Introduction to Clinical Pathology

Introduction - Clinical Pathology

• Clinical pathology is a medical specialty that analyzes bodily fluids, tissues, and cells to diagnose disease.
• The tools used in clinical pathology include clinical chemistry, haematology, and anatomical pathology.

The Sections of Clinical Pathology

• Anatomical Pathology
  • Histology and Cytology
• Haematology
• Blood Bank
• Chemical Pathology

Chemical Pathology

• Chemical Pathology is the area of clinical pathology concerned with fluid analysis for diagnosis and treatment.
• Sub-specialities include:
  • General or routine chemistry
  • Special chemistry
  • Clinical endocrinology
  • Toxicology
  • Therapeutic Drug Monitoring
  • Urinalysis
  • Fecal analysis

Types of Specimens Used in Chemical Pathology Laboratory

• Serum
  • Yellow watery portion left after blood clots and cells are removed
• Plasma
  • Prepared by centrifuging whole blood collected with an anticoagulant
  • Used for parameters like fibrinogen, glucose, and clotting factors.
• Urine
  • Analyzed for a wide range of diseases
• Other body fluids

Test Panels

• Basic Metabolic Panel (BMP)
  • Includes 8 tests: sodium, potassium, chloride, bicarbonate, BUN, creatinine, glucose, calcium.
• Comprehensive Metabolic Panel (CMP)
  • Includes 14 tests: all BMP tests plus total protein, albumin, ALP, ALT, AST, bilirubin.

Electrolytes

• Substances whose molecules dissociate into ions when dissolved in water.
• Medically significant electrolytes include:
  • Sodium (Na)
  • Potassium (K)
  • Chloride (Cl)
  • CO2 (in its ion form HCO3-)

Calcium Metabolism

• Calcium is the most abundant mineral in the body.
• The body maintains adequate calcium levels through a process called calcium homeostasis.
• Disruptions to this mechanism can lead to hypercalcemia or hypocalcemia.

Calcium Fractions

• Calcium in serum exists in three forms:
  • Ionized (Ca2+) – physiologically active (50%)
  • Protein-bound (approximately 80% to albumin) – 40%
  • Complexed (citrates, phosphates etc) – 10%

Calcium Reference Intervals

• Serum total calcium reference range is 2.25 – 2.75 mmol/L.
• Serum ionized calcium reference range is 1.1 – 1.4 mmol/L.
• Serum albumin concentration should be measured alongside serum total calcium.

Causes of Hypercalcemia

• Common
  • Malignant disease (e.g., some lung cancers)
  • Hyperparathyroidism
  • Vitamin D toxicity (excessive intake)
• Uncommon
  • Renal failure
  • Sarcoidosis
  • Multiple myeloma

Causes of Hypocalcemia

• Hypoparathyroid
  • Postoperative
  • Idiopathic
  • Post radiation
• Nonparathyroid
  • Vitamin D deficiency
  • Malabsorption
  • Liver disease
  • Kidney disease
  • Vitamin D resistance
• PTH Resistance
  • Pseudo-hypoparathyroidism

Renal Function Tests

• Used to evaluate kidney function and identify potential problems.

Biochemical Tests of Renal Function

• Glomerular Function Tests
  • Measurement of GFR (clearance tests)
    • Creatinine clearance
    • Serum creatinine
    • Serum blood urea nitrogen (BUN)

Glomerular Filtration Rate (GFR)

• Provides an index of functioning glomeruli.
• Estimates the degree of renal impairment.
• The rate in millilitres per minute that substances are cleared from the circulation through the kidney’s glomeruli.

GFR via Clearance Studies: Criteria for Substances

• Criteria for a suitable marker for clearance studies:
  • Freely filterable at the glomerular barrier
  • Not reabsorbed by the tubules
  • Not secreted by the tubules
  • Present at a stable plasma concentration
  • If exogenous - nontoxic
  • Reliable assay procedure

Determination of Clearance

• Involves accurately timed urine sample plus representative blood sample(s).
• Clearance (C) = (U x V) / P
  • Units: mL/min
  • U: urinary concentration of substance
  • V: rate of urine formation (mL/min)
  • P: serum concentration of substance

GFR Determination Using Inulin

• Inulin is completely filtered at the glomerulus, but neither secreted nor reabsorbed by the tubules.
• This property makes inulin clearance a highly accurate measure of GFR.
• Inulin Clearance - potentially most accurate approach - Gold Standard.

Tubular Function Tests

• Include:
  • Urinalysis
    • Appearance
    • Specific gravity and osmolality
    • pH
    • Glucose
    • Protein

Urinalysis

• A physical and/or chemical examination of urine.
• Consists of various chemical and microscopic tests to screen for:
  • Urinary tract infections
  • Renal disease
  • Diseases of other organs that result in abnormal metabolites in the urine.
• Can reveal diseases like diabetes mellitus, glomerulonephritis, and urinary tract infections.

Types of Urinalysis

• Macroscopic Examination
• Chemical Analysis (Urine Dipstick)

Liver Function Tests

• Used to:
  • Detect the presence of liver disease
  • Distinguish between types of liver disorders
  • Gauge the extent of known liver damage
  • Monitor response to treatment

Routine Liver Function Tests (LFTs)

• Some liver function tests are associated with:

  • Functionality (e.g., albumin)
  • Cellular integrity (e.g., transaminase)
  • Conditions linked to the biliary tract (e.g., gamma-glutamyl transferase and alkaline phosphatase)

• Include:

  • Transaminases (Alanine and Aspartate aminotransferase (ALT & AST))
  • Alkaline phosphatase (ALP)
  • Bilirubin (direct and total)
  • Gamma glutamy transferase (GGT)
  • Albumin

Alkaline Phosphatase (ALP)

• Increased activity can be caused by:
  • Physiological:
    • Infancy
    • Puberty
    • Pregnancy
    • Intestinal isoenzymes
  • Bone disease:
    • Hyperparathyroidism
    • Osteomalacia, rickets
    • Paget’s disease of bone
    • Osteomyelitis
  • Hepatobiliary disease:
    • Hepatitis
    • Cholestasis
    • Cirrhosis
  • Others:
    • Carcinoma of the bronchus

Cardiac Markers Panel

• Used to diagnose myocardial infarction (heart attack).
• Includes:
  • Troponin I (or T)
  • Creatinine kinase (Total)
  • Creatnine Kinase – MB
  • Lactate dehydrogenase (LDH-1)
  • Myoglobin
  • Brain natriuretic peptide.

Cardiac Markers: CK-MB

• Used to assist in diagnosing acute myocardial infarction.
• Measures the blood level of CK-MB, a bound combination of two variants of the enzyme phosphocreatine kinase.

Lipid Profile

• Includes:
  • Total Cholesterol
  • Triglycerides
  • Low Density Lipoprotein - Cholesterol (LDL-C)
  • High Density Lipoprotein- Cholesterol (HDL-C)