate and calcium oxalate crystals: ingestion of
certain food (spinach, tomatoes, berries)
Meat fibers,
None • Presence may suggest maldigestion
starch,trypsin
Undigested
None • Large amounts may suggest maldigestion
food

24
 SECTION THREE
I
~~~~==-------
STE-Rll.:E.
FLWIDSAND PATHOLOGIES
PLEURAL EFFUSION (PLEURAL FLUID)
<
I. ETIOPATHOGENESIS AND MANIFESTATIONS
Collection of fluid abnormally present in the pleural space due to either excess fluid production
and/or decreased lymphatic absorption (normal pleural space contains only ~IO mL off!uid)
Patients may present with pleuritic pain, cough and dyspnea
PE findings: decreased breath sounds, decreased or absent tactile fremiti, dullness on percussion

• Most common cause of pleural effusion

• Diagnostic thoracentesis should be done to verify "transudative" effusion if:
0Effusions are not bilateral & comparable in size
Heart failure 0Patient is febrile
0 Patient has pleuritic chest pain

• Pleural fluid NT-proBNP ,1500 pg/mL is virtually diagnostic of heart failure

• Due to passage of peritoneal fluid from abdomen through the diaphragm
Cirrhosis
• Usually right-sided (hepatic hydrothorax)
• Nephrotic syndrome due to hypoalbuminemia
• SVC obstruction
Otliers • Myxedema
• U rinothorax
• Pulmona embolism may also be exudative)

• Most common cause of exudative pleural effusion

• Acute febrile illness with chest pain, sputum production, & leukocytosis
Parapneumonic • If free fluid separates the lung from the chest wall by >IO mm, a therapeutic
(bacterial thoracentesis should be performed
pneumonia, • The following factors indicate need for a chest tube thoracostomy (CTI)
lung abscess, 0Loculated pleural fluid
bro'nchiectasis, 0Pleural fluid pH <7-20
empyema) 0 Pleural fluid glucose <3-3mmol/L (<60 mg/dL)

0 Positive gram stain or culture of the pleural fluid

0 Presence of gross pus in the pleural space

• Three most common causes: lung CA, breast CA, and lymphoma
• Diagnosis usually by cytologic exam (thoracoscopy is next best procedure if
Malignancy cytology is negative)
• Glucose levels may be low if tumor burden is high
• Pleurodesis or insertion of a small indwelling catheter may be considered
• Diagnosis most commonly overlooked in differentials of undiagnosed effusion
Pulmonary
• If effusion increases in size after anticoagulation, consider recurrent emboli,
·embQlism
hemothorax or a pleural infection
• Most common cause of an exudative pleural effusion in developing countries
• Usually associated with primary TB (hypersensitivity reaction to TB protein)
Tuberculous • Qualitative analysis shows predominantly small lymphocytes
'pleuritis • Diagnosis is established by (in pleural fluid):
0 High levels of adenosine deaminase (>40 IU/L), OR
0Interferon gamma (>140 pg/mL)
• Pleural fluid hematocrit should be obtained if initial tap is bloody
• If pleural fluid hematocrit is,V,
of that in peripheral blood, hemothorax
Hemothorax should be considered and tube thoracostomy should be done
• If pleural hemorrhage ,200 mL/hr, consider angiographic coil
embolization, thoracoscopy or thoracotomy
25
II. CHARACTERISTICS OF NORMAL PLEURAL FLUID
PARAMETER I FINDINGS
Color & appearance • Clear or yellow fluid

pH • 7.60to 7.64
Protein content • 1-2g/dl (<2%)

Cell count • <1,000WBC/mm3

Glucose • Similar to plasma

LDH • <50%of plasma

JIJ. APPROACH TO PLEURAL FLUID ANALYSIS

First step: determine if effusion is exudative vs transudative (use the Light's criteria by
obtaining LOH and protein level from serum and pleural fluid)
Other diagnostics for exudative pleural effusions:
Description of the appearance of the fluid
0

Glucose & protein level

0

Differential cell count

0

Microbiologic studies and cytology

0

Work up for tuberculosis

0

Liaht's Criteria
Exudative pleural effusions meet at least one of the following criteria:
• Pleural fluid protein/serum protein >0.5
• Pleural fluid LDH/serum LDH >0.6
• Pleural fluid LOH >213normal upper limit for serum
These criteria may misidentify-25% of transudates as exudates. If 2:1 of the exudative criteria are
met & patient is clinicallythought to have a transudative effusion, the difference between the protein
levels in the serum and the pleural fluidshould be measured. Ifthis gradient is >31 g/L, the exudative
categorization by these criteria can be ignored because almost all such patients have transudalive
pleural effusion.
Source:LightRW,et [Link];1972
JamesonJL,et al. Harrison's
Principles
of InternalMedicine20thedition,2018

Case 1. A 50-year-old male presented with a few days' history of fever, cough, and
progressive dyspnea. Physical examination revealed right-sided chest lag with dullness
on percussion on right lower lung fields and decreased vocal and tactile fremiti. Chest
x-ray revealed pleural effusion on the right. Thoracentesis drained -600 mL of free-
flowing serosanguineous fluid. Pleural fluid studies revealed glucose of 65 mg/dL,
pH of 7.23, LOH of 500 IU/L, total protein of 50 g/L. Bacterial cultures were negative.
Adenosine deaminase was also normal. Peripheral blood LOH was 350 IU/L and serum
total protein was 60 g/L.

Diagnosis: Parapneumonic effusion

• Note the history signifying progressive pneumonia. This patient is in the early
spectrum of parapneumonic effusion which is due to increased pulmonary interstitial
fluid traversing the pleura to enter the pleural space The pleural fluid in this stage usually
presents with yet negative bacterial cuJcures, fluid glucose still >60 mg/dL, pH >7.20and
LOH <3XULN of serum.
• Nevertheless, the effusion is exudative since patient already met two of Light's criteria:
Pleural fluid protein/serum protein = 50/60 = 0.83 (fulfilling the cutoff of >0.5)
0

Pleural fluid LOH/serum LOH= 500/350 = 1.43 (fulfilling the cutoff of >0.6)
0

26
ASCITES (PERITONEAL FLUID)
I. ETIOPATHOGENESIS
Ascites is the condition of pathologic fluid collection within the abdominal cavity
Occurs if there is a disruption in the pressure forces between abdominal intravascular
& extravascular fluid spaces, which allows extravascular fluid to accumulate
I
; .
I PROTEIN I SAAG
CONDITION
I FINDINGS
(g/L) (g/dl)

Cirrhosis <25
• Straw-colored ;;:1.1
CHF Variable

Neoplasm • Straw-colored, hemorrhagic, mucinous, chylous >25

TB peritonitis • Clear, turbid, hemorrhagic, chylous >25
Pyogenic <1.1
• Turbid or purulent >25
peritonitis
Nephrosis • Straw-colored or chylous <25

LABORATORY FINDINGS

• Absolute PMN count ;,:250/mm'

• Spontaneous/primary
Infectious • Positive gram stain or culture
bacterial peritonitis
•pH<7-o
• Fulfillment of at least 2 (with PMN
Surgical/ count ;,:250/mm'):
perforation • Secondary peritonitis 0Total protein >I g/dL
peritonitis 0Glucose <50 mg/dL
0LOH >225mU/mL
Hemorrhagic • Malignancy, TB, trauma,
• RBC count >50,000
ascites ruptured omental varix
Pancreatic • Pancreatitis • Increased amylase >2000 U/L or
ascites • Intestinal perforation -5-fold greater than serum values
Malignancy • Peritoneal carcinomatosis • Positive malignant cells in cytology
• Biliary or proximal small
• Increased bilirubin >6 mg/dL
Others intestinal perforation
• Chylous ascites • Increased triglycerides >200 mg/dL
Source:JamesonJL, et al. Harrison'sPrinciplesof InternalMedicine20th edition,2018
FeldmanM, et al. Sleisengerand Fordtran'sGastrointestinaland LiverDisease10th Edition;2016

27
II. CHARACTERISTICS OF NORMAL PERITONEAL FLUID
PARAMETER I NORMAL I REMARKS & ABNORMAL FINDINGS
• Opacity of cloudy fluid is caused by neutrophils
0 Nearly clear: ANC <IOoo/mm'
° Cloudy: ANC >5000/mm'
0 Mayonnaise-like: >50,000/mm'
• Pink or bloody fluid
0 Pink: RBC count >IO,ooo/mm'
0 Red: RBC count >20,000/mm'
Clear or 0 Traumatic tap: blood streaked, frequently clots
Color&
transparent to 0 Nontraumatic tap: homogenous, does not clot
appearance
yellow in color • Bloody, non traumatic fluid: seen in portal
hypertension (bloody hepatic lymph from lymphatic
rupture), hepatocellular carcinoma (HCCA), or TB
• Bile-stained ascitic fluid: seen in deeply jaundiced
patients
• Dark brown fluid: seen in biliary perforation
• Tea-colored to jet black fluid: seen in pancreatic
necrosis, malignant melanoma
• Men normally have no or very little intraperitoneal fluid
Amount ~50-75 ml
• Women may have more, depending on menstrual cyclephase

• Elevated counts may be seen in any inflammatory

process, with SBP being the most common cause
<500 WBC/mm3 • Also elevated (with lymphocytic predominance) in:
0 Tuberculous peritonitis
Cell count 0 Peritoneal carcinomatosis
• Elevated absolute PMN count (;:,250/mm') may be seen
in any inflammatory process (SBP is the most common)
<250 PMN/mm3
• Presence of neutrophils leads to a shimmering effect
when glass tube is rocked back & forth in front of a light
Determined by • >2.5g/dL: heart failure, early Budd-Chiari syndrome,
Total serum protein IVC obstruction, sinusoidal obstruction syndrome
protein concentration & • <2.5g/dL: malignancy-related ascites, massive liver
portal pressure metastases, HCCA, late Budd-Chiari syndrome
Best interpreted
Albumin
using SAAG
• See next section(SAAG)

Concentration in • May be low (up too mg/dL) in SBP or intestinal

Glucose fiuid is similar to perforation because glucose is consumed by ascitic
serum fluid-stimulated neutrophils and/or bacteria
Concentration in
cirrhotic
ascites • Elevated ascitic fluid LDH may be seen in SBP (due to
LDH
usually less than release ofLDH from neutrophils)
half of the serum
Concentration
• Elevated in acute pancreatitis & intestinal perforation
in ascitic fiuid
due to release ofluminal amylase into the ascitic
Amylase usually half of
the serum value fluid (usually >2000 U/L & -5x higher than the
simultaneous serum values)
(~50 U/L)

• Biliaryperforation or proximal small intestinal

Bilirubin 0.7-0.8 mg/dl perforation: ascitic fluid bilirubin concentration
greater than serum bilirubin (and >6 mg/dL)

28
 I NORMAL I
I
PARAMETER REMARKS & ABNORMAL FINDINGS

• Chylous ascites: ascitic fluid TG greater than the serum

Concentration
Triglyceride TG and >200 mg/dL (usually >1000 mg/dL)
in fluidsimilar
(TG) • Cirrhosis: neither transparent nor frankly milky (TG
to serum
ranging from 50 mg/dL to 200 mg/dL)
• Gram stain demonstrates bacteria only when >10,000
bacteria/ml are present
Gram stain Absent • Helpful in diagnosing intestinal perforation and
overwhelming infection (advanced SBP or asplenic
pneumococcal sepsis)
• Malignancy is detected when tumor cells line the
Absenttumor
Cytology peritoneal cavity & exfoliate into the ascitic fluid
cells
(peritoneal carcinomatosis)

III. APPROACH TO PERITONEAL FLUID ANALYSIS

Serum Ascites-Albumin Gradient (SAAG)

Replaced the description of"exudative" or "transudative" ascitic fluid
The gradient correlates directly with portal pressures
Specimens (serum & ascitic fluid) should be obtained nearly simultaneously on the same day
Unless a laboratory error has been made, the serum albumin level is always the larger value
SAAG = serum albumin - ascitic fluid albumin

• Portal hypertension • Peritoneal carcinomatosis

• Cirrhosis • Infection (peritonitis, TB)
• Cardiac ascites • Nephrotic syndrome
• Budd-Chiari Syndrome • Pancreatic or biliary ascites
• Portal vein thrombosis • Serositis in connective tissue disease
• Veno-occlusive disease • Bowel obstruction or infarction
• Fatty liver of pregnancy • Postoperative lymphatic leak
• Fulminant hepatic failure
• "Mixed" ascites
• Myxedema
Source:JamesonJL,et al. Harrison's
Principles
of Internal
Medicine
20thedition,2018
Feldman
M,et [Link]
andFordtran's Gastrointestinal
andLiverDisease10thEdition;2016

Case 2. A 62/M presented at the ER for generalized weakness and a progressively

enlarging abdomen. He admits to heavy alcohol intake and binge drinking almost every
other day. PE showed spider angiomata on the chest, globular abdomen with fluid wave,
and an obliterated Traube's space. Paracentesis was done and two liters of straw-colored
fluid were drained. Ascitic fluid studies revealed albumin of 18 g/L, WBC of 350/mm',
and LDH ofuo IU/L. Serum albumin was 40 g/L with serum LDH of280 IU/L.

Diagnosis: Ascites from alcoholic cirrhosis with portal hypertension

• This is a patient with heavy alcohol intake, now presenting with signs of chronic liver
disease and portal hypertension.
• The diagnosis of ascites from alcoholic cirrhosis is supported by a high-gradient SAAG
>II g/L (serum albumin - ascitic albumin= 40 g/L- 18g/L = 22 g/L). Furthermore, the
ascitic LDH (uo IU/L) is less than half of the serum LDH (280 IU/L). The WBC
(350/mm') is also <500/mm' and hence is not indicative of inflammation or infection.

29
CEREBROSPINAL FLUID (CSF)
I. ETIOPATHOGENESIS AND MANIFESTATIONS
CSF is a clear fluid circulating in the intracranial and spinal compartments formed as
an ultrafiltrate of plasma
Usual indications for lumbar puncture
0 Diagnostic: CNS infections, autoimmune diseases, CNS vasculitis, subarachnoid
hemorrhage, malignancy
0 Therapeutic: benign intracranial hypertension, acute communicating hydrocephalus
0 Delivery of intrathecal drugs: chemotherapy, antibiotics

II. CHARACTERISTICS OF NORMAL CSF FLUID

CSF composition usually maintained constant, but various conditions cause distinct
alterations in CSF findings
Total volume is ~140 mL in adults
PARAMETER I NORMAL VALUES
Color & appearance • Clear and colorless

Glucose • 50-75 mg/dL(2.8-4.2 mmol/L)

Protein • 15-60 mg/dL(150-600 mg/L)

Cell Count • 0-5 cells/uL (0-0.5 x 106 cells/L)

• 0-5 cells/uL
0 Neutrophils:0-6%
WBCs 0 Lymphocytes:40-80%
0 Monocytes: 15-45%
RBCs • None

LDH • <40 units/L

Opening pressure • 100-200 mmHp

Cytology • No malignant cells

Culture & sensitivity • No organisms present

III. APPROACH TO CSF FLUID ANALYSIS

CSF analysis usually consists of opening pressure assessment, biochemical analysis,
cytology, micro biologic evaluation, and biomarker assay
• Essential in assessment of various neurologic conditions in conjunction with other
diagnostics (e.g., imaging)
Assessment of meningitis and encephalitis are major indications for CSF analysis
0 Meningitis: classic triad of altered consciousness, fever, and neck stiffness; as well as
other signs and symptoms such as nausea, vomiting, headache, and photophobia
0 Meningoencephalitis: may additionally present with altered sensorium, confusion,
behavioral changes, seizures and focal neurologic deficits

30
A. CSF Findings in Common Meningitic Conditions
I
BACTERIAL
PARAMETER MENINGITIS
I MENINGITIS
TB I MENINGITIS
VIRAL I MENINGITIS
FUNGAL I ASEPTIC
MENINGms
Normal
Normal to
Pressure Increased Increased to mildly Increased
elevated
elevated
Clear to
Color Turbid Turbid Clear Clear
turbid
Normal to Normal to
Glucose <40 mg/dL Low Low
slightly low slightly low
Normal Normal
Markedly
Proteins Elevated to slightly to slightly Elevated
elevated
elevated elevated
RBCs Elevated Elevated Normal Normal Elevated
>100/mm' but
Elevated but Mildly
WBCs 10-2000/mm' not markedly 10-50/mm'
<500/mm3 elevated
elevated
Predominant
PMNs Lymphocytes Lymphocytes Lymphocytes PMNs
WBC
Acid fast India ink for
Gram stain Positive Negative Negative
bacilli cryptococcus

Microbial Positive Positive Negative Positive Negative

culture

B. CSF Findin sin Common Acute Demyelinatin /Inflammatory Disorders

• Pleocytosis, high protein concentration, oligoclonal bands, & lgG index

Transverse
• CSF sugar and pressure usually normal
myelitis
• Elevated CSF IL-6

Multiple • Pleocytosjs (5-50 cells/mm', lymphocytic), elevated protein

sclerosis concentration, elevated IgG index

Guillain Barre • Normal CSF counts, elevated protein concentration

syndrome • Cytoalbuminologic dissociation

• Low cell count with mononuclear predominance

Encephalitis • Normal CSF glucose
• Normal to increased CSF protein

Subarachnoid • Erythrochromic or xanthochromic color

hemorrhage • Predominantly RBC's

Case 3. A 58/M with chronic cough, weight and generalized weakness presented with fever,
progressively worsening headache, nausea, vomiting and increased sleeping time. Cranial CT
scan showed prominent meningeal & basal cistern enhancement. Lumbar tap showed elevated
opening pressures with yellowish turbid CSF. CSF glucose was noted to be low at 50 mg/dL &
total protein was elevated. WBC count was 400/mm' with lymphocytic predominance.

Diagnosis: Tuberculous (TB) meningitis

• This is a typical case of TB meningitis in a patient with concomitant pulmonary
TB. CT findings in this patient are quite typical ofTB meningitis. Note the low CSF
glucose, elevated total protein, & moderately high WBC <500/mm') with lymphocytic
predominance. An AFB smear, if done, would probably show acid fast bacilli as well.

31
PERICARDIAL FLUID
I. ETIOPATHOGENESIS
Pericardia! fluid is the ultrafiltrate of plasma that resides within the pericardia I sac and acts as
a lubricant between the visceral and parietal layer of the pericardium
The composition of pericardia! fluid is believed to be a result of Starling forces and the
gradients between hydrostatic and osmotic pressure of the pericardia! fluid & plasma
Pericardia! drainage and analysis of pericardia! fluid is indicated in the following conditions:
0 Purulent or tuberculous pericarditis
0 Neoplastic pericardia! involvement
0 Pericardia! effusion of unknown origin
0 Massive idiopathic chronic pericardia! effusion
0 Tamponade caused by uncontrolled pericardia! effusion with hemodynamic instability

II. CHARACTERISTICS OF NORMAL PERICARDIAL FLUID

Physiological pericardia! fluid is rich in protein, albumin, LOH and nucleated cells with low
levels of glucose and cholesterol
PARAMETER I NORMAL I REMARKS & ABNORMAL FINDINGS

• Bloody: iatrogenic (e.g., trauma, anticoagulation, post-

invasive cardiac procedures), malignancy, tuberculosis
Color and Clear & straw-
• Milky: lymphatic involvement (e.g., chylopericardium)
appearance colored
• Cloudy & turbulent: increased capillary leakage (if there
is leukocytosis, highly suggests infection)
• Pericardia! sac can hold 80-200 mL of fluid acutely but
Amount 15-50 ml
can handle as much as 2L if fluid accumulates slowly
Total protein 1.7-4.6g/dl • No standardized biochemical test meets statistical
relationship between specific causes of effusion
LOH 141-2613U/L • Light's criteria may be applied to pericardia! effusion,
but should not be used as sole basis for diagnostic approach
Albumin 1.19-3.06g/dl • Low protein levels: suggest transudative causes
• Elevated protein levels: seen in tuberculosis or myeloma

Glucose 80-134 mg/dl • Low glucose: infection, malignancy, lupus, tuberculosis

RBCs None • No standardized criteria to determine cause of effusion, but

elevated WBC counts are highly suggestive of inflammation
WBCs x 106 cells/L
19-2210
• WBC >IO,ooo with neutrophilic predominance: suggests
PMNs 0-116x 106 cells/L bacterial or rheumatic cause
• Lymphocytic predominance: secondary to tuberculosis,
Lymphocytes 19-1634x10' cells/L lymphoma, sarcoidosis, malignancy

Microbial • If bacterial infection is suspected, at least 3 cultures of

Negative
cultures pericardia! fluid for aero bes and anaerobes are done

Malignant Absent
• Cytology aids in identifying malignant causes but has
cells variable sensitivity depending on type of malignancy
Source:FenderEA,et al. Heart;2021
III. APPROACH TO PERICARDIAL FLUID ANALYSIS
Extent to which effusions should be evaluated with fluid analysis is still controversial:
0 Patients with new pericardia] effusion need to be assessed for myocarditis or pericarditis
0 Tamponade, possible purulent effusion, or pericarditis with poor prognostic indications
0 Patients with recurrent or large effusions that do not resolve with treatment
Echocardiography is the imaging modality of choice for the diagnosis of pericardia! effusion
Routine analysis: cell count with differential, glucose, total protein, LOH, gram stain/culture
Special testing may be done depending on the condition being evaluated
0 Malignancy: cytology, tumor markers
0 Tuberculosis: adenosine deaminase, PCR, interferon-gamma
0 Viral cultures: viral infections
0 Molecular analysis for specific infectious processes
32
 Case 4. A 23/M with weight loss, night sweats, afternoon fevers, & enlarging neck masses came
in for dyspnea. PE showed bilateral non-tender matted fixed masses in the supraclavicular
area, distended neck veins, axillary/inguinal lymphadenopathy. Chest x-ray revealed a water- :. •.·
bottle cardiac configuration. Echocardiography showed massive pericardia! effusion but with
no overt signs of tamponade. Pericardiocentesis was done which drained serosanguineous
fluid with presence of atypical round cells on cytology. Pericardia! fluid glucose is 55 mg/dL &
WBC count showed predominance oflymphocytes. Microbial cultures are negative.
Diagnosis: Pericardia! effusion likely from lymphoma
• This is a patient with lymphoma presenting with massive pericardia! effusion. The atypical
round cells seen in cytology points to a malignant etiology. Other pericardia! fluid findings
supportive of a lymphoma include the low pericardia! fluid glucose and the lymphocytic
predominance. The negative microbial culture result makes an infectious cause unlikely.

SYNOVIAL FLUID
I. ETIOPATHOGENESIS
Synovial fluid is an ultrafiltrate of plasma across the synovial membrane enriched with
various compounds produced by synoviocytes
Arthrocentesis with synovial fluid analysis should be attempted in all patients with joint
effusion or signs suggestive of inflammation without a known cause
Important indications include:
Evaluation of septic arthritis in those with acute swollen joint with warmth & tenderness
0Differentiating gout from pseudogout

II. CHARACTERISTICS OF NORMAL SYNOVIAL FLUID

Normally, the biochemical composition of synovial fluid is almost like that of plasma
• Certain conditions alter composition of synovial fluid
PARAMETER
I NORMAL FINDINGS

Color and appearance • Clear and transparent

Viscosity • High due to the presence of hyaluronic acid
Amount (knee) • <3.5 ml
WBC • <200/mm3
PMNs • <25%
Glucose • Similar to plasma
Microbial culture • Negative

III. APPROACH TO SYNOVIAL FLUID ANALYSIS

Laboratory evaluation of synovial fluid usually involves:
0 Physical examination of the fluid: appearance, color, clarity and viscosity
° Chemical analysis: glucose, total protein
0 Microscopic evaluation: cell count and differential, crystal identification
A. Categories ofSynovial Fluid based on Clinical & Laboratory Findings

PARAMETER I ,N~~TORY I INFLAMMATORYI SEPTIC I HEMORRHAGIC

Volume (knee) Often >3.5 Often >3.5 Often >3.5 Usually >3.5

Clarity Transparent Translucent Opaque Bloody

Color Yellow Yellow Yellow Red

Viscosity High Low Variable Variable

WBC 0-2,000/mm 3 >2,000/mm 3 >20,000/mm 3 Variable

PMNs <25% 2:50% 2:75% 50-75%

Culture Negative Negative Often positive Negative

33
B. Microscopic Evaluation of Crystals in Synovial Fluid

CRYSTAL
I ASSOCIATED
CONDITION/$
• Gout and conditions
DESCRIPTION

Monosodium • Needle-shaped with negative/yellow

of impaired uric acid
urate birefringence in compensated polarized light
metabolism

Calcium • Rhomboid-shaped with positive/blue

• Pseudogout
pyrophosphate birefringence in compensated polarized light

Calcium
• Coffin-lid-shaped with no birefringence in
phosphate • Osteoarthritis
compensated polarized light
(apatite)

• Envelope- or pyramid-shaped with

Calcium • Renal diseases on
negative/yellow birefringence in
oxalate dialysis
compensated polarized light
• Hyperlipoproceinemia • Rhombic-shaped with negative/yellow
Cholesterol
& rheumatoid anhritis birefringence in compensated polarized light

• Post-intraarticular • Flat, small, polymorphic with variable

Corticosteroid
steroid injections birefringence in compensated polarized light

Case 5. A45/M presented at the ER for acute swelling of his left knee and left big toe. PE showed
swollen left knee and 1st metatarsophalangeal joint with warmth and tenderness. He reports
attending a party the night before with intake of beer and offal. Arthrocentesis was performed
which drained ~IO mL of yellowish, slightly opaque, non-viscous fluid. Synovial fluid WBC
was 3,000 with PMN predominance. Gram stain was negative.
Diagnosis: Gouty arthritis
• This is a typical case of a patient with gouty arthritis presenting with acute flare after intake of
beer & dietary indiscretion. Synovial fluid analysis is compatible with inflammatory arthritis
due to the high synovial fluid WBC with PMN predominance, plus a negative string sign.
Polarized light microscopy will likely reveal needle-shaped crystals with yellow birefringence.

REFERENCES
1. Brunzel,N. (2018).Fundamentalsof Urine and Body Fluid Analysis,4th Edition. St. Louis, Missouri: Elsevier.
2. Clinical [Link] - Reference Values. Available at hnps://[Link]/rcsite/documems/creden1ial-exams/
clinical-lab•tests•reference•[Link]. Accessed December 5, 2020.
J. Dandona P,Nix D. Wilson 1'.·tF, et al Procalcitoninincreaseafterendotoxin injection in [Link] Journalof Clinical
Endocrinology& Metabolism.1994;79(6):1605-1608.
4- [Link].2016;8(4):226.
doi:10.3390/nu8o40226
5. FenderEA and ZackCJ,Shining a new light on pericardia![Link]. 2021.107(19);1528-1529.
[Link].">Cr
JP,ArberDA GladerBE,et al.(2018).
Wintrobe's [Link](Europe)Ud.
7. Hrishi AP, Se1huramanM. Cerebrospinalfluid (CSF)analysis and interpretationin neurocricicalcare for acute neurological
conditions. IndianJ CritCareMed. 2019;23(Suppl 2):S115-S119,
[Link],KasperDL,Longo DL,FauciAS, HauserSL,[Link]'sPrinciplesof InternalMedicine.20th [Link]
York:McGrawHill Education,2018,
[Link],[Link] imponanceofstooltestsin diagnosisand follow-upofgastrointestinal
disorder.;in [Link].; 20(!);;4(3,-141-8
to. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO Clinical Practice Guideline for the
Evaluationand Managementof Chronic KidneyDisease. KidneyInter.,Suppl. 2013;3:1-150
n. LightRW,MacgregorMl, LuchsingerPC, BallWC [Link]:the diagnosticseparationof transudatesand exudates.
Ann Intern Med. 1972Oct:77(4),507-13.
12. Lippi G. Plebani M. A modem and pragmatic definition of Laboratory [Link] Chem Lab Med. 2020:58(8),1171.
13. McPhersonRAand PincusMR.(2017),Henry'sClinical Diagnosis and Managementby LaboratoryMethods,[Link] Louis,
Missouri:Elsevier.
14. PaganaKD,PaganaTJ,PaganaTN. (2019).Mosby'sDiagnostic& LaboratoryTest Reference.14thed. St Louis,Mo:Elsevier.
15. Poner,[Link] MerckManualof Diagnosis and Therapy,20th [Link],NJ:Wiley,2011.
16. Shelter DE, Russell As. (2021),Synovial fluid [Link] Shmerling RH (Ed.),[Link] 12,2021,from https://
[Link]/contents/synovial-fluid-analysis
17. [Link], Chertow GM, Marsden PA, Taal MW, and Yu ASL (editors).Brenner and Rector'sThe Kidney,10th Edition.
Philadelphia,PA:Elsevier.2016.
18. Strasinger SK and Di LorenzoMS. (2014).Urinalysisand Body Fluids, 6th Edition. [Link]

34
 ELECTROCARD
BASIC CONCEPTS IN ELECTROCARDIOGRAPHY
1. Electrocardiography
2. Standardization

0 BASIC STEPS IN ECG READING

1. Step 1: Determine Heart Rate
2. Step 2: Determine Rhythm
3. Step 3: Measure Intervals
4. Step 4: Determine QRS Electrical Axis
5. Step 5: Check for Chamber Enlargements
6. Step 6: Check for ST and T-wave Changes
7. Step 7: Check for Miscellaneous ECG Findings

0 TREADMILL EXERCISE STRESS TEST

0 PACEMAKERS & PACEMAKER RHYTHMS

1. Overview of Pacemakers
2. Pacemaker Rhythms