Clinicalbiochemistry 2012 Last

See discussions, stats, and author profiles for this publication at: https://www.researchgate.
net/publication/263842348
Clinical Laboratory "Guide for Medical Students"
Book · January 2012

DOI: 10.13140/RG.2.1.4098.6082
CITATION READS
1 25,020
1 author:
Gamal Abdul Hamid

Ministry of Public Health, Yemen
191 PUBLICATIONS 277 CITATIONS
SEE PROFILE
Some of the authors of this publication are also working on these related projects:
Show Your Achievements 😎 View project
plasma medicine View project
All content following this page was uploaded by Gamal Abdul Hamid on 11 July 2014.
The user has requested enhancement of the downloaded file.

Preface
The laboratory is an important part of medical diagnostic procedure, adding

its objective information to the more subjective history and physical
examination of the patient. Clinical laboratory studies have immeasurably
advanced the medical diagnostic process. Definitive diagnosis is now made
earlier as well as more correctly than in the past.
The physician is faced with a host of tests and measurements which can be
done on the patient‟s blood, serum, plasma urine, stool, exudates,
transudates, secretions, or other fluids. The problem is to choose those tests
which will give the greatest amount of information in the most efficient
manner and for the least possible cost.
This guide book will be apply for the opinion of the department members to
enrich it and rewrite it according to the requirements of the curriculum as a
revision for medical students and for candidates taking the master degree in
Health sciences.
I hope this proposal book will be accepted as helpful guide that through
education medical laboratories will be used in such a manner so as to result
in optimal care for all patients.
G.A.H
2012
CLINICAL LABORATORY
GUIDE FOR MEDICAL STUDENTS
Edited by
Associate Professor Dr Gamal Abdul Hamid
CLINICAL LABORATORY GUIDE FOR MEDICAL STUDENTS 7

CONTENTS
Preface 9
1. Introduction 10
2. Cardiovascular System 17
3. Respiratory System 31
4. Renal System 47
5. Acid Base Balance 61
6. Gastrointestinal Tract 75
7. Liver 91
8. Endocrine System 111
9. Diabetes mellitus 137
10. Central Nervous System 149

Cerebrospinal Fluid
11. Articular System 156
12. Infectioius Diseases 170
13. Tumor Markers 180
14. Appendix I : Laboratory Abbreviations 189
Appendix II: Normal Reference Range 1201
12. Bibliography 206

Preface
The laboratory is an important part of medical diagnostic procedure, adding

its objective information to the more subjective history and physical
examination of the patient. Clinical laboratory studies have immeasurably
advanced the medical diagnostic process. Definitive diagnosis is now made
earlier as well as more correctly than in the past.
The physician is faced with a host of tests and measurements which can be
done on the patient‟s blood, serum, plasma urine, stool, exudates,
transudates, secretions, or other fluids. The problem is to choose those tests
which will give the greatest amount of information in the most efficient
manner and for the least possible cost.
This guide book will be apply for the opinion of the department members to
enrich it and rewrite it according to the requirements of the curriculum as a
revision for medical students and for candidates taking the master degree in
Health sciences.
I hope this proposal book will be accepted as helpful guide that through
education medical laboratories will be used in such a manner so as to result
in optimal care for all patients.
G.A.H
2012

INTRODUCTION 1
General practitioners vary in their use of the laboratory services, with

variation of up to 10-fold between comparable practices in the rates of blood
tests requested per patient. Variation occurs not only in the use of the
pathology and radiology facilities, but also in the use of specialist referral.
Pathological and radiological investigations are executed by skilled
personnel using complex techniques. Human and technical errors are
inevitable, as in all branches of medicine. The practicability of a test varies
with the time, expense and skill involved in its performance. The accuracy of
a test is the nearness with which the result approaches the true result. The
precision is the reproducibility of the result on the same sample.
Laboratories should be able to quote a “reference interval” for each test

performed. This is the range within which the result for that test would fall
for 95% of a normal population. It follows that 5% of normal individuals will
have a result outside that reference interval. If a large profile of tests is
performed on one individual, on average 1 in 20 test results will be outside
its reference interval.
Reference intervals for healthy humans may be affected by:

1. Age e.g alkaline phosphatase is higher in growing children
2. Sex e.g creatine kinase is higher in males than females
3. Time of sampling
a. Diurnal variation
b. Random (day to day) variations e.g serum iron
c. Seasonal variation e.g plasma 25-OH vitamin D
4. Postural e.g serum albumin is higher when erect than when recumbent
5. Food intake
a. Fed vs fasted e.g plasma glucose, triglycerides
b. Content of diet e.g plasma urea affected by protein intake
6. Race e.g immunoglobulins higher in African
When age and /or sex have any significant effect on results, age and sex
related reference intervals should be used.
In to be confident that a result is abnormal or a change is clinically significant

one needs to know:
1. The analytical error of the method used
2. The stability of the analyses in health ( i.e physiological variation)

The decision making model is a useful framework for characterizing the role
of laboratory test in clinical problem solving:
History Physical Finding Laboratory Findings

for screening
*Wellness screening
*Case finding
Hypothesis
Laboratory Findings for Diagnosis

*Confirm a diagnosis
*Exclude a diagnosis
Laboratory Findings for Management

*Monitor the course of a disease
*Monitor the therapy
*Stage the severity of a disease
*Provide a prognosis
In addition to their use for diagnosis and management, laboratory

tests are used for screening, of which there are two different types: (1)
wellness screening, in which the individuals are asymptomatic and basically
healthy; and (2) case finding, in which the individuals are symptomatic or
have a disease ( i.e they are patients).

Sample Precautions
Urine
The accurate timing of urine collections frequently has more bearing on the
result than the accuracy of the subsequent chemical analysis.
Serum
1. Avoid taking a blood sample from or near the site of an intravenous
infusion.
2. Avoid prolonged stasis (which increases the concentration of protein-
bound substances).
3. Avoid hemolysis or leaving the sample unseperated for hours (N.B
samples that have been left unseperated may be more difficult to detect as
there is no colour change.
Substances which are present in higher concentration in the cells leak into the
plasma:
e.g Potassium
Phosphate
Acid phosphatase
Aspartate aminotransferase
Lactate dehydrogenase
Storing unseperated blood samples at 4 C slows erythrocyte metabolism and
the ion pumps, accelerating the leak from cells to plasma; room temperature
is often preferable.
3. Use the correct sample tube
4. e.g fluoride/oxalate for glucose (fluoride inhibits glycolysis by erythrocytes
and so preserves glucose, but affects the integrity of the red cell membrane,
so its effect is like hemolysis for other analytes).
5. Do not overfill/underfill tubes or tip contents from one tube to another
e.g sequestrene (EDTA) used for hematology is a sodium or potassium salt
which prevents clotting by chelating calcium, so contamination with this
anticoagulant results in:
Calcium decreases
Na or K increases
Alkaline Phosphate decreases
Common Errors
A result may be erroneous for a variety of reasons. Errors of labeling and
identification will always occur and put at least two patients at risk. They
may happen at any of the several steps between taking the sample and
interpreting the report. Samples must be put into correct prelabelled bottles
and taken promptly to the laboratory.
Samples are often taken by incorrect techniques. Blood is occasionally
taken from an arm into which an infusion is running. Prolonged venous
occlusion before venesection raises the concentration of proteins, cells and
protein-bound constituents in the blood. Clenching the fist raises the
concentration of pyruvate, lactate and creatine kinase. Phosphate, glucose
and some hormone levels vary with the time of day. If blood samples are left
standing, potassium, phosphate and lactate dehydrogenase leak from red

cells into the serum. Hemolysis has a similar effect the concentration of
serum proteins.
Saliva is often sent to the laboratory instead of sputum. Urine collections
are notoriously inaccurate, partly because of difficulties with bladder
emptying and partly because of difficulties patients experience in complying
with instructions. It must be clearly explained that the first urine is discarded
in a timed collection but all other specimens including the last must be
included.
Interpretation of Tests
There can be few tests which when positive indicate the presence of a disease
and when negative indicate its certain absence. The discriminatory ability of
tests is described in terms of sensitivity, specificity and predictive value
Sensitivity
This indicates the percentage of people who actually have the disease in
whom a particular test is positive. Ninety-five per cent sensitivity implies 5%
false negatives. Increase in sensitivity may reduce specificity. Screening tests
should be sensitive.
Specificity
This is the percentage of people without the disease who have a negative test.
Ninety-five per cent specificity implies 5% false positive. Specificity is
sometimes increased at the cost of sensitivity.
Definitive test should be specific.
Predictive value
Predictive value (posttest probability) of a positive test: Probability of a
disease being present if the test is positive.
Positive value (posttest probability) of a negative test: probability of a disease
being absent if the test is negative.
Prevalence (pretest probability): the frequency of patients with a certain
disease in the group being tested with the measurement.
Diagnostic sensitivity: the percentage of true-positive results in healthy
patients
TABLE 1.1: PREDICTIVE VALUE

No with No with negative Total
positive test test result
result
No. with TP FN TP + FN
disease
No. without FP TN FP+TN
disease
Total TP + FP FN +TN TP+FP+TN+FN
TP: true positives; the number of sick subjects correctly classified by the test.
FP: False positives; the number of subjects free of the disease who are
misclassified by the test.
TN: True negatives; the number of the subjects free of the disease who are
correctly classified by the test.
FN: False negatives; the number of sick subjects misclassified by the test.
Prevalence: Percent of total subjects examined who are diseased
Sensitivity: Positivity of the disease

= TP X 100 = T P X100
TP +FN No. disease
Specificity = Negativity in health
= TN X 100 = T N X100
TN +FP No. without disease
Predictive value of a positive test =
= TP X 100 = T P X100
TP +FP No. Positive
Predictive value of a negative test=
= TN X 100 = T N X100
TN +FN No. negative
Range of Normal
The range of normal given for laboratory tests usually includes 95%
of a healthy adult population. Therefore only one in forty will be higher and
one in forty lower, so a slightly abnormal result. Also, a result near the edge
of normal may be abnormal for that individual. Narrowing of the normal
range may be possible if the population group is more clearly defined with
regard to sex, age, race and pregnancy. Serum urea levels are higher in the
old and lower in pregnancy. With some tests, methods differ between
laboratories and the local normal results will vary.
METHODS USED IN THE CHEMICAL PATHOLOGY LABORATORY
• Colorimetric methods:
Analyte reacts with a dye, changing its absorption spectrum (colour).

Measured with a spectrophotometer. Rapid & easily automated. Cheap.
Concentration range: mM to μM. Examples: urea, creatinine, phosphate,
albumin, total Ca2+
• Ion-selective electrodes: Membrane selectively permeable to an ion
generates a membrane potential proportional to concentration of free ion.
Rapid & easily automated. Cheap. Concentration range: mM to nM
Examples: Na+ , H+ (pH meter), free Ca2+
• Enzymatic: Example: lactate dehydrogenase (LDH) catalyses the reaction

5 pyruvate + NADH + H+ The concentration of NADH is easily measurable by
its UV absorbance, allowing the rate of the reaction to be measured. An end-
point method can be used to measure the concentration of a substrate (e.g.
the amount of NADH formed will be equal to the initial lactate concentration)
or a rate method can measure the amount of enzyme. lactate +
+
NAD↔pyruvate + NADH + H The concentration of NADH is easily
measurable by its UV absorbance, allowing the rate of the reaction to be
measured. An end-pointmethod can be used to measure the concentration of
a substrate(e.g. the amount of NADH formed will be equal to the initial
lactate concentration) or a ratemethod can measure the amount ofenzyme.
•Radio-Immuno-Assay(RIA)and related techniques:In the competitive RIA,
the analyte or antigen (Ag) in the sample competes with radioactivelylabelled
analyte (Ag*) for binding to a limiting number of antibody sites (Ab) in the test
tube:
Ag* + Ab→Ag*-Ab
(we measure THIS by means of the radio-label)+
Ag(unknown amount in patient's plasma.)
(the more of this, the less Ag*-Ab is formed)
Ag-Ab
Ag*-Ab can be easily separated from the free Ag* and the amount of labelled
Ag* bound isdetermined byusing a radioactivitycounter.The more unlabelled
Ag in the specimen,the lessAg* will be bound .
The technique hashigh sensitivityi.e.isable to measure lowconcentrationsofAg

(nM to pM range). Automation has been achieved with some but not all
immunoassays in current use, so itcan be a time-consuming method.
•Chromatographic methodsElectrophoresisand otherchromatographic

methodscan be used to separate compounds in plasma orurine, e.g.
-serum proteins (electrophoresis)-amino acids (ion exchange

chromatography)-organic acids (gas chromatography, mass spectrometry)-
isoenzymes (electrophoresis)
•DNA techniques: Analysis of patient’s DNA for specific mutations, or linked

polymorphisms, by molecularbiological techniques, usually involving use of
the versatile polymerase chain reaction (PCR)

REVIEW QUESTIONS
1. Define mean, mode and median?

The mean is the average of a set of measurements. The mode is the most
frequently occurring value in a set of measurements. The median is the
middle measurement after all measurements have been arranged in order of
magnitude.
2. The following indicate the results of screening test “Q”: in screening for
disease “D”
Disease “D”
+ -
Screen test “Q” + 40 10 50
- 30 120 150
70 130 200
The specificity of test “Q” would be:

a. 40/70
b. 120/130
c. 40/50
d. 120/150
3. The positive predictive value would be:

a. 40/70
b. 40/50
c. 120/130
d. 120/150
4. How can accuracy of a measurement be determined?
Accuracy can be determined by comparing the technic in use with another

technic for performing the same measurement. Agreement of the two
measurements by differing technics suggests accuracy. In practice,
automated and hand methods can be assessed against each other, newly
introduced methods against older, established methods and a method of one
laboratory against the same or different method of another laboratory. The
latter often involves use of commercial standards. Testing for recovery of
known amounts of dded material to the sample analyzed is another way of
determining accuracy.

2
CARDIOVASCULAR SYSTEM
Many cardiovascular disorders have a biochemical basis. Rapid and accurate

diagnosis of cardiac problems is a routine requirement in emergency
departments.
In this chapter, we discuss the common emergency disorders e.g AMI,
rheumatic fever, hypertension, congestive cardiac failure and shock and the
information about cardiac enzymes, lipid disorders, Antistreptolysin O and
C-reactive protein.
CARDIAC ENZYNES
LACTATE DEHYDROGENASE (LDH) AND

-HYDROXYBUTRATE DEHYDROGENASE (HBDH)
The enzyme LDH is found in the cells of many tissues especially the
heart, liver, RBC, Kidney, Skletal muscle, brain and lung. Because LDH is
widely distributed through the body, the total LDH level is not a specific
indicator of any one disease or indicative of injury to any one organ. When
disease or injury affects the cells containing LDH, the cells lyse and LDH is
spilled into the blood stream where it is identified in higher than normal
levels. The LDH is a measure of total LDH. Actually five separate fractions
(isoenzymes) makes up the total LDH.
LDH consist of 5 separable proteins, each made of tetrameres of 2 types of
subunits H and M.
TABLE 2.1: THE FIVE ISOENZYMES OF LACTATE DEHYDROGENASE
(LDH), THEIR STRUCTURE, RELATIVE DISTRIBUTION IN SERUM
AND ACTIVITY
Isoenzyme Structure % Causes Speed in
activity electrophoresis
in serum
LDH1 HHHH 30 Heart muscle , RBC, Renal Fastest
LDH2 HHHM 40 Reticuloendothelial system electrophoretic
and heart mobility
LDH3 HHMM 20 Lung and other tissues
LDH4 HMMM 3 Kidney, placenta ,pancreas
LDH5 MMMM 7 Liver and striated muscle Slowest

electrophoretic
mobility
The 5 Isoenzymes can be distinguished by Kinetics, electrophoresis,

chromatography and immunologic characteristic.
Indications
Suspect of myocardial infarction
Follow-up of myocardial infarction
Suspect of pulmonary embolism
Differential diagnosis of icterus
Diagnosis of organic damage

Principle of LDH:
The LDH catalase the NADH2 and independently reduce pyruvate to lactate
in the presence of NAD.
Pyruvate + NADH + H+ <----LDH----->L-lactate + NAD+
Principle of HBDH
This enzyme catalyzes the reduction of oxybutrate in the presence of NADH
hydroxybutrate and NAD. This method is quite similar to the colorimetric
method for LDH.
HBDH activity was principally associated with fast moving of LDH1
characteristic of heart muscle. LDH1 is active against hydroxybutrate and can
be measured as HBDH.
2-Oxybutrate +NADH + H+ <---HBDH---> 2-Hydroxybutrate + NAD
Normal value
Adult LDH 45-90 u/l
HBDH 68-135 u/l
TABLE 2.2:DIFFERENTIAL DIAGNOSIS OF LDH/HBDH QUOTIENT

LDH/HBDH Cause
1.33 - 1.64 Infections, Pulmonary embolism and malignome

Under 1.30 Myocardial infarction and Hemolysis
Above 1.64 Liver damage
INTERFERING FACTORS
Hemolysis of blood will cause false positive LDH levels since LDH exists in
the RBC. Lysis of these cells causes the LDH to pour out into the specimen
blood and falsely elevate the LDH level.
Sternuous exercise may cause elevation of total LDH and specifically LDH1,
LDH2 and LDH5.
Drugs that may cause increased levels include anesthetics, aspirin,
clofibrate, mithramycin, narcotics and procainamide.
Drugs that may cause decreased levels include ascorbic acid.
CLINICAL PRIORITIES
1. Because LDH is widely distributed throughout the body, the total LDH level is
not a specific indicator of any disease or organ injury. Isoenzyme is more
specific and helpful diagnostically.
2. When LDH1 is greater than LDH2 myocardial injury is strongly suspected.
This may be referred to as a “flipped LDH”
3. Isolated elevation of LDH5 usually indicates hepatocellular injury or disease.
Serum LDH Increased in

1. Myocardial infarction: elevation of LDH1 and to a lesser degree LDH2.
2. Pulmonary embolism: in 60 % of patients. LDH3 and LDH4
3. Liver disease: LDH5.
3. Skletel muscle disease: LDH5

4. Progressive muscle dystrophy (DUCHENEN) increase of LDH2-3 and not the
LDH5 of normal skletal muscle.
5. Dermatomyositis, polymyositis: Increases of LDH , CK and GOT
6. Anemia: in intravascular hemolytic anemia and megaloblastic anemia.
Increase of LDH1 and bilirubin and decrease of haptoglobin.
7. Paroxysmal nocturnal hemoglobinuria: Increases of LDH2 and LDH3
8. Malignant tumours: LDH increased and used for control of tumour masses.
9. Lymphoma: Increases of LDH3 and LDH2
CREATINE PHOSPHOKINASE (CK)

CK is found predominantly in the heart muscle, skletal muscle and brain.
Serum CK levels are elevated when these muscles or nerve cells are injured. CK
levels can rise within 6 hours, after damage. If damage is not persistent, the
levels peak at 18 hours after injury and return to normal in 2 to 3 days.
CK splits creatine phosphate in the presence of ADP to yield creatine and ATP.
Creatine phosphate + ADP <---CK--> Creatine +ATP
CK transfers a high-energy phosphate from creatine phosphate to adenosine
diphosphate (ADP) forming creatine and adinosine triphosphate (ATP).For
assay purpose, the ATP thus formed is linked to the reduction of NADP to
NADPH as shown in the following two reactions
Glucose +ATP ---Hexokinase---> G-6-PDH +ADP
Glucose 6-phosphate + NADP---G.6.PDH--> G-6-phosphate+NADPH2
Absorbance spectrophotometry is used to measure the increase in optical
density at 340nm when NADP is reduced to NADPH
NADPH2 is proportionately increased with the activity of CK.
Skletel, heart muscle and brain are rich in this enzyme.
CK-ISOENZYME
MB-Isoenzyme of heart muscle increased in acute myocardial infarction and
cardiac surgery.
CK-Activity between 160 u/l and 1600u/l and CK-MB >6% is diagnostic in
patients with myocardial infarction.
MM ISOENZYME is increased in skletel muscle
BB-ISOENZYME is isoenzyme of brain, increase in malignant hyperthermia,
uremia, lung, cardiac onset with brain anoxia and necrosis of large intestine.
MiMi-ISOENZYME (mitochondrial isoenzyme), is increased in Myocardial
infarction, Reye's syndrome, malignant tumours and necrotic liver diseases.
Normal values: Female < 100 u/l Pathologic > 120 u/l
Male <159 u/l Pathologic > 160 u/l
INTERFERRING FACTORS
 IM injections can cause elevated CK levels.
 Sternous exercise and recent surgery may cause increased levels.
 Early pregnancy may produce decreased levels.
 Drugs may cause increased levels: amphotericin B, ampicillin, some
anesthetics, anticoagulants, aspirin, clofibrate, dexamethasone, lasix, captopril,
colchicine, alcohol, lovastatin, lithium, lidocaine, Propranolol, Succinylcholine
and morphine.

CLINICAL PRIORITIES
1. Avoid IM injection that can cause elevated CK levels.
2. CK-MB is helpful in both quantifying the degree of myocardial infarction and
timing the onset of the infarction.
3. The CK-MB isoenzyme is often used to determine the appropriate of
thrombolytic therapy. High levels may indicate that significant infarction has
already occurred, thus precluding a benefit from thrombolytic therapy.
INCREASE OF CK- AND CK-MB IN HEART DISEASES

1. Myocardial infarction: CK >160u/l and CK-MB >6% (in the first 24 hours).
2. Cardiogenic shock: Like myocardial infarction but CK-MB is not increased in
the first hours.
3. Myocarditis: CK and CK-MB with other signs of myocarditis.
4. Postoperative (heart OP).
5. Cardiac defibrillation
INCREASE OF CK IN
SKLETEL MUSCLES:
(CK-MM) 7. Maligne hyperthermia
1. Body activity (sport) 8. Muscle dystrophy (duchnne)
2. Intramuscular 9. Myasthenia graves and
injection dystrophia myotonia.
3. Operations 10. Intoxication and Alcoholism.
4. Multiple traumas 11. Infectious disease
5. Epilepsy 12. Hypothyroidism.
(convulsion) 13. Hypokalemia
6. Arterial emboli
INCREASE OF CK IN TISSUE DISORDER
1. Necrosis of pancreas
2. Colon cancer
3. Acute liver cell necrosis
4. Pregnancy
a. Skletel muscle CK-MM
b. Uterus muscle CK-BB
5. Malignancy of organs (CK-MM, CK-BB and CK-MiMi)
MYOGLOBIN
Myoglobin is a globin complex similar to hemoglobin but present in muscle

tissue. It is excreted in the urine by way of glomerular filtration. Its excretion
increases in circumstances involving any muscle cell damage. Serum (0-90
ng/ml) and urine (negative) myoglobin measurements are used in the
differential dignosis of darkly pigmented urines and to help substantiate or rule
out a diagnosis of MI. In the presence of a normal total CK concentration, normal
serum and urine myoglobin levels, and electricardiogram (ECG) findings limited
to short-lived ST and T wave changes, MI can usually be ruled out in patients
with unstable angina.

Serum myoglobin levels peak approximately 8 to 12 hours after rise. More
frequently, a return to normal takes at least 24 hours. Serum myoglobin may
appear intermittently in the first 6 to 18 hours after an MI, and serial
determinations may be indicated.
Myoglobin increases can appear in the urine within 3 hours after an MI.
Levels may return to high normal in 30 hours; usually, however, return to
normal takes 72 hours or longer.
MYOGLOBIN LEVELS INCREASED IN
1. Cardiac muscle damage

2. Skletal muscle damage, most frequently in crushing injuries
3. Familial myoglobinuria (Meyer-Betz disease)
4. High fevers, Stress (e.g hyperthermia and vigorous physical activity. In
susceptible persons, fever can cause muscle destruction
5. Uncommon occurances with diabetic acidosis, hypokalemia, or barbiturate
poisoning
Troponon
Cardiac Troponin T (cTnT) and cardiac Troponin I (cTnT) is a sensitive test

during the first 48 hours after AMI with 80% sensitive for up to 5-7 days but not
sensitive from 0-4 hours. Diagnostic efficiency is similar to CK-MB in early AMI
until fifth day.
It is sensitive marker for minor myocardial injury in unstable angina without
AMI .
It is useful in diagnosis of preoperative AMI when CK-MB may be increased by
skeletal muscle injury. CTnT sensitively >CK-MB in first 6-8 hours with better
sepecificity, not increased by skeletal muscle injury or chronic renal diseasecan
remain increased 5-9 daysafter AMI. cTnT is not incraesed by pulmonary and
orthopedic surgery.

GLUTAMATE OXALOACETATE TRANSAMINASE (GOT)
(ASPARTATE-AMINOTRANSFERASE- AST)
GLUTAMATE-PYROVATE TRANSAMINASE (GPT)
(ALANIN- AMINOTRANSFERASE-ALT)
GOT and GPT are all intracellular enzymes involved in amino acid or
carbohydrate metabolism. The enzymes are present in high concentrations in
muscle, liver and brain. Elevation of concentrations of these enzymes, in the
blood indicates necrosis or disease.
AST: L-asparatate + 2-Oxoglutamate  L-glutamate + oxaloacetate
ALT : L-alanine + 2-Oxoglutarate  L-glutamate + Pyruvate
GOT is present in most tissues but especxially in skeletal and cardiac muscle,
liver and kidney. There are two major isoenzymes, cytoplasmic and
mitochondrial. Both enzymes have been demonstrated in plasma following
tissue damage , but their differentiation has not been shown to be of much
diagnostic value.
Normal value: GOT 5-35u/l

GPT 7-56 u/l
INDICATIONS
1. Disease of the liver and biliary tract.
2. Skletel muscle damage
3. Myocardial infarction (GOT)
TRANSAMINASE IN HEART DISEASES

1. Heart infarction:
GOT: 8-12 h after infarction, Maximum 7 times. Normal level after 3-4 days
GOT/GPT >2
2. Heart catheterization: Light increase of GOT, CK and LDH.
3. Postoperation (Heart): After OP increase of GOT, CK and LDH
TRANSAMINASE IN SKLETEL MUSCLE DISEASES

1. Proggressive muscle dystrophy: increase of transaminase (50-150 times).
2. Myositis: in polymyositis increase of transaminase and in dermatomyositis
light increase of GOT with normal level of GPT.
INTERFERRING FACTORS
 Pregnancy may cause decreased AST levels.
 Exercise may cause increased levels
 Drugs that may cause increased levels include; antihypertensive, cholinergic
agents, coumarin type anticoagulants, digitals, erythromycin, INH, methyldopa,
oral contraceptive, opiats, salicylates, verapamil and hepatotoxic medications.
LIPID DISORDERS
Unequivocal evidence has demonstrated an increased risk of coronary heart

disease in persons younger than age 50 who have an elevated total cholesterol
level. However, evidence for elevated triglyceride levels, as an independent risk
factor for coronary heart disease is inconclusive.
Each lipoprotein has a particular combination of lipid (cholesterol, triglyceride
and phospholipid) and protein. The major lipoprotein, can be classified
according to density (weight per volume) or to electrophoretic mobility.
From highest to lowest density, the lipoprotein is: High-density lipoprotein
(HDL), Low-density lipoprotein (LDL), Intermediate-density lipoprotein (IDL),
very low density lipoprotein (VLDL) and chylomicrons.
TABLE 2.3: PATTERN'S OF HYPERLIPOPROTEINEMIA
TYPE
ABNORMALITY PLASMA APPEARANCE
I increase chylomicron creamy superntant,

clear infranatant
IIa increase LDL clear
IIb increase LDL, turbid
increase VLDL
III IDL turbid
IV increase VLDL turbid
V increase VLDL creamy supernatant,
increase chylomicron turbid infranatant
SERUM CHOLESTEROL
Normal value: 150-200 mg/dl
Increased >240 mg/dl in idiopathic hypercholesterolemia, hyperlipoproteinemia,
biliary obstruction, hypothyroidism, nephrosis, pancreatic disease and
pregnancy.
Decreased serum cholesterol in hyperthyroidism, malnutrition, chronic anemia,

cortisone and ACTH therapy, Abetalipoproteinemia and Tangier disease.
SERUM HDL-CHOLESTEROL
HDLs are carriers of cholesterol. They are produced in the liver and to a smaller
degree, in the intestine. The purpose of HDLs is believed to be removal of the
cholesterol from the peripheral tissues and transport to the liver for excretion.
Also, HDLs may have a protective effect by preventing cellular uptake of
cholesterol and lipids. These potential actions may be the source of the protective
cardiovascular characteristics associated with HDLs (good cholesterol) within the
blood.
Normal values: In male > 45mg/dl and female >35mg/dl
HDL INCREASED IN
Vigorous exercise
Moderate consumption of alcohol
Insulin treatment and estrogen
HDL DECREASED <38 mg/dl in men and < 32 mg/dl in women, in stress and
recent illness e.g acute myocardial infarction, stroke, trauma, starvation, obesity,
cigarette smoking, D. mellitus, hypothyroidism, liver disease, nephrosis, uremia,
elevated serum triglceride and familial hypoalphalipoproteinemia.

Patients with very low levels of HDL are some times said to have "a type VI lipid
abnormality. HDL levels are strongly correlated with an increase risk of coronary
heart disease..
INTERFERING FACTORS
 Smoking and alcohol ingestion decrease HDL levels
 Binge eating can alter lipoprotein values
 HDL values are age and sex dependent
SERUM LDL-CHOLESTEROL
LDLs are also cholesterol rich. Cholesterol carried by LDLs can be deposited into
the peripheral tissues and is associated with an increased risk of arteriosclerotic
heart and peripheral vascular disease. Therefore high levels of LDL (bad
cholesterol) are atherogenic. The LDL level should be less than 160 mg/dl in
persons with coronary artery disease and less than 180 mg/dl in those without
disease. LDL is very difficult to isolate and measure. Therefore the LDL is most
usually derived by the FRIEWALD formula. In this formula, LDL is derived by
subtracting the HDL plus one fifth of the triglyceride from
LDL= Total cholesterol-(HDL+ triglyceride)
5
INCREASE LDL >160 mg/dl IN

Familial hypercholesterolemia, familial combined hyperlipidemia, D.Mellitus,
hypothyroidism, nephrotic syndrome, chronic renal failure, pregnancy and diet
high in cholesterol
LDL cholesterol is directly related to risk of coronary heart disease

Desirable level <130 mg/dl
Borderline elevation 130-159mg/dl
Elevation level >160mg/dl
HDL cholesterol is inversely related to risk of coronary heart disease:

Low risk >60 mg/dl
Moderate risk 35-60 mg/dl
High risk <35 mg/dl
VLDL although carrying a small amount of cholesterol is the predominant

carriers of blood triglycerides. To a lesser degree, VLDL, are also associated with
an increased risk of arteriosclerotic occlusive disease.
CLINICAL PRIORITIES
1. Lipoproteins are considered to be predictors of heart disease. Blood levels should
be collected after a 12 to 14 hours fast.
2. HDL is often called GOOD CHOLESTEROL because it removes cholesterol from
the tissues and transports it to the liver for excretion. High levels are associated
with a decreased risk of coronary heart disease.
3. LDL is often called BAD CHOLESTEROL, because it carries cholesterol tissues. High
levels are associated with an increased risk of CHD.

ANTISTREPTOLYSIN O TITRE
This test used primarily to determine whether a previous streptococcus infection

has caused a streptococcal disease, such as glomerulonephritis, rheumatic fever,
bacterial endocarditis and scarlet fever.
The ASO titer is a serologic procedure demonstrating the reaction of the body to
infection caused by group A beta hemolytic streptococci. The streptococcus
organism produces an enzyme called streptolysin O, which has the ability to
destroy (lyse) red blood corpusceles. Because streptolysin O is antigenic, the
body reacts, by producing ASO, a neutralizing antibody. ASO appears in the
serum one week to 4 weeks after the onset of a streptocooal infection; a high titer
is not spcific for a certain type of poststreptococcal disease (i.e GN, RF) but
merely indicates that a streptococcal infection is or has been present.
When ASO elevation is seen in a patient with glomerulonephritis or endocarditis
one can safely assume that the disease was caused by streptococcal infection.
ASO is of no value for diagnosing acute streptococcal infection. Cultures for
streptococci are required for that.
The highest incidence of positive results is during the third week after the onset
of acute symptoms of the streptococcal disease. By 6 months, only 30% of
patients have abnormal titers.
The upper normal limit in normal persons of ASO titre is 150-200 units.
ASO is necessary in
A. Direct diagnostic in scarlet fever, eryspieles, streptococcus pharyngitis and
tonsillitis.
B. Indirect diagnostic in rheumatic fever and glomerulonephritis.
Interfering factors
 Increased beta lipoprotein neutralize ASO and cause false positive ASO titer
 Drugs that cause decreased ASO include antibiotics and steroid
C. REACTIVE PROTEIN
C polysaccharide of the pneumococcus is probably an alpha globulin, perhaps

bound to serum lipid. It is found in the serum of normal individual. Its
production is stimulated by bacterial infections, various pyogenic agents or the
products of injured tissues.
It is often found in the serum of patients with:
 Active bacterial infections
 Active rheumatic fever
 Acute myocardial infarction
 Active rheumatic arthritis
 Active TB
The CRP test is a more sensitive and rapidly responding indicator than the ESR. In
an acute inflammatory change, CRP shows an earlier and more intense increase
than ESR; with recovery, the disappearance of CRP precedes the return of ESR to
normal. The CRP also disappears when the inflammatory process is suppressed
by antiinflammatory agents, salicylates or steroids.
This test is also useful in evaluating patients with an acute myocardial infarction.
The level of CRP correlates with peak levels of the MB isoenzyme of creatine
kinase but CRP peak occur 18-72 hours laters. Failure of CRP to normalize may
indicate ongoing damage to the heart tissue. Levels are not elevated in-patients
with angina.
This test also may be used postoperatively to detect wound infections. CRP levels
increase within 4 to 6 hours after surgery and generally begin to decrease after the
third postoperative day. Failure of the levels to fall is an indicator of
complications, such as infection or pulmonary infarction.
Interfering Factors
 An intrauterine device may cause positive test because of tissue inflammation.
 Oral contraceptives may cause increased levels
 Salicylates and steroids and cause decreased levels.
ACUTE MYOCARDIAL INFARCTION
Ischemic myocardial necrosis is usually resulting from abrupt reduction in

coronary blood flow to a segment of myocardium. It is characterized by
pericardial pain. For ambulatory patients who are seen in the emergency
department with clinical findings of acute myocardial infarction (AMI), decide on
hospital admission by using the history, physical examination, and
electrocardiogram (ECG).
1. Signs and symptoms: The pain of MI, unlike angina pectoris, usually occurs at
rest. The pain is similar to angina in location and radiation but is more severe
and builds up rapidly. Usually it is described as a retrosternal tightness or
squeezing sensation or sometimes a dull ache. Radiation to the left shoulder is
not uncommon. Other symptoms include sweating, weakness, dizziness,
nausea, vomiting, and abdominal discomfort. Abdominal discomfort is
especially common in inferior wall MIs.
2. ECG changes: The classical evolution of changes is from peaked (hyperacute) T
wave, to ST segment elevation, to Q wave development, to T wave inversion.
This sequence may occur over a few hours or may take several days.(Note): If
ECG changes are not present, do not assume an MI has not occurred. If signs
and symptoms suggest MI, it is an MI until proved otherwise.
3. Confirmatory evidence: Evidence of infarction is confirmed by elevation of CK-
MB fraction or Troponin
4. Other diagnostic procedures: Scintigraphic studies including technetium-99
and thalium201 imaging and radionuclide angiography, as well as
echocardiography, may help document the extent of the damage.
Laboratory Finding
A. Myocardial Enzymes: The cardiac enzymes most assayed are creatine kinase
(CK), serum glutamine oxaloacetate transaminase (SGOT) and lactate
dehydrogenase (LDH). Each enzyme has a particular time course for release into
the vascular comparment from irreversible damaged heart cells during acute
myocardial infarction.
For patient admitted to the hospital with clinical findings of AMI, request serial
measurements of CK and CK isoenzyme. Serial measurements of LDH and LDH
isoenzymes may be helpful. Serum transaminse measurements are unnecessary.
When CK measurements are delayed more than 2 hours, the specimen should be
refrigrated or placed on ice.
1. Creatine Phosphokinase (CK): Increase level appeared within 5 hours after

onset. CK-MB, the myocardial component of creatine kinase, is found in blood
within 5 hours of myocardial necrosis.
CK-MB is highly sensitive, and their absences in the serum virtually exclude the
diagnosis of acute infarction.
Routine measurement of CK-MB on admission and 6-8 h for the first 24h will
confirm or reject the diagnosis. Normal CK-MB for 24 h virtually rules out MI.
If the test results show a characteristic rise and subsequent fall of CK and CK-MB
in the context of appropriate clinical findings, conclude that the diagnosis is AMI
2. GOT: GOT start to rise about 8-12 hours after infarction and reached a peak in
the first or second day.
3. LDH: is liberated from hemolysis of red cells and is therefore less specific. It
starts to rise after 24 hours; reaches a peak after 3-5 days. It is useful when the
diagnosis is in doubt several days after possible infarct.
The isoenzymes of LDH that are increased are LDH1 and LDH2. An elevated
LDH1:2 isoenzyme ratios are typical of myocardial infarction and were 96%
sensitive and 97% specific.
TABLE 2.4: TIME COURSE OF RELEASE

OF CARDIAC ENZYMES AND TROPONIN DURING ACUTE
MYOCARDIAL INFARCTION
Become PEAK Return
elevated (HRS) to
(HRS) normal
Myoglobin 3-5h 12 24-30h
CK 4-6h 18h 2-3

days
SGOT 8-12 18- 3-4
36h days
LDH 24-48 72-120 8-
14days
Troponin 4-6 10-24 10

T days
If serial measurements for serum CK, CK-MB, and LDH are normal in a
patient seen early after the onset of clinical findings of AMI, exclude AMI.
There is a relationship between the peak serum concentrations of CK, CK-MB,
and LDH and size of the AMI, with large infarcts producing higher values. This
relation is stronger with CK and CK-MB than with LDH.
In patients with clinical findings of AMI begin thrombolytic therapy as early
as possible without waiting for enzyme and isoenzyme results. Measure a serial
level of serum CK-and CK-MB to monitor therapy.

Because the goal of the thrombotic therapy is to reopen an occluded artery as
soon as possible, the decision to attempt thrombolysis should be based on the
clinical history and ECG rather than waiting for increased enzyme values.
Ideally, in individuals without contraindications thrombolytic agents should be
used within 2 to 3 hours of the onset of findings. Waiting more than 4 hours is
too long.
B: Proteins containing substances: Myoglobin and troponin
Increase serum myoglobin peaks and myoglobinuria often occur and return
to normal earlier than CK, useful for diagnosis within 6 hours of onset of
symptoms.
N.B: Thrombolytic agents (e.g Streptokinase, urokinase, tissue plasminogen
activator alter the enzyme patterns.
Troponin is a protein complex consisting of three isotypes (T,I and C).
Troponin T and troponin I have the potential to become better diagnostic
markers for acute myocardial infarction than existing enzymes (such as CK-MB),
because these cardiac isotype are distinctly different from skletal isotypes. Serum
troponin appears earlier than CK but presents 4 times lareger, diagnostic
effeciency similar to CK-MB in early MI until 5th . At the present time troponins
are mainly used in emergency department, with a center where the patient can
be monitored for several hours while a waiting test results.
Then a decision can be made regarding admission to the cardiac care unit or
discharge to home.
In patient with AMI the following additional abnormal blood test results may
occur:
 Increase Hematocrit. May show a small early increase related to decreased blood
volume followed by a small decrease later.
 Increase leukocytes. Leukocytosis appear within hours of onset of pain, persists
for 1 to 2 weeks, and often reach to 12000-15000/l. Erythrocyte levels, peaks
during the first week, and some times remains increased for 1-2 weeks.
 Increase erythrocyte sedimentation rate, and C - reactive protein (CRP) caused by
inflammatory response associated with the infarct. ESR is increased usually by
the second or third day, peak rate reach in 4-5th day and persist for 2-6 months.
Increased ESR some times is more sensitive than WBCs. Degree of increased ESR
does not correlate with the severity or prognosis.
 Decreased pH with metabolic acidosis caused by tissue hypoxia.
 Decrease arterial pressure of oxygen (PO2) from cardiopulmonary even without
complications.
 Increase glucose related to diabetes mellitus as a predisposing risk factor or
simply secondary to the stress of the infarct.
 In stress hyperglycemia. Hemoglobin A1C is normal.
 Increase urea nitrogen and creatinine related to decreased renal perfusion.
 Decrease potassium caused by either a high level of circulating catecholamines or
previous diuretic therapy. Potassium value < 3.6 mEq/L during admission is a
risk factor for ventricular arrythmia with 6 hours after admission.
 Decrease albumin with severe heart failure from hepatic failure.
 Increase lactate occurs in 60% of patients the day before the developmemt shock.
 Increase triglyceride: peak in 3 weeks; increase may persist for 1 year.
 Increase cholesterol, which may constitute a predisposing risk factor for coronary
heart disease.

CORONARY HEART DISEASE (CHD)
Risk Factors
Increase of serum total cholesterol and LDL cholesterol and decrease of HDL
Increased serum triglyceride is not considered an independent risk factor.
Lipoprotein electrophresis may be indicated if serum triglyceride > 300mg/dl,
fasting serum is lipemic, or there is hyperglycemia, significant glycosuria,
impaired glucose tolerance, increased serum uric acid (>8.5 mg/dl).
Perform laboratory test to rule out diabetes mellitus, liver disease, nephrotic
syndrome, dysproteinemia and hypothyroidism.
RHEUMATIC FEVER
Multisystemic disease of inflammatory lesion with affecting to connective

tissues, which involve predominantly: Joints, heart and kidney. It is most
common cause of acquired heart disease.
Clinical Manifestation: Diagnosis dependes on

1. Modified Jones criteria “1992”
MAJOR CRITERIA MINOR CRITERIA
 Pancarditis  Fever
 Polyarthritis  Arthralgia
 Sydenham‟s chorea  Previous rheumatic heart disease or
 Erythema marginatum rheumatic fever
 Subcutaneous nodules  Increased ESR
 Increased C-reactive protein
 Increased PR interval “1st degree heart block”
Diagnosis is done by 2 major or 2 minor and 1 major criteria

Plus
2. Supported evidence confirming group A streptococcus infection, history of scarlet fever,
group A streptococcal pharingitis culture, rapid Ag detection test (useful if positive
antistreptolysin O titers (ASOT)
Laboratory Finding
Antistreptolysin O titre increase indicates recent hemolytic streptococcus infection
(group A) and indirectly corporates clinical findings of rheumatic fever.
Increased titre develops only after second week and reaches a peak in 4-6 weeks.
Titre is usually more than 250 units and more significant if more than 400-500
units.
Antifibrinolysin (Antistreptokinase) titre is increased in rheumatic fever and in
recent hemolytic infections.
An antistreptozyme (ASTZ) slide agglutination test is very sensitive and therefore
provides evidence useful in excluding the diagnosis of rheumatic fever.
ESR increased is a sensitive test of rheumatic activity, return to normal with
adequate treatment with salicylate.
C - reactive protein parallels ESR. Serum protein is altered, with decreased serum
albumin and increase gamma globulins and fibrinogen is increased.
WBC usually is increased (10,000-16000/l) with shift to left. Increased WBC may
persist for weeks after fever subsides. Count may decrease with salicylate and
ACTH therapy.

Anemia (Hemoglobin 8-11 g/dl) is common.
Slight febrile albuminuria.
Determination of Clinical Activity: follow ESR, CRP and WBC. Return to normal
should be seen in 6-12 weeks in 80-90%. It may take 6 months.
SYSTEMIC ARTERIAL HYPERTENSION
Definition: Increase of blood pressure above normal value for that age.
Etiology: 1. Essential hypertension (80-90%) unknown cause.
2. Secondary hypertension (10-20%)
The main causes of secondary hypertension
1. Renal causes: Pyelonephritis, interstitial nephritis, collagen diseases (e.g SLE),
renal artery stenosis, diabetic kidney and polycystic kidney
2. Endocrine disorders and therapy:
Adrenal gland
Medullary-Pheochromocytoma.
Cortical -Cushing syndrome, Conn's syndrome and deoxycorticosterone
production
due to enzyme effects
Oral contraceptive
Estrogen therapy
3. Pregnancy.
4. Coarctation of aorta
5. Others
Ovarian tumours (produce various steroid hormones
Poisoning during acute phase
Raised intracranial pressure
Investigations
After the diagnosis of hypertension is established, a number of simple laboratory
tests will be useful to screen for specific causes of secondary hypertension and to
serve as baselines prior to treatment with diuretics. Renal status can be evaluated
with a urine analysis, and serum (blood) urea nitrogen (BUN) and serum
creatinine determinations. A serum potassium level will screen for
mineralocorticoid-induced hypertension and will also be useful as a baseline
prior to initiating diuretics therapy. For patients with hypertension under age 25
or with the abrupt onset of severe hypertension after age 50, further test for
causes of secondary hypertension are warranted. In such patients, particularly if
an abdominal bruit heard, renovascular hypertension should be screened for
with a rapid sequence intravenous pyelogram and radioisotopic
(Creatinine increased, urea nitrogen increased and potassium decreased).
To diagnose coaractation of the aorta, request appropriate radiographic studies

in the context of consistent physical and electrocardiaographic findings
To diagnosis Cushing‟s syndrome: hypertension, central obesity, glucose
intolerance, weakness (Hypokalemia), depression. Measure a 24-hour urine free
cortisol level or perform an overnight dexamethasone suppression test by giving
the patient an oral dose of 1 mg of methasone at 10:00 pm, and measuring the
serum: plasma cortisol concentration at 8:00 a.m, the next morning. A level < 5

g/dl (138nmol/L), typically 1to 2 g/dl (280 nmol/L) is typically of Cushing‟s
syndrome.
To diagnose pheochromcytoma the following manifestations are associated with

this disease: Hypertension, weight loss, glucose intolerance, “spells” of
palpitations, perspiration, pounding headache, and pallor {the four Ps}, tremor,
and nervousness. The measurements of 24 hours urinary metanephrine excretion
or a 12-hours overnight urine collection for metanephrine and creatinine are
important for diagnosis.
In unstressed patients the 24 hours metanephrine test is nearly 100% sensitive
and has almost no false-negative results. A normal urinary metanephrine:
creatinine ratio is <1.2 g metanephrine per milligram of creatinine (0.69
mmol/mol creatinine) patients with the disease will have higher ratios.
To diagnose primary hyperaldosteronism (hypertension and hypokalemia) it is
important to begin by measuring urinary potassium level when the serum
potassium level is low because a urinary potassium level < 30 Meq/L excludes
hyperaldosteronism. Plasma rennin activity (PRA) is a good initial screening test
for primary hyperaldosteronism. Low PRA is highly suggestive of primary
hyperaldosteronism.
A high PRA level is constituent with renovascular hypertension or
pheochromocytoma
(Secondary hyperaldosteronism)
In a patients with hypertension who are on drug therapy monitor the patients for
possible adverse effects of drugs, For example, beta blocker, can cause high
serum potassium and triglyceride concentrations and decreased HDL
cholesterol, glomerular filtration rate and PRA.
CONGESTIVE CARDIAC FAILURE
The diagnosis of CCF is usually established on clinical grounds. However, in

occult cases liver enzymes may be quite elevated, and the patient may appear
jaundiced. In high output CCF, blood test may help to elucidate specific
etiologies such as hyperthyroidism, beriberi (depletion of thiamine) Paget's
disease (elevation of alkaline phosphatase) or anemia.
In patients with clinical findings of congestive heart failure assess organ
dysfunction by requesting determinations of serum electrolytes, glucose, urea,
nitrogen, creatinine and liver function, arterial blood gas analysis and urinalysis.
Liver Function Test

 BSP(Bromosulphaphthalin) Retention is the most frequently abnormal test.
Retention followed I.V injection is a sensitive index of liver function
 Serum bilirubin is frequently increased
 Urine urobilinogen is increased.
 Serum LDH is increased in 40% of patients.
 Serum alkaline phosphatase show mild to moderate increase in 45% of cases.
 SGOT and SGPT are increased in 12% of patients
 Hypoalbuminemia is common.
 Prothrombin time may be slight increased.

Fluid and Electrolyte
 Urine sodium increase
 Plasma sodium and chloride tend to fall but may be normal before treatment.
 Total body sodium is markedly increased.
 Plasma potassium normal or slight increased.
 Potassium may be decreased because of the treatment.
 Hyperaldosteronism, sodium increase and potassium decrease because the loss
with urine.
Renal Changes
 Slight albuminuria is common.
 Isolated RBCs, hyaline and granular casts.
 Urine is concentrated with specific gravity > 1020
 Oliguria is characteristic feature of right-sided failure.
In patient with congestive heart failure receiving drug therapy, monitor the
patient for possible adverse effect of drugs for example, thiazide and loop
diurectics can cause alkalosis, decrease serum potassium, magnesium,
glomerular filtration rate, and lithium clearance and increased serum glucose,
uric acid, calcium, total cholesterol, LDL, cholesterol and triglyceride etc.
In patients with CHF the following additional abnormal blood test result
may occur:
Decrease hematocrit, mild even when red blood cell mass is increased.
Decease magnesium caused by anorexia, malabsorption, and excessive use of
diuretic agents; when less than 1.6 mEq/L (0.80 mmol/L), associated with
worse prognosis related to ventricular arrythemia and sudden death.
Increase magnesium associated with worse prognosis related to severity of
disease and poor organ function.
Decrease cholesterol possible with severe congestion of the liver.
SHOCK
Etiology and Pathophysiology
1. Hypovolemic Shock
Inadequate intravascular volume (absolute or relative) produces diminished
ventricular filling and reduced stroke volume that unless compensated for by
increased heart rate results in decreased cardiac output.
2. Acute Hemorrhage
It is a common cause of hypovolemic shock. Hypovolemic shock may follow
increased losses of other body fluid e.g perforation of the GI tract or
pancreatitis. It usually associated with arising Hb or Hct (due to
hemoconcentration a fluid is redistributed).
Fluid may be lost from the GIT due to vomiting or diarrhoea, excessive renal
fluid in DM, Diabetes insipidus, adrenal insufficiency. Hyopovolemic shock
may also be due to inadequate fluid intake, often associated with moderate
increases in fluid loss.
3. Cardiogenic Shock
These is primary reduction in cardiac output in these cases either because of
some mechanical obstruction (Ball-valvo, thromus, massive pulmonary
emobolism, extreme aortic or mitral stenosis) or because a suden impairment
of cardiac function (acute myocardial infarction). This type of acute circulatory
failure is sometimes termed cardiac shock or cardiogenic shock.
4. Vasodilation: Wide spread vasodilation may occur following severe

cerebral trauma or hemorrhage (neurogenic shock), hepatic failure or
ingestion of certain drugs or poisons.
Shoch associated with bacterial infection (bacteremia or septic shock) may be
partly due to the effects of endotoxin or other chemical mediators on resistant
vessels, resulting in vasodilation and decreased vascular resistant.
Laboratory Findings of Shock
The urine
The urinary output is diminished and in severe shock there may be complete
anuria. Renal clearance studies show a depression on renal blood flow and of
glomerular filtration.
Volume: normovolumic patient= 50 ml/h
In hypovolumia, normal kidney may lower 24 hours
Urine output to 300-400 ml
Specific gravity > 1.020 with low urine output suggests patients is fluid
depleted
< 1. 010 with low urine output suggest renal insufficiency.
The blood
A leukocytosis is common, especially in hemorrhagic shock, but leukopenia
may be present in severe shock as in gram-negative bacterimia.
A depression of circulating eosinophils is evidence of adrnocorticoid response
to injury.
Hemoconcentration
Hemoconcentration is usual in shock due to burns, due to dehydration and
some cases of abdominal injuries.
Hemodilution
Hemodilution is observed in shock due to hemorrhagic, skletal trauma and
crushing wounds.
Hyperglycemia: occurs early and is believed to result from a compensatory
secretion of epinephrine.
Acidosis
Acidosis is usual in well-developed shock. It is due to an accumulation of
lactic, phosphoric and pyruvic acids in the blood. Lactic and pyruvic acids
increase of excessive production in the skletal muscles and because of
impairment of liver function. The increase in phosphates is due to impaired of
renal excretion.
Excess lactate
Hyperlactemia occurs in a variety of diseases but usually in association with a
corresponding increase in the level of blood pyruvate

In such circumstance rise in lactate is accounted for by the rise in pyruvate
through the laters effects in the lactate dehydrogenase system. But in other
circumstances lactate accumulates in the blood and has been termed: excess
lactate.
Excees lactate also reported in cases of acute myocardial infarction associated
with shock.
Urea and Nonprotein Nitrogen

Urea and nonprotein nitrogen mey be elevated because of increased
catabolism and deficient renal excretion.
Potassium may be increased because of increase protein catabolism, impaired
renal excretion or adrenal cortical deficiency.
Occasionally there is a marked elevation in serum Glutamic oxaloacetic
Transaminase (SGPT) activity is possibly high because of central necrosis of
the liver.

REVIEW QUESTIONS
1. The following statements concern Answer 1

hyperlipidemia a. F
b. F
a. Familial hypercholesterolemia is an c. T
autosomal recessive condition d. T
b. Eruptive xanthomas are a clinical Familial
feature of familial hypercholesterolemia
hypercholesterolemia (FH) is an autosomal
c. Raised circulating low density dominant condition.
lipoprotein cholesterol levels are a risk Tendon xanthomas are
factor for coronary heart disease found in FH while
d. Lipoprotein lipase deficiency cause eruptive Xanthomas are
type I hyperlipidemia found in sever
(Chylomicronemia syndrome) hyperglycemia.
2. The following are causes of Answer 2

secondary hyperlipidemia: a. T
a. Treatment with B-blocker drugs b. T
b. Alcohol abuse c. F
c. Diabetes insipidus d. F
d. Hyperthyroidism e. T
e. Cholestasis
3. The following statements Answer 3

concern cardiac enzymes and a. F, b. F c. F
myocardial infarction: d. T
a. Increased serum CK activity in Increased CK may result
apatient with characteristic chest from causes other than
pain is diagnostic of myocardial myocardial infarction,
in. infarction such as intramuscular
b. The cardiac isoenzyme of CK injection given to heart
(CK-MB) increase later than total chest pain. Increased in
CK following myocardial CK-MB occurs slightly
infarction. earlier than total CK, the
c. The time of maximum increase latter peaking at 24
in CK following myocardial hours postinfarction
infarction is approximately 12 continuing increases in
hours. CK in the absence of
d. Continuing increased serum CK injections and skeletal
activity suggests infarct extension. muscle damage suggests
infarct extension.
4. The following endocrine Answer 4

conditions are causes of a. T
hypertension b. T
c. F
a. Pheochromcytoma d. T
b. Primary hyperparathyroidism There is no evidence for
c. Hypothyroidism an increased incidence of
d. Conn‟s syndrome hypertension in
hypothyroidism

5. With respect to arteries and Answer 5
atheroma a. T
a. Elevated levels of LDL increases b. T
the risk of atheroma c. F
b. Elevated levels of HDL reduces the d. F
risk of atheroma LDL carries 70% of the
c. LDL carries 40% of the serum serum cholesterol
cholesterol
d. Good control of diabetes is
unrelated to outcome in atheroma
6. In Rheumatic Fever Answer 6

a. a. Definitive diagnosis requires A, C, D and E are false
the presence of three of the five B is true
Jones criteria
b. b.Erythema marginatum may Diagnosis of rheumatic
be seen in 50% of the cases. fever requires the
c. c. Mitral value involvement presence of two of the
alone is uncommon five major criteria. Mitral
d. d. Fever is one of Jones major valve involvement alone
criteria is seen in 60-70% of
e. e. It is classically preceded by cases. Classically an
infection with a lancifield group B infection with a lancified
streptococcus. group A streptococcus
precedes the onset of
rheumatic fever by one
to five weeks.
7. Which of the following, Correct answer is B

according to the National The Cholesterol
Cholesterol Education Education Program
Program, defines high blood defines a high blood
cholesterol? cholesterol as follows:
a. TC=200 mg%, LDL=130 Total cholesterol= 240
mg% mg% (6.2 mmol/l),
b. TC=240 mg%, LDL=160 LDL= 160 mg% (4.1
mg% mmol/l)
c. TC=280 mg%, LDL=190
mg%
d. TC=320 mg%, LDL=220
mg%
e. TC=360 mg%, LDL=250
mg%
8. What is the single most important The correct answer

risk factor for coronary artery is B
disease? The single most
a. An elevated HDL level important risk
b. An elevated LDL level factor for coronary
c. An elevated triglyceride level artery is an
d. An elevated total blood cholesterol elevated LDL. The
second most
important risk is a
depressed HDL

9. What are isoenzymes?
Isoenzymes are enzymes having multiple molecular forms but similar

chemical functions (that is, acting on the same or similar substrates to catalyze
the same chemical reaction.
10. List four diseases or conditions in which the LHD5 level is usually
elevated?
It is usually elevated in acute viral hepatitis, shock, and other conditions with
hepatocellular necrosis, infectious mononucleosis, metastatic cancer in the
liver and necrosis of skeletal muscle.
11. Which serum lipoprotein fraction carries most of the cholesterol?
The low-density or beta lipoprotein carries most of the cholesterol.
12. List four diseases in which there is usually an increase in the level of serum
cholesterol?
An increase is usually found in hypothyroidism, nephritic syndrome,

obstructive biliary tract disease and idiopathic hypercholesterolemia.
13. List four diseases in which there is usually a decrease in the level of serum
cholesterol?
A decrease is usually found in hepatocellular disease, hyperthyroidism,

cachexia, systemic infections, and certain hematologic diseases (i.e pernicious
anemia, IDA and hemolytic anemia).
14. A patient has moderately severe myocardial infarct while in the hospital.
Describe the changes most often seen in the following enzymes: SGOT, SGPT,
LDH and CPK?
The CPK level increases by 6 hours after onset of pain, peaks at 18-24
hoursand is normal by days. The LDH level increase within 24 hours, reaches
a maximum at 3 days, and decreases to normal at 10-14 days. The SGOT level
increases within 8-12 hours and reaches the maximum in 18-36 hours; it then
return o normal within 4 days. The SGPT levels remains normal or slightly
elevated.

RESPIRATORY SYSTEM
3
Many diseases affect respiratory system. Some of these diseases are part of the
curriculum requirement of the medical student of medical schools.
In this chapter, we discuss the information about sputum and pleural effusion,
and also we discuss the interpretation of laboratory data in respiratory
disorders.
SPUTUM
Tracheobronchial secretions are often collectively referred to as sputum. Sputum
is constituted by plasma, water, electrolytes and mucin. As it comes out, it is
contaminated by nasal and salivary secretions and normal bacterial flora of the
oral cavity.
Macroscopical Examination of Sputum
A normal sputum is clear and watery (colourless and odourless) and any
opalescence is because of cellular material suspended in it. Sputum may be
described as serous (liquid), mucoid, purulent, bloody or combinations of these
e.g., seropurulent, mucopurulent.
The characteristics of the sputum must be noted:
Mucoid sputum is seen in tracheobronchitis and asthma.
Greenish sputum suggests pseudomonas infection
Pink, frothy sputum is seen in pulmonary oedema.
"Rusty" sputum is typical of pneumonical pneumonia.
Copious sputum separating into layers is characteristics of bronchiectasis.
Milky sputum is seen in bronchoalveolar carcinoma
Dark brown sputum (with fecal odour): Amoebic liver abscess rupture into
bronchus.
Red currant jelly is common in Klebsiella pneumonia.
Foul-smelling sputum suggests anaerobic infection.
Suppurative pulmonary disorders such as lung abscess, cavitary Tb, or gangrene
produce most putrid odours.
Cheesy masses are fragments of necrotic pulmonary tissue seen in pulmonary
gangrene or tuberculosis.
Bronchial casts are branching tree-like casts of bronchi from which they have
been expectorated.
Broncholiths (lung stones) are formed due to calcification of necrotic/infected
tissues within a larger bronchus or cavity.
Foreign bodies are usually objects inhaled by a child.
Parasites are that can be seen in sputum are ascaris, echinococcus granulosis and
toxocara conis.

Microscopical Examination of Sputum
Direct unstained specimen (cell, curshmann's spirals, elastic fibres, fungus)

Gram stain to exclude bacteria e.g pneumococci
Ziehl-Neelson-stain for tuberculosis
Methylene blue stain for echinococcus and mycosis
Lieshman stain can be done for blood cells.
Buffered crystal violet used for epithelial cells.
Sputum cytology: Sputum for cytology examination is indicated for any patient
in whom the diagnosis of cancer of the lung is considered. Bronchoscopy and
percutaneous lung biopsy have supplanted the need for sputum cytology to a
large degree. Now its greatest use is in patients who have abnormal chest x-ray
film results, productive couph, and nothing visible on bronchoscopy. It is also
used to monitor smokers who have had some atypical changes on prior
examination of the lower respiratory tract.
Sputum Culture and Sensitivity

Sputum culture is indicated in any patient with a persistent productive couph,
fever, hemoptysis, or a chest x-ray picture compatible with a pulmonary
infection. This test is used to diagnose pneumonia, bronchiectasis, bronchitis or
pulmonary abscess. Bacterium, fungus can be cultured. Sputum cultures are
obtained to determine the presence of pathogenic bacteria in patients with
respiratory infections, such as pneumonia. A Gram stain is the first step in the
microbiology analysis of sputum. Though sputum staining, bacteria are classified
as gram positive or gram negative. This may be used to guide drug therapy until
the C&S report is complete. The sputum sample is then applied to a series of
bacterial culture plates. The bacteria that grow on those plates 1 to 3 days later
are then identified. Determinations of bacterial sensitivity to various antibiotics
are done to identify the most appropriate antimicrobial drug therapy. This is
done by observing a ring of growth inhibition around an antibiotics plug in the
culture medium.
Tuberculosis Culture: TB culture, BACTEC, PCR

TB culture is indicated in any patient with a persistent cough, night sweats,
anorexia, weight loss, ferver and hemoptysis. This diagnosis should be especially
considered in high risk patients, such as those who are immunocompromised,
alcoholic or have had a recent response to TB.
The diagnosis of TB can be made only by identification and culture techniques
for growth, identification, and susceptibility testing of acid fast mycobacterium
takes 4-6 weeks.
The BACTEC method is a radiometric culture technique in which the grow
medium for culturing mycobacteria is supplanted with a substrate labeled with
radioactive carbon (14C ).
Polymerase chain reaction culture methods also have recently been developed
with the addition of a DNA polymerase; genetic chromosomal parts can be
multiplied. This allows amplification of genomes, which then can be detected by
genetic DNA probes.
Pleural Effusion: Pleural fluid is normally produced by parietal pleura and

absorbed by the visceral pleura, as a continuous process. Although healthy
individuals form 600-800 ml of fluid daily, the normal volume of fluid in each
pleural space is estimated at less than 10 ml. This fluid is formed by the filtration

of blood plasma through the capillary endothelium. The fluid is reabsorbed by
lymphatic vessels and vennules in the pleura.
Signs and Symptoms
Dyspnea, Pain of pleurisy, decrease breathes sounds, egophony.

X-ray evidence of pleural fluid.
Pleural thoracentesis: Should be performed to confirm the presence of fluid and
to determine its characteristics including colour and consistency. Specimens
should be taken for chemical, bacteriological and cytology examination.
1. Clinical Chemistry: Protein, specific gravity, glucose, amylase, LDH,
cholesterol, LE cells, RF and CEA
2. Bacteriology: Gram stain, Z.N.S and culture
3. Cytology: Malignant cells and cell count and differential
Characteristic of Effusion
It is important to determine either serous fluid is an exudate or transudate.

Exudates: Appearance usually cloudy.
SP.G > 1016g/l , Protein >3g/dl , (WBC >1000/l
RBC: few or may be bloody. Glucose may be decreased because of bacteria.
Pleural fluid to serum LDH>0.6
Exudate with neutrophilia is found in pneumonia, tuberculosis, pulmonary
infarction, pleuritis, subphrenic abscess and pleura empyema.
Exudates with Eosinophilia are found in echinococcus, Churge Strauss syndrome
and malignant lymphoma.
Hemorrhagic exudate is found in bronchial carcinoma, tuberculosis, and
pleuramesotheliom, trauma, hemorrhagic diathesis and pulmonary embolism.
Transudate: Appearance clear, Sp.G <1016g/l Protein <3g/dl
(WBC <1000/l mainly lymphocytes, RBC are few.
Glucose is equivalent to serum.
Pleural fluid to serum glucose ratio of =1.0
It is common In CCF, Hypoproteinemia, (Nephrotic syndrome) liver
cirrhosis, superior vena cava obstruction and early atelectasis.
NB:
Presence of malignant cells in papnicolau-stained smear of pleural fluid is
diagnostic of pleural carcinomatosis.
LE cells may be seen in pleural fluid in SLE
Glucose concentration <10 gm/dl are rare except in rheumatoid pleural effusion.
Very high pleural fluid amylase values are characteristics of pancreatitis pleural
effusion.
Pleural Fluid Finding in Various Clinical Conditions
TB-Effusion: Exudate, usually a bloody effusion

High protein and lymphocytosis
Acid fast smear are positive (20%) and culture is positive in 67% of cases and
histology positive in 95% of patients

Malignancy: Neoplasm affecting the pleura primarily”mesothelium” or
secondary (breast, lung, ovarian) secretes excess volumes of fluid into the pleural
space. It is exudative in type of fluid, or by metastasis to lymph nodes
obstructing lymph drainage, giving transudate type fluid. Low PH and Glucose
indicate a poor prognosis with short survival time.
Characteristic"effusion" is moderate to massive, frequently hemorrhagic,
moderate WBC count with predominance of mononuclear cells and 50% have
RBC > 10000/l
Pulmonary Infarction Effusion: Small volume, serous or bloody, predominance

PMNs, may show many mesothelial cells; this typical pattern is seen in 25% of
patients. Effusion occurs in 50% of patients with pulmonary infarct, is bloody in
40-70% of patients.
Congestive Cardiac Failure: Effusion is predominantly right sided or bilateral. If

it is unilateral or left sided in patients with CCF; rule out pulmonary infarct.
Pneumonia: Parapneumonic effusion is exudate type of effusion occurring in

course of pneumonia.
Empyema: Is most often the result of a pneumonia, occasionally follow surgery,

pleuritis, or trauma. WBCs are usually >50000/l, low glucose and low PH.
Rheumatoid Effusion:"Classic picture" is cloudy greenish fluid with 0 glucose

level (is <30mg/dl in 25% of cases).
NB: Blood specimen should always be drawn at the same time as the serous fluid
for determination of glucose, protein, LDH amylase and others.
Arterial Blood Gas Analysis
Normal value Criteria value

PH 7.34 – 7.44 <7.25 >7.55
Pco2 35 – 45 mmHg (torr) <20 >60
HCO3 22 –26 mEq/L <15 >40
PO2 75 – 100 mmHg (torr) <40
O2 saturation 95 – 100% 75% or lower
Measurement of ABG provides valuable information in assessing and managing

a patient‟s respiratory and metabolic (renal) acid base and electrolyte
homeostasis. It is used to assess the adequacy of oxygenation.
ABGs are used to monitor patients on ventilators, monitor critically ill
nonventilator patients, establish preoperative baseline parameters, and regulate
electrolyte therapy. Although O2 saturation monitors can accurately indicate O2
ABGs are still used to monitor O2 flow rates in the hospital and at home.
PH: The PH is the negative logarithm of the hydrogen ion concentration in the
blood. It is inversely proportional to the actual hydrogen concentration.
Therefore, as the hydrogen ion concentration decreases, the PH increases and
vice versa. The acids normally found in the blood include carbonic acid
(H2CO3), dietary acids, lactic acid, and ketoacid. The PH is a measure of

alkalinity (PH>7.4) and acidity PH<7.35. In respiratory or metabolic alkalosis the
PH is elevated, in respiratory or metabolic acidosis the PH is decreased. The PH
is usually calculated by a machine that directly measures PH.
PCO2: The PCO2 is a measure of Partial pressure of CO2 in the blood. CO2 is
carried in the blood as follows:
10% in the plasma and 90% in the RBCs. PCO2 is a measurement of ventilation.
The faster and more deeply the patient breath, the more CO2 is blown off. And
PCO2 levels drop.
PCO2 is therefore referred to as the respiratory component in acid base
determination, because this value is primarily controlled by the lungs. As the
CO2 level increases, the PH decreases. The Co2 level and the PH are inversely
proportional.
The PCO2 in the blood and the cerebrospinal fluid is a major stimulant to the
breathing center in the brain. As PCO2 levels rise, breathing is stimulated. If
PCO2 levels rise too high, breathing cannot keep up with the demand to blow off
or ventilate. As PCO2, levels rise further, the brain is depressed and ventilation
decreases further, causing coma.
The PCO2 is elevated in primary respiratory acidosis and decreased in primary
respiratory alkalosis. Because the lungs compensate for primary metabolic acid
base derangements, PCO2 levels are affected by metabolic disturbances as well.
In metabolic acidosis the lungs attempt to compensate by blowing off CO2 to
raise PH. In metabolic alkalosis the lung attempt to compensate by retaining CO2
to lower PH.
HCO3- or CO2 content: most of the CO2 content in the blood is HCO3- . The
bicarbonate ion (HCO3) in a measure of the metabolic (renal) component of the
acid-base equilibrium. The kidney regulates it. This ion can be measured directly
by the bicarbonate value or indirectly by the CO2 content. It is important not to
confuse CO2 content with PCO2. CO2 content is an indirect measurement of
HCO3- . PCO2 is a direct measurement of the tension of CO2 in the blood and is
regulated by the lungs.
As the HCO3- level increases, the PH also increases; therefore the relationship of
bicarbonate to PH is directly proportional.
HCO3- is elevated in metabolic acidosis. The kidneys also are used to
compensate for primary respiratory acid base derangements. Fore example in
respiratory acidosis the kidneys attempt to compensate by reabsorbing increased
amount, of HCO3- . In respiratory alkalosis the excrete HCO3- in increased
amount, in an attempt to lower PH through compensation. In diabetic
ketoacidosis, HCO3- ion doses decrease, because it is used directly to neutralize
the plasma diabetic ketoacidosis.
PO2: This is an indirect measure of the O2 content of the arterial blood; PO2 is a
measure of the tension (pressure) of O2 dissolved in the plasma. This pressure
determines the force of O2 to diffuse across the pulmonary alveoli membrane.
PO2 increase (hyperoxia) and PO2 decrease (hypoxia). For example
Hypoventilation leads to increase of PCO2, decrease PH and PO2 (Respiratory
acidosis).
Hyperventilation leads to decrease PCO2, increase PH and PO2 (Respiratory
alkalosis).

O2 saturation: is an indication of the percentage of hemoglobin saturated with
O2. When 92% to 100% of the hemoglobin carries O2, the tissues are adequately
provided with O2, assuming normal O2 dissociation. As the PO2 decreases the
percentage of hemoglobin saturation also decreases.
ACUTE PHARYNGITIS
1. In acute patients (>18 years) with a sore throat, determine their management
by the presence or absence of four key clinical findings: (1) temperature > 100 F
(37.8; (2) tonsillar exudates; (3) anterior cervical Lymphadenopathy; and (4) lack
of cough.
When all four findings are present, treat immediately without a rapid
streptococcal antigen test or throat culture. Only three findings must be present
for treatment in the emergency treatment.
When some of these findings are present, obtain a rapid streptococcal antigen
test or throat culture. If the rapid test is negative, obtain a throat culture.
2. Use good technique when obtaining a throat culture and performing

laboratory test.
3. Perform follow up cultures in patients with persistent clinical findings or with
unusually high risk of acute rheumatic fever.
BRONCHIAL ASTHMA
Asthma is due to hyperactive airways that constrict and secrete excessive mucus
in response to a variety of stimuli (allergens, infections, noxious fumes, cold air
and other irritants). The airway obstruction is due to a combination of
bronchoconstriction, mucosal edema and inspissated mucus and is usually
reversible.
Differential diagnosis
Bronchopulmonary neoplasm
Cardiac asthma
Acute bronchitis
Diagnosis: By means of clinical manifestation.
Laboratory Finding
Sputum: The sputum is usually white and mucoid and contains no blood or pus
unless an underlying infection is present.
Eosinophil: sputum has eosinophilic staining properties, not seen in chronic
bronchitis.
Charcot-Leyden Crystals: seen almost only in the sputum of bronchial asthma
cases. The crystals are colourless, pointed hexagons and variable in size. These
are derived from disintegration of eosinophils; hence they stain strongly with
eosin.
Curschmann's Spirals: Are characteristic of bronchial asthma sputum but may be
seen in other respiratory disorders. macroscopically they can sometimes be
recognised by the naked eye and appear as yellow-white, mucoid, wavy threads
frequently coiled into little balls.
Blood:

Increase of eosinophils (5-8).
PCO2 may be increased in late stages.
In patients with severe respiratory distress there is decrease PO2 and increase of
PCO2.
Ig level: increased of IgE and normal or increased of IgG.
Lung Function Test: This test must be done before and after B2-
sympathikomimetics.
Allergy skin test is used to exclude allergic cases.
CHRONIC BRONCHITIS
Chronic bronchitis is characterized by increased mucous secretion by the

tracheobronchial tree, resulting in cough productive of mucous present at some
time of the day for at least three months in two consecutive years.
Etiology
Cigarette smoking
Air pollution
Poorer social and economic circumstances.
DIAGNOSIS
Signs and symptoms

Bronchography may reveal dilated enlarged ducts of hypertrophied glands and
the bronchi.
Laboratory Findings
Leukocytosis (5000-10000/l ) in infections
Increase eosinophil in allergy. ESR increase or normal
Sputum: This may be catarrhal or cellular. Macroscopically the sputum is
tenacious, white and mucoid in appearance. Intercurrent infections make it
purulent yellow green in colour. The average volume expectorated is about 60
ml/day. A decreasing volume implies improvement. Presence of necrotic tis-
sue/elastic fibres indicates abscess formation or bronchiectasis. Examination of
the gram stain usually reveals the presence of mixed organisms.
Bronchoscopic secretion for culture and sensitivity
BGA

THE PNEUMONIA
Definition: Inflammation of the lung
Classification of the Pneumonia
A. Primary pneumonia
(1) Bacterial pneumonia: Pneumococcus, Streptococcus, Staphylococcus, H.
influenza, Kliebsiella pneumonia, pseudomonas, Proteus, Legionella pneumonia,
Tbc, Y. pestis, Y. Tularensis.
(2) Primary atypical pneumonia
-Viruses, chlamydia-Ornithosis, mycoplasma, rickettsia.
(3) Lung mycosis
(4) Eosinophils infiltration (Loeffler).
(5) Chronic Eosinophil pneumonia
(B) Secondary Pneumonia

Lung oedema, infarct, congestion
Bronchiectasis, Bronchus stenosis, and Bronchial carcinoma.
Intoxication: Nitrous gas, uremia
Aspiration pneumonia: stomach content, blood, foreign bodies, paraffin.
For patients with clinical findings of pneumonia request a chest X-ray, complete
blood count (CBC) and leukocyte differential count.
If sputum is available, consider obtaining a gram stain and culture, if the clinical
findings are severe enough to require hospitalization, consider obtaining two
blood cultures, serology, and arterial blood gas analysis.
Consider mycoplasma pneumonia, Legionnaires disease, influenza, primary

tuberculosis, Chlamydia pneumonia, and other causes of atypical pneumonia in
patients with the following clinical findings:
1. Occurrence in young adults
2. Onset over several days
3. Mild fever; patient not apparently severely ill
4. No or small amounts of mucopurulent sputum.
5. Minimal pleurisy; small or no effusion
6. Normal to slightly increased white blood cell count.
7. Patchy pneumonitis or nonhomogenous segmental infiltrate on radiograph.
Consider pneumococcal pneumonia, Hemophilus influenza, staphylococcal

pneumonia, gram-negative pneumonia, and supportive pulmonary disease in
patients with the following clinical findings:
1. Patient more often elderly or chronically ill

2. Abrupt onset
3. High fevers; chills; patient possibly weak, cyanotic, or confused
4. Purulent sputum
5. Pleurisy and pleural effusion
6. Leukocytosis
7. Lobar or segmented consolidation on radiograph

In debilitated elderly persons and patients with predisposing conditions
probable causative bacteria are as follows:
1. Chronic obstructive pulmonary disease (COPD): S. pneumonia and H.

Influenza,
2. Chronic alcoholism: S. pneumoniae, anaerobic bacteria (aspiration
pneumonia). H influenzae, klebsiella pneumoniae, staphylococcus aureus, and
Mycobacterium tuberculosis.
3. Post influenza bacterial pneumonia: S. pneumoniae, S. aureus, and H.
influenzae
4. Elderly nursing home patients: S. pneumoniae, S. aureus, K. pneumoniae and
H. influenzae.
5. Patients with mental obtundation, swallowing problems, esophageal
disorders, seizures disorders, and poor dental hygiene: usually mixed aerobic
and anaerobic bacteria (aspiration pneumonia).
6. Cystic fibrosis: pseudomonas erogenous and S. aureus
7. Immunocompromissed hosts: multiple causes, including gram-negative bacilli
(e.g. Escherichia coli, k. pneumonia, P. erogenosa), S. aureus and other
bacteria and viral (e.g. cytomegalovirus), fungal (e.g. Aspergillus) and
protozoal pathogens.
In patients with Mycoplasma pneumonia, Legionnaires‟ disease, influenza,

primary tuberculosis, and other causes of atypical pneumonias, laboratory test
results are as follows:
Mycoplasma Pneumonia
Hemolytic anemia caused by cold agglutinins may occur with Mycoplasma
pneumonia, but clinically significant hemolysis is rare. A positive direct
coombs‟ test result occurs in up to 83% of patients. The leukocyte count may
be normal to slightly increased, with a minimal left shift and possible mild
lymphopenia. The erythrocyte sedimentation rate (ESR) increases to more
than 40 mm/hour in at least two thirds of cases. In the sputum mononuclear
cells predominate over neutrophils in a ratio of approximately 60-40
(occasionally neutrophils predominate), and a Gram stain shows no bacteria;
there may be some erythrocytes. The organism can be cultured from the
sputum or posterior pharynx but takes 2 to 3 weeks to grow. A nucleic acid
probe for Mycoplasma pneumoniae is available but is not always positive in a
patient with disease. An enzyme-linked immunosorbent assay (ELSA) test for
M. pneumoniae antibody is also available, but acute and convalescent sera are
required. A diagnosis can be made by demonstrating a specific IgM titer of 1:4
or greater or by a single complement-fixing antibody titer of 1:256 or greater.
Legionnaires’ disease
The leukocyte count is normal to moderately increased with a left shift in
patients with Legionnaires‟ disease. There is moderate neutrophilia in the
sputum, and a Gram stain shows weakly staining Gram–negative bacteria.
The organism can be cultured from sputum, lung tissue, or pleural fluid and
can be directly identified in secretions and tissues using an
immunofluorescent technique vary from 30% to 70%.

Clinically the patients presented with diarrhea, confusion and delirium in
conjunction with pneumonia.
Pneumococcal Pneumonia
PP is characterized by homogenous consolidation of one or more lobes or
segments.
Laboratory Finding
Leukocytosis with neutrophilia
with toxic granulation
with deviation to the left
ESR: severe or moderate increased if persist we must suspect complication as
abscess and others. CRP: increase
Proteinogram: Albumin decrease and increase of 2 globulin and fibrinogen.
Sputum: In pneumococcal pneumonia, the sputum characteristics change with
the stage of the disease. Early lobar pneumonia sputum is scanty and transparent
with occasional flecks. In red hepatization stage the sputum becomes rusty red in
colour, tenacious and mucopurulent. Microscopically many intra and
extracellular organisms, epithelial cells leukocytes and red cells are seen. Daily
sputum Gram stains should be performed on these patients for two reasons; to
follow the effect of treatment and to rule out secondary infection.
THE ATYPICAL PNEUMONIA
Common manifestations are fever, toxemia, headache, malaise, anorexia and dry
cough
Laboratory Finding:
WBC: normal, leukopenia, some times monocytosis/lymphocytosis relative.
ESR: moderate increase.
Serological test: Crioaglutinins
THE ADENOVIRUSES
Epidemic
Cold agglutination test positive
PNEUMOCYSTIS CARINII PNEUMONIA

Children
Immune deficiency: Cytotoxic, leukemia, tumour patients, AIDS.
Patient with HIV become vulnerable to p.carinii pneumonia when the CD4
helper cells count <200/l
Diagnosis: Requires histopathologic demonstration of the organism with
methenamine silver, Giemsa, Wright stain or monoclonal antibody stain, with
specimen obtained by transtracheal aspiration, transthoracic needle aspiration,
open lung biopsy or induced sputum or bronchoscopy. And serology and
culture.
CYTOMEGALOVIRUS PNEUMONIA: (Herpes virus group)

In immune deficiency patients e.g. leukemia, tumors and transplantation
patients.
Cytomegalo-IgM antibodies in Immunfluorescence test.

BRONCHOPNEUMONIA
Laboratory Finding
WBC is increase 15000-30000/l with neutrophilia, some times leukopenia (bad
prognosis)
ESR is increased
Sputum: increase in quantity and is mucopurulent.
LUNG ABSCESS
Lung abscess is a suppurative infection of the lung resulting in destruction of

lung parenchyma with the formation of a cavity containing fluid and air.
Etiology:
Aspiration of infectious material into the lung in surgery of the oral cavity or
tonsils
Cancer patients
Pneumonia caused by staphylococcus aureus and klebsiella.
Bronchial obstruction
Metastases
Amoebic abscess
Laboratory Finding
Sputum
Primary Abscess: sputum is copious, forms several layers on standing and has a
putrefied smell, occasionally is scanty or absent.
Culture and sensitivity for the etiological diagnosis of Staphylococcus, Klebsilla,
Aerobic and Anaerobic anTbc.
Cytology is indicated to exclude malignant cells by using transtracheal aspir-
ation, transthoracic aspiration or fiberoptic bronchoscopy.
Blood
Blood culture: may be positive in acute stages.
ESR is increased
WBC 15000-30000/l in acute stages
Hb decreased (Normochromic normocytic in chronic stages.
Albuminuria is frequently present.

LUNG CANCER
PATHOLOGICAL CLASSIFICATION OF CARCINOMAS OF THE LUNG

Squamous carcinoma 30%
Adenocarcinoma 30%
Large cell carcinoma 15%
Small cell carcinoma 25%
SIGNS AND SYMPTOMS OF LUNG CARCINOMA

Peripheral tumour: (Adenocarcinoma +Large cell carcinoma).
Pain from pleural or chest wall involvement
Cough
Dyspnea
Lung abscess from tumour cavitations
Central tumour :( Squamous Small cell carcinoma)
Cough, Hemoptysis, wheeze and stridor
Dyspnea from obstruction
Pneumonitis from obstruction
Metastatic tumour spread:
CNS involvement
Liver involvement
Bone and bone marrow involvement.
Other involvement
From paraneoplastic syndromes :( Endocrinopathies)
Peripheral
Clubbing finger (all types)
Neurologic
Eaton-lambert-myasthenic syndrome. (SCC)
Peripheral neuropathy
Subacute cerebral degeneration
Polymyositis.
Hematologic (Adenocarcinoma)
Migratory thrombophlebitis
Non-bacterial thrombotic endocarditis
DIC (Disseminated intravascular coagulation)
Miscellaneous: Anorexia, cachexia, dermatomyositis and nephrotic syndrome.
Laboratory Finding
Sputum-cytology
Biopsy of lymph node for metastases
Biopsies of Bronchus, pleura, lung and metastatic sites.
Transthoracic needle aspiration provides definitive cytologic diagnosis of cancer
in 80-90% of cases.
Hemogram
Anemia in severe stages
Leukocytosis with eosinophilia
ESRis increased

Tumour Markers
1. Neurospecfic endolose (NSE): NSE is a cytoplasmatic enzyme of glycolysis.
(Normal value is 12.5ng/ml). It is pathologic in small cell carcinoma and
neuroblastoma.
2.SCC marker: Squamous cell carcinoma antigen:
is pathologic (80%) in squamous cell carcinoma of lung and cervix and (35%) in
carcinoma of mouth and face.
3. Carcinoembyonales antigen (CEA): is a glycoprotein with carbohydrates (40-
60%) and polypeptide chain.(Normal value is 0.0-4.4 ng/ml). in smokers upto 20
ng/ml. Values >20 ng/ml is diagnostic in malignant diseases.
CEA is a tumour marker in carcinomas of: Bronchi, colorectal, pancreas, breast,
liver and thyroid).
4. Tissue polypeptide antigen (TPA) (normal value is 80u/ml)
Increase in carcinoma of the lung and bladder.
5. CA-125: is a part of glycoprotein component and increase in carcinomas of
ovary, uterus, GI tract, breast and bronchi. (Normal value is 0.0-350u/ml)
Bone marrow aspiration and biopsy to exclude metastases.

Blood smear for metastases
Pleural fluid:
 Gravimetry 1016 or more
 Protein .3g/dl-spontaneous coagulation.
 Increase cells
 Frequently hemorrhagic manifestation.
Endocrinopathies.(From paraneoplastic syndromes)

Ectopic PTH and hypercalcemia (squamous)
Inappropriate ADH and hyponatremia (SCC)
Ectopic ACTH and Cushing‟s syndrome (SCC)

PULMONARY EMBOLISM
Pulmonary embolism is the impaction in the pulmonary vascular bed of

previously detached thrombus or foreign matter. Its major complication
pulmonary infarction, is the necrosis of lung parenchyma resulting from
interferancy with blood supply.
Etiology
THROMBI-DVT, Atrial fibrilation and post myocardial infarction.
Risk factors:
Smoking, obesity, pregnancy, right heart failure, polycythemia, nephrotic
syndrome, anti-thromin III deficiency and splenectomy.
If the results of a V/Q lung scan and /or pulmonary angiography are
consistent, the diagnosis of pulmonary embolism is confirmed. Decreased
arterial PO2 and compatible Q lung scan are sensitive but not specific for
pulmonary embolism.
Diagnosis
1. Sign and symptoms
2. ECG
3. Chest szintigram ( perfusion lung scan) and angiography
4. Laboratory findings
Laboratory Findings
 BGA : Respiratory partial insufficiency by hyperventilation

 PO2 decrease
 PCO2 decrease
 PH increase
 Serum LDH increase (isoenzyme LDH2,LDH3)
 Serum bilirubin increase and urine urobilinogen increase
 SGOT slight increase
 Leukocytosis
 ESR increase
 Bloody pleural effusion in 1/3-2/3

REVIEW QUESTIONS
1. A 69 year old man presents to the emergency department with A. T

diarrhea, confusion and delirium in conjuction with pneumonia. B. F.
Which of the following organisms is the most likely pathogen? C. F
A. Legionella pneumonia D. F
B. Mycoplasma pneumonia
C. Hemophilus pneumonia
D. Kliebsella pneumonia
2. Each of the following systemic syndromes is associated with lung A. T

cancer : B. T
A. Inappropriate ADH secretion C. T
B. Cushing syndrome D. F
C. Eaton-lambert-mysthnic syndrome
D. Steven-Johnson syndrome
4. 3. The most useful guide to initial therapy for community

aquired pneumonia A. T
5. A. Sputum Gram smear B. F
6. B. ECG C. F
7. C. Chest X-ray D. F
8. D. Arterial blood gas
4. In respiratory insufficiency (defined as a PO2 less than 8 kpa or 60

mmHg A. T
A. There is always a disturbance in ventilation/perfusion ratio B. F
B. The Pco2 is always raised C. T
C. The kidney resonds to a raised PCO2 by retaining bicarbonate D. T
D. Acute shifts of K+ between ECF and ICF may occur if the acid-base
disturbance is actively treated with NaHCO3
5. An increased plasma [HCO3+] in an arterial blood specimen might A. F

be expected in: B. T
A. Acute hyperventilation due to hysteria C. F
B. Acute respiratoty failure due to neuromuscular paralysis D. T
C. Ammonium chloride ingestion E. F
D. Hypokalemia due to inappropriate secretion of ACTH by a
carcinoma of the lung
E. starvation
6. A diagnosis of acute, symptomatic pulmonary embolism can be A. F

excluded when which of the following is normal: B. T
A. Chest x-ray C. F
B. Perfusion lung scan D. F
C. Bilateral leg venography
D. CT scan of the pulmonary arteries
7. Exudate pleural effusion characterized by: A. T

A. Protein > 3 g/dl B. F
B. WBC < 1000/cumm C. F
C. Glucose is equivalent to serum D. T
D. Specific gravity > 1016 g/l

8. Red currant jelly sputum is characteristic of :
A. Pulmonary edema A. F
B. Klebsiella pneumonia B. T
C. Pulmonary tuberculosis C. F
D. Pneumococcal pneumonia D. F
9. Sputum with colorless crystals, pointed hexagons and variable in
sizeand stain strongly with eosin: A. F
A. Mycoplasma pneumonia B. F
B. Pulmonary edema C. T
C. Bronchial asthma D. F
D. Pulmonary embolism
Questions 10-13 about sputum characteristics
10. A
10. Rusty sputum 11. C
11. Pink frothy sputum 12. D
12. Red current jelly 13. B
13. Greenish sputum
A. Pneumococcal pneumonia
B. Pseuomonas infection
C.Pulmonary edema
D. Klebsiella pneumonia
Questions 14-15 about pleural effusion

14. Exudates 14. A, B, E,
15. Transudate F,H
A. Specific gravity > 1016g/l E. Neutrophilia 15. C, D, G

B. Protein > 3g/dl F. Pleural fluid to serum LDH>0.6
C. Seen in CCF, liver cirrhosis G. Pleural fluid to serum glucose>1
D.Glucose equivalent to serum H. Tuberculosis

4
RENAL SYSTEM
Kidneys are each composed of appronimately are millon similar functional

units called nepheron consists of a small tube, the upper and of which is
dilated to form an epithelial sac (Bowman‟s capsule). Freely comunicating
loops of capillanes which arise from afferent arterioles lie with in the Sac and
with it forms the glomerulus. The glomerli lie in the cortex of the kidney and
are sourrounded by convolutions of the proximal & distal tubules. From most
glomsuli the proximal convoluted tubule leads to a thin segment which enters
the medulla and which ultimately forms the loop of henle. Each loop consists
of thin descanding limbs which are arranged parallel, same of which pentrate
as for the renal papillae. The ascanding limb of the loop then returns towards
the renal cortex and enlarges there to form the distal convauted tubule. These
altimately end in collecting ducts which once more descend in to the
medullary region, lying between the loops of hemle, and drain urine into the
renal pelvis at the renal papillae. For a short distance the afferent arterioles
and distal convoluted lubules are in contact and at this point the tubular cells
become tall and columrar in character, formin macula densa. The wall of the
arteriole is thickened by cells which contain large secretory granules. These
structures are together constlute the juxta glomerular complex which is
belived to be the source of remin and to be intivately concerned in the
regulation of the volume of the extracellular fluids and blood pressure.
The Function of Kidneys

Regulation of the water content of the body.
Regulation of the electrolyte content of the body.
Maintenance of the normal acids base equilibium of the blood.
Retention of other substances vital to body economy, e.g. glucose, amino
acids, phosphate, bicarbonate, proteins.
Excretion of waste metabolic products, toxic substances and drugs.
Hormonal function.
Sumary:-
Excretion of most substances depends intially on normal permeability.
The Diagnosis of Renal Disease

In the majrty of patients suffering from renal disease, symptoms and signs are
not usually referred to the anatomical site of the kidneys. This is due to the
fact that clinical features of renal disease most frequently arise from the
abnormalties in the clinical comporition of the body or from hypertension.
Their True origin there fore is suspected only after detection of urinary
abnormalties.
Examination of urine is of great value in diagnosis any renal disease. It include
determination of volume of urine passed in 24 hrs, the presence of abnormal
urinary constitunets and bacteriological examination, specific gravity and

hydrogen in concentration (PH of urine) in addition it may be necessary to
obtain further informationby coma or all of the following investigations.
Chemical analysis of the blood and urine.
Tests of glomerlare & tubular function.
Radiological examinations.
Routine & microscopic examination of routine will be death in the practice.
Renal Function Test

Renal function tests are useful in evaluating the severity of kidney diseases
and in following its progress. They can be divided into specific aspects of
nephron function, such as glomerular filtration, blood flow and tubular
transport.
The Glomerular Filtration Rate: (GFR): is equately estimated from the

endogenous creatinine clearance. The normal value for men is from 140 to 200
L/day. (70+/- 14/min/m2 and for women, is from 120 to 180 L/day (60+/- 10
ml /min/m2).
Serum concentration of creatinine varies inversely with the GFR and therefore
is a useful index of the GFR if production related to muscle mass; age and
metabolism (increased in uremia) are considered. The upper limit of serum
creatinine concentration in men with normal GFR is 1.2 mg/dl, in women
1mg/dl.
A formula useful for calculating the creatinine clearance (Cl creat) by
estimation of the GFR, from the serum creatinine concentration in men is:
Cl creat = (140-age year )(Kg body weight)
(72)(Serum creatinine mg/dl)
In women, the calculated values are multiplied by 0.85
Creatinine clearance is not useful for detecting early kidney damage due to
hypertrophy of residual glomeruli. After loss of 50 to 75% of the normal
glomerular filtration surface, a decrease in creatinine clearance is clearly
detectable. Thus a normal creatinine clearance can not exclude the presence of
mild disease.
Serum creatinine measurements: Creatinine is a spontaneous decomposition

of creatine is used as an index of renal function. This is possible because
creatinine production and excretion are reasonably constant in the absence of
muscle disease.
Creatinine is increased in:
1. Late stage of renal failure
2. Prostatic obstruction
3. Carcinoma of bladder
4. In uremia
5. Bichloride poisoning (acute condition).
6. Intestinal obtsruction (when marked oliguria or anuria.
Blood urea nitrogen (BUN) is the end product of the metabolism of the protein
substances. It is unsuitable as a single measure of renal function (the blood
concentration is influenced by variations in urine flow rate as well as the
production and metabolism of urea). The BUN/creatinine ratio often is used
to differentiate prerenal, renal or postrenal (obstructive) azotemia. A ratio > 15
is abnormal and suggests prerenal or postrenal azotemia. The BUN/creatinine
ratio also is elevated whenever urea production is increased by diet, total
parentral nutrition or glucocorticoid therapy, with some neoplasms and
antibiotics and with excessive protein catabolism as seen in infections and
uncontrolled diabetes mellitus.
Common causes of prerenal azotemia include shock, ECF depletion, massive
GI hemorrhage, severe heart and liver failure and bilateral tight renal artery
stenosis. The BUN/Creatinine ratio is normal in renal azotemia. A low ratio is
found in pregnancy, overhydration, severe liver diseases and malnutrition.
Renal biopsy is performed to:

1. Help establish a histologic diagnosis
2. Help estimate prognosis and the potential reversability.
3. Estimate the value of therapeutic modalaties
4. Determine the natural history of renal disease
The only absolute contraindication to a biopsy is an uncontrollable bleeding
disorder.
Urine cytology:
Is helpful in screening for possible urinary tract neoplasia in high risk
populations (e.g petrochemical workers, patients with painless hematuria
from nonrenal causes) and in following patients after resection of bladder
tumors.
Abnormal cytology is seen in 70% to 85% of patients with known urinary tract
epithelial neoplasia, but inflammatory or reactive hyperplastic lesions of the
urinary tract or cytotoxic drugs for nonurogenital carcinoma may produce
falsely positive results.
Diagnostic accuracy may be increased for bladder neoplasms by vigorous
bladder lavage with a small volume of 0.9% sodium chloride solution ( 50 ml
pushed in and then aspirated by syringe through a catheter). The cells
collected in the saline are concentrated and examined.
ACUTE RENAL FAILURE (ARF)
The clinical conditions associated with rapid, steadily azotemia, with or without
oliguria (<500 ml/day).
Etiology
The causes of ARF can be grouped into 3 diagnostic catagories:
1. Pre-renal:
 Fluid and electrlyte depletion
 Hemorrhage, Septicemia, Cardiac failure
 Liver failure, Heatstroke, Burn
2. Post-renal
 Prostatism
 Bladder, Pelvic or Retroperitoneal tumors
3. Renal
 Acute tubular injury
 Acute glomerulonephritis
 DIC
 Arterial or venous obstruction
 Acute tubulointerstitial nephritis
 Intrarenal precipitation (Hypercalcemia, urates, myeloma protein
Pathophysiology
Prerenal azotemia: Is caused by inadequate renal perfusion due to
extracellular volume depletion. Cardiac or hepatic failure or sepsis. Oliguria
occur as a result of reduced GFR and enhanced Na and water resorption,
normal responses to an inadequate circulating blood volume.
Intrinsic renal causes of ARF are multifactorial, the most common being
prolonged renal ischemia or a nephrotoxin. In experimental studies the factors
that initiate and those that maintain ARF may differ.
At least 4 mechanisms appear responsible for hypofiltration:
1. A marked decrease in renal blood flow
2. A reduction in glomerular permeability
3. Tubular obstruction from cellular and interstitial swelling and /or blockage
from cellular debris.
4. Diffusion of glomerular filtrate across injured tubular epithelium. These
factors are interdependent but all are not necessarily present in every patient.
Postrenal azotemia: Usually is associated with glomerular and tubular
dysfunction and the urinary changes may mimic those in patients with
primary renal injury
Laboratory Findings of ARF

 Urinary sediment: In prerenal azotemia the sediment usually unremarkable.
This may also be true with obstructive uropathy. With primary renal injury,
the sediment contains tubular cells, tubular cell casts and many brown
pigmented granular casts. Urinary eosinophils suggest allergic
tubulointerstitial nephritis. Red cell casts suggest vasculitis or
glomerulonephritis.
 A progressive daily rise in serum creatinine is diagnostic of ARF
 Renal failure index(urine NA (mmol/l) % U/P creatinine ratio
 <1 in prerenal azotemia or acute glomerulonephritis
 >2 in patients with postrenal or other renal causes of ARF
 U/P osmolality ratio
 >1.5 in prerenal
 1 to 1.5 in postrenal , renal and AGN
 Fractional excretion of Na (U/P sodium % U/P creatinine)
 <0.01 in prerenal and AGN
 >0.02 in renal
 >0.04 in postrenal
 Urine sodium (mmol/l)
 <20 in prerenal
 <30 in AGN
 40 in renal and postrenal
Characteristic laboratory findings in ARF are those of progressive azotemia,
acidosis, hyperkalemia and hyponatremia. A modest daily rise in serum
creatinine (1 to 2 mg/dl) and urea nitrogen (10-15mg/dl) usually occur.
A rise of serum creatinine > 2 mg/dl/day suggests that overproduction is
occuring from rhabdomyolysis.
Acidosis is ordinarily moderate with plasma Co2 content between 15 and 20
mmol/l.
Serum K concentration increases slowly.
Hyponatremia usually is moderate (serum Na 125 to 135 mmol/l and is
related to a surplus of water.

The hematologic picture is that of a normochromic-normocytic anemia of
moderate severity. Hematocrit usually ranges from 25 to 30%.
ARF from acute tubular injury may have 3 typical phases: prodromal, oliguric
and postoliguric
Prodromal phase: Varies in duration according to cause.
Oliguric phase: urine output 50-400 ml/day
Oliguric period 10-14 days
Serum creatinine typically increase by 1-2 mg/dl/day
The urea nitrogen increase by 10 to 20 mg/dl
In postoliguric phase urine output gradually returns to normal level. However
serum creatinine and urea level may not fall until several days later. Tubular
dysfunction may persist and is manifested by Na wasting and polyuria.
CHRONIC RENAL FAILURE
The clinical condition resulting from a multitude of pathologic process that lead
to derangement and insufficiency of renal excretory and regulatory function
(uremia)
Etiology and Classification:

CRF may result from any cause of renal dysfunction of sufficient magnitude:
The functional effects of CRF can be grouped into 3 stages:
1. Diminished renal reserve:
 Loss renal function
 Homeostasis preserved
 Sign of secondary hyperparathyroid
2. Renal insufficiency:
 Azotemia
 Increase creatinine and urea
 Electrolyte disturbance
3. Uremia :
 Increase azotemia
 GFR <6 ml/min/m2
Laboratory findings of CRF

 Characteristic findings are those of nitrogen retention, acidosis and anemia.
 Urea and creatinine are elevated
 Plasma sodium concentrations may be normal or reduced.
 Acidosis is moderate with the plasma Co2 content between 15 and 20 mmol/l
 Hypocalcemia and hyperphosphatemia are found regularly
 The serum K is normal or only moderately elevated (<6.5mmol/l)
 Urinary volume often is relatively fixed between 1 and 4 L/day and does not
respond readily to variations in water intake
 The findings on urinalysis depend on the nature of the underlying disease, but
broad (especially waxy) casts often are prominent in advanced renal
insufficiency of any cause.

 The hematologic picture is normochromic normocytic anemia of moderate
severity. Hematocrit usually ranges from 20-30% except in the patient with
polycystic kidney disease, who may have a Hct of 35 to 50%.
NEPHROTIC SYNDROME
It is a predictable complex that follows a severe prolonged increase in

glomerular permeability for protein. The main features are
 PROTEINURIA >2gm/m2
 HYPOALBUMINEMIA <3gm/dl
 GENERALIZED EDEMA
 LIPEMIA
Proteinuria is sufficient to cause hypoalbuminemia and sufficient to cause
edema.
NS occurs at any age; in children, it is most common between ages 1.5 and 4
years.
Etiology
Diseases Associated With NS:
1. Primary renal disease:
 Minimal changes disease (MCD)
 Focal glomerulosclerosis (FGS)
 Membrane glomerulonephritis (MGN)
 Membranoproliferative glomerulonephritis (MPGN)
2. Secondary
 Metabolic – DM, amyloidosis
 Immunologic : SLE, sarcoidosis, polyarteritis nodosa, sjogern syndrome
 Neoplastic: leukemia, lymphoma, multiple myeloma, carcinoma.
 Nephrotoxic drugs: Gold, pencillamine, NSAID, lithium
 Allerginic : Insectstings, snake venoms, antitoxins
 Infective: Bacterial: postglomerulonephritis, endocarditis, leprosy, syphilis
hepatitis, malaria, schistosomiasis, filariasis
 Others: Toxemia of pregnancy, malignant hypertension.
Laboratory Findings of Nephrotic Syndrome
The initial urinalysis shows marked proteinuria, with an excretion of 2

gm/m2/day or more simply, a rondom urinary protein creatinine ratio>2.
The urine sediment usually contains hyaline, granular, fatty, waxy and
epithelial cells casts; microscopic hematuria and RBC casts also may be
present depending on the etiology of the glomerular disease.
Leukocytes are prominent in exudative diseases and SLE. Amyloid fibrils may
be seen on electronmicroscopy.
Hypoaluminemia
Albumin is <2.5 gm/dl and in children it is some times <1gm/dl values as
low as 0.2 gm/dl have been recorded. Decrease of 1 and  globulin with
increase of 2 globulin. -globulin is normal or increase. In SLE, the 
globulin may be normal or raised.
Urine sodium is <1 mmol/l in the accumulation phase of nephrotic edema.
Urine K usually high. The K: Na ratio is >1
Aldosterone secretion is elevated during this stage but may be normal at other
times.
Lipemia: Increase total cholesterol, triglyceride, free and esterified lipid levels
(upto or even exceeding 10 times normal) are associated with severe
hypoaluminemia.
Lipiduria: It is determined by sudan staining of casts containing lipid

granules identifying macrophages and renal tubular cells containing fatty
droplets(oval fat bodies) and finding anisotropic crystals (doubly refractile fat
bodies) with polarized light microscopy.
Anemia: microcytic anemia may be present because of the urinary loss of
transferrin.
Coagulation disorders: are common perheps because of the loss of factors
IX,XII and thrombolytic factors (urokinase and antithrombin III) in the urine
and increase serum levels of factor VIII, fibrinogen and platelets.
ESR increased due to increased fibrinogen
Diagnosis of Nephrotic Syndrome

Diagnosis of nephrotic syndrome is based on the clinical features and
laboratory findings but definitely by renal histology (Renal biopsy).
Severe proteinuria (>2 gm/m2/day) urinary protein: creatinine ratio >2) is the
cardinal finding and is essential to the diagnosis. The selection of a single
value for the seperation of nephrotic and non-nephrotic-range proteinuria is
arbitrary. However it is useful because that principally affect the
extraglomerular vasculature and /or tubulointerstitial areas do not commonly
evoke proteinuria of this magnitude
MCD occurs most commonly in children and is characterized by NS without
hematuria, hypertension or azotemia.
MPGN is a disease of children present with NS in 60-80% with macroscopic
hematuria in 50% and with azotemia and hypertension in a smaller
percentage.
FGS is commonly presents with hematuria, hypertension and renal
dysfunction in association with NS.
MGN, Ns of insidious onset occur often with microscopic hematuria.

ACUTE GLOMERULONEPHRITIS (NEPHRITIC SYNDROME)
A disease characterized pathologically by diffuse inflammatory changes in the

glomeruli and clinically by the abrupt onset of hematuria with RBC casts, mild
proteinuria, and in many case hypertension, edema and azotemia.
Etiology
The prototypic glomerular disease of acute onset is poststreptococcal
glomerulonephritis (PSGN). In this immune complex (IC) disease, Group A
Beta hemolytic streptococcal antigens (nephritis strain 1,4,12,29) provoke
antibody response and the resulting antigen-antibody complex.
Diseases associated with acute nephritis syndrome (GN)

Primary:
 Membrane proliferative GN
 Mesangiocapillary GN
 Intramembranous dens deposit disease
 Mesengial proliferative GN
 IgA nephropathy
 Pauci-immune rapidly progressive GN(RPGN)
Secondary (multisystem disease –associated) glomerular diseases

 Post infection- bacterial, viral, parasites
 Collagen-vascular disease
 Hematology dyscraisis
Clinical Laboratory
The urine may be scanty and appears brown, smoky bloody. From 0.5 to 2 gm
of protein/m2/day may be excreted or a random urinary protein: creatinine
ratio <2 may be found.
Urinary sediment contains:
 WBC, RBC, renal tubular cells
 Casts containing RBCs, WBC casts, granular casts (protein droplet) are
common.
 The RBC cast is pathognomonic of any form of glomerulonephritis but in
association with clinical feature.
 Increase of ASO, antistreptokinase, antihylouronidase
 Serum C3, C4 diminished during active stage of disease and return to normal
with 6-8 weeks in 80% of patients
  globulin and  globulin in serum are increased
 Cryoglobulinemia usually persist for several months
 Renal function follow up is important:
 Serum creatinine concentration (increase) blood urea increases
 Urinary creatinine clearance
 GFR return to normal over 1-3 months
 Proteinuria persist for 6-12 months
 Microscopic hematuria for several years.

RENAL TUBULAR DISORDERS
Renal tubular disorders may occur as part of the general nephron damage
occurring in renal failure. This section deals with those disorders in which
there is only tubular dysfunction.
Classification
1. Multiple tubular disorders-Fanconi syndrome
2. Isolated tubular disorders
a. Renal glycosuria
b. Renal tubular concentrating defects
c. Aminoacidurias
d. Familial hypophosphatemia
e. Batter‟s syndrome
f. Pseudohypoparathyroidism
FANCONI SYNDROME
Characterized by
1. Glycosuria
2. Phosphaturia
3. Aminoaciduria
4. Tubular proteinuria
5. Hypouricemia
Renal tubular acidosis and a defect in urinary concentrating ability usually

occur as well.
Causes
1. Inborn errors of metabolism, e.g
a. Cystinosis
b. Glycogen storage disease
c. Glactosemia
d. Wilson‟s disease
2. Acquired
a. Exogenous toxic substance
b. Multiple myeloma
Common Presenting Features

1. Failure to thrive (in infancy)
2. Vitamin D resistant rickets
3. Polyuria / polydipsia

RENAL TUBULAR ACIDOSIS (RTA)
Usually an inherited metabolic disorder but may be acquired (e.g in chronic
liver disease). Also occurs as part of the Fanconi syndrome.
Defect:
Related of failure of renal tubular hydrogen ion transport and hence failure of
bicarbonate reabsorption. There are two types:
1. Distal RTA (or classical RTA).
2. Proximal RTA (affecting the proximal tubule)
Distal RTA
Distal tubular hydrogen ion transport has a low capacity but can normally
work against a high pH gradient. In distal RTA, this transport mechanism is
defective and hydrogen ion cannot be excreted against a significant pH
gradient.
Features
1. Urine pH always above 5.4
2. Chronic hyperchloremic acidosis
3. Vitamin D resistant rickets caused by the chronic acidosis
4. Renal calculi and nephrocalcinosis
5. Hypokalemia
N.B Hypokalemia is usually associated with alkalosis. Hypokalemic acidosis
should arouse suspicion of a renal tubular disorder.
Tests
1. Early morning urine pH

Normal people produce acid urine at this time
A pH of < 5.4 excludes distal RTA
2. Capillary (for arterial) blood pH and simultaneous urine pH
If the patient is acidotic and the urine pH is > 5.4 RTA is confirmed
3. Urinary acidification test
Should not be performed if the patient is acidotic
Normal individuals should pass at least one urine specimen with a pH of <
5.4

RENAL CALCULI
Pathogenesis
1. Supersaturation of the urine with the crystalloid component of the stone
caused by:
1. Increased urinary excretion of the crystalloid
2. Variation of the pH of the urine resulting in diminished crystalloid
solubility
a. Calcium salts and magnesium ammonium phosphate are less soluble at
alkaline pH
b. Uric acid is less soluble at acid pH
3. Diminished urine volume
Types of Renal Stone Disease

1. Calcium stone disease (approximately 80-85%)
2. Infected stone disease (approximately 10%)
Stones composed of magnesium ammonium phosphate. Main factors are high
urine pH and ammonium concentration (urea-splitting organisms produce
both of these)
3. Uric acid stone disease (approximately 5%) The main factors are low urine
pH and increased urinary uric acid excretion
4. Cystine stone disease (approximately 1%)
CALCIUM STONE DISEASE
1. Majority of stones are calcium oxalate with or without calcium phosphate

2. Calcium phosphate content depends largely on the prevailing urinary pH
3. Causes:
a. Idiopathic calcium stone disease (85%)
b. Primary hyperparathyroidism (10%)
c. Renal tubular acidosis
d. Gross hyperoxaluria
Hereditary hyperoxaluria
Enteric hyperoxaluria: intestinal oxalate absorption is increased-
usually associated with Crohn‟s disease or small bowel resection
e. Miscellaneous
Vitamin D intoxication
Sarcoidosis
Milk-alkali syndrome
Immobilization
Cushing‟s syndrome and steroid treatment

REVIEW QUESTIONS
1. Creatinine clearance measurement

A.T
A. Provide an index of the number of functioning B.F
glomeruli C.T
B. Correlate well with inulin clearance at all levels of the D.F
glomerular filtration rate (GFR) E.F
C. Should be related to body surface area in children
D. Are invalid if performed on 12 hour urine collections
E. Give misleadingly low results if there is marked
proteinuria
2. Plasma urea
A. Is a useful screening test for the presence of renal A. F
tubular disease B. T
B. Is often reduced in patients with hepatic failure C. T
C. is more affected than plasma (creatinine) by changes in D. F
diet. E. T
D. Increase whenever plasma (amino acids) increases
E. Rises in acute renal failure in proportion to the rate of
tissue catabolism
3. Patients with chronic renal failure and a metabolic A. T

acidosis: B. T
A. Have an increased solute load per functioning nephron C. F
B. Often have a high plasma (phosphate) and a low D. T
plasma (calcium) E. F
C. May develop osteomalacia because of inability to
hydroxylate I -hydroxycholecalciferol
D. Often have an increased plasma (magnesium)
E. usually cannot excrete an acid urine
4. Renal calculi are a presenting feature or recognized A T.
complication of : B.F
A. Idiopathic hypercalciuria C.T
B. Cystinosis D.T
C. Renal tubular acidosis E.T
D. Treatment with antimictic drugs
E. Primary hyperoxaluria
5. In which of the following characteristics is the renal D. The renal filtrate
filtrate more like plasma than like urine? has a pH of 7.4 and
A. Specific gravity has an osmolality
B. pH and specific gravity
C. Osmolality which approximates
D. All of the above a protein-free
plasma solution
6. A normal adult would have a creatinine clearance of C. Creatinine
approximately: clearance may
A. 50 ml/min decline with age.
B. 50 mg/min
C. 105 ml/min
D. 105 mg/min
7. Serum urea nitrogen/creatinine ratios, derived from a A. F
common sample, are normally between B. F
A. 5:1-10:1 C. T
B. 10:1-15:1 D. F
C. 15:1-25:1
D. 25:1-40:1
8. Which is the normal range for urinary pH? A is true

A. 6-8
B. 4-10
C. 7.4-7.8
D. 1-6
E. 7-14
9. The lowest urine osmolality/serum osmolality ratios A is true

are seen in cases of:
A. Diabetes insipidus
B. Fluid restriction
C. Renal calculi
D. Peritonitis
E. Intestinal obstruction
10. Nephrotic syndrome characterized by: A. T

A. Generalized edema B. T
B. Lipemia C. F
C. Hyperalbuminemia D. F
D. Gross hematuria
11. Plasma creatinine:
A. Is a useful screenibg test for the presence of renal A. F
tubular disease B. F
B. Is often reduced in patients with hepatic failure C. F
C. Increases whenever plasma failure {amino acids} D. F
increase E. T
D. Rises in acute renal failure in proportion to the rate of
tissue
Catabolism
E. Rises in acute renal failure in proportion to the rate of
tissue catabolism
12. In patients who are found to have proteinuria:
A. Urine protein electrophoresis should be performed if A. T
multiple myeloma is suspected B. T
B. Transient proteinuria occurring only after severe C. F
physical exercise is rarely of pathological significance D. T
C. The amount of protein exreted, if proteinuria is
persistent, indicates the severity of the underlying renal
disease
D. Due to the nephritic syndrome, this is likely to respond
to steroid treatment if the proteinuria is selective.

13. Renal calculi may be composed of : A. T
A. Calcium oxalate B. F
B. Cholesterol C. T
C. Cystine D. T
D. Uric acid E. F
E. Hypoxanthine
14. In acute renal failure, in the oliguric phase: A. F

A. Chemical investigations help to determine the etiology B. F
B. Plasma urea rises more rapidly in patients with acute C. F
glomerulonephritis than when renal failure follows major D. T
surgery E. T
C. The urine usually has high osmolality, relative to
plasma
D. Plasma {K+} is usually high
E. Plasma { Na+} is often low
15. Low threshold (renal) amino aciduria occurs in: A. F

A. Acute hepatic necrosis B. T
B. Cystinuria C. T
C. Hartnup disease D. F
D. Heavy metal poisoning E. F
C. Cystinosis
16.Results for creatinine clearance measurements may be

considerably reduced ( below 80 mL/min) in patients: A. T
B. T
A. With persistent hypotension C. T
B. With prostatic obstruction D. T
C. Treated with cimetidine E. T
D. Taking Salicylates
E. Whose urine collections are incomplete

5
ACID BASE BALANCE
Acids according to the Bronstand and Lowry definition are substances which
can donat hydrogen ions and bases are substance which can accept hydrogen
ions in an aqueous solution produces a measurable hydrogen ions
concentration which depends on temperature. This concentration is often
extraordinary small (e,g 10 mmol/l) as a result of which the negative decimal
P logarithum is used for the sake of simplicity. This called the PH; in the
example the PH is 7.
An aqueous solution is neutral:
Neutral at PH= 7
Acid at PH<7
Alkaline at PH>7
The hydrogen ion concentration of extra cellullar fluid is normally regualated

with a great percision ., despite the large amount of acid generated each day as
an end-product of metobolism.Any defect in its homeostasis can lead to
significant and life –threatening pathology .[H+] is kept constant by the
following mechanisms.
1) Chemical buffers
2) Role of lungs
3) Role of the Kidneys
4) Role of liver.
Buffers
Control acid- base homeostasis
Bicarbonate 50% H2O = CO2 Buffering system instant.

/H2CO3/+HCO3 Physiological mechanism
Lungs {minutes}
Protein Kidneys {Hours /days}
Hemoglobin 38%
Plasma protein 6% Liver {Hours /days}
Phosphate
Amonia
Buffers are minimizing the change in the pH of solution when acids or bases
are added.
Most buffers consist of a weak acid and its salt with a base.

The Henderson equation:
Expresses the relation between [H] and the ratio of buffer member in the
solution
[H+]= Kx-------
K= first ionization constant of carbonic acid =7.94x10-7
[HCO3] can be replaced by S.Pco2(S=solubility coefficceint of co2=0.23mmol/l
Thus [H=}=7.94x------- x10
TheHenderson –Hasselbalch equation
PH=pK+log ------(or S Pco2) (S=0.03)
Thus: pH=6.10+log [HCO3]
0.03Pco2
(__metabolic or non respiratory parameter)
(Respiratory parameter)
The function of proteins in aqueous solution is strongly dependent on PH. For

which reasons the body is regulate the PH within very narrow limits. The
following are involved in this regulation:
 The buffer system of the body by temporarily restricting changes in acid
concentration. These may be seperated into protein buffers made up of red cell
hemoglobin and plasma proteins, phosphate buffer and carbonic acid
bicarbonate buffer.
 The lungs as excretory organ, for carbon dioxide which acts as an acid in
aqueous solutions.
 The kidney which excretes hydrogen and bicarbonate ions.
From the physiology point of view the carbonic acid-bicarbonate buffer is the
most important buffer in the body.
It is chemically characterized by reaction equation:
CO2 + H2O <------- > H2CO3 < ------------- > H+ + HCO3-
Regulated by the lung Regulated by the kidney

Which establishes the relationship of the important parameter of acid
base balance
PH = 7.62 + lg {HCO3-}
PCO2
HCO3- = actual bicarbonate (mmol/l)
PCO2= arterial partial pressure of CO2 (mmHg)
TABLE 5.1: NORMAL VALUES OF ARTERIAL BLOOD GAS ANALYSIS
PARAMETER NORMAL RANGE
PH 7.34-7.44
PCO2 35-45mmHg
Actual bicarbonate 22-26mmol/l
Standard bicarbonate 20-28mmol/l
Base excess -3 to +2.5mmol/l
Buffer base About 48 mmol/l
 Standard bicarbonate: it is the amount of CO3H ion in blood : if Bicarbonate
decreased and PH decreased -------- Metabolic acidosis
 If SB and PH are increased ----- Metabolic alkalosis
 BE (Excess of Base : It is the difference between BB (Buffer base) normal and
BB of the patient
 Decreased in metabolic acidosis
 Increased in metabolic alkalosis
 BB(Buffer base) total amount of bases of the organism(CO3H, Hb, protein
PH
Low Normal High
Acidemia No disturbance or mixed Alkalemia
Low High High Low

HCO3- PCO2 HCO3- PCO2
Metabolic Respiratory Metabolic Respiratory

Acidosis Acidosis Alkalosis Alkalosis
TABLE 5. 2: VALUES OF PARAMETERS (PH, PCO2, STANDARD

BICARBONATE AND BASE EXCESS
DISORDER PH pCO2 HCO3 BE(mmol/l
mmHg mmol/l
Normal 7.35-7.45 35-45 20-28 -3 to 2.5
Comp. R. Acidosis N I I I I
Uncomp. R. Acidosis D I I N –I N –I
Comp. Metab. Acidosis N D DD DD
Uncomp. Meta. Acidosis D N-D DD DD
Comp. R. Alkalosis N DD D D
Uncomp. Resp. Alkalosis I DD N–D N –D
Comp. metabo.alkalosis N I II II
Uncomp. Metabolic. I N –I II II
Alkalosis
N: normal I: increase D: decrease
Compensation
In chronic respiratory disturbaces, renal adjustment of the plasma {HCO3-}
will usually occur to bring the pH back towards normal.
In metabolic disturbances respiratory adjustment of the Pco2 will usually
occur to bring the pH back towards normal. If the kidneys are functioning
normally, they will then excretes acid or base in an attempt to correct the
metabolic disturbance it self.

TABLE 5. 3: CAUSES, SYMPTOMS AND LABORATOR DATA
CAUSE SYMPTOMS LABORATORY FINDINGS
Respiratory acidosis: Dyspnea, PH decrease
Alveolar hypoventlation caused by tiredness, PCO2 increase
obstruction of trachea or bronchial weakness, SB increase
asthma, extensive atelectasis , fibrosis, disorientation Na increase : when PH is acid,
+
pneumothorax , pleural adhesion, protein take H and release Na
scleroderma, mysthenia graves, Cl decrease because cl enter in the
poliomyelitis ,polyneurophathy, spinal cell in order to permit go out
trauma, cerebral tumor CO3H
K increase: increase hydrogen ion
and enter cell with K
Metabolic acidosis: Kussmaul PH decreased
Excessive intake unmetabolizable acid, respiration, PCO2 normal or decreased.
renal and intestinal losses of alkali, reduction in BS decreased
reduced renal excretion of acid. cardiac EB decreased
Increased endogenous acid production in output, drop Na decreased it lost with urine
starvation, DM, shock, hypoxia, sepsis, in blood
alcoholism, poisoning with pressure, K increase it is changed with H+
methylalcohol, paraldehyde, ethylene cardiac in the cells
glycol and salicylate thiamine deficiency arrythmiasis
CAUSES SYMPTOMS LABORATORY DATA

Respiratory alkalosis: Anxiety, PH increase
Alveolar hyperventalation following da dyspnea, PCO2 decrease
costa syndrome, head injury, paraesthesiae, SB, BB normal or decrease.
encephalitis, meningitis, hyperthermia, tendency to Na decrease; joint to protein and
shock, sepsis, poisoning with salicylate, cramps, release H+
alcohol, chronic liver disease, high hyperventilati Cl is free joint to CO3H and lost
altitude, anemia, disorder of pulmonary on, tetany. with urine
difussion , cardiac failure, mechanical K decrease; changes with H+ and
hyperventilation. enter the cell.
Metabolic alkalosis:
Diuretic therapy, losses of gastric juices, Respiratory
congenital chloride losses, Zollinger – depression, PH increase
Ellison syndrome, excess of lack of PCO2 normal or increase
mineralocorticoids, hypokalemia and activity,
hyperaldosteronism in right heart failure cardiac Na increase; lost with urine.
and liver cirrhosis, excessive alkali intake arrythmias.
with restricted renal function, chloride K decrease;change with H+ .
deficiency.
Anion-gap
This is calculated from the concentration of electrolytes in plasma thus:
Anion gap= ({Na+ }+{K+}) – ({Cl-}+ {HCO3-})
Anion gap of greater than 20 mmol/l is almost certainly pathological and
demonstrates the build up in plasma of an abnormal concentration of an anion
other than chloride or bicarbonate:
Diabetic ketoacidosis: Ketacid anions
Renal Failure : a range of acid anions
Lactic acidosis : Lactate
Methanol poisoning : Formate
Ethylene poisoning : Oxalate

Lactic acidosis
Causes
1. Tissue hypoxia: (a) hypoxemia (b) hypovolemia
2. Diabetes; usually associated with phenformin therapy
3. Idiopathic
4. Some inherited disorders e.g glycogen storage disease type I
Laboratory Assessment
Sample Requirements
For complete elucidation of acid-base status, anaerobic samples are essential.
Ideally, arterial blood is taken into a heparinised syringe (ensuring that no air
bubbles are included) and the syringe is capped immediately. The results on
carefully collected capillary blood agree well with arterial blood unless there
is impaired peripheral blood flow.
Sample stability
Samples must be analysed within 20 minutes cooled to 4C when they can
generally be stored for an hour or two.
N.B Samples with a high leukocyte count will deteriorate more rapidly and
the only safe solution is to analyse all samples immediately.
Parameters measured or calculated
1. pH
Measured directly using a specially designed pH electrode
2. Pco2
This is a good measure of respiratory disturbance and is not affected by
metabolic disturbances
Metabolic disturbances might have been expected to affect the Pco2 e.g in a
metabolic acidosis; the addition of fixed acid will shift the following
equilibrium to the left by increasing the hydrogen ion concentration:
H2O + CO2 < --------> H2CO3 < ----------> H+ + HCO3-
Thus the Pco2 will tend to rise, but no passage through the lungs, the extra
CO2 will be lost and so in arteria blood, the Pco2 will be unchanged.
3. Metabolic Component
a. Bicarbonate ( i.e actual bicarbonate)
Not ideal for assessment of metabolic disturbances because it is affected by
respiratory disturbance e.g in a respiratory acidosis, the bicarbonate
concentration will rise because the following reaction will be shifted to the
right by the increased Pco2:
H2O + CO2 < -------------> H2OC3 < -------------> H+ + HCO3-

b. Standard bicarbonate
This is the bicarbonate concentration of fully oxygenated blood at 37C after
equilibration of the whole blood at a Pco2 of 40 mmHg (5.3 kpa). Thus any
change in the bicarbonate concentration caused by a change in Pco2 ( i.e
caused by respiratory disturbance ) will very largely be removed, so standard
bicarbonate is a good measure of metabolic disturbance.
c. Base excess
This is the concentration of base in whole blood as measured by titration with
strong acid to pH 7.4 at a Pco2 of 40 mmHg (5.3 kpa) at 37C. For negative
values the titration is carried out with strong base.

WATER AND ELECTROLYTE BALANCE
Water is the greatest single constituent of the body, representing about 60% of
the total body weight in a average adult:
Body water is distributed among three compartments separated by semi-
permeable membranes. These compartments are:
1) Water with in the cells. (Interacellular water) about 40% body weight.
2) Water with in the blood vessels (intravascular water plasma) about 5% body
weight.
3) Water in the tissue spaces between the blood vessels and cell (Interstitial
water) about 15% body weight.
Division of body water may be made of two classes intracellular & extra
cellular . In the adult about one third of the total body water is extra cellular.
Replacement of Water
The store of water in the body in normally replenished in two ways:
1) foods as meat ,fruit‟s, and vegetables, which are from 60% to 97% water.
2) By Metabolism: The combustion of foods tuffs yields water of oxidation. The
metabolism of each 100 calories of fat, carbohydrate or protein releases about
14 ml of water.
Loss of Water
Water leaves the body through the kidney, lungs, skin, and gastercutestinal
tract. In the normal individual, loss from the gastro intestinal tract in the saliva
and stool is very small.
However, two vital needs demand a continual expenditure of water.
1) Removal of body heat by evaporation of water for dissipation of heat the
average adult leses a minum of 800 ml daily through skin and lungs. This
volume is increased by hot, dry environments.
2) Excretion of urea, metabolic products and mineral salts. For minimal urinary
function the average adult excretes about 900 ml of water daily.
Water Balance
In normal subject water intake is equal to water out put. The volume of urine
which is required for excretion of waste products is at least 500 ml and if to
this minimal urine output is added the in sensible fluid loss through the lungs
and the skin the daily obligatory water loss of a normal active adult in a
temperate climate is seen to be 1500ml which is about 2% of the body weight.
An adult patient who completely deprived of fluid may lose, therefore, up to
2% of his body weight per day. If these is no additional loss of fluid, the daily
fluid intake, to prevent any risk of water depletion, should be 2000-2500ml.

The main function of water is as the solvent for biological system. The water
content of the human body depends on age and sex.
TABLE 5.4: DAILY WATER BALANCE IN ADULTS:

Water intake
 Water intake in form of fluids 1000 – 1500 ml
(volumes of drinks including soups
 Water intake in form of semi-solid 700 ml
and solid foods.
 Water from oxidation 300 ml
TOTAL DAILY WATER INTAKE 2000 – 2500
Water output
 Water loss in urine 1000-1500 ml
 Water loss through skin 500 ml
 Water loss through lung 400 ml
 Water loss in stools 100 ml
TOTAL DAILY OUTPUT 2000 – 2500 ml
DISORDER OF WATER BALANCE

There are two fundamentally different disorders of water balance:
dehydration and overhydration. Depending on the extracellular sodium
concentration, one can distinguish hypotonic, isotonic, hypertonic
dedydration and overhydration.
Hypotonic dehydration
Fluid deficit associated with sodium deficiency. The low osmolarity of the
extracellular space produces a reduction of the exracellular volume and an
increase in intracellular volume.
Isotonic dehydration
Deficiency of sodium and water. The extracellular volume is reduced with a
normal sodium osomality while the intracellular volume is normal.
Hypertonic dehydration
Water deficiency with elevation of serum osmolarity and reduction of the
extra-cellular volume. As a result of diffusion of water, the intracellular
volume is also reduced and its osmolarity increased.
Hypotonic overhydration
Excess of water, with elevation of extracellular and intracellular volumes. The
osmolarities of the serum and the intracellular space are reduced.
ISOTONIC OVERHYDRATION
Excess of water and sodium. The serum osmolarity is normal, the extracellular
volume elevated and the intracellular volume normal.

SODIUM
The normal level of sodium in serum is 136-148 mmol/l.(milli Eq/l). Sodium
is the chief base of the plasma and its fund ion appears to be chiefly
physicochemical in connection with the maintance of osmotic pressure and
acid base balance. In a normal subject sodium and chloride intake equals
sodium and chloride output, and any minor discrepancies are balanced by an
alleration of the sodium and chloride concentrations in the extracellular fluid.
Sodium Excretion
Under moderate environmental temperature and in a normal health, the chief
regulation of sodium occurs with in the kidney. For purposes total urine sodium
per the kidney. For paretical p hormone of the pituitary tends to promote
sodium excretion from the kidney to some extent and to markedly favor water
resorption from the distal tubules.
Dehydration: Water & Sodium Depletion:

Water Depletion:
The syndrome of water depletion occurs when fluid intake is insufficient, and
there is continuing loss of water or fluid of low sodium concentration.Reduction
in water usually causes thirst, and the conscios response is to drink. If restoration
of water balance is delayeed, plasma osmolality rises and physiological response
occur as follows:
1) Release of ADH, which thereby reduces the continuing loss of water in urine.
2) Transfer of water from the ICF to the ECF>
Causes of water depletion

Cause Examples
Reduced intake
Unableto get water Infancy, unconsciousness,exterme weakness,
Water not available People lost in the desert, shipwrecked
Inability to swallow Any cause of dysphagia
Nausea Various causes
Increased losses Fever, hot and dry environment(tropics, stokers
1) Skin etc.), thyrotoxicosis.
2)Lungs Fever , hyper ventaltion
3)Urine Diabetes insipidus, nephrogenic diabtes insipidus
In water depletion the concentration of sodium & chloride in the ECF,

and the osmotic pressure of ECF gradually rise. The plasma Na may exceed
160 mmol/l. A rise in the plasma urea is late, and retention of nitrogenous
waste occurs when the urine flow falls below 30ml/n. Effects tends to be
severe in infants and the old because of poor renal compensating capacity, and
in infants also because of relatively smaller fluid reserves.
The primary loss of water of the ECF (to urine, skin and lungs) is
replaced from the intracellular fluid, to maintain as for as possible the osmotic
pressure of the plasma & tissue fluid. The concentration of the ions in the
plasma rises because there is a lag in water-electrolyte adjustment. The
osmotic pressure of ICF rises. As replacement of ECF is not complete there is a
fall in the plasma volume, and slowly progressive haemoconcentration and
circulatory changes.
Symptoms begin to appear when about 2 liters of water has been lost.
The Main Symptoms are: apathy, thirst, and dryness of the mouth and
tongue: There is slight loss of skin turger and there is oliguria with urine of
high specific gravity. If renal function is unimpaired a daily urine volume of
less than 750 ml means that a patient has water depletion; a severely
dehydrated patient may excrete in a day only 500 ml of urine at & specific
gravity of 1.040.
The treatment of choice is water by mouth (or by gastric tube). Cential
the daily volume exceeds 1500ml. If oral route is not possible or insufficient,
Water must be given I.V. as 5% glucose. Oral salts or intravenous saline must
not be given; any addition to extracellular sodium with draws more water
from the cell.
Sodium depletion or Hyponatermia:
Hyponatremia occurs when

1.Diminished intake of sodium.
2.General loss of both Na & H2O & Replaced only by water.
3.Hemodilution.
4.Loss of Na containing fluids occurs from burns, severe exudative skin
lesion.
5.Massive sweating.
6.Excessive urinary sodium loss due to diuretics.
7.Addison‟s disease.
8.Chronic nephritis.
9.Ketoacidosis.
10.Paralytic ileus.
11.Oedema.
When sodium is lost from the body ,the ECF becomes hypotonic water leaves
the ECF in a attempto to restore the plasma osmatic pressure. Rather more water
is lost from the tissue fluid than from the plasma as the osmotic action of the
proteins tends to hold water in the plasma.
The reduction in ECF volume causes the following physiological responses:
1. Reduction in GFR.
2. Stimulation of aldosterane production.
3. Secretion ADH
4. Reduction in natriuretic hormone secretion
Hypernatermia
Occurs when excessive intake of sodium of deficient excretion of sodium. It is
difficult to cause sodium intexication by excessive oral intake of sodium. (by
dirinking sea water) I.V. Saline may, however easily cause sodium overload and
this appears when water deplation is treated by satene,
1. Excess adrenocartical hormones, wheither calerogenic or in conn‟s syndrome
or custing syndrome, may cause marked sodium retention.
2. Over secreation of adrenocortical hormons following major operations.
3. Head injury or intra crainal lession in association with water depletion.
4. Severe heart failure because bbof the secondary renal impairment, there may
be retension of sodium and water, and a high plasma and ECF volume.
5. Renal failure, hypoproteinemia, during development of ascctes or in
hypertensive renal failure the ECF is retaining ever more water then sodium,
so there is hyponatercemia.
When the sodium intake exceeds the possible rate of excretion (350
mmol/l).Sodium intoxication will happen.
There is an increase in the ICF volumes so the rise in plasma sodium & chloride
concentration is small. There may be a metabolic acidosis. Water passes from to
JCF to the ECF in an attempt to maintain the plasma osmotic pressure.
There is raised central venou pressure, peripheral oedema (Which indicates a
high body sodium and becomes apparent when the volume of the ECF has
increased by more than 10%), and pulmonary oedema with eventual respiratory
failure. , lab, Hypokalaemic alkosis due excess aldostrone: ↑ Plasma which may
be with in the word range but, 140-low urinary Sodium in early stages.
Water Excess
Water excess, usually called water in toxication, occurs when the urine volume is
low, especially if a patient is given large volumes of a salt poor fluid and above
all in chronic renal failure. Water intoxication does not occur if renal function is
normal: Retention of water is particularly likely to occur within 24 hour of a
major trauma or operation, probably due to in approprate over secretion of
antidiuretic hormone. Water in toxication may be produced of hyponateria is
misdiagnosed as water depletion and treated with water. Excess I.V. glucose can
cause dilution hyponatraemia, during I.V. adminstiation of oxgtocin to induce
labor. Dilution concentration of sodium and chloride fall.
The sympotoms, less severe than in sodium deficiency, are headache, anorexia,
lethargy and bradycardia, and eventual convulsions & delirium probably to due
to over hydration of brain cells.
The treatment is to stop the intake of water and to give intravenus hypertonic
saline. Water loss, as sweat may be oncouraged by hot godles.
POTASSIUM
Potassium is the principal cation in the cell and it is present in a relatively low
concentration in ECF. The normal rang of plasma potassium concentration is 3,8-
5,0 mmol/l.
Potassium moves from the ECF into the ICF when either protein is being
deposited or glucose is being taken and metabolized, or during alkolosis.
Potassium moves from the ICF into the ECF, and can then be lost from the body
in the urine, when body protein is being catabolized in stravation or after stress
or trauma. During exercise, after loss of water sodium & chloride from the body,
or during acidosis.
Potassium is freely filtered by the glomeruli and meabsorbed in the proximal
tubules: Urinary potassium is derived from the distal tubular secretion in
excharge with sodium.
Renal mechanisms are more competent in excreting excess potassium than in
conserving diminished K+
The body contains about 3500 mmol (150g) of K+ . The average intake in an adult
is about 100 mmol [49] , 24 honr, of which at least 80% is crocreted in urine & less
than 20% in the faeces.

Hyper Kalaemia:
In clinical practice hyper kalaemia is not common as hypo kalaemia. It may
occur:
1. Excessive intake
2. Impaired function of the kidneys
3. Acidosis (Hydrogen ions displace potassium ions from the cell)
4. Haemolysis or break down of leukemic leuxocyles (fals only high potassium).
The chief tonic effect of hyper kalaemia is on neuromuscular conduction
especially in the heart: and signes develops with distinctive
electrocardiogragic changes of an absent P wave, broad QRS complen, and
particularly of high T waves. At high plasma levels (10 mmol/l) Q-U block
and cardia arrest can develop.
Hypokalaemia
Hypokalaemia is usually associated with general cellulary deficiency of
potassium.Hypokalaemia is commonly:
1) Disease of the gastro intestinal tract, especially when assocaited with
diarrhae.
After prolonged use of purgatives. Large quanties of K+ can be lost in the
feaces and in the vomit.
In diabetic come there may be considerable los of body K+ in to the
urine.Insulin treatment healts the loss of K+ because restoration of
intracellular glucose metabolism fixes K+ in the cell, but the shift to the cells
lowers the plasma potassium level still further. Prolonged treatment with I.V.
glucose like wise shifts potassium from plasma to cellbs.
Excessive urinary of loss of K+ due to prolonged diuresis from any cause
(many diaretics, such as the thiazides, and espically frusamide) can cause
sever hypocalcaemia, and excessive K+ will be excreted in any prolonged
acidosis.
Hypocalemian may occur in chronic pyelonephritis with mainly tubalus
disorders.
Investigations of electrolyte Disturbances:

Before making a request, some assement should be made as to know whether
the result of estimation will aid diagnosis or treatment.
The student should be or the following point in mind:-
1) Plasma sodium should be estimated regularly.
a).In the unconscious patients and in infants losing fluid; because of the
dangerous of hypernatermia.
b).In the dehydrated patients, or those with abnormal losses, to help diagnosis
and to indicate the type of replacement fluid.
2) Plasma potassium (and bicarbonate) should be estimated regularly on any
patient in whom there is a cause for abnormal levels
a. In patients with abnormal losses from the gastro-intestinal tract or kidneys
(especially due to diuretic, or steroid or ACTH therapy).
b.In patients on potassium therapy.
c.In patients in renal failure.
d.In patients in diabetic coma or precoma.
Group 1 and 2 are numerially small compared to estimations actually
requested.

3) In the conscious, normally hydrated patient, with no abnormal losses plasma
sodium rarely helps. Mild hypo natraemia is common but treatment in such
subjects is usually contra-indicated. Unless renal failure is present, potassium
estimation is also unhelpful in such subjects.

REVIEW QUESTIONS
1. Increased plasma [K] may be caused by:

A. Renal failure A. T
B. The presence of leukemic cells B. T
C. Hyperaldosteronism C. F
D. Hypercatabolic state D. T
E. Insulin-screenibg tumors E. F
2. Metabolic acidosis:
A. commonly accompanies hypokalemia A. F
B. Is a common feature in ketosis B. T
C. Is accompanied by a fall in plasma (total CO2), C. T
and a compensatory fall in Pco2 D. T
D. May be caused by severe diarrhea E. F
E. Is a common cause of a decreased anion gap
3.Which blood gas value will be most altered in the C. For every degree
febrile patient? above or below
A. pH normal temperature
B. PCO2 there is a 6% change
C. PO2 value
4. What is the normal ratio of bicarbonate to D. A bicarbonate/
carbonic acid? carbonic acid ratio of
A. 1:1 20:1 is required to
B. 5:1 maintain
C. 10:1 physiological pH at
D. 20:1 7.40
5. Which buffer system acts as the primary regulator

of plasma pH? A is true
A. Bicarbonate/carbonic acid buffer system
B. Phosphate buffer system
C. Hemoglobin buffer system
D. Plasma protein buffer system
6. What is the normal plasma and urine osmolality?

It is 280 to 295 mOsm/kg in plasma and 500 to 800 mOsm/kg in urine.
7. What is the normal serum potassium level?
It is 3.6 to 5.0 mEq/L
8. What effects does potassium deficiency have on intracellular and

extracellular pH?
It leads to intracellular acidosis and extracellular alkalosis.

6
GASTROINTESTINAL TRACT
Gastrointestinal tract problems are common health problems in our country.

Malabsorption, pancreatitis, gastric and duodenal ulceration, ulcerative colitis
and Crohn‟s disease are important causes of morbidity and carcinomas are
common cause of mortality. Chemical tests play a relatively minor part in the
investigations.
This chapter will discuss the chemical tests which will help in the diagnosis of
gastrointestinal tract diseases.
Physiology
Gastric Secretion
Function
1. Acid – initiates protein digestion
2. Pepsin – digests protein
3. Intrinsic factor – for absorption of vitamin B 12
Control
1. Vagal – stimuli from cerebral cortex
a. Initiated by sight, smell, and taste of food
b. Can also be caused by hypoglycemia
2. Gastrin- released by gastric antrum in response to
a. Gastric distension and the presence of food in the stomach
b. Hypercalcemia
Pancreatic Secretion
The pancreas is responsible for the secretion of most of the important digestive
enzymes but 90% of the pancreas may be removed before protein digestion is
impaired.
1. Bicarbonate
Function: Neutralization of gastric acid to achieve optimum pH for pancreatic
enzyme activity
Control: Secretion released in response to acid and food entering the duodenum.
2. Proteolytic enzymes
a. Trypsinogen --------> Activated
b. Chymotrypsinogen --------> in the
c. Proteolastase ----------> duodenum
d. Procarbopeptidase ---------->
Function: Protein breakdown to oligopeptides aminoacids response to acid and

food entering the duodenum.
Vagal stimulation and cholinergic agents potentiate the effects of secretion and
pancreozymin production, but vagotomy does not result in clinically
recognisable impairment of digestion.

3. Amylase
Function: Hydrolyses polysaccharides (starch and glycogen) to disaccharides
(maltose, sucrose, lactose)
Control: pancreozymin
Enzymes for digestion of fat

Function
a. Lipase: Hydrolyses triglyceride to fatty acids and monoglyceride
b. Colipase: counteracts the inhibition of pancreatic lipase by bile salts
Control: pancreozymin
Biliary Secretion
Bile salts are the major digestive components of bile
Function: To emulsify fat entering the duodenum
Control: Gall bladder contraction stimulated by cholecystokinin
Normal Intestinal Absorption

1. Protein absorption depends on
a. Normal pancreatic amylase (Polysaccharides)
b. Normal intestinal mucosa (active transport mechanisms
2. Carbohydrate absorption depends on
a. Normal pancreatic amylase (Polysaccharides)
b. Intestinal disaccharides)
c. Normal intestinal mucosa – active transport mechanisms (monosaccharides)
3. Fat absorption depends on
a. Bile salts – emulsfy fats
b. Normal pancreatic lipase – to digest trigycerides
c. Normal intestinal mucosa – for chylomicron formation
4. Calcium absorption depends on
a. Low level of intestinal phosphate and fatty acids
b. Presence of vitamin D (which in turn depends on normal fat absorption since it
is a fat soluble vitamin)
c. Normal intestinal mucosa
5. Iron absorption depends on:
a. Iron being in the ferrous form
b. Active transport mechanism
6. Vitamin B12 absorption depends on:
a. Normal intrinsic factor
b. Intact mucosa in distal ileum
c. Normal intestinal flora (some bacteria compate for B12
TABLE 6.1 : MAJOR SITES OF ABSORPTION IN THE SMALL INTESTINE

Proximal Mid Distal
Iron Aminoacids Bile salts
Calcium (monosaccharides) Vitamin B12
Water soluble vitamins (aminoacids)
Monoglycerides
Fatty acids
Monosaccharides
(aminoacids)

G.I Hormones
A diffuse endocrine system exists throughout the gastrointestinal tract producing
a variety of hormones which play an important part in the control of digestion.
Some of these have already been mentioned but in man the role of the others is,
in many instances not very clear.
TABLE 6.2 : LOCATION AND PROPOSED ACTION OF THE BEST

KNOWN G.I HORMONES
Gastrin Antrum of the Stimulates gastric acid secretion

stomach and
proximal small
intestine
Secretin Duodenal and Stimulates secretion of bicarbonate-

jejunum rich pancreatic-juice
Glucagon Pancreas Insulin antagonist
Pancreatic Pancreas Inhibits pancreatic enzyme secretion
polypeptide
Pancreozymin Small intestine Stimulates pancreatic enzyme
(cholecystokinin) secretion and gall bladder
contraction
Gastric inhibitory Small intestine Stimulates insulin release in
polypeptide response to oral glucose
Vasoactive Small intestine Increases intestinal motility
intestinal
polypeptide (VIP)
GASTRIC FUNCTION TEST

Gastric function tests can provide information about (1) the rate of gastric
emptying; (2) the ability of the stomach to secrete intrinsic factor, acid and
pepsin; and (3) the rate of secretion of acid. In a clinical problem, the information
required should be decided upon and then the test chosen which yields this
information in the simplest way and with the least discomfort for the patient.
Rate of Gastric Emptying

This can be studied radiologically. The simplest clinical test is to measure the
resting juice volume after an overnight fast; this is normally less than 150 ml.
Two charcoal biscuits may be given on the previous evening when more than
traces of charcoal should be present in this juice next morning.
Gross Examination
1. Amount: normal fasting content is 50-100 ml
2. Colour:
a. Blood is red or the colour of coffee ground if acid hematin is formed.
b. Fresh bile is yellow; old bile is green
c. In stasis, food colours may persist.
3. Odor
a. Normal is sour or slight rancid
b. Fecal in intestinal obstruction
c. Ammoniacal in uremia
4. Reaction: Acidic normal pH
5. Rate of secretion:
a. Mean values for basal rate of secretion of acid: 1.5-2.5 mEq/l
b. Mean values for 12 hour nocturnal secretion in a normal person
volume 580 ml
Free acid 29 mEq/l
Chemical Examination
1. Blood: May be due to one of the causes of hematemesis, or may be due to
trauma of passing a tube. Do guaiac or benzidine tests.
2. Qualitative test for free HCL (Topfer's test): To 5 drops of gastric juice in
evaporating dish add 1 or 2 drops of 0.5% alcoholic solution of
dimethylaminoazobenzene (Topfer's reagent) Cherry-red colour occurs with
HCL.
Microscopic examination
Place one drop of sediment on a slide and coverslip it. Look for undigested food
particles, blood, mucus, bacteria, tissue fragments, parasites, sarcinae,
yeasts.Lactobacilli are large nonmotile rods which stain brown with Gram's stain
and form lactic acid; they occur in stasis in the absence of HCL.
Exfoliative cytologic preparation of fresh gastric washings should be used in the
search for gastric neoplasms.
Gastric Test Meals

Procedures
If the test is to be performed in the morning give nothing orally after supper the
previous night.
Augmented Histamine Test (AHT)

A dose of 0.04 mg per kg body weight is the optimum dosage that can be given.
All parietal cells capable of acid secretion are stimulated by histamine,
functioning parietal cell mass. The AHT or the analogous Histalog test is now
established as definitive tests for the diagnosis of anacidity.
A history of bronchial asthma or urticaria, the presence of severe cardiac,
pulmonary or renal disease and paroxysmal hypertension or other possible signs
and symptoms of pheochromocytoma are contraindications to the performance
of this test.
Method
1. Following a 12 hour fast, basal secretion is collected for 1 hour as previously
described.
2. Thirty minutes before completion of the basal secretion collection, a suitable
dose of antihistamine is given IM e.g 10 mg chlorpheniramine malaete or 50 mg
diphenhydramine hydrochloride.
3. After the conclusion of the basal secretion study, histamine acid phosphate is
administered SC in a dose of 0.04 mg per kg body weight.
4. Gastric contents are then collected in 15 minute samples for 1 hour.
5. The volume, pH and titrable acidity are measured for each sample and the acid
output is calculated. From these the 1-hour or maximal acid output in mEq is
computed.

Interpretation
The maximum rate of acid secretion is characteristically attained within 15
minutes after histamine injection and is maintained for approximately 30
minutes. By 60 minutes after histamine injection acid secretion usually falls to the
basal level. The maximum output, representing the sum of the acid.
The upper limit of normal is 30 mEq HCL secreted in the 30 minute period
between 15 and 45 minutes after the histamine injection. Values higher than the
stated upper normal limit are usually found in duodenal ulcer and Zollinger-
Ellison syndrome. Anacidity in the augmented histamine test is most commonly
found in adults with pernicious anemia or gastric carcinoma, it has also been
reported in other conditions e.g hypochromic anemia, rheumatoid arthritis,
steatorrhea, aplastic anemia, myxedema, nutritional megaloblastic anemia .
The basal and AHT are used as determining factors for gasterectomy or
vagotomy. It has been suggesred that an increased functioning parietal cell mass
evidenced by an elevated maximal acid output indicates the need for gastric
resection. Whereas, raised basal secretion with normal or only slightly elevated
maximal secretion is taken as an indication for vagotomy.
Histalog Test
Histalog (3 b-aminoethyl pyrazole dihydrochloride, Betazole), an analogue of
histamine can be used instead of histamine.
Advantages? Lesser side effects and obviation of the need to give antihistamine.
The augmented Histalog dosage is 1.7 mg/kg given IM. The test is similar as
ATH except the (1) no antihistamine is needed and (2) eight instead of four 15-
minutes post-Histalog samples are collected.
The peak acid secretion in Histalog test is reached in the second to fifth 15
minutes period. The peak secretory rate may last for 45 to 90 minutes.
Test Using Pentagastrin as Stimulus

A synthetic pentapeptide structurally related to the terminal tetrapeptide of
gastrin has been prepared. This compound in a dose of 6g/kg BW is given by
IM or SC injections.
Pentagastrin is given at the end of the basal 1-hour collection. If given
subcutaneously, collection should be continued for four 15-minute period as in
the augmented histamine test. If given intramuscularly, the collection period can
be shortened to 1/2 an hour and the collection between 10 and 30 minutes after
injection regarded as the 'peak 20 minute' output.
Insulin Test
Acid secretion is stimulated by hypoglycemia caused by insulin administration.
Gastric secretion in response to insulin hypoglycemia probably occurs only if the
vagi are intact.
The major stimulus is transmitted via vagus nerve and can be removed by
vagotomy.
It is usual to give soluble insulin 15-20 units intravenously at the end of the basal
hour. Juice collection is continued in 15-minute periods for 2 hours and the blood
sugar is estimated every 1/2 an hour. Normally, the peak 1-hour secretion
corresponds to the 1-hour response after histamine, provided that the blood
sugar falls by 30 mg per cent. In the original test gastric stimulation was assumed
if there was a rise in the concentration of acid of 10 mEq/l above the base line if
the resting contents were an acid, or of 20 mEq/l above the mean basal secretion
if this contained acid. A negative result was discounted if the blood sugar did not
fall to 50 mg per cent or if gastric secretion could not be demonstrated in
response to histamine. It is now suggested that a rise in acid concentration of 20
mEq/l over the basal level during the first hour after insulin is the most certain
indication of incomplete vagotomy; the significance of a rise in the second hour is
less certain.
Other Diagnostic Methods

1. Mycobacterial culture
2. Exfoliative cytology
Examination of Duodenal Contents
Duodenal Drainage
Indications
1. For diagnosis of liver or biliary tract disease. Drainage may be done to help
diagnose exacerbations of chronic infections early so that they can be controlled
2. For other diagnostic purposes relating to parasites, pancreatic enzyme etc.
3. For therapeutic drainage in cholangitis or biliary obstruction
Method for Diagnostic Drainage

1. Give nothing orally after midnight.
2. In the morning intubate (Levintube) to a length of 50 cm. Withdraw gastric
specimen.
3. With patient erect or lying on his right side before the fluoroscope, feed and
massage tube into middle third of the duodenum. Now aspirate duodenal
contents for 5-30 minutes and lable "A" this evacuation specimen is of little value
for bile study.
4. Slowly inject 50 ml of warm 33% magnesium sulfate through the tube to relax
sphincter of Oddi. Clamp tube for 5 minutes then drain for 30 minutes and level
"B". Gallbladder bile is first dark, then lighter. If no "B" bile is obtained, inject
another 50 ml of magnesium sulphate. If still unsuccessful, inject 30 ml of olive
oil.
5. During the final period of 30 minutes, try to collect yellow hepatic bile.Lable it
"C".
Examination for Diagnosis

1. Note density colour, and flocculi in all 3 specimens.Test for bile, blood,
reaction and ferments as necessary.
2. Microscopy: This is important in detecting early cholelithiasis (gall sand). Note
pus cells, bacteria, cellular elements and crystals.
3. Giardia or other parasites may be present.
4 culture for bacteria, especially typhoid bacilli.
Interpretation
1. Absence of dark "B" bile indicat loss of gallbladder function. No bile may
appear in common duct obstruction.
2. In cholelithiasis, many cholesterol and calcium bilirubinate crystals appear in
"B" and "C" bile.
3. In biliary tract inflammation there is much yellow cellular and bacterial
material in "B" and "C" bile.
4. Blood visible in advanced carcinoma.
PEPTIC ULCER
Circumscribed ulceration of the mucous membrane penetrating through the

muscularis mucosa and occuring in areas exposed to acid and pepsin.
Gastric ulcer (GU): along the lesser curvature of the stomach
Duodenal ulcer (DU): In the first few cm of the duodenum
Postbulbar ulcer: In the doudenum beyond the bulb.
Marginal or stomal ulcer: at the margin of anastomosis
Peptic ulcer occurs only if the stomach secretes acid.
Diagnosis
1. Symptoms
2. Endoscopy. With a cytologic search
3. X-ray studies with barium.
4. Gastric Analysis
Gastric secretory studies may be useful to demonstrate achlorhydria or
hypersecretion. To obtain reliable findings, the position of the aspirating tube is
checked by fluoroscopy and the adequacy of drainage is also checked by hand
aspiration.
Achlorhydria (e.g in pernicious anemia) is diagnosed by the failure of gastric
juice pH to fall below 6.5 with maximum stimulation (pentagastrin 6 ug/kg sc)
Gastric analysis is indicated where ulcer recur frequently or respond poorly to
treatment. High rates of basal and stimulated secretions may suggest Zollinger-
Ellison syndrome; the diagnosis is confirmed by an elevated fasting serum
gastrin associated with hypersecretion. All DU patients should have fasting
serum gastrin measured if the ulcer recurs after elective ulcer surgery should
have preoperative gastric analysis.
Pancreatic Function Tests
Compositipon of Pancreatic Juice

Obtain specimen by duodenal drainage; it is mixed with bile. The flow of
pancreatic juice is stimulated by an injection of secretin. Secretin is a hormone
normally produced by upper intestinal mucosa in response to the presence of
acid. The flow of pancreatic juice begins 5 minutes after a meal, is at its height in
2-3 hours, and lasts 6-8 hours in (see phyiology of pancreatic secretion)
Secretin Test of Pancreatic Function

The stomach and duodenum of the fasting subject are intubated seperately. The
position of the tube checked radiologically.
The gastric and duodenal sections of the tube are aspirated continuusly at 4 cm
Hg using two Robert's pumps. The collection must be closely supervised and
suction interrupted intermittently if flow ceases.
After an initial collection for 10 minutes which is discarded, secretin 1 unit/kg
body wt, is given iv over 2 minutes. Four successive 20 minutes specimens are
now collected and labelled:
0-20', 20-40', 40-60' and 60-80 minutes after secretin
The volume, pH and bicarbonat, the total amylase content may also be measured

Interpretation of Result
Normal values
1. Total volume more than 2 ml/kg body weight.
2. Maximum bicarbonat concentration is more than 90 mEq/l
After secretin stimulation the volume and bicarbonate are the most important
measurements. A decrease in both volume and bicarbonate suggests complete
obstruction of the pancreatic ducts, as by tumor. A low volume with normal
bicarbonate concentration suggests partial obstruction of the pancreatic duct. If a
tumor is suspected cytological examination of the duodenal aspirate may be
helpful.
A normal volume with a low bicarbonate concentration suggests chronic
pancreatitis.
PANCREATITIS
Acute pancreatitis is the term usually reserve for an acute inflammation that
resolves both clinically and histologically (e.g pancreatitis associated with biliary
tract calculi.)
Chronic pancreatitis: indicates that histologic changes persist even after the
etiologic agent (usually alcohol) has been removed.
ACUTE PANCREATITIS
Causes
Biliary tract disease (Gall stone)
Alcoholism
Drugs
Infections (mumps)
Trauma, post surgery, ERCP
Metabolic disorder (uremia)
Almost all patients suffer of sudden abdominal pain that reacts rarely; pain is
first felt in the lower abdomen.
The patient appears acutely ill and is sweating. Pulse rate is usually 100 to 140
beat/minute. Respiration is shallow and rapid and postural hypotension.
Abdomen: abdominal distension in 20%. There may be ascites. Mild to moderate
muscular rigidity in the upper abdomen. Bowel sound may be hypoactive.
Laboratory Diagnosis
1. Serum amylase (N.V 53-123 u/l) estimation has been widely used in the
diagnosis of acute pancreatitis. Serum amylase activity rises within hours
following episodes. Values over 5 times the upper limit of normal is suggestive
of the diagnosis. Values may return to normal within 5 days following a mild
edematous attack.
Values over 1000 unit per hour (in urine) or higher are seen, almost exclusively in
patients with acute pancreatitis.
2. Serum Lipase: (4-24 u/l) It s less sensitive than amylase. It provides
confirmatory evidence for the diagnosis when positive.

3. Urine amylase: Hyperamylasuria persists for a few days longer than
hyperamylasemia. High serum amylase with a normal urine amylase suggests
macroamylasemia.
4. Amylase clearance: Creatinine clearance ratio incease in acute pancreatitis.
More specific than serum amylase elevation but some times elevated in other
conditions
5. Serum trypsin: More specific than amylase because it is only produced by the
pancreas but is more difficult to measure (radioimmunoassay).
The Hct may be as high as 50-55% as a result of third space fluid losses.
Hyperglycemia may occur.
Serum Ca++concentration may be reduced as early as the first day, probably
because of loss of serum albumin into retroperitoneal spaces as part of the
chemical burn.
In alcohol related pancreatitis serum bilirubin may rise.
Chest X-Ray - Abdomen ultrasound, CT scan and ERCP (Endoscopic Retrograde
cholangeopancreatography) are important for the diagnosis.
CHRONIC PANCREATITIS
There is variable degree of fibrosis and atrophy in pancreatic parenchyma.

Causes: Alcohol is a common cause. Rare causes: stone, Carcinoma, stenosis of
pancreatic duct and Hyperparathyroidism
Serum amylase like in acute
Serum lipase is of little value in the diagnosis of chronic pancreatitis.
Diabetes mellitus is present if 2h postprandial serum glucose is > 200 mg/dl or 2
fasting serum glucose levels are > 120 mg/dl.
The most sensitive test of pancreatic exocrine function is the Secretin test.
Duodenal Content
HCO3 < 90 mEq/l suggestive chronic pancreatitis
Low volume <2ml/kg, normal HCO3 (>90 mEq/l, and normal enzyme
concentration suggest pancreatic cancer
Other tests
1. Lundh test:
-Measure of tryptic activity in duodenal juice following a test meal.
-Require duodenal intubation
-Cheaper, simpler and better tolerated than the secretin test
- Limitations (a) technical difficult (b) assumes an intact small inestine (c) can not
distinguish between cancer and inflammation
2. Fecal Fat excretion: Increase in pancreatic malabsorption
3. Glucose Tolerance Test: Often abnormal in chronic pancreatitis
Radiological Aids: Ultrasound and ERCP.
CANCER OF PANCREAS
Adenocarcinoma of the exocrine pancreas arises from duct cells 9 times more
often than from acinar cells; 80% occur in the head of the gland and may produce

obstructive jaundice. Tumor in the body and tail may cause splenic vein
obstruction, splenomegaly, gastric and esophageal varices and GI hemorrhage.
Diagnosis: Routine laboratory test are often normal. If bile duct obstruction or
liver metastasis is present; alkaline phosphatase and bilirubin may be increased.
Serum lipase is elevated more than amylase. Hyperglycemia occurs in 50%.
Pancreas associate antigens including the monclonal antibodies CA19-9, CA50,
DU-PAN-2, SPAN-1, PCAA, CEA and pancreatic oncofetal antigen.
The most commonly used tests are ultrasound, CT and ERCP.
MALABSORPTION SYNDROME
Any condition in which there is impaired alimentary absorption of single or

multiple substances. Thus it would be perfectly reasonable to call pernicious
anemia. In which there is malabsorption of vitamin B12.
STEATORRHEA
Failure of absorption results in deficiency of other substances such as calcium,
folic acid and protein. It is the passage of excessive fat in the stools and in
moderate and severe cases they are abnormal to the necked eye? They are loose
and watery or bulky and paler than normal. In normal subjects excretion of fat in
the faeces is of the order of 2g per day, but since there may be fluctuation from
intestinal hurry, diarrhea, and intercurrent illness the daily upper limit of the
normal fat excretion is placed at 6 gram.
Greater amount than this, whether there are symptoms or not, indicates
steatrrhea.
Etiology of Malabsorption Syndrome
1. Deficiency of biliary and pancreatic secretions, liver cell jaundice and chronic
pancreatitis.
2. After gastrectomy
3. Abnormal bacterial activity in small gut e.g jejunal diverticulitis and Whipple's
disease.
4. Disease of small bowel e.g Hodgkin‟s disease, Lymphomas, Crohn's disease
and amyloidosis.
5. Defect of gut mucosa: Celiac disease
6. Small bowel resection
7. Drugs: Antibiotics e.g neomycin
8. Endocrine disease: Addison's disease, thyrotoxicosis
9. Deficiency of intestinal enzymes
10. Intestinal worms and parasites.

TABLE 6.3: THE ACCOMPANIMENTS OF STEATORRHEA
Substance malabsorbed Possible effect
1. Fat Steatorrhoea
2. Protein loss of weight
Edema
Osteoporesis
3. Water Nocturia
4. Calcium and vit. D Osteomalacia
Tetany
Secondary or tertiary
Hyperparathyroidism
5. Potassium Lassitude
Muscle weakness
Tetany
Anemia
6. Vitamin. K Bleeding tendency
7. Iron Anemia
Folic acid Glossitis and anemia
Vitamin B12 Neuropathy, anemia, glossitis
8. Other vitamins Pellagra, beriberi, dry skin
Clinical Features of Malabsorption Syndrome

Common symptoms
1. Diarrhea, steatorrhea, wasting, signs of deficiencies.

2. Attacks of abdominal pain and rumbling.
3. Anemia is due to 2 factors:
(a) Blood loss in the stool from ulceration in a distended of gut (IDA)
(b) Megaloblastic anemia due to vitamin B12 deficiency may occur. Bacterial
growth in the gut leads to binding of vitamin B12 which is not available for
absorption (Body store of Vitamin B12 are there for low.
4. Nutritional deficiencies: (a) iron, (b) folic acid (c) vitamin B12 (d) Vitamin K
Diagnosis of Malabsorption Syndrome
Suspicious should be raised when cases of

Perniciuos anemia with
Intestinal colic and distension

The diagnosis can be facilitated by the following tests
1. Intestinal function tests
2. The blood may show iron deficiency anemia or macrocytosis with

megaloblastic change in the marrow and the vitamin B12 level in the serum may
be low.
3. Occult blood may be found in the faeces
4. A blind loop is demonstrated by careful radiological examination of the small

bowel.
5. Intestinal intubation reveals bacterial contamination of the small bowel.
6 The urine may contain increased indoxyl sulphate-indican. This is a simple and
useful test for possible intestinal contamination.
Tests of Absorption
1. D-Xylose absorption
The patient fasts overnight and after emptying the bladder in the morning drinks
approximately 450 ml of water in which 25 g of xylose are dissolved. The
container should be washed out with a further 50 ml of water which are given to
the patient to drink. a further 250 ml of water are taken 1 and 2 hours later.
Urine is collected for 5 hours and xylose estimated colorimetrically.
Normal absorption is shown by the excretion of 5 g or more in 5 hours.
Falsely low values may be obtained in persons over 60 years old or those who
have a low glomerular filtration rate.
Normally the blood xylose level rises to more than 15 mg per 100 ml at 30
minutes and more than 35 mg per 100 ml at one hour after 25 g of xylose is taken
by mouth.
2. Vitamin B12 deficiency or absorption ( see schilling test)
3. Folic acid deficiency

The serum folate level can be assayed by a microbiologic technique such as that
using Lactobacillus casei
Normal 6-21 mug/ml
Possible deficiency not causing anemia 3-6mug/ml
Deficiency usually causing anemia less than 3 mug/ml
Folate deficiency can also be detected by measuring the urinary excretion of

formimino glutamic acid, FIGLU, after a loading dose of histadine. FIGLU is an
intermediate in the breakdown of histadine to glutamic acid and it is excreted in
the urine when further metabolism is blocked by folate deficiency. FIGLU can be
estimated by electrophoresis, or by a spectrophotometric method.

The patient takes 15 g of histadine hydrochloride dissolved in a glass of water
and urine is collected for 8 hours. Normal excretion of FIGLU is 17 mg or less in
the 8 hours.
4. Glucose Tolerance Test
N.B: Certain specific disroders affect both intestinal and renal epithelial
transport. In Hartnup disease there is impaired transport of neutral amino acids,
and deficiency of sme essential amino acids (especially tryptophan) may occur.
In cystinuria the basic amino acids and cystine are affected; however, there is no
associated nutritional defect despite the fact that lysine is an essential amino acid.
These disorders are investigated by examining the pattern of amino acids
excreted in the urine by chromatography.
GASTROINTESTINAL HORMONE SECRETING TUMORS

These are rare tumours, many of which arise in the pancreas. A single tumour
may secrete more than one peptide.
Gastrinoma
60% malignant
Gastrinomas are usually islet cell tumors of the pancreas. They cause type I
Zollinger-Ellison syndrome:
1. High gastric acidity
2. Recurrent peptic ulceration
3. Persistent diarrhea (some patients)
May be part of multiple endocrine adenopathy type 1
Type II Zollinger Ellison syndrome (hyperplasia) of the G cells of the gastric

antrum.
Investigation
Gastric function tests (overnight collection of gastric secretion and the
pentagastrin test) have now been largely superseded by the measurement of the
plasma gastrin.
Plasma gastrin levels may also be high in:
1. Hypercalcemia (which stimulates gastric release
2. Achlohydria (lack of inhibitory feedback to gastrin release
(a) Atrophic gastritis
(b) Pernicious anemia

Glucagonoma
60% malignant
1. Characteristic skin rash (skin biopsy shows necrosis and lysis of the epidermis
with a normal dermis.
2. Mild diabetes
3. 90% occur in women
Vipoma
Verner-Morrison syndrome) mostly malignant. These secrete vasoactive

intestinal polypeptide (VIP) and are usually islet cell tumors of the pancreas
2. Continuos watery diarrhea
3. Hypokalemia
4. Dehydration
5. 75% occur in men
MID SMALL BOWEL FUNCTION
The Investigation of FatT Absorption:

Steatorrhea or Excess stool fat is absolute evidence of malabsorption when it is
present. For an adult eating a usual diet with a daily intake of 100 gm, a fecal fat
loss of >17 mEq/day is abnormal. Accuracy of stool collection during a period of
typical daily routine is more important than strict balance studies. It is feasible
and advantageous to measure fecal fat at 3 or 4 day collection is usually
adequate.
Normal fecal fat 15-22 of dry weight (>25% suggests Steatorrhea)
Normal fat balance (on 100 g fat diet) excretion of > 6g/24 hours suggest
steatorrhea.
Microscopical Examination of Stool
Undigested food fragments: Hypermotility

Short intestin (gastrocolic fistula)
Greasy stool: in Jaundice

Pancreatic Carcinoma
Primary Biliary cirrhosis
Fat globules with undigested meat fibers: suggest of pancreatic insufficiency
Parasites for Ova and cysts

REVIEW QUESTIONS
1. Plasma amylase activity may be considered increased in patients

with: A. T
A. Acute pancreatitis B. B
B. Perforated peptic ulcer C. T
C. Acute parotitis D. F
D. Carcinoma of the pancreas E. F
E. Malignant hyperpyrexia
2. The standard xylose absorption test:
A. Require a complete 24-hr-urine collection A. F
B. Depends, for a normal result, on intestinal, hepatic and renal B. F
function all being normal C. T
C. Gives low results if there is bacterial colonization of the small D. F
intestine E. F
D. Is usually abnormal in patients with malabsorption due to
pancreatic disease
E. Is unsuitable for monitoring the response to a gluten free diet.
3. Malabsorption of fat occurs in patients with:
A. Zollinger-Ellison syndrome A. T
B. Bacterial colonization of the upper small intestine B. T
C. Biliary cirrhosis C. T
D. Crhon‟s disease affecting the terminal ileum D. T
E. Abetalipoproteimenmia E. T
4. In patients with chronic pancreatitis giving rise to steatorrhea
A. The urinary amylase:creatinine clearance ratio is often considerably A. F
increased B. F
B. The oral glucose tolerance test usually shows a “flat” response C. F
C. Secretin injections are used to test for reduction in the enzyme D. T
activity of duodenal aspirate E. T
D. Disaccharide tolerance tests are not indicated
E. Plasma (calcium) and (phosphate) are often reduced, and alkaline
phosphatase activity increased.
5. A normal xylose absorption test depends on:
A. Normal intestinal absorption alone A. F
B. Both normal intestinal absorption and pancreatic function B. F
C. Normal intestinal absorption, pancreatic and renal function C. F
D. Both normal intestinal and renal function D. T
E. Normal intestinal absorption, pancreatic and hepatic function E. F
6. Gastrin
A. Is released in response to reduction in gastric acidity A. T
B. Is released in response to hypoglycemia B. F
C. Is used, in the form of pentagastrin, to rest maximal acid production C. T
by the stomach D. T
D. Is present in plasma is greately increased concentration in the
Zollinger-Ellison syndrome.
Which of the following condition is most often associated with the 7. B
various chemical abnormalities? 8. C
A. - cell adenoma of the pancreas 9. D
B. Bronchial carcinoid 10. F
C. Acute pancreatitis 11. C

D. Chronic pancreatitis
E. Acute parotitis
F. Carcinoma of the ampulla of Vater
7. Increase urinary excretion of 5-hydroxyindole metabolites

8. Plasma (calcium), 6mg/dl refrence values, 8.9-10.4mg/dl
9. Plasma (glucose), 182 mg/dl, 2 hr after a 75 g oral glucose load
10. Plasma alkaline phosphatase activity, 300 u/l ( refrence values 38-
126 u/l)
11. Methemalbuminemia
12. The pentagastrin test is used: A. T
A. To investigate suspected Zollinger-Ellison syndrome B. T
B. To help establish a diagnosis of pernicious anemia C. F
C. To differentiate between benign and malignant gastric ulcers D. T
D. To differentiate between giant hypertrophic gastritis and
hypersecretory gastropathy
13. Malabsorption of fat occurs in patients with: A. T
A. Zollinger-Ellison syndrome B. F
B. Carcinoid tumors C. T
C. Biliary cirrhosis D. T
D. Crohn‟s disease affecting the terminal ileum E. F
E. Hartnup disease
14. What is histalog?
It is a histamine, 3-beta-aminoethyl pyrazole dihydrochloric acid (betazole),

and it is a satisfactory substitute for histamine for gastric secretory studies.
15. Do patients with pernicious anemia and other patients with achlorhydria
have high, low, or normal serum gastrin levels?
Their serum gastrin levels are high. This apparently is because secretion of
HCL inhibits secretion of gastrin.
16. What is the normal basal gastric secretory volume?
It is 50 to 100 ml /h

LIVER 7
The liver plays an important role in many metabolic processes. The liver is the
center of metabolic activity for carbohydrate, protein, and lipids. It exchanges
substances with the plasma adding some for the distribution in the body and
removing others, often with subsequent metabolism. Bile is formed by the liver,
and it is the organ responsible for the detoxication of many drugs and
carcinogens.
Structure of the liver

Only about 60 % of the cells in the liver are hepatocytes, the remainder are
endothelial (Kupffer) cell lining the hepatic sinusoids (30%) and vascular and
supporting tissue cells (10%).
The functional unit of each liver acinus consist of the portal tract, surrounded by
radiating cords of hepatocytes. Blood enters the acinus via the portal tract and
passes along the sinusoids towards the centeral vein. Heptocytes in the
periportal area zone1, receive relatively well oxygenated blood, where as the
hepatocytes surrounding the centeral vein, zone3, receive blood that lost much of
its oxygen and exchanged other substances wih cells of zone 1 and 2.Cell in zone
3 are the most susceptible to anoxia and to injury by a wide range of toxic
substances.
Cells in zone 1 have relatively high concentrations of aminotransferase and
alkine phosphtase while cells in zone 3 are relatively deficient in these enzymes.
Differences in localization of enzymes help to explain why some patients with liver
disease may have normal enzyme activities in the plasma.
The Liver Function

The principal functions of liver may be summarized as follows:.
(i) Carbohydrate Metobolism :Sugars, and carbon residues from protein and
fat are converted to glycogen. Glycogen is stored as a carbohydrate reserve,
being to glucose.
(ii) Protein Synthesis: Many of the plasma proteins, including special carrier
proteins and most of the coagulation factors, but with the important exception
of the immunoglobins, are synthesised in hepatic cells.
(iii) Lipid metabolism – Synthesis of almost all lipoproteins, phospholipids,
cholesterol and endogenous triglycreride. Occurs in the liver and the
breakdown products of cholesterol are excreted in bile. Fatty acids reaching
the liver from fat stores are metabolised in the tricarboxylic acid cycle. Any
excess is incomporated into endogenous trigyceride, or is converted into
ketones.

(iv) Excretion and Detoxication:- the parenchyma cells of the liver, which
comprise 60% of its mass, are responsible for the conjugation of bilirubin and
for its excretion into the billiary tract. Bile pigments and cholesterol are
excreted in the bile.
Many drugs are detoxicated by liver and some are excreted in bile. Detoxication
occurs through the microsomal drug metobolizing system of the liver which is
induced by many drugs such as phenobarbitone.
Ammonia, derived from amino acid metabolism or produced in the bowel by
bacteria, is converted to urea and so rendered non-toxic.
Steroid hormones are inactivated by conjugation with gucuronate and sulphate
in the liver and are excreted in the urine. Many of the clinical findings of liver
failure, such as gynaencomastia, testicular atrophy, spider naevi and liver palms
are though to be due to failure to detoxicate steroids.
Storage Function: In addition to glycogen, vitamin A, D and B12 are stored in the
liver.and it is a major site of iron storage.
Bilirubin Metabolism
The catabolism of heme yield bile pigements, sources include the Hb of
degnerating RBCs, RBC precursors in the marrow, and heme proteins of liver
and other tissues. There is no evidence for the direct synthesis of bilirubin from
heme precursors. Bilirubin a pigmental organic closely related to porphyrias and
other tetrapyrolles, is an insoluble waste product. To be excreted, it must be
made water soluble; this transformation is the overall purpose of bilirubin
metabolism, which takes place in 5 major steps:
1. Formation: About 250 to 350 mg of bilirubin forms daily; 70 to 80% is derived
from the breakdown of senescent RBC. The remaining 20 to 30% the early-
labeled bilirubin comes from other heme protein located primarily in the bone
marrow and liver. The heme moiety of Hb is degraded to iron and the
intermediate product biliveridin by the enzyme heme oxygenase. Biliveridin is
converted to bilirubin via another enzyme biliveridin reductase.
2. Plasma transport: Because of internal hydrogen bonding, bilirubin is not water
soluble. Unconjugated (indiret-reacting) bilirubin is therefore transported in the
plasma bound to albumin and cannot pass the glomerular membrane; thus it
does not appear in urine.
3. Hepatic uptake:
The details of bilirubin uptake by the liver and the importance of intracellular
binding proteins (e.g ligandin or gama protein) are unclear. Bilirubin uptake is
rapid and probably involves active transport but does not include uptake of the
attached serum albumin.
4. Conjugation: Free bilirubin is concentrated in the liver, then conjugated with
glucuronic acid to form bilirubin diglucuronic or conjugated "direct-reacting"
bilirubin. This reaction, catalyzed by the microsomal enzyme glucuronyl
transferase, renders the pigment water soluble. Undersome circumstances,
glucuronyl transferase forms only bilirubin monoglucuronide, with the second
glucuronic acid moiety being added at the bile canaliculus via a different enzyme
system, but this reaction is not widely considered physiologic.
5. Biliary excretion: Conjugated bilirubin is secreted into the bile canaliculus with
other bile constituents. Other organic anions or drugs can affect this complex
process. In the gut, bacterial flora deconjugates and reduces the pigement to
various compounds called stercobilinogens. Most are excreted in the feces and
lend the stool its brown colour; substantial amounts are absrobed and reexcreted
in the bile, and small amounts reach the urine as urobilinogen. The kidney can

also excrete bilirubin diglucurnide but not unconjugated bilirubin. This explains
the dark urine typical of hepatocellular or cholestatic jaundice, whereas urinary
bile is absent in hemolytic jaundice.
Abnormalities at any of the above steps can result in jaundice. Increased
formation, impaired hepatic uptake, or decreased conjugation all cause
unconjugated hyperbilirubinemia. Impaired biliary excretion produces
conjugated hyperbilirubinemia. In practice, hepatic disease and biliary
obstruction create multiple defects, resulting in a mixed hyperbilirubinemia.
Figure : Metabolism of bilirubin

JAUNDICE
A yellowish discoloration of the skin, sclerae, and other tissues due to excess of
circulating bilirubin.
Mild jaundice, best seen by examining the sclerae in natural light, is usually
detectable when serum bilirubin reaches 2 to 2.5 mg/dl.
Three main varities are usually recognized; these are:
1. Hemolytic jaundice 2. Liver cell jaundice 3.Obstructive jaundice
Classification of Jaundice
No single classification is satisfactory for all purposes; Howerever Jaundice
can be clssified acocording to:
 Anatomical site of pathological lesion that produce the jaundice e.g.
prehepatice. Hepatic and posthepatic.
 Type of disorder: hemolytic, hepatocellular and cholestatic jaundice.
Anatomical
Site of Type Typical disease Cause
lesion.
Prehapatic Hemolytic Congenital Increased destruction of
spherocytosis Rbcs leading to excess
production of bilirubin.
Hepatic Hepatocellular Icterus Conjugation defect

neonatorum paranchymal cell damage.
infective hepatitis Fibrous obstruction to
Cholestatic biliary cirrhosis biliary out-flow.
Post hepatic Cholestatic Carcinoma of the Mechanical obstruction of

Head of the the bile duct
pancrease.
Unconjugated Hyperbilirubinemia:
1. Hemolysis
2. Gilbert's syndrome: Mild unconjugated hyperbilirubinemia is the only
significant abnormality, which is important clinically only because it is often
misdiagnosed as chronic hepatitis. Its pathogenesis is uncertain. These appear to
be complex defects in the hepatic uptake of bilirubin, which usually flactuates
between 2 and 5 mg/dl and tends to increase with fasting and other stress. In
addition, glucuronyl transferase activity is low (may be related to type II crigler-
Najjer syndrome).
Gilbert's syndrome can be easily differentiated from hepatitis by normal ranges
of liver function tests, absence of urinary bile, and characteristic bilirubin
fractionation. Hemolysis is differentiated by the absence of anemia or
reticulocytosis. Liver histology is normal.
3. Crigler-Najjar syndrome: A rare inherited disorder associated with glucuronyl
transferase deficiency. It occurs in 2 forms: patients with autosomal recessive
type I (complete) diseases have severe hyperbilirubinemia and usually die of
kernicterus by age 1 year. Patients with autosomal dominant type II (partial)
disease have less severe hyperbilirubinemia (<20 mg/dl) and usually survive
into adulthood without neurologic damage.

Obstructive Jaundice
Obstruction to the outflow of bile from the biliary tract leads to retention of bile
pigment, largely conjugated bilirubin in the blood.
Causes
Intrahepatic:
A. Acute:
1. Viral hepatitis
2. Drugs: chloropromazine, methyltestosterone, oral contraceptive.
3. Last three months of pregnancy
4. Intrahepatic neoplasm and lymphoma (HD)
B. Chronic:
1. Primary biliary cirrhosis
2. Drugs
3. In infancy- congenital obliteration of the bile duct.
4. Of unknown cause
5. In ulcerative colitis
Extrahepatic:
1. Neoplasm: ampula of vater/head of pancreas/bile duct/Gallbladder
2. Gall stone in common bile duct
3. Stricture in common bile duct
4. Rarely-chronic pancreatitis and parasites
Clinical Picture
1. Jaundice
2. Hepatomegaly and splenomegaly
3. Tenderness
4. Skin excoriation with pruritus
5. The urine is dark (because of bile pigment)
6. The stools are pale because they contain no bile pigment.
Diagnosis
History and physical examination
Jaundice with pale stools and dark urine and pruritis.
Raised serum bilirubin with a high percentage of conjugated bilirubin and a
raised serum alkaline phosphatase and some times a raised serum cholesterol.
The elevation of the serum lipids seen in obstructive jaundice may be
associated with the presence of a specific lipoprotein (Lipoprotein X).
Investigations
1. Liver function tests and serum amylase estimation. The serum amylase may be
elevated if there is pancreatic duct obstruction by a neoplasm or in pancreatitis.
2. Test for occult blood in the feaces, possibly indicating intestinal cancer.
3. Abdominal ultrasound to exclude gall stone and pancreatic tumor.
4. Percutaneous needle biopsy of liver.
5. ERC (Endoscopic Retrograde Cholangiography)
6. An ACTH or corticosteroid test may help to differentiate intrahepatic
obstruction due to hepatitis from other types of intrahepatic and extrahepatic
obstruction.

Liver Cell Damage
Damage to liver cells interfers with uptake of bilirubin. Its conjugation and
excretion into the biliary tract.
Causes
Acute
1. Viral hepatitis
2. Drug hepatitis.
3. Liver cell poison- Carbon tetrachloride, alcohol
4. Spirochaetal: weil's disease, canicola fever
5. Infectious mononucleousis
Chronic
Cirrhosis with liver cell failure
Congenital hyperbilirubinuria.
Diagnosis
History and examination very important
Jaundice
Dark urine and some pallor of the faeces but without persistent pruritus,
suggestive liver cell disease.
LFT
Increase of bilirubin and levels of SGOT, SGPT
Serum albumin decreased
Globulin level increased (due to Gama and Beta fractions)
1. Blood Investigations
Leukopenia : in viral hepatitis

Leukocytosis: In Weil's disease, alcoholic hepatitis and hepatic necrosis
Serum tests for Weil's disease and infectious mononucleousis
Identification of Australia antigen is of diagnostic help in serum hepatitis
Liver biopsy: Prothrombin time should be normal
3. Vitamin B12 and serum Fe levels raised in liver cell disease.
TABLE 7.1: THE THREE MAIN VARITIES OF JAUNDICE

FEATURE OBSTRUCTIVE LIVER CELL HEMOLYTIC
Colour Yellow-green Orange-yellow Pale yellow
Pruritus ++ and persist + not persist Normal
Urine Dark (conjugated) Dark (conjugated) Normal or dark
Faeces Pale Pale
N
Liver size Increase I-N–D Spleen +
Other sign GB palpable spleen +
Positive LFT Increase conjugated bilirubin Increase conjugated Unconjugated

Increase Alkaline phosphatas High transaminase
Raised cholesterol ++ Flocculation test
Raised alpha globulin
Raised beta globulin
Positive lipoprotein X
Coomb's test
Special test: Occult blood in stool Liver biopsy Blood picture Saline
Barium meal fragil
Liver biopsy Vitamin B12 Haptoglobin
Cholangiography Serum Fe LE cells
Ultrasound Hb- electrophoresis
LABORATORY EVALAUTION OF LIVER
The liver is a complex organ with interdependent metabolic, excretory and

defense functions.
Use of several screening tests improves the detection of hepatobiliary
abnormalities helps differentiate the basis for clinically suspected disease, and
determines the severity of liver disease.
Liver Function Tests (LFTs)

A. Serum
1. Bilirubin: Hyperbilirubinuria results from increased bilirubin production;
decreased liver uptake and/or conjugation or decreased biliary excretion. Defects
in bilirubin production, hepatic uptake, or conjugation cause unconjugated
bilirubin in serum to increase; the last elevates conjugated bilirubin in serum and
allows bile to appear in urine.
Serum bilirubin may not be a particularly sensitive index for liver disease or
prognosis, but it is established and necessary.
Total bilirubin is normally 1 mg/dl. The only value of fractioning bilirubin into
the total and direct-reacting components is to determine unconjugated
hyperbilirubinemia.
2. Alkaline Phosphatases (AP)

AP is a group of isoenzyme with a common capacity to hydrolyze organic
phosphatase ester bonds in an alkaline medium, generating an organic radical
and an inorganic phosphate.

Alkaline phosphatase in serum normally comes from the liver and bone and,
during pregnancy and from the placenta. It is also present in some tumors (e.g
Bronchogenic carcinoma).
Bone growth in children causes an age dependent rise in normal values
particularly in infants of <2 years. Thereafter, the alkaline phosphatase activity
declines, reaching normal adult levels after a spurt during adolescent growth. It
is slightly increased in older people.
During pregnancy, serum levels rise two-four-fold by the 9th month and then
return to normal by 21 days postpartum.
Alkaline phosphatase increases markedly in diseases that impair bile formation
(cholestasis) and to a lesser extent in hepatocellular disease. Values in cholestasis,
whether from intrahepatic causes (primary biliary cirrhosis, drug-induced liver
disease, liver transplantation rejection) or graft vs-host (GvH) disease, will be
similarly elevated and less distinguishable from extrahepatic causes (duct
obstruction from stricture, stone, or tumor), all rising some fourfold.
Isolated elevation (other LFT are normal) occur in granulomatous or focal liver
disease e.g abscess, neoplastic infiltration, or partial bile duct obstruction.
For Hodgkin's lymphoma, the cause of the isolated alkaline phosphatase
elevation is unknown.
3. Serum Protein: The liver synthesizes most proteins in serum: alpha and beta-
globulin, and clotting factors (but not gama-globulin, which is produced by B-
lymphocytes).
Hepatocytes also make specific proteins: alpha1antitrypsin (AAT, which is
absent, in ATT deficiency). Ceruloplasmin reduced in Wilson's disease),
respectively, in hemochromatosis. These and some other serum proteins increase
in response to tissue injury e.g. inflammation
4. Serum Albumin: The main determinant of plasma oncotic pressure transports

numerous substances (e.g unconjugated bilirubin). Serum bilirubin is decreased
in chronic liver disease (e.g cirrhosis, ascites) because of the increased volume of
distribution. Alcohlism and malnutrition also depress albumin synthesis.
Hypoalbuminemia also results from excess albumin loss from the kidney
(nephrotic syndrome), gut (protein-losing gastroenteropathies) and skin (burns).
5. The Alanine Transaminase (ALT-formerly SGPT) is found primarily in liver

cells and therefore has greater specificity for liver disease. In most liver diseases,
the AST increase is less than that of ALT (AST/ALT ratio <1), except in alcohol-
related liver injury where the ratio frequently is >2 (the basis for this is the
greater need of pyridoxical 5' phosphate as a cofactor for ALT; this cofactor is
deficient in the alcoholic, limiting the rise of ALT.
TRANSAMINASE IN DISEASES OF THE LIVER AND BILIARY DUCT
1. Acute viral hepatitis: in the first week of icteric phase, increase of GPT (20-100
times) and GOT of 10-100 times.
2. Cholestatic hepatitis
3. Necrotic hepatitis: GOT/GPT is >0.7
4. Acute alcoholic hepatitis: Increase of GT, AP and Bilirubin

GOT/GPT is >2 and GT GT/GOT is >2
5. Right heart failure and Respiratory insufficiency: GOT/GPT is about 1
6. Chronic active hepatitis: increase of LDH, GGT and Transaminase.
GOT/GPT >1 and GGT/GOT is 1-3.
7. Liver cirrhosis: GOT/GPT is normal or >1
8. Alcoholic cirrhosis: Increase of GGT, Transaminase and IgA, GT GT/GOT is
>2
9. Posthepatic cirrhosis: Increase of Transaminase (5times), GGT and IgG.
GGT/GOT <2.
10. Biliary cirrhosis: GT GT/GOT is >6, Increase of IgM and Mitochondrial AB
(+)
11. Liver cirrhosis: increase of LDH, Gamma GT and Transaminase.
12. Obstructive jaundice: Increase of Transaminase (5-20 times). GOT/GPT <1
B. URINE
1. Urine Bilirubin :( normally absent) can be detected at the bedside with a

commercial urine test strip. In unconjugated hyperbilirubinemia, bilirubinuria is
also absent; its presence confirms that any raised plasma levels are from
conjugated hyperbilirubinemia. An early sign of hepatobiliary disease can be
bilirubinuria, which develops in acute viral hepatitis even before jaundice
appears.
Urobilinogen is normally present in trace amount (17 umol/l) in the urine and
also can be assessed by commercial test strips. This intestinal metabolite of
bilirubin becomes elevated from hemolysis or mildly impaired hepatic uptake
and excretion.
Urobilinogen is too nonspecific and difficult to interpret.
c. OTHERS
1. Gamma-Glutamyl Transferase (GGT)

GGT is an enzyme present in the liver, pancreas and kidney that transfers the
gamma-glutamyl group from one peptide to another peptide or to an L-amino
acid.
Levels of GGT are elevated in hepatobiliary and pancreatic disease that obstruct
the common bile duct but are normal in pregnancy and bone disease. GGT levels
parallel those of alkaline phosphatase in cholestatic conditions.
Because it is not physiologically elevated in pregnancy or childhood, GGT has a
role in detecting hepatobiliary disease.
Drugs and alcohol injection, which induce microsomal enzymes, also elevate
GGT; alone, it is a poor marker for alcolholic liver disease. Combined with
transaminases, the detection of alcohol abuse becomes more secure.
2. Prothrombin Time (PT): PT involves the interactions of fibrinogen,

prothrombin and factors V, VII, and X which the liver synthesis. Vitamin K is
necessary for prothrombin and factors VII and X production in an active form.
Vitamin K deficiencies result from either inadequate intake or malabsorption.
Malabsorption of vitamin K as a cause of a prolonged PT can be shown by giving
it parentrally (eg. 10 mg s.c) and finding a significant improvement 24 to-48

hours later when the PT is repeated. But it fails to revert to normal in response to
parenteral vitamin K in some diseases for example in patients with alcoholic
cirrhosis.
In acute viral or toxic hepatitis, an abnormal PT prolonged> 5 second above
control is an early indicator for fulminant hepatic failure.
3. Serum Immunoglobulings
Rise in most cases of chronic liver disease when the reticuloendothelial system is
defective or bypassed by vascular shunts. The inability to clear portal venous
blood of transient bacteremia from normal colonic flora results in chronic
antigenic stimulation of the extrahepatic lymphoid tissue and
hypergammaglobulinemia. Serum globulin levels rise slightly in acute hepatitis
and more markedly in chronic active hepatitis, particularly that of the
autoimmune variety. IgM is quite elevated in primary biliary cirrhosis (PBC),
IgA in alcoholic liver disease and IgG in chronic active hepatitis.
4. Bromsulphthalein (BSP) Excretion: It is a very sensitive test of liver disease,

reflux of BSP from the liver cell into the circulation 90 minutes after the injection
is diagnostic of Dubin-johnson syndrome.
5. Serum Bile Acid: It is very sensitive test of hepatobiliary disease especially

when measured 2 hours after a meal. Technically it is difficult to measure and it
is not generally available.
6. Hepatitis B antigens: For the diagnosis of hepatitis B infection
7. Antibody Titers
a. Mitochondrial Antibodies:
Are positive, usually in high titers in >95% of patients with PBC, these
heterogenous Abs are also present in 30% of patients, with "autoimmune"
chronic active hepatitis (HBs Ag negative) and in some cases of connective tissue
disease.
b. Antinuclear factor in chronic active hepatitis
c. Smooth muscle antibody: These have been found in the serum of about50%
of patients with chronic active hepatitis. In most of these patients LE cells test
is also positive.
8. Full blood count and blood film: May suggest

a. Liver disease (Target cells)
b. Alcohol abuse (high mean corposcular volume)
c. Hemolysis
d. Tests for Specific Disorders Affecting the Liver
1. ALPHA-FETOPROTEIN (AFP): Synthesized by fetal liver, is normally

elevated in the mother and newborn. By 1 year of age, infants achieve normal
adult values (>20 ng/ml). Marked elevations develop in primary hepatocellular
carcinoma. AFP is a useful screening test, since few other conditions cause >400
ng/ml. These include embryonic teratocarcinoma, hepatoblastomas, infrequent
hepatic metastasis from the GIT and perheps some cholangiocarcinoma. In
fulminant hepatitis, AFP can be >1000 ng/ml; lesser elevations (100-400 ng/ml)
occur in acute and chronic hepatitis.

2. Wilson‟s disease: Serum copper and ceruloplasmin and urinary copper
3. Hemochromatosis: Serum iron and total iron binding capacity and serum
ferritin
4. Alpha-1-antitrypsin deficiency: Serum alph-1-antitrypsin
HEPATITIS
An inflammatory process in the liver characterized by diffuse or patchy
hepatocellular necrosis affecting all acini.
The major causes of hepatitis are specific hepatitis , viruses, alcohol and drugs.
Less common etiologies include other viruses (infectious mononucleosis, yellow
fever and cytomegalovirus (CMV).
Parasites infections (e.g schistosomiasis, malaria and amoebiasis) affect the liver
but do not cause a true hepatitis.
Pyogenic infections and abscesses are also generally considered to be separate
problems. Involvement of the liver with TB and other granulomatous
infiltrations is some times called "granulomatous hepatitis" but produces clinical
biochemical and histological features different from that diffuse hepatitis.
Causes of hepatitis
1) Viral infection
 Hepatitis A Virus.
 Hepatitis B Virus.
 Hepatitis C Virus.
 Hepatitis D Virus.
 Hepatitis E Virus
 Hepatitis F Virus
 Hepititis G Virus.
 Hepatitis TT Virus.
 EBV, CMV, Herpes simplex.
2) Autoimmune disorders.
 Chronic autoimmunne hepatitis.
3)Miscellaneous
 Wilsons disease
 Alfa1 antitrypsin deficiency.
ACUTE VIRAL HEPATITIS

Diffuse hepatocellular inflammatory disease caused by specific hepatotrophic
viruses.
This is a common, important group of world wide diseases share clinical,
biochemical and morphologic features, but are due to different viruses.

Etiology
Many viruses have been identified as causal agents of hepatitis in humans. Two
viruses (HAV and HEV) may be classified as waterborne or foodborne, and are
transmitted by the oral route.
Three other viruses (HBV, HCV and HDV) are bloodborne. These viruses have a
life cycle in the blood and are transmitted percutaneously by blood or blood
products and may also be transmitted with body fluids.
Other virus: CMV and EBV
HEPATITIS A VIRUS
A small virus of about 27 m.m in diameter classified as enterovirus genus with

the picornaviridae and it has been classified as enterovirus.
Affect all age groups.
Hepatitis A virus is excreted in the faeces for 1 to 2 weeks before the onset of the
disease; shedding of the virus is relatively brief and may have ceased by the time
the patient seeks medical attention.
Serum antibody of the IgM class against Hepatitis A is usually detected at the
onset of illness and persists for about 10 weeks.
This assay is the test of choice for the diagnosis of acute hepatitis A.
Serum antibody IgG class appears more slowly, persists for many years and
indicates immunity to the disease. The IgM and IgG are carried out by the
technique of enzyme- linked immunosorbent assay (ELIZA).
HEPATITIS B VIRUS (HBV)
The consequence of Hepatitis B infections is extremely variable. The incubation

period may range between 6 weeks and 6 months. The infection may be
characterized by:
1. An acute illness with jaundice followed by recovery
2. A subclinical infection followed by recovery
3. An acute illness that progress to chronic active hepatitis
4. A subclinical infection followed by chronic active hepatitis
5. A fulminant fatal disease.
Hepatitis B is the most thoroughly characterized and complex agent. The
infective ("Dane") particle consist of an inner core plus an outer surface coat The
former contain circular double stranded DNA and DNA polymerase, and it
replicates within the nuclei of infected hepatocytes. Surface coat is added in
axcess; it can be detected in serum by immunologic means as hepatitis B surface
Ag.
At least 4 distinct Ag-Ab systems are

intimately related to the HBV:
1. HBV surface Ag (HBs Ag, Australia Ag)
Is associated with the viral surface coat;
its presence in serum usually provides the
first evidence of acute B infection and
implies infectivity of the blood.
(several antigenic subtypes are of
epidemiologic interest but little
clinical significance.)
HBsAg characteristically appears during the incubation period, usually 1-6
weeks before clinical or biochemical illness develops and disappears during
convalescence.
The corresponding Ab (Anti-HBs) appear only weeks or months later after
clinical recovery, and usually persist for life; thus its detection indicates past HBV
infection and anti HBs does not develop; these patients usually develop chronic
hepatitis or become asymptomatic carrier of the virus.
2. Core Ag (HBc Ag) is associated with the viral inner core. It can be found in
infected liver cells but is not detectable in serum except by special techniques that
disrupt the Dane particle. Ab to the (anti-HBc) generally appears at the onset of
clinical illness, with gradually distinguishing titre thereafter, usually for years or
life.
In chronic situations, anti-HBc is mainly of the IgG class, whereas in acute
infection, IgM anti-HBc predominates.
3. The e Ag (HBe Ag) appears to be a peptide derived from the viral Core. Found
only in HBs Ag-positive serum, it tends to parallel the production of DNA
polymerase by the virus. Its presence therefore reflects more active viral
replication and is generally associated with greater infectivity of the blood and a
likelihood of progression to chronic liver disease. In contrast, presence of the
corresponding Ab (anti-HBe) points to relatively lower infectivity and usually
pretends a benign outcome.
4. The hepatitis D virus (HDV, delta agent) is a unique, defective RNA virus that
can replicate only in the presence of HBV, never alone.
Symptoms and Signs

Varies from minor flu to fulminant, fatal liver failure dependent on the patient;
immune response.
The Prodromal Phase: begin suddenly with anorexia, malaise, nausea, vomiting
and fever.
Distaste for cigarettes.
Urticaria eruptions and arthralgias occasionally.
Icteric Phase:
After 3-10 days dark urine appears, followed by jaundice. Systemic symptoms
typically regress at this point and the patient feels better despite worsening
jaundice. Jaundice usually peaks within 1 to 2 weeks then fades during 2 to 4
weeks, recovery phase.
PHYSICAL SIGNS:
Jaundice, Hepatomegaly, mild splenomegaly
Diagnosis
a. General
1. Clinical - symptom and sign
2. ALT transaminase is typically correlates with clinical severity. The ALT is
typically higher than AST.
3. Urinary bile
4. Serum bilirubin
5. Alkaline phosphatase increased
6. Prothrombin time prolonged
7. Leukopenia with atypical lymphocytosis.

b. Specific:
1. Liver biopsy is not usually needed but should be considered if the diagnosis is
uncertain.
2. HBs Ag, HBc Ag. Anti-HBc in acute HBV
3. HBV is specifically diagnosed by identifying HBsAg in serum with or without
concomitant anti-HBc.
4. Failure to detect HBs Ag does not entirely exclude HBV
5. In such cases the isolated presence of anti-HBc of the IgM class may establish
the diagnosis.
6. Anti-HBe and Anti-HBs after 2-6 months (positive)
7. HBs Ag and HBe Ag more than 12 months positive (posibility of chronic)
Hepatitis A Hepatitis B
Incubation period about 30 days about 100 days
Route of infection Fecal- oral Blood,sexual route
Usual onset Abrupt & febrile Insidious, usually afebrile
Duration of jaundice shorter longer
Abnormal LFT preceded by often preceded by

symptoms symptoms several days
several days
HB Ag in blood more often found and
less often found Patient blood highly
infectious
HEPATITIS C
The hepatitis C virus is now thought to be responsible for the majority of cases of
parentally transmitted non A, non B Hepatitis and for 20 to 50% of cases sporadic
viral hepatitis in the united state.
The acute phase of hepatitis C is usually mild, and the patient is often antiietric.
Clinically, the illness is indistinguishable from other forms of viral hepatitis. The
symptoms and signs of hepatitis C infection, although non-specific, include
fatigue, anorexia, nausea, jaundice, fever and tender hepatomegaly. Elevated
ALT and or antibody to hepatitis B Core antigen (anti HBc Ag).
By methods of genetic engineering reagents were developed using ELISA
technique and were able to detect HCV antibodies in the sera of patient or
donors.
RIBA-1 recombinant immunoblot assay is suggests to have improve specificity
compared with ELISA-1.
With first generation testing, HCV antibodies are usually detectable in about 15
weeks (range 10-52 weeks) following acute infection.
The ELISA and RIBA tests detect only the presence of antibodies to HCV
antigens. The detection of serum or liver HCV RNA using polymerase chain
reaction (PCR) techniques offers advantages on both fronts. The PCR technique is
currently the most sensitive method of detecting HCV RNA.

THE HEPATITIS DELTA VIRUS
The hepatitis Delta virus (HDV) is unique among virus-like agent. Infection with
HDV, therefore, may occur in patients with acute or chronic HBV infections and
in the latter is often associated with severe and progressive liver disease,
including chronic active hepatitis and cirrhosis. HDV has also been implicated in
cases of fulminant hepatitis.
The hepatitis Delta agent consists of a 37 mm particle resembling a large HBs Ag
spherical particle and sharing HBsAg coat and antigenic specificities of the strain
of HBV that is also present. Delta antigen can be detected in the nuclei of HBV-
infected hepatocytes during the late incubation period and early acute phase of
infection.
HEPATITIS E VIRUS
Hepatitis e virus is the proposed name for the agent or groups of serologically-
related viruses that cause entrically transmitted nonA-non-B (ET-NANB)
hepatitis.
The symptoms and physical finding are similar to those for hospitalized patients
with icteric HAV or HBV. Followings an incubation period of 40 days and a
prodrome of 1-10 days, symptoms of nausea, vomiting, abdominal pain, pruritus
and joint pain. a rash and diarrhea are unusual. Most people have fever and
hepatomegaly. Bilirubin levels ranges 2 to 22 mg/dl, transaminase are increased.
The most common cause of death was bleeding.
ET-NANB hepatitis should be considered in any person who resides in an area
where HAV is endemic or who has travelled to such an area, if that individual
develops an HAV-like illness, a cholestatic form of liver disease, or fulminant
hepatitis during pregnancy.
Exclusion of Hepatitis A and B infection is essential, thus, IGM anti-HAV,

HBsAg and IGM should not be present in the serum specimen.
Immune elctronmicroscopy, or solid phase modification of the technique, remain
the most useful test for diagnosis of ET-NANB hepatitis at this time.
Recently an ELISA assay as well as westernblot assay and fluorescent antibody
blocking assay were developed for the serological diagnosis of anti E IgM and
IgG antibodies.
CHRONIC HEPATITIS
A spectrum of disorders merging between acute hepatitis and cirrhosis.
Hepatitis lasting 6 months is generally defined as "Chronic" though this is
arbitrary.
Chronic classified as chronic persistent or chronic active forms.
CHRONIC PERSISTENT HEPATITIS

This follows typical acute hepatitis
Persistently high aminotransferase values with vague or no symptoms are
characteristic.
The diagnosis depends on needle biopsy, which shows portal mononuclear
infiltrate without significant fibrosis.
Recovery is usual, though the disorder may persist for years.

CHRONIC ACTIVE HEPATITIS
More common in female than in male
Pathology: The liver is enlarged in the early stages and the disease progress it
shrinks, and becomes coarsely cirrhotic.
Microscopically:
 Liver cell injury (active phase)
 Swollen liver cells with hyaline degneration of the portal tracts are infiltrate by
lymphocytes and plasma cells.
 Piecemeal necrosis.
Clinical Picture:
Young, icteric female with
 Hepatosplenomegaly
 Cutaneous stigmata of liver disease
 Amenorrhea
 Pyrexia and jaundice
Other organs, involved leading to the following manifestations:
 Arthralgia, and arthritis
 Skin rash
 LE cells in blood
 Renal disease: nephritis, UTI, renal tubular acidosis.
 Ulcerative colitis
 Pneumonia, pleurisy and pericarditis
 Diffuse pulmonary fibrosis, pulmonary hypertension
 Hemolyic anemia with coomb's test.
 Hashimoto's disease, DM, sjogern's syndrome.
Diagnosis
1. Liver Function Test

 Moderate (Jaundice) raised bilirubin
 Raised positive Flocculation test
 Increase Transaminase
2. SERUM REACTION
 Positive ANF (Antinuclear factor)
 Positive rheumatoid Factor
 Serum against smooth muscle (SMA)
 Coomb's test may be positive
 LE cells may be positive
 Liver biopsy
CIRRHOSIS OF LIVER
Cirrhosis is a disease in which the following histological features are present:
1. Fibrosis
2. A loss of normal hepatic architecture due to the formation of regeneration
nodules.
3. Evidence of liver cell damage.
Types of cirrhosis: 3 main types.

1. Micronodular: This shows fine thombnail appearance of the liver which is
often enlarged and in which histologically there is a formation of fine uniform
regeneration nodules of about 5mm in size.
2. Macronodular cirrhosis: a coarse, irregular surface is apparent. The liver is
often small and regeneration nodules are varying sizes from 1 cm to the size of
an orange.
3. Mixed: The regeneration nodules are of varying size.
Clinical Results of Cirrhosis

1. Liver cell failure: Jaundice and Hypoalbuminemia
2. Portal hypertension: Esophageal varices (bleeding)
Splenomegaly, Abnormal collateral vessels
(hepatic and prehepatic coma), Vascular shunts (cyanosis)
3. Neoplastic changes: Hepatoma
4. Hormonal imbalance: cause of skin lesion and spider naevi
Cause of amenorrhoea and infetility
Cause of retention.
Clinical Varities of Cirrhosis

1. Alcoholic cirrhosis
2. Cryptogenic cirrhosis unknown (25% viral hepatitis)
3. Hemochromatosis 4. Primary biliary cirrhosis
5. Chronic active hepatitis
6. Hepatolenticular degneration (Wilso's disease)
7. Schistosomal fibrosis 8. Cardiac cirrhosis.
ALCOHOLIC CIRRHOSIS
The precise reason why alcoholic cirrhosis develops is unknown.
Alcoholic can produce a fatty liver with fat droplets in all liver cells, but there is
little knowledge concerning the reason why some patients go on to develop
cirrhosis.
Pathology:
The liver is often enlarged and an even micronodular type of cirrhosis may be
present. The liver looks greasy and histologically shows fatty change in the liver
cells.
Fatty infiltration is indicative of recent drinking and when drinking stops the fat
disappears.
Histologically one other feature is often seen and this is a peculair hyaline
degneration of the perinuclear cytoplasm in the damaged liver cells-Mallory's
alcoholic hyaline.
Clinical Feature Special Features

More common in male Delirium tremenn's
Jaundice ++ /liver enlarged Peripheral neuritis
Spleen, Ascites Dupytren's contractures
Bleeding varices/hepatic coma Pancreatitis,Zeive's syndrome.
(Hemolysis &lipedemia)

Diagnosis
History of alcoholism
C/F and examination
Jaundice and elevated transaminase
Abdomen ultrasound: fatty liver
Liver biopsy: is the only secure diagnosis
Elevated GGT, and alkaline phosphatase
Anemia- macrocytic with MCV> 100 fl- returns slowly to normal after cessation
of drinking.
Thrombocytopenia is common (directly or secondary to hypersplenism)
PRIMARY BILIARY CIRRHOSIS

Pathology
The liver is large dark green, and finely cirrhotic microscopically; perilobular
fibrosis
Lack of bile duct in the portal tracts
Features of intrahepatic obstruction
Clinical Pictures
Mild aged female with mild obstructive jaundice
Pruritus before jaundice, the skin covered with scratch marks.
The liver is large and firm.
Spleen is usually palpable.
The urine is dark, the faeces pale
Xanthomata occur on the eyelids, feet and hands.
Finger clubbing is common.
Bone pain, bone thining due to osteoporosis, osteomalacia and secondary
hyperparathyroidism may occur.
The osteomalacia is caused by malabsorption of vitamin D associated with the
steatorrhea of bile salt deficiency.
Abdominal pain due to peptic ulceration
Bleeding due to prothrombine deficiency may occur.
Complications: portal hypertension, hepatic coma and fluid retention
Helpful Investigations
1. LFT: Serum bilirubin 5-10 mg conjugated
Increased alkaline phosphatase
Flocculation test positive
2. Barium meal: may show varices and peptic ulceration
3. Bone radiographs
4. Serum lipid increased (total), phosphlipid, cholesterol
5. Mitochonderial Antibody is positive
Confirm diagnosis with (1) liver biopsy and (2) ERCP- is the most useful tests

REVIEW QUESTIONS
1. In the following conditions, the plasma activities of both

alkaline phosphatase and gamma-glutamyl transferase are A. T
likely to be increased B. T
A. Alcoholic cirrhosis C. F
B. Carcinoma of the head of the pancreas D. F
C. Metastatic carcinoma of the prostate E. F
D. Normal pregnancy, third trimester
E. Osteomalacia
2. The following plasma enzyme measurements are A. T
frequently increased in acute viral hepatitis at the preicteric B. F
stage: C. F
A. Alanine aminotransferase D. F
B. Alkaline phosphatase E. T
C.Pseudocholinesterase
D. Creatine kinase
E. Aspirtate aminotransferse
3. Increased plasma (unconjugated bilirubin) occurs in: A. T
A. Hemolytic anemia B. T
B. Pernicious anemia C. T
C. Gilbert‟s syndrome D. F
D. Dubin-Jhonson syndrome E. T
E. Hepatocellular jaundice
4. Conjugated hyperbilirubinemia: A. T
A. Occurs in uncomplicated post-hepatic jaundice B. T
B. Occurs in the Rotor syndrome C. F
C. Severe enough to cause clinical jaundice is always a D. F
contraindication to the performance of a E. T
bromsulphthalien test
D. Is a feature of acholuric jaundice
E. Of long standing is often associated with multiple defects
of clotting factor.
5. In the bromsulphthalein (BSP) test: A. F
A. BSP is injected intramuscularly and blood samples are B. T
taken at standard times (e.g 5 and 45 min) there after. C. T
B. BSP is being used to test hepatic transport of anions D. F
C. Cover 95% of the injected BSP is cleared by the liver, in E. F
healthy people, within 45 min.
D. BSP is mainly conjugated with glucouronic acid in the
liver before being excreted in the bile.
E. The main value lies in determining the severity of liver
disease in patients with other evidence of abnormal liver
function.
6. In patients with alcoholic cirrhosis:
A. The prothrombin time, if prolonged, usually fails to A.T
respond to parenteral vitamin k therapy B.T
B. Measurement of plasma (albumin) provides a good C.F
index of severity in the later stages of the disease. D.F
C. Plasma (IgG) tends to be increased to a greater extent E.T

than (IgA) or (IgM).
D. Plasma cholinesterase activity is often increased.
E. Jaundice usually only becomes clinically apparent after
plasma gamma-glutamyl transferase activity has become
abnormal
7. 7. Chronic cholestasis often causes a marked increase in
plasma activity of: A. T
8. A. Alkaline phosphatase B. F
9. B. Amylase C. F
10. C. Aspartate aminotransferase D. T
11. D. Gamma-glutamyl transferase E. F
12. E. Heat-stable lactate dehydrogenase
8. Increased serum direct bilirubin in combination with pale (D) is true
fecal pigmentation, and increased alakaline phosphatase in answer
pruritic patient.
A. Viral hepatitis
B. Acute hemolytic anemia
C. Neonatal physiological jaundice
D. Biliary stricture
9. A delayed prothrombin time may be indicative of liver (A) Several
dysfunction. Correction of the prothrombin time by clotting
administration of vitamin K indicates: factors (I, II,
A. Obstructive hepatic disorder V, VII and X)
B. Diffuse hepatocellular disease affect the
C. Fatty liver prothrombin
D. Glycogen storage disease time. Factors
II, VII and X
are vitamin K
dependent
10. In the pre-icteric stage of infection with hepatitis A virus, A. T

there is often: B. F
A. Increased urinary urobilinogen excretion C. T
B. Decreased plasma (albumin) D. F
C. Increased plasma (bilirubin) E. T
D. Decreased plasma (Na+)
E. Increased plasma aminotransferase activity
11. In patients with alcoholic cirrhosis: A. T

A. A prolonged prothrombin time usually fails to revert to B. T
normal in response to parenteral vitamin K C. F
B. Plasma {albumin} provides a good index of severity in D. F
the later stages of the disease E. F
C. Plasma (IgG) tends to be increased to a greater extent
than (IgA) or (IgM)
D. Plasma cholinesterase activity is often increased
E. Plasma gamma-glutamyl transferase activity, if high
provides a sensitive means of confirming the diagnosis

ENDOCRINE SYSTEM
8
ANTERIOR PITUITARY AND HYPOTHALAMUS
The hypothalamus secretes a number of hormones or factors that pass down

the hypothalmo-hypophyseal portal blood vessels to the pituitary. The control
the release of hormones from the anterior pituitary, in some cases by
stimulating hormonal release cand in others by inhibiting it. The hormones
produced by the target glands controlled by the anterior pituitary may exert
negative feedback effects on the secretion of the corresponding hypothalamic
hormone (e.g plasma {free cortisol} influence the output of
corticotrophinreleasing hormones is also influenced by stimuli from higher
central nervous system centres.
The pituitary gland is located at the base of the brain just below the optic
chiasm and just above the sphenoid sinus. It is divided into two lobes. The
anterior lobe and the posterior lobe. It is now clear that the pituitary gland is
subservient to influences from the hypothalamus which
stimulate or inhibit the release of anterior pituitary hormones.
HORMONES OF THE ANTERIOR PITUITARY GLAND:
The anterior pituitary gland contains five types of cells. Four cell types each
produce a different hormone-growth hormone, prolactine (PRL). Thyroid
stimulating hormone (TSH), and adrenocortictropic hormone (ACTH), while a
fifth cell type produces two related hormones- the
gonadotropin, Lutenizing hormone (LH) and follicle stimulating hormone
(FSH)
TABLE 8.1 ANTERIOR PITUITARY HORMONES
Hypothalam Hormone Structure Target cell Feedback control

ic factor Hormone or
compound
GHRH (s) GH Protein Bone , soft tissue GH release-
inhibiting hormone
Dopamine PRL Protein Breast Dopamine
CRH ACTH Protein Adrenal cortex Cortisol
GnRH (s) LH Glycoprotein Gonads Gonadal steroid
GnRH (s) FSH Glycoprotein Gonads Gonadal steroid
and inhibin
TRH (s) TSH Glycoprotein Thyroid gland Free T4, freeT3
Control of Secretion: Examples

Thyroid stimulating hormone (TSH) acts on the thyroid gland to increase the
synthesis and release of thyroid hormone, thyroxine (T4) and triiodothyronine
(T3); as well as promote growth of thyroid cells.
Thyroid hormone exerts an inhibitory effect on the pituitary; TSH is
suppressed by a slight increase in thyroid hormone and rises exponentially as
thyroid hormone level decrease.
TSH secretion is pulsatile within a narrow range (0.5 to 4 mu/l and shows a
diurnal variation (slight higher at night.
Lutenizing hormone (LH) and follicle stimulating hormone (FSH). The

relationship between the gonadotropin and the gonads is quite complex. A
simple generalization is that LH stimulates sex steroid synthesis and is
inhibited by rising levels of gonadal steroids.
FSH stimulates gametogenesis: feedback on FSH is exerted by sex steroids and
possibly by factors produced by the gonds.
Testing Anterior Pituitary Reserve
Abnormalities of pituitary hormones may be single or multiple, deficiency or

excess. There is no single test of pituitary function; one must test specifically
for the hormones of interest.
Patients with pituitary adenoma are the largest group for whom testing of
pituitary function is indicated. Large tumors may cause compression and
destruction of normal pituitary tissue, resulting in deficiencies of one , several,
or all of the anterior pituitary hormones.
Infiltrative or infectious disorders, such as sarcoidosis may also compromise
pituitary function.
Another cause, less common now than in the past, is postpartum pituitary
necrosis (Sheehan‟s syndrome).
Clinically significant anterior pituitary hormone deficiencies that should be
tested for include TSH, ACTH and gonadotropin in children and adults as
well as GH in children.
NB: A persistent elevation despite conditions of supression indicates an
abnormality.
TABLE 8.2 STIMULATION AND SUPPRESSION

HORMONE SUPPRESSION STIMULATION
PRL L-dopa, TRH, domperidone, phenothiazines
bromocriptin
LH, FSH Esterogen, Gn. RH, Clomiphen
Testosterone
TSH T3, T4 TRH
ACTH Dexamethasone Insulin-hypoglycemic, Metyrapone,
CRH
GH Oral glucose Insulin-hypoglycemic, L-dopa,
Glucagon, GHRH

GROWTH HORMONE
Normal secretion of growth hormone is episodic, with several peaks, during a
24 hours period, particularly after stress or exercise and an hour or so after
onset of deep sleep. Increase in plasma glucose normally cause a decrease in
GH and hypoglycemia stimulates a rise of GH.
The effects of GH on cartilage and possibly other tissues occur through the
generation of another group of hormones, the somatomedin. The most
important of these compounds is somatomedin-C, also known as insulin-like
growth factor-1 (IGF-1)
GH has divergent effect on carbohydrate metabolism, initially an injection of
GH cause a fall in blood glucose; chronic GH excess inhibits glucose entry into
cells, antagonistic to the action of insulin. This leads to glucose intolerance and
in some cases, overt diabetes.
GROWTH HORMONE DEFICIENCY

GH deficiency is the most common pituitary hormone deficiency state but is
clinically significant only in children, when it results in short stature.
GH deficiency as an isolated defect is often due to deficient production of
GHRH by the hypothalamus, but GH deficiency alone or in combination with
other hormone deficiencies may also result from pituitary or hypothalamic
tumors, such as craniopharangioma.
Clinical Features
Growth hormone delay: Short stature
Mild obese
Diagnosis of Growth Hormone Deficiency

The diagnosis of GH deficiency based on a reduced magnitude or
Number of GH secretory episodes in multiple samples obtained
during a 24 hours period.
Somatomedin-C levels are usually low in children with GH deficiency, and
Somatomedin-C measurement is a good screening test for GH deficiency. (it
has a longer half life than GH.) Normal value is 0.4 - 2u/ml.
The following tests are recommended when isolated GH deficiency is

suspected:
1. Post-exercise or sleeping GH levels:
Exercise and the early stages of sleep are associated with increased GH
secretion. A high GH level excludes GH deficiency and no further tests would
then be required.
2. Clonidine stilmulation test: a fairly recently introduced test which is safe and
reliable. Clonidine stimulates GH release.
3. Insulin stress test: It is the refrence test
Hypoglycemia stimulates GH release.
Probably only indicated now if the clonidine test shows an abnormally
low GH response
ACROMEGALY
Chronic hypersecretion of growth hormone (GH), usually by a pituitary
adenoma, leads to the syndrome of acromegaly in adults and to pituitary
gigantism in children.

Acromegaly is an uncommon condition but accounts for approximately 10%
of all pituitary tumors. It usually occurs in middle decades of life, though it
can occur at any age.
Most patients with acromegaly or pituitary gigantism have a pituitary tumor
shown by CT scan or found at surgery. The character of these tumors is
variable.
Most contain secretory granules by electron microscopy that can be shown by
immunperoxidase staining to contain GH.
Chronic hypersecretion of GH, though increased production of somatomedin,
leads to the recognizable increase in growth of soft tissue, cartilage and bone
that are characteristic of acromegaly. Thickening of the skin is due to
interstitial edema, deposits of hyaluronidase and increased connective tissue.
Clinical Presentation
Coarsening of facial feature
Enlargement of hands, feet and jaw
Headache
Evidence of peripheral neuropathy muscle weakness
Joint pain and stiffness
Visual field defects
Skin changes (Thickening, coarseness,, increase sweating)
Hirsutism
Endocrine changes: galactorrhea and menstrual disturbance
Diagnosis of Acromegaly
Patients with active acromegaly have abnormal dynamics of GH secretion.
A simple diagnostic approach is to measure serum GH one hour after the oral
administration of 100g of glucose. Clearly elevated GH level (>10ng/ml) after
oral glucose, combined with the clinical picture makes the diagnosis of
acromegaly secure, while a normal level of GH after oral glucose (<5ng/ml)
essentially rules out the diagnosis. Only a small percentage of subjects being
investigated for acromegaly will have a post-glucose GH level that is
intermediate (5 to 10 ng/ml). In these patients, other tests can be used to
define their status.
GH stimulates the production of insulin-like growth factor-1 (IGF-1)

predominantly in the liver; IGF-1 levels can be determined to assess disease
activity in acromegalies, reflecting over all GH secretion. Unlike GH, IGH-1
levels do not fluctuate widely throughout the day.
Measurements of somatomedin-C reflect the integrated production of GH,
and serve as a useful confirmatory adjunct to GH measurements as a
screening test to rule out acromegaly.
Others: CT and MRI
PROLACTIN
This hormone acts in concert with other hormones. It increases mammary
growth and lactation in the steroid-prepared breast.
Estrogens may increase prolactin secretion. Galactorrhea can be associated
with a pituitary tumor.
Normal values:
Female 0 - 23 ng/dl Male 0 - 20 ng/dl

Prolactin is a pituitary hormone essential for initiating and maintaining
lactation.
The sex difference in Prolactin does not occur until puberty, when increased
Oestrogen production results in higher Prolactin levels in women.
Increased Values Are Associated With

 Galactorrhea
 Disease of hypothalamus and pituitary
 Prolactin-secreting pituitary tumors
 Irritative chest wall lesions
 Ectopic production of malignant tumors
 Hypothyroidism
 Renal failure
GALACTORRHEA
Lactation in men or in women who are not breast feeding an infant.
Etiology
In both sexes, prolactinomas are the most common secretory tumors of the
pituitary, producing excessive quantities of PRL. The majority of tumors in
women are microadenomas (<10 mm) but, a small percentage are
macroadenomas (>10 mm) at the diagnosis.
Hyperprolactinemia and galactorrhea also may be caused by ingestion of
several drugs including phenothiazine, alpha methyldopa and opoids.
Primary hypothyroidism must be ruled out, since increased TRH stimulates
increased secretion of both TSH and PRL
Other causes of prolactinemia: Post OP of pituitary, chronic renal failure,
bronchogenic carcinoma, hypernephroma and chest wall lesions (surgical
scars, trauma and herpes Zosters
Diagnosis of Galactorrhea
Amenorrhoea is commonly associated with galactorrhoea in women.
The first diagnostic objective should be to document hyperprolactinemia in
the basal state in general basal PRL level serum to correlate with size of a
pituitary tumor can be used to follow patients over time.
Serum gonadotropin and esteradiol level are either low or in the normal range
in hyperprolactinemia women.
Primary hypothyroidism is easily ruled out in the absence of elevated TSH.
CT or MRI is the method of choice to identify individuals with
microadenomas.
Visual field examination is indicated in all patients with macroadenomas and
in many patients who elects medical treatment.
HYPOFUNCTION OF THE ANTERIOR LOBE

Hypopituitarism In The Adult
Endocrine deficiency syndromes due to partial or complete loss of anterior
lobe pituitary function
Causes
A. Primary causes (primary hypopituitarism)
 Pituitary tumors

 Infarction or ischemic necrosis of the pituitary
e.g Sheehan' syndrome, DM, SCA, sarcoidosis
 Inflammatory process; meningitis, pituitary abscess
 Infiltrative disorder: histiocytosis X, hemochromatosis
 Iatrogenic, radiation, surgery
 Autoimmune
B. Secondary: affecting hypothalamus
 Hypothalamic tumor
 Inflammation, trauma, post OP
Diagnosis
1. X-ray of the sella turcica
2. CT, MRI
3. Position emission tomography
4. Cerebral angiography
When panhypopituitarism is suspected, initial evaluation should be aimed at

detecting TSH and ACTH deficiencies as both are life-threatening.
To Evaluate Patient for Hypothyroidism

T4, T3 and TSH levels can be determined by radioimmunassay. All should be
low. Since elevated TSH levels indicate primary abnormality of the thyroid
gland.
The administration of 200-500g synthetic thyrotropin-releasing hormone
(TRH) given IV over 15-30 second, may help to identify those patients with
hypothalamic as opposed to intrinsic pituitary dysfunction. Peak levels of TSH
in response to TRH are generally observed 30 minutes after injection.
A delayed rise in plasma TSH levels may see in individuals with
hypothalamic disease (tertiary hypothyroidism).
Patient with hypothyroidism secondary to pituitary deficiency do not release
TSH in response to TRH.
The rise is exaggerated in primary hypothyroidism.
It is assumed that patients with a hypothalamic disorder having deficient TRH
reserve and a normal pituitary reserve to TRH, usually release normal
amounts of TSH in response to TRH although the release may be delayed and
prolonged.
Evaluation of ACTH Secretion: The most reliable method for evaluating

ACTH (as well as GH and PRL) reserve is by means of the insulin tolerance
test.
Insulin Tolerance Test: Regular insulin at a dose of 0.05 u/kg bw is given iv

over 15 to 30 sec. And venous blood samples are obtained for determination of
GH, cortisol and glucose at zero time and at 20, 30, 45, 60 and 90 minutes later.
If test results do not shown at least a 50% fall in serum glucose levels to values
<40mg/dl, the test should be repeated.
An insulin tolerance test alone will not differentiate between primary
(Addison‟s disease) and secondary (hypopituitary) adrenal insufficiency.
Decrease of glucose to below 40 mg/dl and increase cortisol to a peak of
>580nmol/L

PRL levels are not regularly depressed in patient with panhypopituitarism.
GH measurements are helpful only when performed after one of several
provocative stimuli, and since GH responses are generally abnormal in
individuals with diminished thyroid or adrenal function, testing should be
conducted only after adequate hormone replacement therapy.
Measurement of Serum LH and FSH Levels

In the basal state is most helpful in the evaluation of hypopituitarism in
postmenopausal women not taking exogenous oestrogen, in which circulating
gonadotropin concentration are normally high (>40 miu/ml). Basal LH and
FSH levels are less helpful in other patients. Although gonadotropin levels
will be LOW in panhypopituitarism overlap exist, with the normal ranges for
LH and FSH. Both should increase in response to synthetic gonadotropin
releasing hormone (GnRH) 100ug iv, with LH peaking about 30 minutes and
FSH 40 minutes after GnRH administration.
However normal diminished or absent response to GnRH may occur in
hypothalamic-pituitary dysfunction.

POSTERIOR PITUITARY
The posterior lobe of the pituitary gland consists of nerve fibres that store the
two hormones that are produced in the supraoptic and paraventricular nuclei
of the hypothalamus.
Oxytocin is released in response to suckling and serves to stimulate lactation
and uterine contractions.
The other hormone of the posterior pituitary, Antidiuretic hormone (ADH) or
vasopressin is involved with regulation of water balance.
ADH is the only one of these hormones of general clinical significance.
ANTIDIURETIC HORMONE: N.V: 1 - 5 pg/ml

ADH increases renal tubular reabsorption of water (antidiuretic action) and
raises blood pressure by constricting arteries and capillaries (vassopressor
effect).
Clinical Disorder
1. Deficiency of ADH: ADH deficiency produce diabetes insipidus if the
anterior pituitary still functioning.
2. Excessive ADH: inappropriate ADH secretion syndrome.
DIABETES INSIPIDUS (DI)

A temporary or chronic disorder of the neurohypophyseal system due to
deficiency of vasopressin (ADH) and characterized by excretion of excessive
quantities of very dilute (but otherwise normal) urine and by excessive thirst.
Etiology and Pathophysiology

DI may be complete, partial, permanent or temporary. All of the pathologic
lesions associated with DI involve the supraoptic and paraventricular nuclei of
the hypothalamus or a major portion of the pituitary stalk. Simple destruction
of the posterior lobe of the pituitary leads to temporary, unsustained DI. The
posterior lobe is the major site for ADH storage and release, but ADH is
synthesized within the hypothalamus.
Causes
I. Cranial Causes of DI
1. Primary (idiopathic), in which there is a marked decrease in the
hypothalamic nuclei of the neurohypophyseal system,
2. Secondary (acquired) due to a variety of pathologic lesions including,
hypophysectomy, cranial injury, skull fracture, neoplasms (suprasellar and
intrasellar), histiocytosis X, granulomas (TB), vascular lesions and
infections.
NEPHROGENIC DIABETES INSIPIDUS

1. Familial
 X-linked recessive inheritance
 Autosomal recessive
2. Acquired
 Decrease potassium and increase calcium
 Drugs (lithium)
 Chronic renal disease
SYMPTOMS OF DI:
Polydipsia
Polyuria >3 l/day) of a very dilute urine (specific gravity usually <1.005 )
Nocturia
Dehydration and hypovolemia may develop rapidly if urinary losses are not
continuously replaced.
Evaluation of ADH Deficiency

Study for intracranial lesion: LP, skull film, EEG, chest X-ray (metastasis) and
bone marrow (multiple myeloma)
The simple measurement of a urine volume of more than 3 litre daily and if >
5 liters/day is strong presumptive evidence of deficiency.
Blood glucose, serum calcium and potassium should be measured to exclude
common causes of nephrogenic diabetes insipidus.
(1) Water Restriction
Volume and concentration (specific gravity or mOsm/kg) are determined at
each voiding.
Urine flow should reach less than 0.5 ml/minute and urine concentration
should be greater than 800 mOsm/kg) specific gravity.
Dehydration is continued until
 Orthostatic hypotension and postural tachycardia appear
 5% or more of the initial body weight has been lost or
 The urinary concentration does not change >0.001 sp.gr. or 30 mOsm/l in
sequentially voided specimens.
At this point, serum electrolyte and osmalility are again determined and give
vasopressin.
Response to Vasopressin: This test differentiates diabetes insipidus from

vasopressin resistant polyuria due to other causes e.g
 Potassium depletion
 Hypercalcemia
 Chronic renal failure
 Congenital nephrogenic failure
 After renal transplantation
 Sjogren‟s syndrome
 Obstructive uropathy
Urine volume and specific gravity and symptoms of polyuria and polydipsia
are obsereved before and after repeated sc injections of 0.2 ml (4 units)
vasopressin every 4 hours day and night for 24 hours or before and after a 1
hour of infusion of aqueous vasopressin (5mu/minute)
Patients with chronic nephritis or vasopressin-resistant DI experience no relief
of symptoms during test period. In DI or psychogenic polydipsia, symptoms
may improve, urine volume may decrease, and urine specific gravity may
increase to 1.015 or more.
Other Investigations
Therapeutic trails of low dose desmopressin (10-20g intravasally for 2 weeks
given if vassopressin assays are unavailable.
MRI scans to detect cranial lesion.

THYROID HORMONES
Iodine, ingested in food and water, is actively concentrated by the thyroid
gland, converted to organic iodine by peroxidase, and incorporated into
tyrosine in intrafollicular thyroglobulin. The tyrosine are iodinated at either
one (monoiodotyrosine, MIT) or two (diiodotyrosine, DIT) sites and then
coupled to form the active hormones diiodotyrosin+diiodotyrosine
>tetraiodothyronine (thyroxine,T4) diiodotyrosin+monoiodotyrosin>
triiodothyronine
Thyroglobulin, a glycoprotein containing and within its matrix, is taken up
from the follicle as colloid droplets by the thyroid cells.
The major thyroid transport protein is thyroxine binding globulin (TBG),
which normally accounts for about 80% of the bound thyroid hormone. Other
thyroid binding proteins, including thyroxine binding prealbumin (TBPA)
and albumin.
All reactions necessary for T3 and T4 formation are influenced and controlled
by pituitary thyrotropin (thyroid stimulating hormone, TSH)
TSH secretion is influenced by thyrotropin-releasing hormone (TRH), an
amino acid peptide synthesized in the hypothalamus.
Physiology Effects of Thyroid Hormone

Thyroid hormones have 2 major physiologic effects
1. The increase protein synthesis in virtually every body tissue (T3 and T4
enter cells, bind to discrete nuclear receptors and influence the formation of
mRNA.
2. They increase O2 consumption by increasing the activity of the ATPase (NA
pump) primarily in tissues responsible for consumption (i.e liver, kidney,
heart and skletel muscle.
Thyroid Function Test

Thyroid Stimulating Hormone (TSH)
Is measured by RIA and is the best available for demonstrating primary
hypothroidism and for distinguishing between primary and secondary
hypothyroidism.
In primary hypothyroidism TSH is elevated, whereas in secondary
hypothyroidism it is usually low or normal.


Free T4 (FT4)
N.V 1 - 2.3 mg/dl ( 0.8-1.5ng/dl)
It is the physiologically active form of thyroxine. In plasma 99.98% of T4 is
bound to serum proteins and only a small fraction is free. Currently, direct fT4
measurement is by equilibrium dialysis which is labourous and expensive;
indirect measurement of fT4 is in reality estimates of hormone concentration,
fT4 estimates are reasonably accurate.
Total T4
Serum total T4 measurement is available and reliable. However, total T4
measurements have limited diagnostic value because serum levels are affected
by drugs and proteins.
Triiodothyronine (T3)
N.V: 250 - 390 pgldl (60 -180ng/ml)
The majority of peripheral T3 comes from conversion of T4 to T3 in peripheral
tissue, mostly hepatic conversion. A small fraction 20%) is directed by thyroid
gland it self. In patients with
Acute or chronic non-thyroidal illness, serum T3 is depressed whereas reserve
T3 (rT3) is increased.
Serum T3 determination is helpful when a patient has hyperthyroidism with
normal serum total T4 and fT4 fractions. In this setting, the patient may have
elevated T3 levels suggesting toxicosis.
Thyrotropin-Releasing Hormone (TRH)

Serum TSH is determined before and after an IV injection of 500g of synthetic
TRH.
Normally, there is a rapid rise in TSH of 5 to 25 u/ml, reaching a peak in 30
minutes and returning to normal by 120 minutes. The rise is exaggerated in
primary hypothyroidism.
Patients with hypothyroidism secondary to a pituitary deficiency do not
release TSH in response to TRH.
It is assumed that patients with a hypothalamic disorder having deficient TRH
reserve and a normal amounts of TSH in response to TRH.
The TRH is also useful in the diagnosis of hypothyroidism when TSH release
remain suppressed, even in response to injected TRH, because of the pituitary
effects of the elevated free T4 and free T3 on the pituitary thyrotropic cells.
Thyroid Binding Globulin

Increased in hypothyroidism, pregnancy, estrogen therapy, oral contraceptive,
acute intermittent porphyria and prolonged perphenazine therapy
Decreased TGB level in Nephrotic syndrome, markrd hyperproteinemia,

uncompensated acidosis and acromegaly.
Thyroxine Determination by RIA

N.V: 5-12g/dl
The test measures the level of total circulatory-thyroid using a
radioimmunassay procedure.
Treatment of thyroid disorders with potassium iodide or lugols's solution can
be monitored with the use of this test

Increased values in: hyperthyroidism, acute thyroiditis, early hepatitis and
idiopathic TBG elevation.
Diminished values in hypothroidism, chronic thyroiditis, nephrosis,
idiopathic TGB decreases.
Long Acting Thyroid Stimulator (LATS)

Normally found in 5% of healthy.
It is an important test in patients with thyroid disease, especially in identifying
persons with malignant exophthalamus and Graves‟s disease.
Antibodies
Serum thyroid autoantibodies are characteristic of autoimmune thyroid
disease, such as Hashimoto's and Grave's disease. The principle
autoantibodies are antithyroid peroxidase (anti TPO), preciously known as
AMA (antimicrosomal antibody), antithyroglobulin (anti-Tg), and TSH
receptor antibodies immunassay.
Fine Needle Aspiration (FNA) Biopsy
Radioactive Iodine Uptake (RAI)

It is of value in the diagnosis of hyperthyroidism, in which the RAI uptake is
elevated, but is useless in the diagnosis of hypothyroidism.
RAI uptake is particularly useful in calculating the dose when is used as the
treatment modality.
Thyroid Scanning With Radioactive or Technetium 99M

It is not a routine test. It is useful in delineating structural abnormalities of the
thyroid e.g to distinguish Grave's disease from multinodular goiter and a
single toxic adenoma or to determine the functional state of a single nodule
(hot vs cold)
HYPERTHYROIDISM
Grave's disease is characterized by hyperthyroidism and one or more of the

following: goiter, exophthalamus and pretibial myxedema. The cause of the
hyperthyroidism is not completely understood but is probably immunologic.
Patients with grave's disease have circulating thyroid stimulator in their
serum known as thyroid-stimulating immunoglobulin (TSI) or Thyroid-
stimulating antibodies (TSAb) which are 7s IgG.
TSI are of particular interest because they are antibodies directed against the
TSH receptor and specifically stimulate the activity of the thyroid. The
antibodies presumably arise secondary to a defect in suppressor T
lymphocytes, which permits a clone of helper T lymphocytes, which permits a
clone of helper T lymphoocyte to interact with specific thyroid antigens,
proliferate and interact with B-lymphocytes producing TSI.

Symptoms and Signs of Hyperthyroidism
More common signs: goiter's, tachycardia, warm, tremor, moist skin, eye sign
and atrial fibrillation.
More frequent symptoms: nervousness, increase activity, increase sweating,
tachycardia, insomnia, weakness.
Types of Hyperthyroidism
Most Common Very Rare

Grave's disease TSH producing tumor of pituitary
Toxic multinodular goiter Metastatic embryonal Ca. of testis
Toxic adenoma Choriocarcinoma
Thyrotoxicosis factitia Strauma ovarii
Silent thyrotoxicosis Metastatic follicular thyroid cancer
1. Severity of hyperthyroidism does not correlate with thyroid hormone levels
2. Serum total and free thyroxine (T4) is increased.
3. Serum T3 concentration on RIA is increased in upto 85 of patients (T3/T4
>20:1)
4. Serum TSH is decreased in all form of thyrotoxicosis, except the very rare
cases of pituitary neoplasms that secrete TSH.
5. Serum thyroxine-binding globulin (TBG) is normal.
6. Microsomal antibodies are found in moderate to high titers in most patients
with grave's disease.
7. Other thyroid autoantibodies are thyroid-stimulating immunoglobulins
(TSI) and TSH-binding inhibitory immunoglobulins (TB II) found only with
grave's disease.
8. Thyroid suppression test: T3 administration decreases RAIU (Radioactive
iodine uptake) in normal people but not in hyperthyroid persons. (Now
replaced by TRH.
9. Salivary excretion and urinary excretion of RAI are increased.
10. Iodine tolerance test shows increased utilization of iodine.
11. Serum cholesterol is decreased and total lipids are usually decreased
12. Glucose tolerance is decreased with early high peak and early fall.
13. Hyperglycemia and glucosuria are present.
14. Liver function test show impairment
15. Creatinine excretion in urine and creatine tolerance is increase.
16. Normal serum creatine excludes hyperthyroidism
17. Serum total and ionized calcium are increased in 10% of patients.
18. Unusual laboratory manifestations of hyperthyroidism include increased
alkaline phosphatase, hypoproteinemia malabsortion and anemia.

HYPOTHYROIDISM (MYXOEDEMA)
The characteristic reaction to thyroid hormone deficiency in the adult:

Primary hypothyroidism, the most common form, is probably an autoimmune
disease, usually occurring as sequel to Hashimoto's thyroiditis.
Posttherapeutic hypothyroidism is the second most common following RAI
therapy or surgery for hyperthyroidism.
Goitrous hypothyroidism may occur in endemic goitre.
Iodine deficiencydecrease thyroid hormonogensis-TSH is released -
thyroid gland enlarged under stimulus of TSH.
Secondary hypothyroidism occurs when there is failure of the hypothalamic-
Pituitary axis due to either deficient secretion of TRH from the hypothalamus
of lack of secretion of TSH from the pituitary.
Clinical Feature
The most common: Tiredness, weight gain, cold intolerance, goitre,
hyperlipedemia, bradycardia, aches and pain, delayed relaxation of reflexes,
and dry skin
DIAGNOSIS OF PRIMARY Vs SECONDARY HYPOTHYROIDISM

In secondary hypothyroidism is a history of amenorrhoea.
In secondary hypothyroidism, the skin and hair are dry, breast is atrophic, the
heart is small without accumulation of the serous effusions in the pericardial
sac, and BP is low.
A hypoglycemia is found because of concomitant adrenal insufficiency or
growth hormone deficiency.

 Is low in secondary hypothyroidism
 Is very high in primary hypothyroidism (no feedback)
The serum TSH is the most simple and sensitive test for diagnosis of
primary hypothyroidism
The Serum Cholesterol is low in secondary hypothyroidism and
high in primary hypothyroidism
The TRH Test
TSH is not released in hypothyroidism secondary to pituitary failure.
TSH is released in hypothyroidism secondary to hypothalamic failure.
Serum T4 and free thyroxine concentration are decreased
Serum T3 concentration (RIA) is decreased
TSH stimulation (20 units/day for 3 days) increases RAIU to normal (20%) in
secondary but not in primary hypothyroidism.
Laboratory findings indicative of other autoimmune diseases (e.g pernicious
anemia and primary adrenocortical insufficiency occur with increased
frequency in primary hypothyroidism.
Salivary excretion and urinary excretion of RAI are decreased.
Iodine tolerance test shows decreased utilization of iodine.Serum cholesterol
is increased
OGTT is flat and IVGTT is normal. The anemia is normocytic normochromic
MYXOEDEMA COME
Hypoglycemia, hyponatremia, and serum creatinine are increased
Arterial Pco2 may be increased and Po2 is decreased
ADRENAL GLAND
The adrenal glands are located extraperitoneally at the upper poles of the
kidneys.
Histologically, they are divided into medulla, derived from ectodermal tissue
and the cortex, derived from mesodermal tissue.
The adrenal cortex produces 4 major groups of hormones:

1. Glucocorticoids (cortisol, cortisone)
2. Androgen( anderostendione, dehydroepiandrosterone
3. Mineralocorticoids (aldosterone, corticosterone)
4. Estrogen and progesterone
Adrenal corticoid production is controlled by a number of factors originating

in the hypothalamic-pituitary system. ACTH secretion and lysing eosinophilic
and lymphocytes.
Clinical Disorders
A. Excess
1. Glucocorticoids: Cushing's syndrome
2. Androgen Excess: Adrenogenital syndrome in female
Macrogenitalosomia in male
3. Aldosterone excess: Primary hyperaldosteronism
B. Deficiency
1. Acute Addisonian crisis
2. Chronic Addison‟s disease.
ADRENAL CORTICAL HYPERFUNCTION
Hypersecretion of one or more adrenocortical hormones produces clinical

syndromes.
1. Excessive production of androgens results in adrenal virilism;
2. Hypersecretion of glucocorticoids produces Cushing‟s syndrome
3. Excess aldosterone output result in aldosteronism.

CUSHING'S SYNDROME
A constellation of clinical abnormalities due to chronic exposure to excesses of
cortisol or related corticosteroids.
Etiology:
Hyperfunction of the adrenal cortex may be ACTH-dependent or it may be
independent of ACTH regulation, e.g production of cortisol by an
adrenocortical adenoma or carcinoma.
The administration of supraphysiologic quantities of exogenous cortisol or
related synthetic analogous suppresses adrenocortical function and mimics
ACTH-dependent hyperfunction.
ACTH-dependent hyperfunction of adrenal cortex may be due to:
1. Hypersecretion of ACTH by the pituitary
2. Secretion of ACTH by a non-pituitary tumour such as small cell carcinoma
of the lung(the ectopic ACTH syndrome).
3. Administration of exogenous ACTH ّ
CUSHING'S DISEASE: Hyperfunction of the adrenalcortex resulting from

pituitary ACTH excess.
Clinical Features
Moon facies with a plethoric appearance.
Truncal obesity with prominent supraclavicular and dorsal cervical fat pads
"buffalo hump".
Skin thin and atrophic
Purple striae may appear on abdomen
Hypertension, renal calculi, osteoporosis
Glucose intolerance
Reduced resistance to infection
Psychiatric disturbance
Female menstrual irregularities
Virilism (increase androgen)
Laboratory Findings
Glucose tolerance is diminished. GTT is frequently diabetic in type.
Glucosuria appear in 50% of patients.
Fasting blood glucose may be elevated.
Insulin tolerance is increased. Occasional polydipsia and polyuria are seen.
Usually moderate increase in serum sodium and decrease in serum potassium
are found. Hypokalemic alkalosis occurs in 10% of patients.
Hypokalemia alkalosis may indicate extraadrenal neoplasia such as a
bronchogenic carcinoma causing increased production of ACTH with
increased secretion of mineralocorticoids and glucocorticoids; occurs in 30-
50% of such patients.
Urine potassium is increased; sodium is decreased.
Salivary sodium potassium ratio is decreased
Hematological Changes
WBC is normal or increased with relative lymphopenia is frequent.
Eosinopenia is frequent.
Hematocrit is usually normal; if increased it indicates an androgenic
component.

Osteoporosis causes changes. Serum and urine calcium may be increased.
Urinary 17KS level are usually increased (>25mg/24hours)
Urinary 17OHKS are increased (>10mg/24hours)
The night collection sample is equal to or greater than the day sample
(opposite pattern in normal person). ACTH stimulation produces the lowest
urinary 17-OHKS in Cushing's syndrome due to adrenal carcinoma and the
highest 17OHKS due to adrenal adenoma.
Plasma cortisol is normally 5 to 25 g/dl in the early morning hours (6-8 AM)
and declines gradually to <10 in the evening (6 PM and later) Patients with
Cushing's syndrome usually have elevated morning cortisol production, so
that evening plasma cortisol levels are above normal and total 24hours cortisol
production is elevated.
Free urinary cortisol, the best assay for urinary excretion, is elevated in
Cushing's patients and is subject to only minimal increased in obese patients
(normal 20 to 100g/24hours).
Dexamethasone Test
A.CLSSIC LOW-DOSE DEXAMETHASONE SUPPRESSION TEST
Dexamethasone, 2 mg/day administred p.o for 2 days in 8 divided doses.
Normal individuals almost totally supress cortisol production (24-hours
urinary cortisol excretion<10g. Used for the positive diagnosis of Cushing‟s
syndrome.
B. OVERNIGHT DEXAMETHASONE SUPPRESSION TEST

Dexamethasone, 1mg administred p.o at 11 pm. Plasma cortisol is measured
the next morning at 08 am . Normal individuals almost totally supress cortisol
production (plasma cortisol<20ng/ml) Used for the positive diagnosis of
Cushing‟s syndrome.
C. CLASSIC HIGH-DOSE DEXAMETHASONE SUPPRESSION TEST:

Dexamethasone, 8 mg/day administred p.o for 2 days in 8 divided doses.
Patients with Cushing‟s disease show partial suppression of cortisol
production (a significant decrease in 24-hours urinary 17-OH steroid or
cortisol excretion, usually more than 50%. Patients with other causes of
Cushing‟s syndrome (ectopic adrenocorticotrophin-ACTH-syndrome, adrenal
tumors) typically show no significant variation of cortisol production.
The plasma ACTH level will be markedly elevated in the ectopic ACTH
syndrome (usually > 200ng/ml) and will be too low to measure in Cushing's
syndrome due to adrenal tumor, except in the rare instances where the
adrenal tumor produces ACTH.
Patients with Cushing's disease usually have moderately elevated plasma
ACTH values (75 to 200 ng/ml)
Laboratory tests also favouring ectopic ACTH as the cause of Cushing's

syndrome include hypokalemic alkalosis with a serum of <3.0 mEq/L and
HCO3+ of >30mEq/l. Serum cortisol of > 200ug/dl at AM and urinary free
cortisol excretion of >450mg/24hours.

Test with Metyrapone
Will often useful information in the determining the etiology of the Cushing‟s
syndrome. Inhibition of 11-B-hydroxylase by metyrapone results in reduced
blood levels of cortisol and loss of cortisol inhibition by ACTH.
The ability of the pituitary to respond to this stimulus by release of ACTH
may be measured by 11-deoxycortisol (compound s).
Patients with pituitary-dependent Cushing‟s disease have marked increase in
plasma compound s but patients with adrenal tumour or the ectopic ACTH
syndrome fail to show this increase.
ALDOSTERONISM
Aldosteronism is the most potent mineralocorticoid produced by the adrenal.
It causes Na retention and K loss. In the kidney, aldosterone causes transfer of
Na from the lumen of the distal tubules into the tubular cells in exchange for K
and hydrogen.
Aldosterone secretion is regulated by the renin-angiotensin mechanism and to
a lesser extent by ACTH. Renin; a proteolytic enzyme, is stored in the
juxtaglomerular cell of the kidney.
Reduction in blood volume and flow in the afferent renal arterioles induces
secretion of renin. Renin causes transformation of angiotensinogen (an alpha
globulin) in the liver to angiotensin I, a 10 amino acid polypeptide, which is
converted to angiotensin II, an 8 amino acid peptide.
Angiotensin II causes secretion of aldosterone and to a much lesser extent, of
cortisol and deoxycorticosterone. The Na and water retention resulting from
increased aldosterone secretion increases the blood volume and reduces renin
secretion.
Aldosterone is measured by radioimmunassay.
PRIMARY ALDOSTERONISM (CONN'S SYNDROME)
Causes: 1. Adenoma; usually unilateral of the glomerulata cells of the adrenal

cortex
2. Adrenal carcinoma or hyperplasia
Manifestations
 Weakness, parasthesias
 Transient paralysis, Tetany
 Diastolic hypertension
Laboratory Findings
Excessive mineralocorticoid hormone secretion by adrenal cortex causes renal
tubules to retain sodium and excrete potassium.
The clssic biochemical abnormalities are urinary aldosterone,
Plasma renin and serum potassium measurements.
Urinary aldosterone is increased on normal-salt diet (not detectable on all

days) can not be reduced by high sodium intake.
24 hours urinary aldosterone is best initial screening procedure
(normal salt intake, no drugs)
Plasma renin is markedly decreased (normal or increased in secondary
aldosteronism.

Hypokalemia (usually <3.0 mEq/l is alleviated by administration of
spironolactone and by sodium restriction but not by potassium replacement
therapy.
Saline infusion causes significant fall in serum potassium and in corrected
potassium clearance. This hypokalemia induced by sodium loading is a
reliable screening test.
Saline infusion (2 L normal saline in 4 hous) suppress plasma aldosterone to 5
ng/100 ml in hypertensive patients without primary aldosterone but not in
patients with primary aldosteronism since plasma aldosterone levels vary
from moment to moment, a single specimen may not properly adrenal
secretion.-
Urine is neutral or alkaline (PH 7.0) and not normally responsive to

ammonium chloride load. Its large volume and low specific gravity are not
responsive to vasopressin or water restriction decreased tubular function,
especially reabsorption of water).
Proteinuria is intermittent or persistent.
There is hyperkaluria even with low potassium intake.
Sodium output is reduced.
Glucose tolerance is decreased in 50% of patients.

Plasma cortisol and ACTH are normal.
Urine 17KS and 17OHKS are normal
Serum magnesium falls
Total blood volume increases because of increased plasma volume.
Salivary Na-K ratio <0.65 is consistent with diagnosis but a higher ratio does
not exclude it.
Measurments of aldosterone in blood from periphery and both adrenal veins
confirms diagnosis by elevated level from side of lesion; opposite side has
level close to that in peripheral blood. This also distinguishes unilateral
adenoma from bilateral adenoma and hyperplasia and indicates location on
lesion for surgeon.
CT scan demonstrates the tumor.

HYPOFUNCTION
ADDISON'S DISEASE
An insidious, usually progressive disease resulting from adrenocortical
hypofunction.
Etiology
70% idiopathic atrophy of adrenal cortex (Autoimmune)
30% destruction of the gland by granuloma
e.g TB, Neoplasm, Amyloidosis or inflammatory necrosis
Drugs e.g ketoconazole.
Pathophysiology
The principal hormones produced by the adrenal cortex are cortisol
(hydrocortisone, aldosterone and dehydroepianderosterone (DHEA). Adults
secrete about 20 mg of cortisol, 2 mg of corticosterone and 0.2 mg of
aldosterone daily.
Although considerable quantities of androgens are normally produced by the
adrenal cortex, these exert their chief physiologic activity after conversion to
testosterone and dehydrotestosterone.
In Addison's disease, there is increased excretion of Na and decreased

excretion of K, chiefly in the urine, which is isotonic, and also in the sweat,
saliva, and GI tract. A low blood concentration of Na and Cl and a high serum
K result. Inability to concentrate the urine combined with changes of
electrolyte balance; produce severe dehydration, increased plasma
concentration, decreased circulatory volume, hypotension and circulatory
collapse.
Laboratory findings
Serum Na decreased <130 mEq/L , Serum K increase > 5 mEq/L
Serum chloride decreased,
Sodium-Potassium ratio is 30:1
BUN is increased
Blood volume is decreased; hematocrit level is increased (because of water

loss)
Fasting hypoglycemia is present with a flat or glucose tolerance curve and

insulin hypersensitivity.
IV GTT shows a normal peak followed by severe prolonged hypoglyemia.
Anemia: Normocytic, is slight to moderate but difficult to estimate because of
decreased blood volume. Neutropenia; relative lymphocytosis and
eosinophilia is also present.
Increased blood ACTH (200 - 1600 pg/ml) with variation between morning
and evening levels in primary adrenal hypofunction but decreased or absent
ACTH in pituitary hypoadrenalism.
Increased ACTH level is quickly suppressed by replacement therapy.
REMEMBER: An elevated plasma ACTH level in association with a low

plasma cortisol level is diagnostic .

Blood cortisol level is markedly decreased <5ug/dl and fail to rise to more
than twice this level 1 hour after injecting of ACTH, (CONSYTROPIN); This is
a reliable easy screening test to establish primary adrenocortical insufficiency.
Urine 17OHKS are absent or markedly decreased

Urine 17KS are markedly decreased.
To Distinguish Between Primary and Secondary Adrenal

Insufficiency:
1. The plasma ACTH concentration is high (50 pg/ml) or more if adrenal
failure is caused by adrenal disease.
2. Patients with pituitary failure have a low ACTH concentration.
3. If ACTH determination is not available, a metyrapone test should be done.
Metyrapone Test
Administer metyrapone 30mg/kg orally at midnight with a little food to avoid
gastric irritation.
The plasma cortisol at 8 AM the following morning should be <10ug/dl and

the plasma 11-deoxycortisol (Compound-S) should be 7 to 22 ug/dl.
Patients with primary adrenal failure will have low level of both; those with
hypopituitarism will respond to consyntropin but not to metyrapone.
TO DISTINGUISH BETWEEN HYPOTHALAMIC AND PITUITARY

FAILURE:
One can use the response to corticotropin-releasing hormone (CRH).
After 100ug (or 1ug/kg) IV, the normal response is a rise of plasma ACTH of
30 to 40 Pg/ml; Patients with pituitary failure do not response, but those with
hypothalamic disease usually respond.
Plasma and urinary cortisol levels are usually determined by
radioimmunassay.
MEDULLARY FUNCTION
ADRENAL MEDULLARY HORMONES
1. EPINEPHRINE
2. NOREPINEPHRINE
Epinephrine lead to increase of cardiac output and rate, BP(systolic), blood
glucose, basal metabolic rate, sweating, mydriasis.
Norepinephrine: Bradycardia, vasoconstriction and BP (diastolic)

PHEOCHROMOCYTOMA
It is a tumour of chromaffin cells that secretes catecholamine causing

hypertension. 80% of these tumors are in adrenal medulla and 20% other
neural crest cells.
Clinical Features
Hypertension: Paroxysmal in 45% and persistent in 50%.
Other manifestations are tachycardia, tachypnea, sweating, clammy skin,
severe headache, tremor, angina, palpitation, nausea, vomiting, visual
disturbance, retinopathy and cardiomegaly.
Laboratory Findings
Blood and urine levels of norepinephrine and to a lesser extent epinephrine
are increased, usually even when patient is asymptomatic and normotensive.
Urine VMA (vanillymandelic acid; A catacholamine metabolite excretion is
considerably increased. This determination is simple method for diagnosis.
(Beware of false increase due to foods (e,g vanilla, fruits especially bananas,
coffee, tea and drugs e.g vasopressor agents ingested within 72 hours before
the test.
Hyperglycemia and glucosuria found in 50% of patients during attacks.
GTT show diabetic curve.
Provocative Test
Glucagon (0.5 to 1 mg injected rapidly IV( with provoke a rise in BP >35/25
mmHg within 2 minutes in normotensive patients with pheochromocytoma.
Phentolamine mesyrate must be available to terminate any hypertensive crisis.
If a patient with pheochromocytoma is hypertensive, phentolamine 5 mg
injected IV will cause a fall in BP > 35/25 mmHg within 2 minutes. False
positive results occur in patients with uremia, stroke and malignant
hypertension, and in those taking certain
pharmacological agents.
Pheochromocytoma is present if a fall in BP=35/25 mm/Hg. A fall in glucose
> 18mg/dl or rise in insulin >13uu/ml
A test using oral clonidine has been described. Forty eight hours after
discontinuing all drugs that act on the sympathetic nervous system, the patient is
given 0.3 mg of clonidine. Blood is drawn for plasma catecholamine
determinations prior to and 3 hours
following the administration of clonidine. The normal response is a fall of plasma
norepinephrine values to normal (<400ng/ml) and a fall of at least 40% from
basal values. Patients with pheochromocytoma maintain elevated values.
Other investigations are CT scan, MRI (Magnetic Resonance Imaging),
IV pyelography and nuclear imaging techniques (e.g
metaiodobenzylguanidine containing which is useful to locate tumor for
surgery).

REVIEW QUEATIONS
1. The following are features of an Answer:

addisonian crisis A, B and D are False
A. Low serum ACTH concentration C and E are true
B. Hyperkalemia Addison‟s disease is primary
C. Metabolic alkalosis adrenal failure; therefore
D. Hyperglycemia adrenocorticotropic hormone
E. Uremia (ACTH) levels are high and these
are associated with skin
pigmentation. Lack of
mineralocorticoids leads to salt and
water loss and hyponatremia and
uremia can occur but are not
inevitable features unless severe
disease is present.
2. Aldosterone secretion is stimulated by: A, C and D are False

A. Angiotensinogen I B is true
B. ACTH The rennin-angiotensin system is
C. Recumbency the main controlling mechanism of
D.Hypovolemia aldosterone secretion, angiotensin II
being the major stimulus. However
adrenocorticotropic hormone
(ACTH) produces transient increase
in aldosterone secretion.
3.
4. 3. Growth hormone secretion A and D are true
5. A. Occur in short burst B and C are flase
6. B. is inhibited by stress In resting adults growth hormone is
7. C. is stimulated by glucose often undetectable in serum
8. D. is stimulated by interleukin-I between secretory bursts which last
1-2 hours. Secretion is stimulated by
stress, hypoglycemia, exercise and
interleukin I.
9.
4. The following statements concern A, C, D, and E are true
acromegaly; B is false
A. a clinical feature is overgrowth of
skin and subcutaneous tissue Acromegaly cause overgrowth of
B. it is the result of a basophil tumor soft tissues and bones and gigantism
C. it may cause diabetes insipidus may result if it occurs before the
D. it may be accompanied by glucose epiphyses fuse. Some tumors are
intolerance composed of acidophil or
E. it may be accompanied by chromophobe cells. /sporadic cases
galactorrhea of diabetes insipidus occur, as a
result of the local effects of the
space-occuping lesion, while growth
hormone has anti-insulin effects.
Galactorrhea can occur because
hyperprolactinemia is found in
approximately 50% of patients.

5. Plasma (total T4) is increased in
A. Women taking estrogen-containing oral contraceptives (A) is the

B. Patient treated with corticosteroids correct
C. Epileptics treated with phenytoin answer
D. Patients who have recently been investigated by contrast
radiography
6. The response to the TRH is: A. T

A. Exaggreated (i.e a marked increase in plasma (TSH) in primary B. F
hypothyroidism C. T
B. Normal in mild hyperthyroidism D. T
C. Impaired in secondary hypothyroidism
D. Often used to measure anterior pituitary reserve
7. Production of ADH A. F
A. Occurs in response to a fall in plasma osmolality B. T
B. Occurs in response to a fall in ECF volume C. T
C. In excess of physiological requirements tends to cause D. T
hyponatremia
D. Occurs in some patients following head injury
8. Plasma {ACTH} is most likely to be reduced in patients with: (A) is the

A. Adenoma of the adernal cortex true answer
B. Addison‟s disease
C. Chromophobe adenoma of the pituitary
D. Ovarian granulosa cell tumor
9. In the assessment of the thyroid ststus?

A. Basal plasma (TSH) serves to distinguish primary from A. T
secondary hypothyroidism B. F
B. Response of plasma (TSH) to TRH injection should be assessed in C. T
all patients with hypothyroidism before treatment is started. D. F
C. Measurement of blood (TSH) sholud be used to screen for
neonatal hypothyroidism
D. Plasma (TSH) remains raised in hypothyroid patients receiving
adequate drug treatment.

10. Plasma {total T3} A. T
A. Is influenced by changes in plasma {thyroxine-binding globuline} B. F
B. Is normal in patients who are clinically hyperthyroid whenever plasma C. F
{total T4} is normal D. T
C. Is often high in elderly patients who have a non-thyroidal illness E. F
D. Is often low in middle-aged patients soon after a myocardial infarction
E. Is nearly always low in patients with primary hypothyroidism
11. Plasma (total T4) tends to fall in euthyroid patients treated with: A. T
A. Salicylates B. T
B. Cortisol in high dosage C. T
C. Potassium iodide D. T
D. Phenytoin E. T
E. Lithium
12. A clinical diagnosis of primary hypothyroidism would be supported A. T
by: B. F
A. A low plasma (free T4) C. F
B. a greatly increased basal plasma D. T
C. Little or no TSH response to TRH injection E. F
D. Increased plasma (triglyceride) in a fasting specimen
E. Increased plasma {HDL cholesterol}
13. A patient with untreated adrenal insufficiency is liable to have: A. T
A. Hyponatremia B. F
B. hypokalemia C. F
C. Hypocalcemia D. F
D. Hypomagnesemia E. T
E. Fasting hypoglycemia
14. The response to the TRH test is: A. T

A. Exaggerated in primary hypothyroidism B. F
B. Normal in mild hyperthyroidism C. T
C. Impaired in secondary hypothyroidism D. T
D. Used to measure anterior pituitary reserve E. F
E. Usually assessed by measuring plasma {total T4} or {free T4}
15. A diagnosis of pituitary-dependent cushing‟s syndrome is supported A. T

by finding: B. F
A. An increased urinary cortisol: creatinine ratio C. T
B. An increased plasma cortisol response in an insulin-hypoglycemia test D. F
C. An increased plasma {ACTH}
D. Absence of a response in the high-dose dexamethasone test

DIABETES 9
MELLITUS
There is no doubt that this disease afflicted man for thousands of years, but it
was described as a medical condition for the first time by a Greek physician
called Aretaeus. His actual description literally means Melting down of flesh
and limbs to urine”. It was named diabetes from the Greek word meaning”
siphon” because of polyuria and polydipsia that characterized it
Definition: is a generalized metabolic disorder in subjects of heredity
predisposition characterized by weakness, lassitude, loss of weight or failure
to grow in the young, hyperglycemia and glycosuria, fat and protein
breakdown, water and electrolyte, acid base balance disturbances, polyuria
and polydipsia.
In long standing cases of treatment prolongs the life secondary abnormalities
ultimately cause-
1) Renal failure due to pathological changes of the kidney is called Kimmelstil
Wilson syndrome.”
2) Changes in the retinal vessels is called diabetic retinopathy leading to
blindness.
3) Changes in the vessels of central and peripheral nerves leading to cerebral
infraction.
4) Peripheral neuropathy due to affecting of the peripheral nerves”Vasa
Vessera”.
5) Changes in the coronary vessels leading to ischemic heart disease and heart
failure.
Other diabetic important complications are-
A) Premature onset of cataract of eye lenses “diabetic cataract”.
B) Increased susceptibility to infections pyogenic or otherwise the most
important thing is tuberculosis.
Chemical Pathology
The hyperglycemia characteristic of diabetes arises from two main sources:-

1) Reduced rate of removal of glucose from the blood by peripheral tissues;
2) An increased release of glucose from the liver into the circulation.
Consequences of hyperglycemia and glycosuria:

When the glucose concentration exceeds the capacity of the renal
tubules to reabsorb it from the glomerular filtrate, glycosuria 180mg/dl. (renal
threshold) Glucose increases the osmolality of the glomerular filtrate and thus
prevents reabsorption of the water as the filtrate passes down the renal
tubular system. In this way the volume of urine is markedly increased in
diabetes and polyuria and nocturia. This in turn leads to the loss of water and
minerals which results in thirst and polydipsia.. In acute cases, or in more
progressive cases where the condition remains undetected for along period of
time and particularly if the fluid intake has been low because of a mental for
other reasons , severe depletion of water and electrolytes may occur As the
concentration of glucose in the blood rises, the extra cellular fluid becomes
hypertonic and water leaves the cells. In early stages, before the volume of

extra cellular fluid is grossly reduce the patient will show relatively few
clinical signs. If the loss continuesdepletion of ECF will occur with the
development of the clinical features of severe dehydration.
Consequences of poor glucose utilization:
Impaired utilization of carbohydrate results in a sense of fatigue, and causes
two main compensatory mechanisms to operate in an attempt to provide
alternative metabolic substrate. Both of these lead to loss of body tissue, that is
wasting, which may occur in spite of a normal or even an increased intake of
food, and which is additional to any loss of weight resulting from loss of
body fluid.
1) Increased Glycogenlysis and gluconeogenesis:
Glycogen and protein are present in cells associated with water and intra
cellular electrolytes. As glycogen and protein are catabolised, glucose,
nitrogen water and electrolytes particularly potassium are released into the
extra-cellular space. An increased urinary excretion of poatassium,
magnesium and phosphorus therefore occurs in uncontrolled diabetes.
2) Increased Lipolysis:
This is seen as a raised fasting plasma concentration of non-esterified fatty
acids (NEFA) and a diminished fall in plasma NEFA in response to a
carbohydrate load. The extent to which increased lipolysis occurs is
proportional to the degree of insulin deficiency. If the latter is marked, the
normal response to feeding, namely suppression of lipolysis, may completely
lost and the plasma concentration of NEFA may remain consistently elevated
to three or four times of normal level.
Fatty acids are taken up by the liver and dehydrates through eight steps
with in the mitochondria of the liver cells . Each stage yields one molecule of
acetyl coenzyme A. Normally, most of these molecules enter the citric acid
cycle by condensing with oxaloacetic acid, but in severe diabetes more is
formed than it can enter the citric acid cycle. Instead, acetyl coenzyme A is
converted to acetoacetic acid. Most of this is then reduced to beta-
hydroxybuteric acid, while some is decarboxylated to acetone. These ketone
bodies when formed in small amounts are usually oxidized and utilized as
metabolic fuel. Moreover, the role of utilization of ketone bodies is limited.
When the rate of production by the liver exceeds that of removal by the
peripheral tissues, then the blood level rises. Ketone bodies raise the osmality
of the plasma and lead to the withdrawal of water from the cell. They are
strong acids, which dissociates readily and release hydrogen ions in the body
fluids. The fall in pH is reduced by the buffers in the blood, the most
important being bicarbonate. The dissociation of carbonic acid is reduced and
the ratio of bicarbonate to carbonic acid falls and the measurement of plasma
bicarbonate will show low value than the normal. Ketoacidosis occurs. The fall
of pH and increase of Pco2 in the arterial blood stimulate pulmonary
ventilation so that clinically hyperpnoea or “air hunger” is observed.

Normal Control of Energy Metabolism
INSULIN
1. Polypeptide hormone (molecular weight about 6000).

2. Secreted by the beta cells of the pancreatic islet.
3. Composed of two chains, A and B, held together by disulphide linkages
4. Synthesised as a single polypeptide chain (pro-insulin, molecular weight
about 9000). A central peptide (C-peptide) is split off to leave the A and B
chains of insulin.
5. When insulin is released from the islets, equimolar amounts of C-peptide
are released at the same time.
Actions of insulin
1. Reduces hepatic glucose production by:
a. Reducing glycogenolysis . (Glycogen and adrenaline moblise glucose from
glycogen by activating hepatic phosphorylase. Insulin opposes this)
b. Reducing gluconeogenesis-again antagonising glucagon
2. Stimulates glucose transport into cells (except brain, liver and erythrocytes)
3. In adipose tissue, insulin reduces the release of free fatty acids and stimulates
the storage of triglyceride. (The consequent reduction in plasma free fatty
acids is probably the main reason for the anti-ketotic effect of insulin, though
it may also have some direct anti-ketotic effect on the liver.
Other hormones
The other important hormones known to be involved in control of energy
metabolism and have actions which tend to antagonise insulin;
a. Glucagon
b. Adrenaline
c. Cortisol
d. Growth hormone
Classification of Diabetes Mellitus and Related Conditions

1. Diabetes mellitus
I. Insulin-dependent (IDDM) or type I ; formerly known as “juvenile-onset”
II. Non-insulin-dependent (NIDDM) or type II ; formerly known as maturity-
onset
Can be subdivided into:
a. Obese
b. Non-obese
III. Secondary diabetes associated with:
a. Pancreatic disease
b. Hormonal disorders (e.g cushing‟s)
c. Drug or chemical agents
d. Insulin receptor abnormalities
e. Genetic syndrome
f. Miscellaneous
2 Impaired glucose tolerances
3. Statistical risk classes
I. Previous abnormality of glucose tolerance
II. Potential abnormality of glucose tolerance e.g relative with diabetes,
HLA type with increased risk

Insulin-dependent diabetes mellitus
1. Onset usually in childhood or youth
2. Florid symptoms often including weight loss
3. Rapidly progressive course and lethal in the absence of insulin treatment
4. Prone to develop ketoacidosis
5. Etiology:
I. Genetics-associated with possession of HLA-DR4
II. Viral infection appears to be the most probable agent linking the
genetic susceptibility with beta cell damage and failure perhaps directly or by
way of intermediary autoimmune processes.
Non-insulin-dependent diabetes mellitus

1. Onset usually at an older age than IDDM (though there is a distinct subgroup
with onset in youth and a strong familial tendency-previously called‟
maturity-onset diabetes of youth”
2. Symptoms often less marked than IDDM and often associated with obesity.
3. Can often be controled with diet +/- or hypoglycemic agents
4. Much less prone to ketoacidosis than IDDM
5. Etiology
I. Genetic susceptibilty seems to play an even more important role than in
IDDM.
II. Often associated with tissue resistance to the effect of insulin-obesity often
appears to be important in this.
Impaired Glucose Tolerance

1. Mildly impaired glucose tolerance isufficient to warrant a diagnosis of
diabetes
2. Includes those previously called „Chemical‟, “borderline‟, subclinical or
early diabetics.
3. Annually, 2-4% of these develop unequivocal diabetes
4. Virtually no risk of clinically significant diabetic retinopathy or
nephropathy.
5. Double the normal risk of coronary heart disease
6. In pregnancy, some believe it should be treated as diabetes
Metabolic defect in uncontrolled diabetes mellitus

The basic defect is insulin deficiency (relative or absolute). This leads to:
1. Hyperglycemia caused by:
I. Increased hepatic glucose production (now believed to be the cause of
hypoglycemia) this results from unopposed action of the insulin above)
II. Impaired insulin utilization in turn caused by:
a. Raised circulating free fatty acid levels, free fatty acid can be used as an
alternative substrate by many tissues and when present in sufficient
concentration, they inhibit glucose utilization.
b. Reduced direct action of insulin on glucose uptake in peripheral tissues- this is
now thought to less important than (a).
2. Increased plasma concentration of free fatty acids, ketone bodies and

triglycerides
I. Insulin lack causes lipolysis in adipose tissue thus releasing fatty acids into
the circulation
II. Increased circulating free fatty acid concentration in turn stimulates hepatic
synthesis of ketone bodies and triglycerides
Symptoms of Diabetes Mellitus
Some or all of the following may be present
1. Polyuria and polydipsia-if hyperglycemia is sufficient, the renal tubular
maximum for glucose reabsorption will be exceeded leading to glucosuria and
consequent osmotic diuresis. The polydipsia is secondary to this.
2. Weight loss
3. Recurrent infections-related to the consistently high plasma glucose
concentrations. Urinary infections related to the glucosuria
4. Symptoms related to the complications of diabetes.
Diagnostic Criteria
1. Random venous plasma glucose of 8 mmol/l or more or
2. Fasting venous plasma glucose of 8 mmol/l or more
If diabetic symptoms are present, one abnormal value is sufficient to confirm
the diagnosis, otherwise any abnormality should be confirmed by repeat
testing.
Postprandial values below 8 mmol/l or fasting values below 6 mmol/L on at

least two occasions exclude the diagnosis of diabetes
An oral glucose tolerance test is indicated:

1. When random or fasting plasma glucose fall in the equivocal range.
2. In pregnancy glucosuria
Glucose Tolerance Test

Both the British Diabetic Association and the World Health Organisation now
recommend using a 75 g oral glucose load.
1. The patient should not have been on a low carbohydrate diet for the three
days prior to the test.
2. The patient should fast overnight. On the day of the test he/she should eat
nothing and drink nothing but water.
3. Take a fasting blood sample for glucose estimation
4. Give 75g of glucose dissolved in water. This may be flavoured with squash
if desired or special sachets of flavoured glucose can be used
5. Take further blood samples for glucose estimation at 30, 60, 90, and 120
minutes.
If it is desired to assess the renal threshold for glucose, urine samples may be
collected for glucose estimation basally and at 60 and 120 minutes

TABLE 9.1: DIAGNOSTIC VALUES FOR 75 G ORAL GLUCOSE
TOLERANCE TEST
Glucose concentration (mmol/l)
NB: Conversion factor of mg/dl mmol/L is 0.05552
Venous Capillary
Whole Plasma Plasma
blood Whole
blood
Diabetes Mellitus  7.0  8.0  7.0  8.0
Fasting and /or
Two hours after glucose load 10.0  11.0  11.0  12.0
Impaired glucose tolerance < 7.0 <8.0 < 7.0 < 8.0
Fasting
And
Two hours after glucose load 7.0 – 10.0 8.0 – 11.0 8.0 -11.0 9.0 – 12.0
Clinical Significance
The glucose tolerance test (GTT) is based on the fact that a nondiabetic
individual removes a test load of glucose from circulation at a faster rate than
an individual with diabetes. As glucose is absorbed into the blood stream, the
nondiabetic‟s blood sugar rises to peak levels of 150-160 mg/dl (8.3- 8.8
mmol/l), triggering the release of insulin to meet the challenge; the urine
usually remains free of glucose and the blood sugar returns to fasting levels 2-
3 hours after glucose ingestion. In individuals with diabetes the blood sugar
peak levels are much higher, glucose is present in the urine, and the return to
fating levels is delayed due to a leak of insulin response to the glucose.
The rate of oral glucose absorption from the gastrointestinal tract influences
the insulin response. Therefore an intravenous glucose tolerance procedure
should be used when malabsorption or erratic states of absorption are
suspected.
The intravenous method should be used in patients with impaired absorption
such as occurs in sprue, celiac disease, Addison disease, hypopituitarism, or
hypothyroidism, which give a virtually flat oral glucose tolerance curve. The
procedure is also advantageous in thyrotoxicosis, in which absorption is
accelerated, thus giving a hyperglycemic curve, and in organic or functional
hyperinsulinism, in which it is important to know that the full glucose dose
enters the system.
Conditions such as pregnancy, endocrine disorder, prolonged physical
inactivity, infectious diseases, surgery, acute illness, trauma, and pyrexia can
influence the outcome of the glucose tolerance test and reduce the significance
of the findings.

Variation and Interpretation
Several systems for interpreting GTT
results take into account not only the
highest blood sugar level attained
during testing but also the pattern of
test values after peak. Abnormal glucose
curves are usually diagnostic of diabetes
mellitus, although various other curves
indicate that additional disease,
particularly hormone disorders.
In general, patients with diabetes
demonstrate the following:
 Elevation fasting blood glucose and
glucosuria in the fasting urine
specimen.
 Glucose peak values of a healthy
person
 Glucose peak values that persist
for longer periods of time than
normal-frequently for as long as 4
hours
 Urine specimens that exhibit FIGURE :Glucose tolerance curve
glycosuria in degrees that parallel 1. DM, Mysthenia gravis, brain injury,
blood glucose values. cushing pituitary basophilism, acromegaly
A correction factor for older (early) and hemochromatosis
individuals is recommended to prevent 2. Alimentary glycosuria and infusion of
the false diagnosis of mild diabetes in glucose
persons who are actuall normal for 3. Hypogonadism, hyperthyroidism, and
their age. Normal test values should be emotional strain
increased by 10-15 mg/dl for 4. Normal to second hour curve continues as in
individual in their 60s and by 20-30 insulin shock, spontaneous hypoglycemia and
mg/dl for those in their 70s. hypoadrenalism
5. Renal glycosuria
6. Pituitary fatigue
7. Pituitary deficiency and myxedema
8. Anorexia nervosa, hyperinsulinism and
Addison disease.
Adapted fromJudith Byrne: Laboratory test.
1981.
Acute Complications of Diabetes

1. coma/precoma
I. Hypoglycemia
II. Ketoacidosis
III. Hyperosmolar non-ketotic coma
IV. Lactic acidosis
N.B It should be stressed that non-metabolic comas are just as common in
diabetics as non-diabetics and are generally associated with some loss of
glycemic control.
2. Infection
3. Acute neuropathy

Hypoglycemia
Hypoglycemia is the most common cause of unconsciousness in the diabetic
taking insulin. It may also occur in patients on sulphonylurias, though this is
less common.
Ketoacidosis
If the metabolic defect in uncontrolled diabetes is sufficiently severe, it may
lead to ketoacidosis. This occurs mainly in IDDM when untreated,
inadequately treated or when some precipitating factor (e.g infection) causes
increased secretion of insulin-antagonist hormones.
Features
1. Hyperglycemia-leading to osmotic diuresis which in turn causes:
I. Sodium and water depletion and hence hypovolemia
II. Potassium depletion-but despite total body potassium depletion, the
plasma potassium may be high before treatment because of a shift of
potassium out of cells caused by:
a. Acidosis
b. The fact that insulin normally drives potassium into cells. This shift of
potassium out of cells accentuates the urinary potassium loss.
III. Phosphate depletion
2. Markedly increased ketone body production leading to:
i. Ketonuria and the small of acetone on the breath
II. Severe metabolic acidosis-caused by the ketone bodies: beta hydoxy-
butyrate and acetoacetate. (4+ketonemia is necessary to make a diagnosis or
ketoacidosis).
III. Hyperventilation (Kussmaul respiration) an attempt to compensate for the
metabolic acidosis
3. Impairment of consciousness-related to the metabolic disturbances.
Hyperosmolar non-ketotic coma

1. Generally occurs in the elderly
2. Occurs most often in NIDDM
3. Pathogenesis obscure, but many cases are associated with a high
carbohydrate intake, e.g carbohydrate-rich drinks
4. Absence of significant ketoacidosis
5. Hyperglycemia- (plasma glucose often>50 mmol/l)osmotic diuresis
water and electrolyte depletion, water loss often being relatively greater than
sodium loss hypernatremia (50% have plasma sodium>150 mmol/l).
Dehydrationhigh plasma urea (often>20mmol/l). All these changeshigh
plasma osmolality (often >360 mmol/kg)
Lactic acidosis
1. Rare cause of metabolic acidosis in the diabetic
2. Usually related to the use of biguanides (phenformin and metformin)-the
incidence has dropped sharply with the decreased use of these drugs
3. Plasma glucose may be high, low or normal
Chronic Complication of Diabetes

1. Diabetic retinopathy
2. Diabetic nephropathy
 Proteinuria is the clinical hallmark

 Once established, progressive deterioration of renal function is inevitable
4. Diabetic neuropathy: osmotic and autoimmune neuropathy
5. Atheroma: Occurs earlier and more extensively than in the non-diabetic
6. Diabetic foot
 Caused by:
a. Neuropathic damage
b. Ischemic related to atheroma
MONITORING OF TREATMENT
Good control is important in reducing the likelihood of complications.
1. Urine testing
 The renal threshold for glucose is usually about 10 mmol/l, so urine
testing is useless for plasma levels below this
2. Blood/plasma glucose
 Venous blood samples may be taken periodically, but this cannot be
performed frequently enough to provide a really reliable assessment of
glycemic control (unless the patient is in hospital)
 Capillary blood samples can be taken by the patient and blood glucose
assessed immediately by means of a stick test or dried blood spots (on special
filter paper) can be sent to the laboratory through the post.
3. Glycated hemoglobin (i.e glycosylated hemoglobin or hemoglobinA1c
 During the life-span of the erythrocyte, its contained hemoglobin
becomes slowly modified by non-enzymatic reaction with glucose. The rate of
this glycation is dependent on the prevailing plasma glucose concentration
and once formed the glycated hemoglobin remains in the red cell. The
proportion of hemoglobin which is glycated gives an estimate of the glycemic
control over the preceeding 6-8 weeks.
 Useful for assessing long term control, but short term swings
between hyperglycemia and hypoglycemia can only be detected by serial
glucose measurements.
 Poor index of control in patients with anemia or increased red cell
turnover.
HYPOGLYCEMIA
Causes
I. Reactive postprandial hypoglycemia
1. Related to gastric surgery
2. Idiopathic
3. Rare causes in infants and children e.g fructose intolerance,
galactosemia
II. Fasting hypoglycemia
1. Insulinoma
2. Extrapancreatic tumours especially saromas (e.g retropertitoneal
fibrosarcoma)
 By secretion of a pro-insulin-related peptide
 Tumor usually palpable or visible on X-ray of chest or abdomen
3. Ethanol-induced (Ethanol inhibits gluconeogenesis, but normally blood
glucose can be maintained from glycogen reserves. However, if glycogen
reserves are slow, as in alcoholics who drink but do not eat, hypoglycemia
may occur.
4. hypopituitarism/adrenal insufficiency
5. Severe liver disease
6. Factitious hypoglycemia: patient surreptitiously taking insulin or a
sulphonylurea drug
7. Other cause in childhood
 Temporary neonatal hypoglycemia as in small for-dates babies and babies
of diabetic mothers
 Ketotic hypoglycemia: usually in boys aged 1-8 years who often have been
small foe-dates when born
 Nesidioblastosis (rare): Persistent hypoglycemia occurs in the neonate.
 Rare inherited disorders e.g type I glycogen storage disease and
galactosemia
Diagnosis
Reactive Hypoglycemia
In suspected reactive hypoglycemia, an oral glucose tolerance test with
samples taken up to 5 hours, will determine if hypoglycemia develops with
coincident symptoms.
Fasting Hypoglycemia
1. Most causes of fasting hypoglycemia in adults, other than insulinoma, can
be easily recognized clinically
2. Measurement of plasma insulin during hypoglycemia is helpful,
inappropriately high levels are found with:
a. Insulinoma
b. Factitious hypoglycemia
c. Nesidioblastosis
In these situations, the excess insulin prevents ketosis
Most insulinomas are easily diagnosed by plasma glucose and insulin assay
during a presenting hypoglycemic episode or after an overnight fast. If
hypoglycemia doesn‟t occur with an overnight fast, the following are probably
now the tests of choice:
1. Induce hypoglycemia with injected insulin and then measure plasma C-
peptide. Normal patients will show suppression of C-peptide, reflecting
suppression of their own endogenous insulin release (C-peptide is secreted
from the islet cells on an equimolor basis with each insulin molecules) or
2. Measure fasting pro-insulin (the tumorous are always moderately
undifferentiated and secrete a high proportion of pro-insulin)-this would be
the easiest diagnostic method, but unfortunately, pro-insulin assays are not
widely available yet.

REVIEW QUESTIONS
1. In the measurement of glucose concentrations:

A. Enzymic and reductive methods are equally satisfactory at all A. F
levels B. F
B. Analysis on plasma tend to give lower results than analyses C. F
on blood D. T
C. There is no significant difference between results obtained on E. T
capillary and on venous specimens
D. Sodium fluoride is used as preservative as it inhibits
glycolysis
E. Reflactance meters can be used satisfactorily by patients to
control their insulin dosage.
2. In the performance of an oral glucose tolerance test A. F

A. The patient‟s carbohydrate intake should be restricted to B. T
50gm/dl for 3 days prior to the test, and the patient should fast C. F
beforehand overnight D. F
B. The patient should not have been unusually energetic before E. T
the test
C. Nervous patients may smoke during the test to relieve their
anxiety.
D. During the test, if lying down, the patient should lie on the
left side
E. The test should be prolonged if reactive hypoglycemia is
suspected.

3. The renal threshold for glucose
A. Usually rises with age A. T
B. Is sometimes exceeded during an oral glucose tolerance test in B. T
normal individuals C. F
C. Is unaltered by pregnancy D. F
D. Is often reduced in patients with diabetes mellitus E. T
E. Can be determined by giving an intravenous infusion of 5%
glucose.
4. Hypoglycemia
A. Should always be investigated by means of an enzymic A. T
technique B. F
B. Is defined as a plasma (glucose) below 3.0 mmol/l (55 mg/100 C. T
ml) D. T
C. In a fasting patient, not treated with insulin, is due to
insulinoma if fasting plasma {insulin} is increased
D. Stimulates the production of glucagon. A. T
B. F
5. Which of the following may be associated with fasting C. T
hypoglycemia? D. T
A. Addison‟s disease (primary adrenocortical failure)
B. Hereditary fructose intolerance (B) is
C. Hypopituitarism the
D. Acute hepatic failure correct
answer
6. A fruity odor in freshly voided urine can usually be
attributed to :
A. Proteus infection
B. Diabetes mellitus
C. Diabetes insipidus {C}
D. Aminoaciduria shock
causes a
7. All of the following conditions may cause polyuria except decrease
A. Diabetes mellitus d blood
B. Diabetes insipidus flow to
C. Shock the
D. Water loading kidneys
8. The best method to monitoring of treatment of DM

A. Urine strips test B is the
B. Glycated hemoglobin HgbA1C correct
C. GTT answer
D. Rondom bloog glucose

10
CENTRAL NERVOUS
SYSTEM
CEREBROSPINAL
FLUID
Examination of the cerebrospinal fluid (CSF) is used in the clinical

investigation of the central nervous system, which consists of the brain, spinal
cord and peripheral nerves.
The brain is about one-fifth of the body weight and lies within the cranial
cavity. It is divided structurally into the cerebrum (greater brain), the brain
stem consisting of the midbrain, ponsvarolii and medulla oblingata, and lastly the
cerebellum or lasser brain.
The four irregularly shaped ventricles, namely the right and left lateral, and
third and fourth ventricle, play an important part in the formation of CSF.
Completely surrounding the brain and spinal cord are three membranes
known as dura mater (outer membrane), the arachnoid mater (middle
membrane) and pia mater (the inner membrane). The pia mater and arachnoid
mater are separated from each other by the subarachnoid space. Between the
tough outer coat (dura mater) and arachnoid mater is the subdural space
containing a small amount of tissue fluid.
FORMATION OF CSF
Within the lateral ventricles are the choroids plexuses, where the CSF is
formed. They are a network of complex capillaries projecting into the
ventricular cavities, covered only by the pia mater and a single layer of cells
lining the ventricular system of the brain. The CSF formed by the choroids
plexuses passes into the third ventricle via the interventricular foramen
(foramen of Monoro), then by the aqueduct of the midbrain into the fourth
ventricle. From the roof of the fourth ventricle the CSF flows through the
foramina into the subarachnoid space to completely surround the brain and
the spinal cord. At the same time, CSF also flows from the floor of the fourth
ventricle downwards through the central canal of the spinal cord. The
production of the CSF is balanced by an equal absorption of fluid, probably
taking place in the blood capillaries of the arachnoid mater. By this process the
total volume of CSF is completely returned to the circulating blood every 6-8
hours.

FUNCTION OF CSF
1. Supports and protects the delicate structures of the brain and spinal cord
2. Acts as a cushion and shock absorber
3. Used as a reservoir to regulate the contents of the cranium, i.e if the volume
of the brain or blood increases, CSF drains away; if the brain shrinks, more
fluid is retained.
4. Keeps the brain and spinal cord moist.
5. May act as a medium for the interchange of metabolic substances between
nerve cells and the CSF.
OBTAINING CSF
Specimen of CSF are obtained by introducing a long needle between the third
and fourth lumbar vertebrae into the spinal subarachnoid space, with the
patient‟s back flexed to separate the vertebrae. The cord ends at the level of
the first lumbar vertebra and cannot be damaged by the needle entering the
subarachnoid space an inch or so lower.
A lumbar puncture is far safer than a cisternal puncture, which involves
passing the needle between the occipital bone and the atlas into the cisterna
magna at the base of the brain.
COMPOSITION OF THE CSF
The volume of the CSF average between 120 and 150 ml, and is produced at
the rate of about 0.3 ml per minute (430 ml/day). It consists of water,
dissolved oxygen and a number of solids. The specific gravity is about 1.005,
pH 7.4-7.6, and it contains up to 5 lymphocytes per mm3 . It is clear, colourless
fluid and should show no coagulum or sediment on standing. The
composition is very similar to that of plasma, except in protein concentration
(table 1). CSF can therefore be considered an ultafiltrate of blood.
TABLE 10.1 : COMPOSITION OF CSF

Plasma CSF
Total Protein (g/L) 6.0-8.0 0.15-0.45
Glucose (mmol/l) 3.0-5.3 2.8-4.4
Chloride (mmol/l) 96-106 120-130
A sample of CSF sent to the laboratory for routine examination requires the
following investigations; appearance, cell count, total protein, globulin,
chloride and glucose. In place of the Lange colloidal gold curve and
electrophoresis, which is required in certain hospitals, the estimation of the
specific immunoglobulin IgG to that of albumib is a far better parameter to
determine
The diagnostic importance of CSF examination lies in the cytological and

chemical changes produced by certain diseases. Normal ranges and values
obtained in various conditions can be seen in table 10.2.

TABLE 10.2: CHANGES IN CSF IN VARIOUS CONDITIONS
Condition Appearance Cells/l Protein Glucose Cl

And type (g/l) mmol/l (mmol/l)
Normal Clear/colorle <5 lympho 0.15-0.45 2.8-4.4 120-130
ss
Tubercular Clear/ lymphos and  <2.8 85-120
meningitis slight turbid polys
Acute pyogenic Turbid to 3+P 3+ - -

meningitis purulen
Viral menigitis Clear 2+L N -+- N N

Subarachnoid Bloody or N or  polys  2.8-4.4 120-130
hemorrhage yellow
Multipe N to +-L N to 1+ N N
sclerosis Clear
Xanthochromia Yellow N or  N or  2.8-4.4 120-130
lymphos
N= normal, - decrease , L lymphocyte, P polymorphs +- slight increase, 1+
increased, 2+ moderate increase, 3+ markedly increase.
COLOR
Normal cerebrospinal fluid is a colorless liquid with the appearnce of water.

Abnormal coloration may be due to the presence of blood, bile or a yellow
pigment (xanthochromia), which reflects a mixture of bilirubin and other
hemoglobin derivatives. Xanthochromic spinal fluid is caused by old blood or
extremely elevated protein levels in the central nervous system, which may
appear following cerebral hemorrhage or brain tissue destruction. Spinal fluid
discoloration begins 4-5 hours after subarachnoid hemorrhage and usually
remains discolored for 3 weeks after the event. The fluid usually clears within
several days following a traumatic spinal tap.
Normal cerebrospinal fluid is crystal clear. Decreaed CSF transparency, which

can range from slight cloudness to marked turbidity, signifies the presence of
an infectious process such as acute meningitis, purulent meningitis, or
meningoencephalitis. The turbidity is caused by a significant number of
leukocytes. Marked turbidity results from greater than 500 WBCs/l. Fewer
than 200 WBCs/l will not produce visible clouding. However a clear spinal
fluid does not eliminate the presence of such central nervous system disorders
as encephalitis, intracranial hemorrhage, and tuberculosis meningitis.
Blood: Cerbrospinal fluid does not normally contain blood. The presence of
red blood cells indicates either intracranial hemorrhage from such as trauma,
hypertension, cerebral arteriosclerosis, rupture aneurysm, or localized trauma
during the spinal puncture. Folowing the traumatic spinal tap, the red blood
cells generallay diminish after the first test tube of fluid is collected, whereas
cells are evenly distributed among all three collection tubes after a cerebral
hemorrhage. An intracranial hemorrhage may also be identified by
xanthochromia and the presence of creneated red cells, which indicate the
blood, had been in contact wioth the CSF for an extended period of time.

CSF CELL COUNT
The spinal fluid cell count includes an actual enumeration of the cellular
elements in 1 ml3 of CFS and classification of different types of white cells. The
types of white cells present in spinal fluid are determined by performing a
differential count and reporting the percentages of segmented cells (chiefly
neutrophils and mononuclear cells (chiefly lymphocytes). Differential
classification of white cells is generally not significant when the total cell count
is within the normal range but may have an important diagnostic value when
the number of cells is increased. Laboratory determinations of total and
differential spinal cell counts may be used in the diagnosis and treatment of
such central nervous system disorders as meningitis, poliomyelitis and
encephalitis.
Abnormal spinal fluid cell counts may vary from 20-1000 WBCs/l, with the
degree of reaction depending upon the nature and duration of the disease
involved. Moderate cellular increases (300-500/l) generally indicat viral
infection such as poliomyelitis, TB meningitis, neurosyphilis and encephalitis.
Markedly increased cell counts (500/l and over) are found in most types of
meningitis, especially pyogenic meningitis. However a normal spinal cell
count does not necessarily exclude central nervous system pathology, since
values may remain within normal limits in multiple sclerosis, epilepsy, and
brain tumor.
CSF GLUCOSE
Cerebrospinal fluid glucose concentrations are directly related to the rate of
glucose diffusion from the blood and rise or fall in proportion to metabolic
alteration. Any significant variation in blood glucose levels is reflected in CSF
glucose values and causes them to undergo a corresponding change after a 30-
60 minute lag.
Spinal fluid glucose levels are clinically significant when values are decreased,
suggesting the presence of microorganisms, leukocytes, or metastatic cancer
cells that metabolize and utilize the sugar. The most dramatic drop in CSF
glucose occurs with purulent meningitis when the combination of pyogenic
bacteria and leukocyte activity may reduce spinal fluid glucose to zero.
Howevere, low spinal fluid glucose determinations are nonspecific and have
little value in the diagnosis of bacterial meningitis (including tubercular)
unless pleocytosis is present. CSF glucose concentrations provide the sole
differentiating factor between viral and tubercular meningitis and are useful
in the differential diagnosis of these central nervous system disorders.

Decreased CSF glucose (under Incraesed CSF
40 mg/dl) may occur with the glucose (over 80
following mg/dl may occur
 Acute pyogenic meningitis with the following
 Bacterial meningitis
 Brain abscess  Brain tumor
 Fungal meningitis  Diabetes
 Leukemic infiltration  Following cerebral
 Lymphocytic infiltration hemorrhage
 Lymphoma  Hypothalamic lesions
 Melanomatosis  Neurosyphilis
 Meiningeal carcinomatosis  Post-infectious
 Neurosyphilis encephalitis
 Primary tumor of brain (communicable
 Sarcoidosis of CNS disease)
 Subarachnoid hemorrhage
 Systemic hypoglycemia
 Toxoplasmosis
 Tubercular meningitis
Spinal Fluid Protein
Cerebrospinal fluid protein is derived from small quantities of serum protein

diffused from the blood across the blood-brain barrier. The predominant
protein found in normal CSF is albumin. Albumin is a small molecule that
crosses endothelial barrier more easily than globulin and produces an
albumin-globulin (A/G ratio of 4:1 in the CSF.
Increased spinal fluid concentrations frequently provide little additional
diagnostic information, as the increase is often the result of intracellular
proteins released from the disintegration of previously identified erythrocytes
and leukocytes. The appearance of blood in the spinal fluid increases total
protein values by 1 mg/100ml of CSF for every 700-1000 red cells present.
However if elevated total protein values are the only abnormality identified in
a spinal fluid evaluation, it may indicate a serious pathologic condition, since
these disorders would be characterized by the disintegration of cells other
than erythrocytes and leukocytes or by the increased leakage of plasma
proteins through diseased capillary walls.
An analysis of each spinal fluid protein fraction may be obtained by CSF
protein electrophoresis. For example increased -globulin concentration occurs
in multiple sclerosis, CNS syphilis and Subacute sclerosing leukoencephalitis.
Elevation of the -globulin fraction accompany acute meningitis, neoplasm
and cerebral vascular disease processes.
Normal values for spinal fluid protein electrophoresis are as follows:
Prealbumin 3% - 6%
Albumin 45%-68%
1-globulin 3%-9%
2-globulin 4%-10%
-globulin 10%-18%
-globulin 3%-11%

Increased CSF protein may occur with the following:
 Aseptic meningitis  Froin syndrome

 Bacterial  Heavy metal intoxication
meningoencephalitis  Intracerebral hemorrhage
 Brain abscess  Latent syphilis
 Brain tumor  Local anesthesia in spinal
 Cerebral canal
arteriosclerosis  Meningitis
 Contamination with  Mycotic
blood meningoencephalitis
 Degnerative disease  Myxedema
such as ascending  Newborn infants
polyneuritis,  Poliomyelitis
Guillian-barre  Purulent meningitis
syndrome, multiple  Subarachnoid hemorrhage
sclerosis and  Syphlitic
neurosyphilis meningoencephalitis
 Diabetic neuropathy  Tubercular meningitis
 Phenytoin  Vacular malformation
intoxication
 Drugs such as
aspirin,
chloropromazine,
streptomycin and
sulfonamides
 Encephalitis
CSF Chloride
CSF chloride is derived from plasma that has difussed across the blood brain
barrier . Unlike other CSF constituents, chloride occurs in higher
concentrations in the CSF than in the blood plasma.
Decreased CSF chloride may occur with the following:
Bacterial meningitis
Decreased plasma chloride concentration
Tubercular meningitis

REVIEW QUESTIONS
1. What are the normal cerebrospinal fluid (CSF) volume and the normal rate
of formation of CSF in the adult men?
An: The normal CSF volume in adult men is between 120 and 150 ml. The
normal rate of formation is about 430-500 ml/24hours.
2. How much spinal fluid should be withdrawn for analysis?
An: Ordinarily, 6 to 8 ml is divided among three sterile tubes, but up to 20 ml

may be withdrawn when indicated.
3. What is xanthochromia?
An: Xanthochromia is a yellow or orange coloration of supernatant

centrifuged spinal fluid.
4. Which of the three tubes of spinal fluid should be used for the cell count?
An: Use the third tube, because it is least likely to be contaminated with blood.
5. How does the spinal fluid glucose level relate to the blood glucose level in
the absence of central nervous system diseases?
The spinal fluid glucose level is approximately two thirds of the blood glucose
level, but when the blood glucose level is abnormally high, the ratio falls
below 0.6. Rapid changes in blood sugar also alter the relationship, since
equilibrium requires 2 hours.
6. How should spinal fluid be processed in the bacteriology laboratory?

Centrifuge the specimen, and use sediment for smears (Gram stain and India
ink (for Cryptococcus) and culture. Use blood agar, chocolate agar, brain-heart
infusion broth at 37C with added CO2 (candle jar), and thioglycollate broth at
37 0C . If yeasts are suspected (lymphocytic pleocytosis), add Sabouraud‟s
glucose agar at room temperature and at 37 0C. Use media appropriate for
acid fast organisms and guinea pig inoculation when indicated.
ANSWER THE FOLLOWIN QUESTIONS

7. Explain the pathogenesis of yellow xanthochromia?
8. How soon does yellow xanthochromia appear after subarachnoid
hemorrhage, and how long does it last?
9. What is the normal spinal fluid cell count?
10. What is the normal range of chloride concentration in CSF?

ARTICULAR SYSTEM
Rheumatic Diseases 11
Arthritis and rheumatism are among the commonest afflictions of mankind.

Rheumatoid arthritis has a prevalence of about 3 per cent in Western
industerialised countries, which rises to 17 per cent in women aged over 75.
Indeed it is estimated that few people will escape a rheumatic condition in
their lives. One in five consultations in general practice is for such conditions.
However, the number of rheumatologists is relatively small and many other
doctors are called upon to treat rheumatic patients. In our curriculum the
student have to study the most common diseases of articular system and the
important investigation related to articular diseases.
Immune mechanism
 Many rheumatological conditions are characterized by abnormal types or
amounts of serum immunoglobulin/antibodies.
 Antibodies can cause disease by two main mechanisms :
1. Cytotoxic mechanism (a type II immune reaction): antibodies are formed
against inappropriate targets (e.g normal tissue)
2. Immune complex mechanism ( a type III immune reaction)
 Inflammatory response is initiated.
- Complement is activated
- Leukocytes are recruited
- Cells coated with antibody are destroyed
- Cell functions are altered
 Immune mediated disease represents an imbalance of inflammatory vs anti-
inflammatory mediations
IMMUNOGENETICS AND DISEASE
- Cell surface molecules called human leukocyte antigen (HLA) or major

histocompatibility complex (MHC) play a role in mediating immune reactions.
- The genes that encodes HLAs are on chromosome 6

- There are three classes of MHC

Table 11.1: Classes of major Histocompatibility complexes (MHCs)
MHC Types Location Function

classes
I HLA-A, B, C All cells Recognized by CD8+ T
lymphocytes
II HLA-DP, DQ, Antigen Presenting Recognized by CD4+
DR cells”mononuclear T lymphocytes
phagocytes, B-
lymphs
III Complement In plasma Chemotaxis, Opsonizate
components lysis of bacteria and cells
HLA and Disease

Individuals with certain HLA types may have increased risk of certain
immune-mediated disease.
Mechanism is not well understood
May be due to
- Molecular mimicry
- Effects on T-cell development
- Inheritance with other pathogenic alleles
- Spurious correlations
Table11.2 : HLA-Associated Rheumatic Disease

HLA-Type Associated conditions Comments
B27 Ankylosing spondiltid In AS, relative risk=70-90
Reiter‟s syndrome In Reiter‟s, relative risk=40
Psoriasis arthritis Psoriasis also associated with B38
IBD arthropathy
DR4, DR1 Rheumatoid arthritis 93% of patients have HLA type
DR3 Sjogern‟s syndrome DR3 associated with many non-rheumatic
SLE conditions (celiac disease, Type I DM,
Rheumatoid arthritis chronic active hepatitis

Table 11.3: Classification of Arthritis and characteristic features
Classification Characteristic feature
Seropositive rheumatic diseases -Skin-nodules, ulceration, rash,
1. Connective tissue disease mucosal ulcers
Rheumatoid arthristis (RA) Raynaud‟s phenomenon
Systemic lupus erythematosus (SLE) Sicca syndrome
Antiphospholpid antibody syndrome (APS) Neurological involvement
Scleroderma/progressive systemic sclerosis Positive serology
(PSS) Constitutionally unwell
Polymyositis (PMY), dermatomyositis(DMY)
Mixed connective tissue disease (MCTD)
Sjogern‟s syndrome
2. Vasulitis
Polyarteritis nodosa (PAN)
Microscopic polyangitis
Wegener‟s granulomatousis
Predominantly cutaneous vasulitis
Giant cell arteritis
Involvement of axial skeleton
Seronegative rheumatic disease Anterior uveitis, conjunctivitis,
Ankylosing spondylitis Enthesitis, Sacroiltis, dactilitis
Reactive arthritis Urethritis, Psoriasis,
Psoriatic arthritis Family histrory
Inflammatory bowel disease (IBD) HLA-B27 association
Crystal induced Remitting recurring pattern

Gout (monosodium urate) Mono or oligoarthristis
Pseudogout (calcium pyrophosphate Tophi
dihjydrate) Renal involvement
Hydroxyaptite deposition disease
Specific/ infections Acute monoarthritis or malignancy

polyarthritis
Constitutional symptoms
Degenerative Insidious onset
Non-articular rheumatism Generalized non-articular pain

Trigger points
Strong association with psychotic
illness
Investigations
Blood work and urinalysis
General: CBC, BUN, creatinine (these will affect therapeutic decision
Acute phase reactants- ESR, C3, C4 and fibrinogen, serum proteins, alpha-2,
gammaglobin, CRP, albumin
ESR is important in diagnosing GCA
Remember: ESR >100 is found in GCA, CTD, SBE, osteomyelitis, TB, renal cell
carcinoma, multiple myeloma and paraproteinemia
Urinalysis to detect disease complications (proteinuria, active sediment)
Serology autoantibodies
Table 11.4 : Autoantibodies and Their Prevalence in Rheumatic Diseases
Autoantibody Disease Normals Comments
RF RA 80% <5% Levels correlates with disease
Sjogern‟s 30% severity in RA
ANA SLE 95%

Other CTD (e.g <5% Sensitive but not specific for SLE
RA, PSS
Levels correlate with disease
Ant-dsDNA SLE 30-70% 0% activity
Specific but not sensitive for SLE

Anti Sm SLE <30 0% Subacute cutaneous LE and
mothers of babies with neonatal
Ant Ro (SSA) Sjogern‟s 40-95% lupus
SLE 25% Usually occur with anti-Ro
Ant-La (SSB) Sjogern‟s 40%

SLE 10% By definition present in APS
only small subset of SLE
Antiphospholipid APS <5% patients develop clinical
antibodies (LAC, SLE 31-40% syndrome of APS
ACLA)
Anti-histone Drug induced SLE

>90% In MCTD
Idiopathic SLE
Anti-RNP >50% 0% In MCTD
MCTD
Anti-centrome 0% Nonspecific and poor sensitive
Anti- CRES >80% Specific but not sensitive
topoisomerase 0% Specific but not sensitive
C-ANCA PSS 26-70% 0%
Active Wegner‟s
Anti-J0-1 10% 0%
Anti-MI-2 0%
Polymyositis 10-
30%
Dermatomyositis
Rheumatoid Factor (RF)
- Autoantibodies (IgM>IgG>IgA) directed against Fc domain of IgG
- Not specific for RA, 5% of healthy people are positive and 10-20% of people
over age 65% are positive.
- Increased in most seropositive diseases, SBE, bacterial and viral infections (i.e
hepatitis C) and many other conditions.
- Method of detection
1. Nephelometry
2. Latex fixation
3. Sheep red agglutination
4. Reported as dilution at which patient‟s serum has no remaining activity
(1:80 suspensions, 1:160 is positive)

Antinuclear Antibodies (ANA)
- Antibodies directed against nuclear components (DNA, RNA, histones,
Centromere, Sm)
- LE cell preparation – indirect test of ANA
-LE cells are PMNs that have phagocytosed extruded nuclei of other cells
- Typical of SLE, seen in RA, PSS, infections
- Fluorescent ANA test

- Fluorescent markers bind ANA
- SLE shows rim or homogenous pattern, PSS, Sjogern‟s, RA and MCTD
shows speckled pattern
- Anti DNA Ab test

- Abs are directed against single stranded (ss) or double stranded (ds)
DNA
- Lupus characterized by anti-dsDNA Ab
- Crithidia test is specific for dsDNA
- Elisa for Farr (radioimmunassay) is both specific to disease and specific to

change in disease reactivity
Antibodies against Clotting Factor

- Present in SLE
- Tested by anticoagulant activities; PTT
- Confirmed by 50:50 test and serology
Antibodies against Erythrocytes

Tested by hemoglobin level, direct Coomb‟s test, reticulocyte count, leukocyte
count, and platelet count.
Antigen-Antibody (Ag-Ab) complexes:

- Can detect them with the following tests:
1. Low serum C3 and C4 levels
2. Lupus band test on tissues biopsy
- Immuno-fluoresenct Ab against IgG and C3 at the dermal-
epidermal junction
3. Light microscopy for ragocytes, which are PMN, that have engulfed Ag-
Ab complexes
Synovial fluid
Synovial fluid is a transparent, viscous fluid secreted by the synovial
membrane. This fluid is found in joint cavities, bursae, and tendon sheaths. Its
function is to lubricate the joint space and transport nutrients to the articular
cartilage. Impaired function of synovial fluid with age or disease may play a
role in the development of degenerative joint disease (osteoarthritis). A variety
of disorders produce changes in the number and types of cells and the
chemical composition of the fluid. Analysis of synovial fluid plays a major role
in the diagnosis of joint diseases.

Anatomy and physiology of joints
Diarthrodial joints are lined at their margins by a synovial membrane
(synovium), with synovial cells lining this space. The lining cells synthesize
protein and are phagocytic. Mechanical, chemical immunological or
bacteriological damage may alter the permeability of the membrane and
capillaries to produce varying degrees of inflammatory response. In addition,
inflammatory joint fluids contain lytic enzymes that produce depolarization of
hyaluronic acid, which greatly impairs the lubricating ability of the fluid.
Arthrocentesis
Arthrocentesis constitutes a liquid biopsy of the joint. It is a fundamental part
of the clinical data base, together with the medical history, physical
examination, and plain radiographic films. Analysis of aspirated synovial
fluid is essential in the evaluation of any patient with joint disease because it
provides a better reflection of the events in the articular cavity, to blood tests.
Arthrocentesis is the process performed by a physician for obtaining synovial
fluid. It is readily obtained by aspiration from most joints. Frequent sites of
aspiration include the knee, shoulder, elbow, wrist, interphalangeal joint, hip,
and ankle. As with other procedures involving potentially infectious fluids,
gloves should be worn, when performing an aspiration or handling of the
fluid. Infiltration of the site with lidocaine to decrease pain into the deeper,
pain-sensitive structures of the capsule or periosteum increases the risk of
injecting anesthetic into the joint space and can interferes with the results of
some assays.
Three Most Important Tests of synovial fluid (The three Cs)

- Cell count and differential
- Crystal examination
- Culture and Gram stain
Gross Examination
Synovial fluid is normally present in very small amounts in the synovial

cavity surrounding joints. When fluid is present in amounts large enough to
aspirate, there is a disease process in the joint. Normally this fluid is straw
colored and clear. Synovial fluid contains hyaluronic acid, which makes it
very viscous. A small amount of hyaluronidase powder should be added to all
joint fluids before cell counts are performed or cytocentrifuge slides are
prepared to liquefy these fluids. If a crystal analysis is to be performed, an
aliquot of fluid should be removed for this purpose before the hyaluronidase
is added.
Differential
Cells that are normal in synovial fluid are lymphocytes,

monocytes/histiocytes, and synovial cells. Synovial cells line the synovial
cavity and are shed into the cavity. They resemble mesothelial cells but are
usually present in smaller numbers.
LE cells may be present in synovial fluid just as in serous fluid. Malignant
cells are rarely seen in synovial fluid but, when present, resemble tumor cells
seen in serous fluids or CSF.

Many neutrophils are present in acute inflammation of joints. As always, a
careful search should be made for bacteria when many neutrophils are seen.
Crystals may be present in synovial fluid, and it is very important to look
carefully for them. These crystals may be intracellular and or extracellular and
will not stain with Wright‟s stain. All synovial fluids should be examined
carefully for crystals using a polarizing microscope with a red compensator.
The most common crystals seen in synovial fluids are cholesterol, calcium
pyrophosphate, and monosodium urate.
Cholesterol crystals are large, flat extracellular crystals with a notched corner.
They are seen in patients with chronic effusions, particularly those with
rheumatoid arthritis.
Calcium pyrophosphate crystals are seen in pseudogout. These crystals are
intracellular and are small rhomboid, pale-like, or rod-like. These crystals are
weakly birefringent when polarized (i.e they do not appear very bright when
polarized). When the red compensator is used, calcium pyrophosphate
crystals appear blue when the longitudinal axis of the crystal is parallel to the
slow component of the compensator.
Monosodium urate crystals are seen in gout. They are large, needle-like
crystals that may be intracellular or extracellular. These crystals are strongly
birefringent when polarized. When the red compensator is used, monosodium
urate crystals appear yellow when the longitudinal axis of the crystals is
parallel to the y-axis.
Microbiology: Bacterial, mycobacterial and funga C & S
Chemical test: Protein, glucose and LDH
Immunology: Complement (C3, C4), Ig, RF, ANA, immune complex, bacterial
antigens and cryoglobulin.

Figure: Examination of synovial fluid

Table 11.5 :Synovial Fluid Analysis
Normal Non- Inflammatory Infectious Hemorrhage
inflammatory
Colour Clear Clear Opaque Opaque Sanguinous
Viscosity High (due to High Low Low Variable

hyaluronidase
WBC/mm3 <200 <2000 <2000 >50000 Variable
%PMN <25% <25% >25% >50% Variable
Example Trauma Seropositive Sprcific Trauma

osteoarthritis Seronegative arthritis Hemophilic
Neuropathy Crystal
Hypertrophic arthropathy
arthropathy
Rheumatoid Arthritis (RA)
Chronic, symmetric, erosive synovitis of peripheral joints (i.e wrists, MCP

joints, and MTC joints) characterized by a number of extra-articular features
Epidemiology
- Incidence 0.6-2.9 per 1000 population
- F: M = 3:1
- Age of onset 20-40
- Genetic predisposition: HLA DR4/DR1 association
Pathogenesis
- Hallmark of RA is hypertrophy of the synovial membrane
- Outgrowth of granulation tissue (pannus) into and over the articular
surface results in destruction of articular cartilage and subchondral bone.
- Initiating event unknown, but appears to involve antigenic stimulation of
susceptible T cells
- Stimulation of T-cells results in
- B and T cell proliferation
- Angiogenesis
- Accumulation of inflammatory cells in the synovium
- Synovial cell proliferation
- Development of rapidly growing pannus
- All pathways lead to destructive erosions with IL-1, IL-6 and TNF playing
major roles.
- Two theories attempt to explain chronic remissions and exacerbations seen in
RA:
1. Sequestered Ag: during inflammation, ICS are deposited at cartilage
bone junction, which is an avasculart area
--- ICS remain free of articulo-endothelial system but are released as
further cartilage breaks down - triggering cascade
2. Molecular mimicry: Cartilage damage-- altered configuration of
cartilage resembles the offending agent --- triggering cascade

Diagnostic criteria (American Rheumatism Association, 1987
4 or more of the following:
1. Morning stiffness (> 1 hour) for 6 weeks
2. Arthritis of three or more joint areas (commonly involved joints include PIP,
MCP, wrist, elbow, knee, ankle, MTP for > 6 weeks.
3. Arthritis in at least 1 of MCPs, PIP, wrist for > 6 weeks
4. Symmetric arthritis for >6 weeks
5. Rheumatoid nodules
6. Serum RF found in 60-70% of RA patients.
7. X-ray changes, erosions or periarticular osteopenia
Investigations:
Full blood count
a. Hemoglobin. Anemia is frequent. It is usually normochromic and
normocytic. The evidence suggests that the anemia is due to iron utilisation
block and as such does not respond to iron therapy. However, many of the
drugs used to treat arthritis cause blood loss from the gut and hence further
investigation of the anemia may be necessary.

b. White cell count. This is usually normal but Neutropenia is seen in the rare
complication of Felty‟s syndrome which also features splenomegay and
evidence of arthritis should suggest systemic lupus srythematousus
c. Platelt count. Active rheumatoid arthritis is usually accompanied by an

elevated platelet count, some times to quite grossly high levels. As the arthritis
improves with time or treatment the platelet level will fall.
Sedimentation rate and similar measures

a. Erythrocyte sedimentation rate (ESR). This is almost invariably raised in
rheumatoid arthritis. The ESR does not always accurately mirror disease
activity.
B. Plasma viscosity. This is an automated test which is favoured by some

laboratories. Apart from giving an indication of disease activity it is
specifically raised, to very high levels, in the rare complication of
hyperviscosity syndrome which can lead to intravascular sludging and
thrombosis.
c. C-reactive protein (CRP). This is one of the acute phase reactants. Many
rheumatologists feel it is the best measure of disease activity. It is becoming
widely available in many laboratories as a standard test. Other acute phase
reactants, such as haptoglobin, alpha-1-antitrypsin and orosmucoid have no
special advantages.
Biochemical tests
a. Urea. The kidney is not usually involved in rheumatoid arthritis but a
rising level might indicate the presence of amyloid in long standing cases,
although proteinuria should have been spotted first.
b. Liver function tests: Although serious liver disease is not seen in

rheumatoid arthritis, alkaline phosphatase acts as an acute-phase reactant and
is frequently elevated. The fraction has been shown to be liver and not bone in
origin.
c. Iron studies: The anemia of rheumatoid arthritis id due to utilisation block.

This means that the serum iron is often at very low levels but the iron-binding
capacity is likely tb be in the low normal eange, meaning that there is not a
lack of iron generally. Ferritin is the means by which iron is stored in tissues.
Some is present in the blood and in patients without inflammatory disease a
low ferritin level is the best evidence of iron deficiency.
Immunological tests:
a. Rheumatoid factor; One of the hallmarks of rheumatoid arthritis is the
presence of the rheumatoid factor in the blood. This is usually a complex of
IGM acting as an antigen with another IgM milecule acting as the antibody.
High titres are common in active rheumatoid arthritis but it is not uncommon
for positive tests to be found in normal people (5%), elderly people (10%), first
degree relatives of rheumatoid suffers (10%) and in certain other diseases such
as subacute bacterial endocarditis. The test therefore needs to be interpreted
with caution. The simplest is the slide latex and sheep cell test (Rose-Waller)

are dilution tests and as such are a little crude in that there is the necessary for
the laboratory to interpret the end-point of the reaction. More recently laser
nephelometry has been introduced, which gives an absolute value for the
amount of complexes present. Each laboratory will set levels at which the test
will be regarded as positive.
b. Antinuclear factor (ANF): Although this test is associated with systemic

lupus erythematosus it is positive in a wide range of disorders, including
rheumatoid arthritis. The test is a marker of tissue damage and if present in
rheumatoid arthritis may herald serious complications, such as vasculitis.
c. Immunoglobulins. These are frequently abnormal in rheumatoid arthritis

but there is no consistent pattern that gives useful information in the
treatment and diagnosis of the individual patient.
d. Tissue typing. Although tissue typing is an immensely powerful research

tool, at this time it has no place in the diagnosis of rheumatoid disesae.
Biopsy
a. Synovial biopsy. Samples taken blindly, at arthroscopy or at operation are
very helpful if the typical appearances of the rheumatoid nodule are found.
b. Nodules. The highest biological correlate known insciece is that between the
rheumatoid nodule and the presence of a positive rheumatoid factor. In
practical terms, if the rheumatoid factor is negative, then the lump on the
elbow is not a nodule.
c. Fluid analysis. The histological examination of fluid removed from joints,
together with culture, is used mainly to exclude other diagnoses, but the fluid
removed from joints, together with culture, is used mainly eo exclude other
diagnoses, but the fluid removed from, say, the knee will be typically
inflammatory in nature with large quantities of inflammatory cells, including
neutrophils and also a wide range of small round cells. A typical cell has been
described- the ragocyte, which is a large cell with a large number of
intracellular inclusion bodies.
Systemic Lupus Erythematosus
Disorder characterized by inflammation in several organ systems and the

production of autoantibodies that participate in immunologically mediated
tissue injury.
Peripheral polyarthritis with systemic involvement of small and large joints

without joint erosion.
Epidemiology
Incidence F:M 10:1
Age of onset in reproductive years 13-40
More common in blacks and Asians
Bimodal mortality pattern
- Early (within 2 years)
- Active SLE
- Active nephritis
- Infection secondary to steroid use
- Late (>10 years)
- Inactive SLE
- Inactive nephritis
- Atherosclerosis possibly secondary to long term steroid use
Proposed etiology
Altered immunity
-Too many autoAbs causing damage by cytotoxic effects or AgAb complexes
- Altered regulating mechanism e.g decreased T-suppression or defective
function
- Hereditary: Common HLA B8, DR3
- Role of estrogen
- Prepubertal and postmenopausal womrn have similar incidence to men
- Men who developed lupus have a higher concentration of estrogen
metabolites.
- Viral infection
- Drugs
- Anticonvulsants (dilantin, Phenobarbital)
- Methyldopa
- Antihypertensive (hydralazine)
- Antiarrhythmics (Procainamide)
- Antihistone antibodies are commonly seen in drug –induced /lupus
- Oral contraceptive pills associated with exacerbation
DIAGNOSTIC CRITERIA
-Person is diagnosed with SLE if any 4 or more of the 11 criteria are present
serially or simultaneously
- 4, 7, 11 rule
- 4 out of 11 criteria ( 4 lab, 7 clinical for diagnosis)
- Many have constitutional symptoms ( fatigue, weight loss, fever at the time
of presentation
Clinical criteria
1. Malar rash: classic “butterfly rash” ; no scarring involved since baqsement
membrane intact
2. Discoid rash : may cause scarring
3. Photosensitivity
4. Oral / nasal ulcers: usually painless
5. Arthritis: non-erosive, symmetric, invoving 2 or more or large peripheral
joint
6. Serositis: pleurisy, pericarditis, peritonitis
7. Neurological disorder:
Laboratory criteria
8. Renal disorder
- Proteinuria, cellular casts (RBCs, Hb, Granular, tubular or mixed
- > 0.5 g/day or 3+
9. Hemorrhage disorder
- Hemolytic anemia, leukopenia, lymphopenia, thrombocytopenia
10. Immunologic disorder
- Positive LE cell preparation, anti-dsDNA Ab, anti-SmAb.
- False positive VDRL
11. Antinuclear antibody (ANA) most sensitive test
Other associated features
- Skin manifestations: urticaria, livedo reticularis, bullae, alopecia
- Vasculitis lesions: periungual telangectasia, Raynaud‟s
- Eye manifestations: conjunctivitis, episcleritis, keratoconjunctivitis
-Neonatal lupus erythematosus
- Subacute cutaneous SLE
- Discoid SLE
Laboratory investigations
- Serologic hallmark is high titre ANA - positive in 98% patients with SLE
- ANA has high sensitivity and therefore is a useful screening test
- Anti-dsDNA Ab and anti-Sm Ab are specific for SLE (low sensitivity)
- Anti-dsDNA, C3, C4 may be useful in following disease activity if serology is
clinically concordant.
- Lupus anticoagulant may cause clotting abnormalities and increased PTT

12
INFECTIOUS DISEASES
INFCTIOUS MONONUCLEOSUS
Infectious mononucleosis is an acute infectious disease due to the Epstein-Barr

(EBV) hepesvirus (human herpes virus 4). It occurs at any age (usual 10 – 25
years.
Transmission: saliva
Laboratory findings
Leukopenia and granulocytopenia are an evident during first week. Later,
leukocytes are increased (usually 10,000 – 20,000/l, because increased
lymphocytes (>50%) many of which are characteristically atypical. Peak
changes occur in 7-10 days may persist for 1-2 months
Heterophil Antibodies: Heterophil agglutination (Paul-Bunnel test) is usually

more than 1:112. Peak titer occurs in 2-3 weeks, duration is for 4-8 weeks. The
agglutination is not related to lymphocytosis or to clinical severity
Antibody to EBV antigen: During acute illness there is always a rise in

antibody to EB.
Virus Capsid Antigen

IgG antibody to VCA persist for life
IgM-VCA disappears after 2-3 months after recovery.
Other antibodies
Anti-EAD (Early Antigen Diffuse
Anti-EAD (Early Antigen Restricted
Other findings
- Evidence of hepatitis
- Increase serum transaminase
- Increase urine urobilinogen
- Serological test for syphilis (transient false positive)
- Occasional; RBC and albumin in urine
- Hemolytic anemia and thrombocytopenia are rare
- In CNS involvement, the CSF may show increase of pressure, abnormal
lymphocytes and protein.

MALARIA
Human malaria is caused by plasmodium falciparum, P. vivax, P. Ovale and

P. Malariae.
It is transmitted by the bite of anopheline mosquitoes
Diagnosis
If febrile patient is a malarious locality or has recently left such an area,
malaria should be considered. Besides malaria there are many causes for acute
febrile Splenomegaly in the tropics. Gross enlagement of the spleen may also
result from tuberculosis, visceral leishmaniasis, schistosomiasis manosoni and
Japonicum and chronic brucellosis as well as leukemia and lymphoma.
Well stained blood films, thick and thin, should be examined and repeated if
necessary. P. Falciparum parasites may be very scanty, especially in those who
have been partially treated. With P. Falciparum only ring forms are normally
seen in the early stages. With the other species all stages of the erythrocyte
cycle may be found. Gametocytes appear after about 2 weeks.
Laboratory Findings
-Anemia is usually hypochromic; may be Macrocytic in severe chronic disease
- Reticulocyte count is increased
- Leukocytes are increased and monocytes are increased in peripheral blood
-Agranulocytosis and purpura thrombocytopenia may occur late
- Bone marrow show erythroid hyperplasia, RBCs containing organisms and
pigmens in R BC cells. Marrow hyperplasia may fail in chronic phase.
- Serum globulin is decreased ( Euglobin fraction); Albumin decreased
- ESR is increased
- Osmotic fragility of RBCs is normal.
Acute hemorrhagic nephritis due to P. Malariae

- Albuminuria
- Hematuria
Blckwater Fever:
Massive intravascular hemolysis due to P. Falciparum, due to irregular
treatment or G-6-PD
Severe acute hemolytic anemia (1-2 million RBCs/ l) with increased bilirubin
and hemoglobinuria
May be associated with acute tubular necrosis with hemoglobin casts,
azotemia, oliguria to anuria.
Parasites absent from blood
Laboratory Findings due to involvement of organs:

- Liver vary from congestion to fatty changes to malarial hepatitis or central
necrosis; moderate increase in SGOT, SGPT and alkaline phosphatase
- Pigment stones in gallbladder
- Cerebral malaria
- Serological tests:

-Indirect Fluorescent antibody tests high sensitivity and specificity and is
useful for diagnostic purpose.
- Indirect hemagglutination can detect anti body many years after
infection and is useful for prevalence studies
Tropical Splenomegaly: In some hyperendemic areas gross Splenomegaly is

associated with an exaggerated immune response to malaria and is seen,
unexpectedly, in adults who have high antibody titers to malaria and low
parasitemia. The condition, which is commoner in females and in certain
racial and family groups is characterized by enormous overproduction of
IGM, levels reaching 3-20 times the local mean values. Much of the IgM is
aggregated with other immunoglobulin or complement and precipitates in the
cold, in vitro. IgM aggregates are phagocytosed by reticuloendothelial cells in
the spleen and liver, and the demonstration of this by immunofluorescence in
a liver biopsy section is diagnostic. Light microscopy of the liver usually
shows sinusoidal lymphocytosis. Anemia and lymphocytosis can be confused
with leukemia.
Leishmaniasis
This group of disease is caused by protozoa of the genus leishmania ,

conveyed to man by female phlebotomine sandflies in which the flagellate
(promastigote) forms of leishmania develop. In man the leishmaniae are
invade blood stream and localize the cells of the monocyte-macrophage
system and found as oval forms known as amastigotes or leishman Donovani
bodies. Leishmaniasis may take the form of a generalized visceral infection,
kala azar, or of a purely cutaneous infections known in the old world as
oriental sore. In south America cutaneous leishmaniasis may remain confined
to the skin or metastasis to the nose and mouth.
Leishmania divided into:

Visceral ---------------- L. Donovani
Mucocutaneous--------- L. Braziliensis
L. Tropica major
L. Tropica minor
L. Mexican
Laboratory finding of Kala azar

- Organism identified in stained smear from spleen, bone marrow, peripheral
blood, liver biopsy, lymph nodes aspirate.
- Culture (incubate at 25C) in (NNN Nicolle-Novy-Mac Neal media) or
incubation into hamster.
- Serological test : Hemagglutination test
Immunofluorescences
ELISA test
- Blood: Anemia, leukopenia and thrombocytopenia

- Bone marrow: hypercellularity with hyperplasia of cell lines, presence of
leishmania bodies (LDB)
- Increase serum globulin with decreased albumin and reversed A/G ratio
- Increased ESR
- Abnormal cephalin fluculation due to increased serum globulin
- Increased protein more than 10 g/dl due to increase of IgG
- Formol gel test positive
- Urine: proteinuria and hematuria
- Laboratory finding due to amyloidosis in chronic cases
- Oriental sore: organism identified by direct microscopy and culture in
scraping from lesion
* The Formol gel (aldehyde) test is performed by adding two drops of

commercial formalin to 2 ml of the patient serum in a tube; the mixure is
shaken and left to stand at room temp. A positive reaction is indicated by
opacity of the serum, which may also become solid and resemble boiled white
of eye within 20 minutes. The formol gel test becomes positive within a month
or two of the development of the disease, and return to negative within 6
months of successful treatment and restoration to normal of the plasma
proteins.
* Leishmania skin test (Montenegro test)

- Delayed hypersensitivity following intradermal injection of 0.2 ml of
leptomonads in formalized saline
- Positive reactioin: local induration at least 5 mm
Represent immunity against reinfection or 2 months of
successful treatment and positive for years
- Negative reaction: in active kala azar

Schistosomiasis
Schistosomiasis is one of the most important causes of morbidity in the tropics

and is being spread by irrigation schemes.
There are many species of the genus schistosoma which commonly cause
disease in mans S. haematobium, S. mansoni, S. Japonicum, S. Mekongi and S.
Intercalatum.
Laboratory findings
Acute
Eosinophilia occurs; may be 20-60%
ESR is increased
Serum globulin is increased
Cephalin Flocculation is positive
Chronic
- Urine: Direct smear for eggs, sedimentation and hatching of miracidia in
diluted urine for S.haematobium, preferably in last portion of urine
passed
-Ova appear in stools (s. mansoni, with single lateral spine; s.Japonicum,
small lateral tubercle or hook.
-Unstained rectal mucosa examined microscopically may show
living or dead ova when stool are negative
-Serologic tests are particularly useful for chronic infections when stools
contain no ova; they are not useful to assess chemotherapeutic cure.
- Fluorescent antibody test requires additional standardization
- Complement fixation test is the best serologic procedure (100% specific
and 95% sensitive)
- Circumoval precipitation test is particularly useful for testing spinal
fluid since it is specific for involvement of CNS; intestinal involvement
alone causes positive reaction with serum but negative reaction with
spinal fluid.
- Cercarienhullen reaction test is performed with living infectious
cercariae and therefore is not useful as a routine procedure.
- Rectal biopsy of mucosal fold may show parasites and granulomatous
lesions and biopsy of vesical mucosa in infection with s. haematobium
- Multiple granulomatous lesions appear in uterine cervix.
- Changes appear that are secondary to clay pipstem fibrosis of liver with
portal hypertension, esophageal varices, Splenomegaly, etc.
- Liver function changes are minimal; increased serum bilirubin is rare,
even with advanced cirrhosis; abnormal BSP is infrequent. Increased
serum globulin is frequent. Serum alkaline phosphatase is elevated in
50% of adult patients but is not useful in children.
- Changes secondary to pulmonary hypertension are seen.

Leptospirosis “Weil’s Disease or Syndrome”
Leptospirosis is an acute and often severe infection that frequently affects the
liver or other organs and is caused by any of several leptospira species ( or of
serogroups of Leptospira interogans). The 3 most common subgroups and
their reservoirs of infection are Leptospira ichterohaemorrhagiae of rats,
Leptospira canicola of dogs and Leptospira Pomona of cattle and swine.
Several other varieties can also cause the disease, but L icterohaemorrhagiae
causes the most severe illness.
The Leptospirae are often transmitted to humans by the ingestion of food and
drink contaminated by the urine of the reservoir animal.
Clinical Features
Fever, chills, abdominal pain, vomiting, myalgia, headache and conjunctivae
Liver enlargement
Icterohaemorrhagiae----------- Weil‟s disease
Laboratory Findings
Anemia is normochromic normocytic
WBCc are normal or 40000/l in Weil‟s disease
ESR is increased
Urine is abnormal in 75%; proteinuria, WBCs, RBCs and casts
Liver function tests is abnormal in 50%
Increased serum bilirubin
Increased alkaline phosphatase
Increased SGOT and SGPT
CSF is abnormal in cases with meningeal involvement (less- equal than two
third of patients).
- Increased cells chiefly mononuclear type
- Increased protein (less- equal than 80 mg/dl)
- Glucose and chloride are normal
- Organism are not found in CSF
Blood culture is positive during first 3 days of disease ( in 90%)
Urine culture may be positive only intermittently and are difficult because of
contamination and low PH. They are rarely positive after the fourth week.
Of the serologic tests the hemolysis test is most useful. Agglutination,
complement fixation and hemolysis antibodies reach peaks in 4-7 weeks and
may last for many last for many years. An increasing titer is diagnostic. An
individual titer of 1:300 is suggestive.

Toxoplasmosis
Toxoplasmosis is a world wide infection caused by toxoplasma gondii which

transmitted from a mother infected during pregnancy to the fetus causes
congenital toxoplasmosis. Infection after birth results from the ingestion of
cysts excreted in the faces of infected cats or from eating undercooked beef or
lamb.
Laboratory Findings
Recognition of organism in appropriate material (CSF, LN, Muscle smear

stained with Wright‟s or Giemsa stain)
Histological examination of tissue e.g. LN and muscle
Serologic tests are sensitive and specific, except for false positive indirect
fluorescent antibody tests in patients with antinuclear antibodies. Most recent
serologic test is IgM indirect fluorescent antibody (IgM-IFA) which appears
early and may disappear or fall to low titer as early as 1 month, absence of
IgM antibodies signifies that infection is not acute.
WBCs vary from leukopenia to leukemoid reaction; atypical lymphocytes may
be found. Anemia is present.
Heterophil agglutination is negative, but hematologic picture may exactly
mimic infectious mononucleosis; Eosinophilia in 10-20% of patients.
Lymph node shows distinctive marked hyperplasia. Organism may be
identified in histologic section.
Disseminated form is an important complication of the immunologically
compromised patient e.g lymphoma, leukemia and immunsuppressive drugs
Cerebral toxoplasmosis is the most common cause of intracerebral mass

lesion, manifested by headache, fever, confusion, lethargic seizures, dementia,
ataxia and hemiparesis. CSF changes and organism can be identified in smear
of sediment. Diagnosis by CT with contrast “multiple ring enhancing lesions.

HIV and AIDs
Microbiology
- Reterovirus
- HIV I : predominant type in N America
- HIV II: has a longer latent period, restricted mainly to W. Africa
Pathogenesis
- Target cell preference for HIV infection is determined by interaction between

the host cell surface molecule, CD4, along with a co-receptor molecule (CCR5
or CXCR4), and the HIV envelope (env) glycoprotein (gp160) as the virus
binds to and enters the host cell.
- Target cells of HIV include CD4 T helper cells, macrophage, monocytes,
microglial cells. Once it enters a cell, HIV can replicate and cause cell fusion (
syncytium formation) or death. Follicular dendritic cells and other antigen-
representing cells, (macrophage, B cells) are involved in the initiation of
propagation of HIV infection in CD4 T cells and can act as viral reservoirs.
- After primary infection, acute viremia occurs with widespread dissemination
of HIV
- Inappropriate immune activation and increased secretion of certain
proinflammatory cytokines upregulate HIV pathogenesis is the high level of
productive infection, which is characterized by a high level of virion turnover
(10 billion virion produced daily).
- Viral replication is partially contained by an appropriate immune response,
resulting in a markedly decreased amount of virus in the blood to a “set
point” which has prognostic significance ( i.e higher the load, the faster the
clinical progression to AIDS and death).
- Virus is not completely eliminated from the body, and a state of chronic
persistent viral replication ensues.
Mechanism of immunocompromise
- The damage infected by HIV infection is mainly the direct active viral
replication in CD4 T cell lysis.
- Causes immunodeficiency, patient becomes susceptible to opportunistic
infections and malignancies
- Decline in CD4 T cell levels and the rise in viral load vary considerably
throught the stage of HIV infection and from person to person.
Mode of transmission
- Sexual intercourse
- Contaminated blood or blood products (iv drug users, transfusion recipients
before 1985, occupational exposure through needles
- Organ tissue transplantation
- Vertical transmission from mother to child, in utero, during delivery or
through breast milk.

CLINICAL PERSPECTIVE
Clinical Features
- 50-70% of persons with primary HIV infection have a clinical syndrome of
“Flu-like” syndrome and signs (fever, sore throat, skin rash,
Lymphadenopathy, Neutropenia, Splenomegaly, myalgia, arthritis)
- Acute syndrome occurs 3-6 weeks to 3 months after onset of acute syndrome.
- Many individual with HIV infection, remain asymptomatic for years.
- In adults, the average time to development of AIDS after initial HIV infection
is approximately 10 years with entiretroviral therapy.
- Systemic complaints such as fever, high sweat, weight loss, and anorexia and
muscle weakness are common.
Diagnosis of HIV infection

- Two or more reactive screening tests ( i.e ELISA) that detect serum HIV
antibodies followed by a confirmatory test ( i.e westerblot or recombinant
ELISA) that detect specific antibodies against HIV antigen.
- False negative possible in recently exposed patient, therefore repeat ELISA at
6 weeks and 3 months to avoid “ window period” if highly suspicious.
- False positive rare
- Other test that can be used to identify HIV include viral culture, P24 antigen
detection DNA, PCR
Diagnosis of AIDS
- CD4 count<200X106 /L or
- Opportunistic infection (PCP, cryptococcal meningitis, CNS toxoplasmosis or
malignancy (e.g Kaposi sarcoma, CNS lymphoma, HIV wasting syndrome,
HIV encephalopathy.
- Other infections suggestive (not diagnostic) of early HIV infection include
oral candidiasis, oral hairy leukopenia, ITP, cervical dysplasia and
multdermatomal herpes zosters.
Evaluation of newly diagnosed HIV infection

- HIV viral load
- CD4 cell count
- CBC, liver transaminase, creatinine, CK
- Serology: hepatitis B and C, toxoplasma, CMV, syphilis
- G6PD assay
- TB skin test
- Pap smear
- Assess for depression

Typhoid Fever
Typhoid fever is a systemic disease characterized by fever and abdominal pain

caused by dissemination of S. typhi or S.paratyphi.
The disease was initially called typhoid fever because of its clinical similarity
to typhus.
Diagnosis
Other than a positive culture, no specific laboratory test is diagnostic for

enteric fever
In 15 to 25% of case, leukopenia and Neutropenia are detectable.
In the majority of cases, the white blood cell count is normal despite high
fever.
Leukocytosis can develop in typhoid fever (especially in children) during the
first 10 days of the illness, or later if the disease course is complicated by
intestinal perforation or secondary infection.
Other nonspecific laboratory results include moderately elvated values in liver

function tests (aminotransferase, alkaline phosphatase and lactate
dehydrogenase).
The diagnostic “gold standard” is a culture for S. typhi or S. paratyphi.
The yield of blood cultures is quite variable: it can be as high as 90% during
the first week of infection and decrease to 15% by the third week.
A diagnosis can also be based on positive cultures of stool, urine, rose spots,
intestinal secretions.
Unlike blood culture, bone marrow cultures remain highly (90%) sensitive  5
days of antibiotic therapy
If blood, bone marrow, and intestinal secretions are all cultured, the yield of a
positive culture is >90%.
Stool cultures, while negative in 60-70% of cases during the first week, can
become positive during the third week of infection in untreated patients.
Although the majority of patients (90%) clear bacteria from the stool by eight
week, a small percentage become carriers and continue to have positive stool
cultures for at least 1 year.
Several serologic tests, including the classic Widal tests for a febrile
agglutinins” are available; however, given high rates of false-positivity and
false negativity, these tests are not clinically useful.
Polymerase chain reaction and DNA probe assays are being developed

13
TUMOR
MARKERS :
Tumor markers are molecules occurring in blood or tissue that are associated
with cancer and whose measurement or identification is useful in patient
diagnosis or clinical management. The ideal marker would be a "blood test"
for cancer in wich a positive result would occur only in patients with
malignancy, one that would correlate with stage and response to treatment
and that was easily and reproducibly measured.
Tumor markers can be used for one of four purposes: (1) screening a healthy
population or a high risk population for the presence of cancer; (2) making a
diagnosis of cancer or of a specific type of cancer; (3) determining the
prognosis in a patient; (4) monitoring the course in a patient in remission or
while receiving surgery, radiation, or chemotherapy.
Tumor marker is normally absent, or present only at low levels in non-

diseased individuals.
• Provides no false positives or false negatives (i.e. it is sensitive and specific),

clearly separating normal and diseased levels.
• Provides a useful “lead time” compared to the usual clinical presentation.
• Is specific for a particular tumour.
• Correlates with tumour mass and stage.
• Is prognostically useful i.e. a rise in level predicts recurrence / relapse.
• Is easily and inexpensively measured in readily available bodily fluids.
There are no tumour markers that meet all of these criteria. In addition, if a
tumour marker is used to detect early stages of cancer, a treatment must exist.
An ideal tumour marker would be useful for screening, diagnosis, prognosis
and staging, monitoring response to therapy, monitoring for recurrence or
remission and tumour localisation. However, of all the tumour markers in use
currently, only PSA has been proven useful for screening. The other markers
are useful as diagnostic aids (e.g. CA 125); for treatment guidance (e.g.
estrogen receptor) and monitoring (e.g. CEA), as well as for staging and
prognosticating.
Carcinoembryonic Antigen
Tumor marker, CEA: Carcinoembryonic antigen (CEA) is a protein found in

many types of cells but associated with tumors and the developing fetus. CEA
is tested in blood. The normal range is <2.5 ng/ml in an adult non-smoker
and <5.0 ng/ml in a smoker. The CEA was one of the first oncofetal antigens to
be described and exploited clinically. It is a complex glycoprotein of molecular
weight 20,000, that is associated with the plasma membrane of tumor cells,
from wich it may be released into the blood.
The CEA was first indentified in colon cancer, an abnormal CEA blood level
is specific neither for colon cancer nor for malignancy in general. Elevated
CEA levels are found in a variety of cancers other than colonic, including
pancreatic, gastric, lung, and breast. It is also detected in benign conditions
including cirrhosis, inflamatory bowel disease, chronic lung disease, and
pancreatitis. The CEA was found to be elevated in up to 19 percent of smokers
and in 3 percent of a healthy control population. Thus, the test for CEA cannot
substitute for a pathological diagnosis.
Alpha-Fetoprotein
Alpha-Fetoprotein is a normal fetal serum protein synthesized by the liver,

yolk sac, and gastrointestinal tract that shares sequence homology with
albumin. It is a major component of fetal plasma, reaching a peak
concentration of 3 mg/ml at 12 weeks of gestation. Following birth, it clears
rapidily from the circulation, having a half life of 3.5 days, and its
concentration in adult serum is less than 20 ng/ml.
AFP is of importance in diagnosing hepatocellular carcinoma and may be

useful in screening procedures.
AFP is a marker for hepatocellular and germ cell (nonseminoma) carcinoma. It

is a glycoprotein produced in large amounts during fetal life and is
homologous to albumin. In healthy adults, less than 10 µg/L of AFP is found
in the circulation. AFP is elevated in normal pregnancy, benign liver disease
(hepatitis, cirrhosis), as well as in cancer.
The AFP is less frequently elevated in other malignancies such as pancreatic

cancers, gastric cancers, colonic cancers, and bronchogenic cancers. This
elevation was not necessarily associated with liver metastases.
CA 125
CA125 is an antigen present on 80 percent of nonmucinous ovarian

carcinomas. It is defined by a monoclonal antibody ( OC125 ) that was
generated by immunizing laboratory mice with a cell line established from
human ovarian carcinoma. It circulates in the serum of patients with ovarian
carcinoma and was therefore investigated for possible use as a marker.
CA125 is often elevated in patients with ovarian cancer, its level following the
patient's clinical course. With surgical resection or chemotherapy, the level
correlates with patient response. Thus, it is superior to other markers such as
CEA.

The CA125 is elevated in other cancers including endometrial, pancreatic,
lung, breast, and colon cancer, and in menstruation, pregnancy,
endometriosis, and other gynecologic and non gynecologic conditions.
CA19-9
CA19-9 is a monoclonal antibody generated against a colon carcinoma cell line

to detect a monosialoganglioside found in patients with gastrointestinal
adenocarcinoma. It is found it to be elevated in 21 to 42 percent of cases of
gastric cancer, 20 to 40 percent of colon cancer, and 71 to 93 percent of
pancreatic cancer, and has been proposed to differentiate benign from
malignant pancreatic disease, but this capability remains to be established.
Prostate-Specific Antigen
The PSA screening test is a blood test that looks for a specific tumor marker. In
general, tumor markers are produced by the tumor itself or by our body in
response to the presence of cancer or non-cancerous conditions. If a tumor
marker level is higher than normal, the patient is examined more closely to
look for cancer or other conditions. The most commonly tested tumor marker
for the prostate gland is prostate specific antigen. It is normally present in low
levels in the blood of all adult men. The normal range is 0 to 4 ng/ml.
PSA is prostate-specific, not cancer-specific. A variety of conditions can raise

PSA levels: prostatitis (prostate inflammation), benign prostatic hypertrophy
(prostate enlargement), and prostate cancer.
PSA is measured in nanograms per milliliter (ng/mL). Most doctors feel that a
blood PSA level below 4 ng/mL means cancer is unlikely. Levels greater than 10
ng/mL mean cancer is likely. The area between 4 and 10 is a gray zone. Men with
PSA levels in this borderline range have about a 1 in 4 chance of having prostate
cancer. A doctor may recommend a prostate biopsy (getting samples of prostate
tissue to look for cancer) for a man with a PSA level above 4 ng/mL.
Bcr-abl
In chronic myeloid leukemia (CML), the cancer (leukemia) cells contain a new,
abnormal gene called bcr-abl. A test called PCR can find this gene in very small
amounts in blood or bone marrow. In someone with blood and bone marrow
findings consistent with CML, finding the gene confirms the diagnosis. Also,
the level of the gene can be measured and used to guide treatment.
Beta-2-microglobulin (B2M)
B2M blood levels are elevated in multiple myeloma, chronic lymphocytic
leukemia (CLL), and some lymphomas. Levels may also be higher in some
non-cancerous conditions, such as kidney disease and hepatitis. Normal levels
are usually below 2.5 mg/L (milligrams per liter). B2M is useful to help
predict the long-term outlook (prognosis) in some of these cancers. Patients

with higher levels of B2M usually have poorer outcomes. B2M is also checked
during treatment of multiple myeloma to see how well the treatment is
working.
CA 15-3
CA 15-3 is mainly used to watch patients with breast cancer. Elevated blood levels
are found in less than 10% of patients with early disease and in about 70% of
patients with advanced disease. Levels usually drop if treatment is working, but
they may go up in the first few weeks after treatment is started. This rise is caused
when dying cancer cells spill their contents into the bloodstream.
The normal level is usually less than 30 U/mL (units/milliliter), depending on the
lab. But levels as high as 100 U/mL can sometimes be seen in women who do not
have cancer. Levels of this marker can also be higher in other cancers, like lung and
ovarian, and in some non-cancerous conditions, like benign breast conditions and
hepatitis.
CA 27.29
CA 27.29 is another marker that can be used to follow patients with breast
cancer during or after treatment. This test measures the same marker as the CA 15-
3 test, but in a different way. Although it is a newer test than CA 15-3, it is not any
better in detecting either early or advanced disease. It may be less likely to be
positive in people without cancer. The normal level is usually less than 40 U/mL
(units/milliliter), depending on the testing lab. This marker can also be elevated in
other cancers and in some non-cancerous conditions, and it is not elevated in all
patients with breast cancer.
CA 72-4
CA 72-4 is a newer test being studied in ovarian and pancreatic cancer and cancers
starting in the digestive tract, especially stomach cancer. There is no evidence that
it is better than the tumor markers currently in use, but it may be valuable when
used along with other tests. Studies of this marker are still in progress.
Calcitonin
Calcitonin is a hormone produced by cells called parafollicular C cells in the
thyroid gland. It normally helps regulate blood calcium levels. Normal calcitonin
levels are below 5 to 12 pg/ml (picograms per milliliter). (A picogram is one
trillionth of a gram.) In medullary thyroid carcinoma (MTC), a rare cancer that
starts in the parafollicular C cells, blood levels of this hormone are often greater
than 100 pg/ml.
This is one of the rare tumor markers that can be used to help detect early cancer.
Because MTC is often inherited, blood calcitonin can be measured to detect the
cancer in its very earliest stages in family members known to be at risk. Other
cancers, like lung cancers and leukemias, can also cause calcitonin levels to be
elevated, but calcitonin blood levels are not usually used to follow these cancers.

Chromogranin A
Chromogranin A (CgA) is made by neuroendocrine tumors, which include
carcinoid tumors, neuroblastoma, and small cell lung cancer. The blood level of
CgA is often elevated in people with these diseases. It is probably the most
sensitive tumor marker for carcinoid tumors. It is abnormal in 1 out of 3 people
with localized disease and 2 out of 3 of those with cancer that has spread
(metastatic cancer). Levels can also be elevated in some advanced forms of prostate
cancer that have neuroendocrine features. The range of normal blood levels varies
between testing centers, but is commonly less than 50 ng/mL (nanograms per
milliliter).
Epidermal growth factor receptor (EGFR)

This protein, also known as HER1, is a receptor found on cells that helps them
grow. Tests done on a piece of the cancer tissue can look for increased amounts of
these receptors, which is a sign that the cancer may grow fast, spread, and be
harder to treat. This means patients with elevated EGFR may have poorer
outcomes and need more aggressive treatment, particularly with drugs that block
(or inhibit) the EGFR receptors.
EGFR may be used to guide treatment and predict outcomes of non-small cell lung,
head and neck, colon, pancreas, or breast cancers. The results are reported as a
percentage based on the number of cells tested. This test is not yet widely
available.
Some lung cancers have defects (mutations) in the EGFR gene that make it more
likely that certain drugs will work against the cancer. These gene changes are more
common in lung cancer patients who are women, non-smokers, or Asian.
Hormone receptors
Breast tumor samples – not blood samples – from all cases of breast cancer are
tested for estrogen and progesterone receptors. These 2 hormones often fuel the
growth of breast cancer cells. Breast cancers that contain estrogen receptors are
often referred to as "ER-positive;" those with progesterone receptors are "PR-
positive."
HER2 (also known as HER2/neu, erbB-2, or EGFR2)

HER2 is a protein that tells some cancer cells to grow. It is elevated in about 1 out
of 5 breast cancers. Higher than normal levels can be found in some other cancers,
too, such as some stomach cancers. The HER2 level is usually found by testing a
sample of the cancer tissue itself, not the blood. Cancers that are HER2-positive
tend to grow and spread faster than other cancers.
All newly diagnosed breast cancers and advanced stomach cancers should be
tested for HER2. HER2-positive cancers are more likely to respond to treatments
which work against the HER2 receptor on cancer cells.

Human chorionic gonadotropin (HCG)
HCG (also known as beta-HCG) blood levels are elevated in patients with some
types of testicular and ovarian cancers (germ cell tumors) and in gestational
trophoblastic disease, mainly choriocarcinoma. They are also higher in some
people with mediastinal germ cell tumors – cancers in the middle of the chest (the
mediastinum) that start in the same cells as germ cell tumors of the testicles and
ovaries. Levels of HCG can be used to help diagnose these conditions and can be
followed over time to see how well treatment is working. They can also be used to
look for cancer that has come back after treatment has ended (recurrence).
An elevated blood level of HCG will also raise suspicions of cancer in certain
situations. For example, in a woman who still has a large uterus after pregnancy
has ended, a high blood level of this marker may be a sign of a cancer. This is also
true of men with an enlarged testicle or anyone with a tumor in their chest.
KRAS
Cetuximab (Erbitux®) and panitumumab (Vectibix®) are drugs targeting the EGFR
protein that can be useful in the treatment of advanced colorectal cancer. These
drugs don't work in colorectal cancers that have mutations (defects) in the K-ras
gene. Doctors now commonly test the tumor for this gene change and only use
these drugs in people whose cancers do not have the mutation.
K-ras mutations can also help guide treatment for some types of lung cancer.
Tumors with the mutations do not respond to treatment with erlotinib (Tarceva®)
or gefitinib (Iressa®).
Lactate dehydrogenase (LDH)

LDH is used as a tumor marker for testicular cancer and other germ cell tumors. It
is not as useful as AFP and HCG for diagnosis because its level can be up with
many other things besides cancer, including blood and liver problems. Still, high
levels of LDH predict a poorer outlook for survival. LDH levels are also used to
monitor the effect of treatment and to watch for recurrent disease.
Neuron-specific enolase (NSE)

NSE, like chromogranin A, is a marker for neuroendocrine tumors such as small
cell lung cancer, neuroblastoma, and carcinoid tumors. It is not used as a screening
test. It is most useful in the follow-up of patients with small cell lung cancer or
neuroblastoma. (Chromogranin A seems to be a better marker for carcinoid
tumors.) Elevated levels of NSE may also be found in some non-neuroendocrine
cancers. Abnormal levels are usually higher than 9 ug/mL (micrograms per
milliliter).
Prostatic acid phosphatase (PAP)

PAP (not to be confused with the Pap test for women) is another test for prostate
cancer. It was used before the PSA test was developed but is seldom used now

because the PSA test is better. It may also be used to help diagnose multiple
myeloma and lung cancer.
Prostate-specific membrane antigen (PSMA)

PSMA is a substance found in all prostate cells. Blood levels increase with age and
with prostate cancer. PSMA is a very sensitive marker, but so far it has not proven
to be better than PSA. Its use in finding or following cancer is still being studied.
Its current use is limited to being part of a nuclear scan (a type of imaging test) to
look for the spread of prostate cancer in the body. Some potential immunotherapy
treatments for prostate cancer based on PSMA are now under study.
S-100
S-100 is a protein found in most melanoma cells. Tissue samples of suspected
melanomas may be tested for this marker to help in diagnosis.
Some studies have shown that blood levels of S-100 are elevated in most patients
with metastatic melanoma. The test is sometimes used to look for melanoma
spread before, during, or after treatment.
TA-90
TA-90 is a protein found on the outer surface of melanoma cells. Like S-100, TA-90
can be used to look for the spread of melanoma. Its value in following melanoma is
still being studied, and it is not widely used at this time. It is also being studied for
use in other cancers such as colon and breast cancer.
Thyroglobulin
Thyroglobulin is a protein made by the thyroid gland. Normal blood levels depend
on a person's age and gender. Thyroglobulin levels are elevated in many thyroid
diseases, including some common forms of thyroid cancer.
Treatment for thyroid cancer often involves removing the entire thyroid gland,
sometimes along with radiation therapy. Thyroglobulin levels in the blood should
fall to undetectable levels after treatment. A rise in the thyroglobulin level after
treatment may mean the cancer has come back. In people with thyroid cancer that
has spread, thyroglobulin levels can be followed over time to evaluate the results
of treatment.
Screening and early detection of cancer

Screening refers to looking for cancer in people who have no symptoms of the
disease. Early detection is finding cancer at an early stage, when it is less likely
to have spread and is easier to treat. Tumor markers were first developed to
test for cancer in people without symptoms, but very few markers have been
shown to be helpful in this way.
A perfect tumor marker could be used as a cancer screening blood test for all
people. The tumor marker would only be found in people with cancer. It
would tell doctors the type of cancer, how much cancer there is, and which
treatment would work best. At this time there are no tumor marker tests that
work like this.
Today, the most widely used tumor marker is the prostate-specific antigen
(PSA) blood test. The PSA test is used to screen men for prostate cancer.
People with prostate cancer usually have high PSA levels. But it's not always
clear what the test results mean – high PSA levels can be seen in men without
cancer, and a normal PSA does not always mean that no cancer is present. At
this time, not all doctors agree that PSA screening is right for all men.
So far, no other tumor marker has been shown to help screen for cancer in the
general population. A few of the markers that are now available can help find
cancer at an early stage when only patients at high risk are tested.
Diagnosing cancer
Tumor markers are usually not used to diagnose cancer. In most cases, cancer
can only be diagnosed by a biopsy (taking out some tumor cells so they can be
looked at under a microscope). Still, markers can help figure out if a cancer is
likely. And if a cancer is already widespread when it is found, tumor markers
can help figure out where it started.
An example is a woman who has cancer throughout her pelvis and belly
(abdomen). A high level of the tumor marker CA 125 will strongly suggest
ovarian cancer, even if surgery can't find the source. This can be important
because treatment can then be aimed at this type of cancer.
Alpha fetoprotein (AFP) is an example of a tumor marker that can be used to

help diagnose cancer. This tumor marker can sometimes be used to help
diagnose liver cancer. The level of AFP can go up with some liver diseases, but
when it reaches a certain high level in someone with a liver tumor, doctors can
be fairly sure that liver cancer is present (even without a biopsy).
Determining the outlook (prognosis) for certain cancers

Some types of cancer grow and spread faster than others. But even within a
cancer type (such as testicular cancer), some cancers will grow and spread
more quickly or may be more or less responsive to certain treatments.
Sometimes the level of a tumor marker can help predict the behavior and
outlook for certain cancers. For example, in testicular cancer, very high levels
of a tumor marker like HCG or AFP predicts for a more aggressive cancer and
a poorer outlook for survival. Patients with these high levels may be given
more aggressive treatment to start.
Seeing if certain treatments are likely to work

Certain markers found on cancer cells can be used to help predict if a certain
treatment is likely to work or not. For example, in breast and stomach cancer,
if the cells have too much of a protein called HER2, drugs such as trastuzumab
(Herceptin®) can be helpful in treatment. If the cancer cells have a normal
amount of HER2, the drugs won't help, so tumor tissue is checked for HER2
before treatment is started.

Determining how well treatment is working
One of the most important uses for tumor markers is to watch patients being
treated for cancer, especially advanced cancer. If a tumor marker is available
for a certain type of cancer, the level of the marker may be able to be used to
see if the treatment is working, instead of doing other tests like x-rays, CT
scans, bone scans, or other tests.
If the tumor marker level in the blood goes down, it is almost always a sign
that the treatment is working. On the other hand, if the marker level goes up,
then the cancer is not responding and the treatment may need to be changed.
(One exception is if the cancer is very sensitive to a certain chemotherapy
treatment. In this case, the chemo can cause many cancer cells to die and
release large amounts of the marker into the blood, which will cause the level
of the tumor marker to rise for a short time.)
Detecting recurrent cancer

Tumor markers are also used to look for cancer that may have come back
(recur) after treatment. Certain tumor markers may be useful once treatment is
complete and there is no sign of cancer in the body. These include:
 Prostate specific antigen (PSA) for prostate cancer
 Human chorionic gonadotropin (HCG) for gestational trophoblastic tumors

and some germ cell cancers
 Alpha fetoprotein (AFP) for certain germ cell cancers and liver cancer
 CA 125 for ovarian cancer
 Carcinoembryonic antigen (CEA) for colon and rectal cancers
Some women who have been treated for breast cancer have blood tests for
levels of the tumor marker CA 15-3. This can sometimes show that cancer has
come back (recurred) before the woman has symptoms or the cancer can be
seen on imaging tests. Many doctors question the test's value, though, because
it isn't clear that it is better to treat recurrent breast cancer before it is causing
symptoms. In studies done so far, starting treatment earlier has not helped
women live longer or feel better.
Findings like this are why many experts do not recommend checking tumor
markers after treatment aimed at curing most cancers. These markers are more
likely to be used to keep an eye on advanced cancer during treatment.
When are tumor markers checked?

Whether or not tumor markers are followed depends on the type of cancer a
person has. Tumor markers may be checked at the time of diagnosis; before,
during, and after treatment; and then regularly for many years to see if the
cancer has come back. During treatment, changes in tumor marker levels can
be a sign of whether treatment is working.

Appendix I
LABORATORY ABBREVIATIONS
ABG Arterial Blood Gas
ABO Major blood group system
Ab Antibody
ACD Acid citrate dextrose (anticoagulant)
ACTH Adrenocorticotropic hormone
ADH Antidiuretic hormone
ADNase Antideoxyribonuclease
AFB Acid fast bacillus; tubercle bacillus
AFP Alpha-fetoprotein
A/g Albumin/globin ratio
Aggl Agglutination
Agn Antigen
AHF Antihemophilia factor
AHG Antihemophilic globulin
ALA -aminolevulinic acid
Alb albumin
ALT alanine amino transferase (same as SGPT)
AMA antimitochondrial antibodies
ANA antinuclear antibodies
aniso anisocytosis
APTT Activated partial thromboplastin time
aq Aqueous

ARD Antimicrobial removal device
As Arsenic
ASA Acetylsalicyclic acid
ASMA Antismooth muscle antibodies
ASO Antistreptolysin O titer
AST Aspartate aminotransferase (as same SGOT)
B Basophil
Barb Barbiturate
Baso Basophil
BC Blood culture
BFP Biologica false positive
BHS Beta-hemolytic streptococcus
bili Bilirubin
BJ Bence Jones protein
Bix Bleeding time
BS Blood sugar
BSP Bromsulphalien
BUN Blood urea nitrogen
BV Blood volume
C and S Culture and sensitivity
C3, C4 Complement
Ca++ , calcium
CBC complete blood count
cc cubic centimeter
CEA carcinoembryonic antigen
CG chorionic gonadotropin

chol cholesterol
CID cytomegalic inclusion disease
CIE counter immunelectrophoresis
CK creatine kinase (same as CPK)
CL- , CL chloride
cl time clotting time
cm centimeter
CMV cytomegalovirus
CO carbon monoxide
coag coagulase or coagulation
Cpd E cortisone (17-OH, 11-dehydrocortisone)
Cpd F cortisol (hydrocortisone, 17-OH cortisone)
Cpd S 11-deoxycortisol
CPK creatine phosphokinase
crit hematocrit
CRP C-reactive protein
cryo Cryoprecipitae; cryoglobulin
CSF Cerebrospinal fluid
Cu Copper
cu mm Cubic millimeter
DC Direct coombs
DIC Disseminated intravascular coagulation
Diff Differential
Dil Dilantin
Dl Deciliter
DNA Deoxyribonucleic acid

DNase Deoxyribonuclease
DNP Deoxyribonuleoprotein
DPH Diphenylhydantoin
11-DOC 11-deoxycorticosterone
E Eosinophil
E1 Esterone
E2 Esteradiol
E3 Esteriol
EBV Epstein-Barr virus
ECL euglobulin clot lysis
EDTA ethylenediamine tetraacetic acid (anticoagulant)
EIA enzyme immunoassay
ELP electrophoresis
EMIT enzyme multiplies immunoassay
ENA extractable nuclear antigen
eo Eosinophil
ESF Erythrocyte stimulating factor (erythropoietin)
ESR Erythrocyte sedimentation rate
EtOH Ethyl alcohol (ethanol)
FANA Fluorescent antinuclear antibodies
FBP Fibrin breakdown products
FBS Fasting blood sugar
FDP Fibrin degradation products
Fe Iron
FFA Free fatty acid
FFP Fresh frozen plasma

FIA Fluorescent immunoassay
fib Fibrinogen
FSH Follicle stimulating hormone
FSP Fibrin stimulating products
FTA Fibrin splitting products
g gram
G neg gram negative
G pos gram positive
G-6-PD glucose-6-phosphate dehydrogenase
GC gonococcus (gonorrhea)
GGT gamma glutamyl transferase
GH growth hormone
GLC gas liquid chromatography
Glob globulin
Gluc glucose
Gm gram
GTT glucose tolerance test
H2O water
HA heterophil antibody
HAA hepatitis associated antigen (Australian antigen)
Hb hemoglobin
HBAg hepatitis B associated antigen
HBDH hydroxybutratic dehydrogenase
-HCG Beta human chorionic gonadotropin
HCl Hydrochloric acid
HCO3 Bicarbonate

hcrit Hematocrit
hct Hematocrit
HDL-C High-density lipoprotein
H&D Hematoxylin and eosin
Hg Mercury
Hgb Hemoglobin
HGH Human growth hormone
5-HIAA 5-hydroxyindoleacetatic acid
HLA Human leukocyte locus-A

hpf High power field
HPL Human placental lactogen
HSV Herpes simplex virus
HVA Homovanillic acid
Hypo Hypochromasia
IAT Indirect antiglobulin test
TIBC Total iron binding capacity
ICDH Isocitrate dehydrogenase
ICSH Interstitial cell-stimulating hormone (luetinizing

hormone)
IDC Indirect coombs
IEP Immunelectrophoresis
IFA Indirect fluorescent antibody
IgA, Immunoglobulins
IgD,
IgE,
IgG,
IgM
IM Infectious mononucleosis
IU International unit
K Potassium

KA King-armstrong
KGS Ketogenic steroid
KS Ketosteroids
l Liter
L Lymphocyte; liter
LAP Leucine amino peptidase; leukocyte alkaline

phosphatase
LATS
LD Lactic dehydrogenase
LDH Lactic deyhdrogenase
LDL Low density lipoprotein
LE Lupus erythematous
LH Luetinizing hormone
Li Lithium
Lipo Lipoprotein
Lmc Lymphocyte
LP Lumbar puncture
LPF Low power field
L/S Lecithin/sphingomyelin ratio
LYMPH Lymphocyte
LYTES Electrolytes
M Monocyte
MEG Microgram
MCH Mean corpuscular hemoglobin
MCHC Mean corpuscul;ar hemoglobin concentration
MCV Mean corpuscular volume
mcU Microunit

mEq Milliequivalent
mg Milligram
MG Magnesium
MHA Microhemagglutination test
MIC Minimal inhibitory concentration
mIU Millinternational unit
mL Milliliter
mm Millimeter
mm3 Cubic millimeter
mono Monocyte
morpho Morphology
mOSM Milliosmole
m Millimicron
N Neutrophil
Na Sodium
nbl Normoblast
NBT Nitro blue tetrazolium
ng Nanogram
NH3 Ammonia
nm Nanometer
non seg Non segmental neutrophil
NPN Nonprotein nitrogen
NRBC Neucleated red blood cell
O and Ova and parasites

P
O2 Oxygen
occ bl Occult blood

OCT Ornithine carbamyl transferase
17 OH 17-hydroxycorticsteroids
(17-
OHCS)
osmo osmolality
P phosphorous
Pco2 carbon dioxide pressure
Po2 oxygen pressure
PA pernicious anemia
Pap papnicolaou smear
PAS periodic acid schiff (stain)
Pb lead
PBG porphobilinogen
PBI protein-bound iodine
PCV packed cell volume
PF-3 platelet factor 3
PF-4 platelet factor 4
pg picogram
pH power of hydrogen
Phb phenobarbiton
PK pyruvate kinase assay
PKU phenylkitonurea
pL plasma
Plt platelet
PMN polymorphonuclear
PNH paroxysmal nocturnal hemoglobinurea
poik poikilocytosis

PP postprandial
PPLO pleuropneumonia like organism
ppt precipitate
PRA plasma rennin activity
PSP phenolsulphthalein
PT prothrombin time
PTA plasma thromboplastin antecedent (factor XI)
PTC plasma thromboplastin component (factor IX)
PTH parathyroid hormone
PTT partial thromboplastin time
qual qualitative
quant quantitative
QNS quantitity not sufficient
RA rheumatoid factor
RBC red blood cells
Reti reticulocyte
Rh Rheusus factor
RIA Radioimmune assay
RNA Ribonucleic acid
RPR Rapid plasma regain
Rub Rubricyte
sal level Salicylate level
SCAT Sheep cell agglutination test
SD Standard deviation
sed rate Sedimentation rate
seg Segmented neutrophil

sens Sensitivity
SG Specific gravity
SGOT Serum glutamic oxaloacetic transaminase
SGPT Serum glutamic pyruvic transaminase
SHCG Serum human chorionic gonadotropin
SK Streptokinase
SLE Systemic lupus erythematosus
SMA Sequential multiple analyzer
sp gr Specific gravity
SR Sedimentation rate
staph Staphylococcus
strep Streptococcus
STS Serologic test for syphilis
SUN Serum urea nitrogen
T and C Type and cross match
T and Type and cross match

M
T3 Triiodothyronine
T4 Thyroxine
TB Tuberculosis; tubercle bacillus
TBG Thyroxine-binding globulin
TBP Thyroxine-binding protein
TBPA Thyroxine binding prealbumin
TBT Template bleeding time
TC Throat culture
TCT Thrombin clotting time
TDM Therapeutic drug monitoring

TGT Thromboplastin generation test
TIBC Total iron binding capacity
TLC Thin layer chromatography
TNTC Too numerous to count
TP Total protein
Trich Trichomonas vaginalis
trig Triglyceride
TSH Thyroid stimulating hormone (thyrotropin)
TT Thrombin time
TV Total volume
U International enzyme unit
UA Urinalysis
UC Urine culture
UCG Urinary chorionic gonadotropin
UIBC Unsaturated iron-binding capacity
VDRL Venereal Disease Research Laboratory
VMA Vanillylmandelic acid
vol Volume
WBC White blood cell; white blood cell count
WNL Within normal limits
WNR Within normal range
X-mtch Cross-match
ZSR Zeta sedimentation rate

Appendix II
Normal Reference Range Table
Hematology Tests Normal Values
47+- 7% (Male)
Hematocrit (Hct) 45+-5% (Female)
38+-4% (Child)
13.0-18 gm/dL (Male)

Hemoglobin (Hb)
11.5-16 gm/dL (Female)
4.5-6.5x106/µL (Male)
Red Blood Cell Count (RBC) 3.8-5.8x106/µL (Female)
3.8-5.5x106/µL (Infant/Child)
White Blood Cell Count (WBC) 4.1-10.9x103/µL

Differential
Polymorphonuclear Cells
35-80%
(polys)
Immature Polys (bands) 0-10%
Lymphocytes (lymp) 20-50%
monocytes (mono) 2-12%
eosinophils (eos) 0-7%
basophils (bas) 0-2%
Platelet Count (Plt) 140-400x103/µL
Red Cell Distribution Width
11.5 – 14.5%
(RDW)
RBC Mean Cell Volume (MCV) 80-100 fL
Mean Cell Hemoglobin

31-36 gm/dL
Concentration (MCHC)
31-63%
CD4+
416-1751/µL (Absolute #)

0.5-1.5% (Adult)
Reticulocyte 1.1-4.5% (Newborn)
0.5-3.1% (Infant)
Prothrombin Time (PT) 12-14 seconds

Partial Thromboplastin Time
18-28 seconds
(PTT)
170-420 mg/dL
Iron Studies
76-198 µg/dL (Male)

Total Serum Iron (TSI)
26-170 µg/dL (Female)
Total Iron-Binding Capacity

262-474 µg/dL
(TIBC)
Transferrin 204-360 mg/dL
Ferritin 18-250 ng/mL (Male)

Conversion
Chemistry Tests Normal values
factor
Aspartate
aminotransferase 5-35 U/L (0-0.5 kat/L 0.01667
(AST)
Alanine
aminotransferase 5-35 U/L (0.0-0.58 kat/L) 0.01667
(ALT)
Albumin 3.5-5.5 g/dl (35.0-55.0 g/L 10.0
Alkaline
phosphatase 38-126 U/L (0.5-2.0 kat/L)
(ALP)
Amylase 60-180 U/L (1-3 kat/L) 0.01667
Bicarbonate
22-28 mEq/L 1.0
(venous)
Bilirubin, direct 0.1-0.3 mg/dL
Bilirubin, indirect 0.2-0.7 mg/dL

Bilirubin, total 0.2-1.0 mg/dL (5.1-17 mol/L 17.1
Calcium 8.9-10.4 mg/dL (2.2–2.6 mmol/L 0.2495
Cholesterol 150-200 mg/dL (3.6-5.2 mmol/L 0.02586
Creatinine 0.5-1.4 mg/dL (38-107 76.28
GGT 4.0-60.0 U/L (0.07-1.0 kat/L) 0.01667
Glucose 75-115 mg/dL(4.16-6.38mmol/L 0.05552
Lipase 0.0-160 U/L (0.0-2.67 kat/L) 0.01667
Potassium 3.5-5.0 mEq/L (3.5-5.0 mmol/L 1.0
Sodium 137-145mEq/L(137-145mmol/L) 1.0
Total Protein 5.5-8.0 gm/dL (55-80 g/L) 10.0
Triglyceride 40-160 mg/dL(0.45-1.81 mmol/L 0.01129
Uric Acid 2.5-8.0 mg/dL(0.12-0.48mmol/L 0.05949
Urea Nitrogen
7-21 mg/dL(0.36-0.71mmol/L 0.0357
(BUN)
Uera (serum) 17-42 mg/dL (2.83-6.99 mmol/L 0.16639
Cardiac Tests
Total CK 10-90 u/L (0.17-1.5 kat/L( 0.0166
CK-MB 0.0-7 g/L
CK-index 0-3
Lactate
100-190 U/L(1.67-3.2kat/L) 0.01667
dehydrogenase
Troponin I 0.0-0.4 ng/ml (0.0-0.4 g/L) 1.0

Troponin T 0.0-0.1 ng/ml (0.0-0.1 g/L) 1.0
Blood Gas
pH 7.34-7.44
pCO2 35-45 mmHg
pO2 75-100 mmHg
HCO3 22-26 mEq/L
Urinalysis
Specific
1.002-1.030 Micro
gravity
pH 5-7 RBCs 0-2/HPF
Protein Negative-trace WBCs 0-2/HPF
Glucose Negative
Ketone Negative
Bilirubin Negative
Blood Negative
Nitrite Negative
Leukocyte Negative
0.2-1.0 Ehr
Urobilinogen
U/dL
Thyroid
T3-total 70-190 ng/dL (1.08-2.92nmol/L) (CF=0.01536)
T4-free 0.8-1.5 g/dL
T4-total 5.5-12.3 g/dL(64.35-154.49nmol/L (CF=12.87)
TBG 12-30 mg/L
Tyroid
Stimulating
0.4-4.5 µIU/mL
Hormone
(TSH)
Endocrine and Tumor
Markers
17-OHCS <4 mg/day
Adrenocorticotrophic
20-100 pg/mL
Hormone (ACTH)
Alpha-Fetoprotein (AFP),
0-44 ng/mL
serum
Beta-HCG <5 mU/mL (Male, non-pregnant Female)
CA 19-9 <40 U/mL
Prostatic Specific Antigen
0-4 ng/mL
(PSA)
Prolactin 0-14 ng/mL

Miscellaneous
Rheumatoid Factor <30 IU/mL
<250 (school age)
Anti-streptolysin O Titer
(ASO)
<125 (adult)
Cerebrospinal Fluid (CSF)

Glucose 50-80 ng/dL
Protein 15-45 mg/dL
RBCs 0/µL
WBCs 0-3/µL

BIBLIOGRAPHY
For Further reading
1. Baker F.J, Silverton R.E and Pallister C.J: Introduction to Medical Laboratory
Technology; 1998
2. Bernardette F. Rodak. Diagnostic Hematology: 1995
3. Clarke A. K: Rheumatology; 1st edition 1986
4. Harold C. Sox: Common diagnostic tests: 1990
5. Jhon A. Koepke/ Jhon F. Koepke: Guide to clinical Laboratory diagnosis.

1987
6. John Bernard Henry: Clinical Diagnosis and Management by Laboratory

Methods (Tood and Sanford). 2001
7. Judith C. Byrne, Dolores F. Saxson, Phyllis K. Pelkan and Patricia M.

Nugent: Laboratory Tests; implication for nusese and applied health
professionals. 1981
8. Kathleen Morrison Tresieler: clinical Laboratory and diagnostic tests. 1995
9. Kathleen Deska Pagana, Timothy J. Pagana: Manual of Diagnostic and

Laboratory tests. 2002
10. Mary Louise Turgeon. Clinical hematology: Theory and procedures: 2 nd

edition 1993
11 Norma J. Walters, Barbara H. Estridge, Anna P. Reynolds: Basic Medical

laboratory techniques, 1990
12. Reynolds D.J, Freeman H.G.M: Aids to clinical chemistry 1986
13. Richard Ravel: Clinical Laboratory Medicine; Clinical Application of

Laboratory Data. 1995
14. Ruth M. Frech: Guide to diagnostic procedures: 1980
15. Smith F. Alistair, Beckett J. Geoffrey, Walker W. Simon and Rae W.H
Petter; Lecture note on Clinical Biochemistry, 6th edition 1998
16. Strand-Elmer; Clinical Laboratory Tests (third edition) 1984
View publication stats

Clinicalbiochemistry 2012 Last

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Clinicalbiochemistry 2012 Last

Uploaded by

Copyright:

Available Formats

See discussions, stats, and author profiles for this publication at: https://www.researchgate.

Clinical Laboratory "Guide for Medical Students"

Book · January 2012

Gamal Abdul Hamid

Show Your Achievements 😎 View project

plasma medicine View project

The user has requested enhancement of the downloaded file.

The laboratory is an important part of medical diagnostic procedure, adding

GUIDE FOR MEDICAL STUDENTS

CLINICAL LABORATORY GUIDE FOR MEDICAL STUDENTS 7

5. Acid Base Balance 61

8. Endocrine System 111

9. Diabetes mellitus 137

10. Central Nervous System 149

11. Articular System 156

12. Infectioius Diseases 170

13. Tumor Markers 180

14. Appendix I : Laboratory Abbreviations 189

Appendix II: Normal Reference Range 1201

12. Bibliography 206

CLINICAL LABORATORY GUIDE FOR MEDICAL STUDENTS 8

The laboratory is an important part of medical diagnostic procedure, adding

CLINICAL LABORATORY GUIDE FOR MEDICAL STUDENTS 9

General practitioners vary in their use of the laboratory services, with

Laboratories should be able to quote a “reference interval” for each test

Reference intervals for healthy humans may be affected by:

In to be confident that a result is abnormal or a change is clinically significant

CLINICAL LABORATORY GUIDE FOR MEDICAL STUDENTS 10

History Physical Finding Laboratory Findings

Laboratory Findings for Diagnosis

Laboratory Findings for Management

In addition to their use for diagnosis and management, laboratory

CLINICAL LABORATORY GUIDE FOR MEDICAL STUDENTS 11

CLINICAL LABORATORY GUIDE FOR MEDICAL STUDENTS 12

TABLE 1.1: PREDICTIVE VALUE

Sensitivity: Positivity of the disease

Specificity = Negativity in health

Predictive value of a positive test =

Predictive value of a negative test=

METHODS USED IN THE CHEMICAL PATHOLOGY LABORATORY

Analyte reacts with a dye, changing its absorption spectrum (colour).

• Enzymatic: Example: lactate dehydrogenase (LDH) catalyses the reaction

(we measure THIS by means of the radio-label)+

Ag(unknown amount in patient's plasma.)

(the more of this, the less Ag*-Ab is formed)

The technique hashigh sensitivityi.e.isable to measure lowconcentrationsofAg

•Chromatographic methodsElectrophoresisand otherchromatographic

-serum proteins (electrophoresis)-amino acids (ion exchange

•DNA techniques: Analysis of patient’s DNA for specific mutations, or linked

CLINICAL LABORATORY GUIDE FOR MEDICAL STUDENTS 15

1. Define mean, mode and median?

The specificity of test “Q” would be:

3. The positive predictive value would be:

4. How can accuracy of a measurement be determined?

Accuracy can be determined by comparing the technic in use with another

CLINICAL LABORATORY GUIDE FOR MEDICAL STUDENTS 16

Many cardiovascular disorders have a biochemical basis. Rapid and accurate

LACTATE DEHYDROGENASE (LDH) AND

LDH5 MMMM 7 Liver and striated muscle Slowest

The 5 Isoenzymes can be distinguished by Kinetics, electrophoresis,

CLINICAL LABORATORY GUIDE FOR MEDICAL STUDENTS 17

TABLE 2.2:DIFFERENTIAL DIAGNOSIS OF LDH/HBDH QUOTIENT

1.33 - 1.64 Infections, Pulmonary embolism and malignome