• Appreciation of the validity of a test result as defined by the sensitivity and specificity of the test.
• Use of CK levels in myocardial infarction as example.
• Factors affecting 'normal' test results (eg. Age-related changes; Time-related changes: circadian/ cyclical/ pulsatile)
• Various laboratory function test systems. Liver function test as example.
• Laboratory tests for diagnosis of specific diseases e.g. tumour markers.
• Urinalysis

• Chemical path (clinical chemistry)
• Haematology
• Med microbiology
• Histopathology

• Assist in DIAGNOSTIC process
• Assess SEVERITY of disease hence to formulate prognosis (eg. Peak CPK level after MI)
• Monitor PROGRESS of Pt and response to Tx (eg. LFT in viral hepatitis)
• Provide data for better UNDERSTANDING of disease

1. Units

• SI (system internationale - eg. mmol/L) vs. Conventional units (eg. Mg/100 ml)

SEE GRAPH

• Normal = mean +/- 2SD
• There are incidences of overlap: defines for any test the sensitivity of the method

To evaluate/ interpret a test it is necessary to know how it behaves in health and disease

1. Sensitivity (true-positive rate). This is the incidence (per cent) of positive results for a test in patients with the particular disease. A test which is always abnormal (or positive) in patients with the disease has 100% sensitivity. If there is overlap between healthy + diseased, it is not 100% [how accurately it picks up the abnormals]

2. False-positive rate. This is the incidence (per cent) of positive results in people known or subsequently proved to be free from the particular disease. If a test is always normal in individuals who do not have the disease, that test has a false-positive rate of 0%. 100 - false positive rate = specificity

Predictive rate of a +ve result = (+ve result + diseased) / (+ve result + no disease) x 100

3. The predictive value of a positive test result. This is the percentage of positive results that are true positives when a test is performed on a defined population containing both healthy and diseased individuals.

1. Normal muscle contains: Mb, Troponin, CK, Myosin, Actin, AST, LDH

Dimer Isoforms Myocardium Skeletal M

• BB: brain, prostate, placental + foetal tissue
• If MB increased, then suggests MI because only 2% is found in SkM

Found: liver dysfunction and bone metabolism

Also: Serum ferritin (upper limit)

• Females 331 picomols/ L
• Males 884 picomols/L

a) Bilirubin

(i) Indirect (85%, water-insoluble): unconjugated; increased haemolysis

(ii) Direct (15%, water-soluble): conjugated; increased in liver + biliary dis

b) Ammonia (NH³). Increase in severe hepatocellular disease + portal HT [Ammonia detoxified to urea in liver]

b) Coagulation factors: II, V, VII, IX & X (also VIII)

• Prolonged PT time: defect in biosynthesis in liver cells, Vit K deficiency (eg. Malabsorption; these factors are all Vit K dependent)
• If prolonged PT - give Vit K injection (if not normalised) - liver dysfunction/ clotting deficiency

a) Serum ceruloplasmin decreased in Wilson's Disease

• Hepatolenticular disease - deposition of copper in liver + basal ganglia of brain
• Ceruloplasmin = carrier protein for copper

b) Urine phenylalanine present in phenylketonuria (inborn error of metabolism)

c) Red cell G6PD enzyme - decrease in G6PD deficiency

• Affects mainly male (X-linked); haemolysis of RBC eg. Moth balls (naphthalene), fava beans, dyes (eg. analine - dye foods, eg. Curry, cheap BBQ pork)
• Ramadan (fast during day, eat during night), dye rice with analine -> rapid haemolysis

• DNA technology

• Using paper strips

a) Glucose

b) Others

• Cholesterol - HDL, LDL
• Potassium
• Creatinine
• Bilirubin

Glucosuria

• Glucose oxidase method
• Plasma glucose > 160-180 mg/dl -> glucose in urine (DM)
• Renal glycosuria - decreased threshold

• Using reducing agent (eg. Benedict's Solution)
• Cupric Sulphate (green) -> Cuprous Sulphate (orange)
• Besides glucose, also positive with lactose ascorbic acid, salicylates (false +ve) which are reducing agents

• Normal excretion 50-150 mg/day
• Microalbuminuria > 150 mg/day (indication of renal damage in DM)

• Tetrabromophenol blue + citrate buffer + protein -> colour change
• False +ve with concentrated urine (phosphate)
• False -ve Bence-Jones protein (Ig light chain)

A) Sulphosalicylic acid (20%)

• 2-3 drops to 5 ml urine

• Acidify urine, bring to boil -> precipitate
• For Bence-Jones protein, precipitates at 60 degrees, disappears on further boiling

Nitrite: N = -ve (infection)

Urobilinogen: N = not increased (haemolysis, liver dis)

Protein: N = -ve (renal disease)

pH: N = acid (alkaline in veggies + infection)

Blood: N = -ve (haematuria)

Specific Gravity: N = 1.010

Ketone: N = -ve (DM, fasting)

BR: N = -ve (bile duct obstruction)

Glucose: N = -ve (DM, renal)

1. RBC

• > 2/HPF, abnormal, Dysmorphic (all different shapes) vs. Isomorphic RBC (all same shape)

Glomerular origin: dysmorphic, due to nephritis (medicine)

Pelvis & Bladder origin: isomorphic (stone in bladder - surgery)

• > 5/HPF, urinary tract infection

• Hyaline casts - Proteinuria (proteins which take shape of renal tubules as they are excreted)
• Granular casts - glomerular disease
• RBC & WBC casts - glomerular disease

• Amorphous phosphate: fluffy precipitate (urine goes alkaline on standing, if you add acetic acid, it disappears)
• Urate - needles or fan shape (eg. Gout)
• Oxalate - envelope shape
• Cystin

Culture; Schistosoma haematobium

1. Clinical use of laboratory data. A practical guide. D. Robert Defour, Williams & Wilkins, 1998.
2. Lecture Notes on Clinical Biochemistry, 5th Edition. L. C. Whitby, A. F. Smith, G. J. Beckett, and S. W. Walker. Blackwell Science, 1998.