GPAT Pathophysiology Syllabus

Which markers are used to assess kidney function and glomerular filtration?

Serum creatinine, blood urea nitrogen (BUN), and estimated glomerular filtration rate (eGFR); creatinine clearance directly estimates GFR.

Give the Cockcroft-Gault formula for creatinine clearance.

CrCl = [(140 - age) x weight (kg)] / (72 x serum creatinine in mg/dL); multiply by 0.85 for females.

What does an elevated BUN:creatinine ratio (>20:1) suggest?

Prerenal azotemia (e.g., dehydration, hypovolemia, reduced renal perfusion) with enhanced urea reabsorption.

What is the difference between nephrotic and nephritic syndrome?

Nephrotic: heavy proteinuria (>3.5 g/day), hypoalbuminemia, edema, hyperlipidemia. Nephritic: hematuria, RBC casts, hypertension, oliguria, and mild proteinuria.

List the four types (Gell and Coombs) of hypersensitivity reactions with one example each.

Type I: immediate/IgE-mediated (anaphylaxis); Type II: antibody-mediated cytotoxic (hemolytic anemia); Type III: immune complex (SLE, serum sickness); Type IV: delayed cell-mediated (TB skin test, contact dermatitis).

What is autoimmunity and name a prototypic systemic autoimmune disease.

Immune response against self-antigens due to loss of self-tolerance. Systemic lupus erythematosus (SLE) is the prototype, with anti-dsDNA and anti-Sm antibodies.

Differentiate primary from secondary immunodeficiency.

Primary: inherited/genetic defects in immune components (e.g., DiGeorge, SCID). Secondary (acquired): from infection (HIV/AIDS), drugs, malnutrition, or malignancy.

What is amyloidosis?

Extracellular deposition of abnormal, insoluble fibrillar protein (beta-pleated sheet structure) in tissues, leading to organ dysfunction.

How is amyloid identified histologically?

Stains pink with Congo red and shows apple-green birefringence under polarized light.

Differentiate AL from AA amyloidosis.

AL (primary): derived from immunoglobulin light chains, associated with plasma cell dyscrasias/multiple myeloma. AA (secondary): derived from serum amyloid-associated protein, linked to chronic inflammation.

What are the cardinal signs of acute inflammation?

Rubor (redness), calor (heat), tumor (swelling), dolor (pain), and functio laesa (loss of function).

List the major chemical mediators of inflammation and their key actions.

Histamine (vasodilation, increased permeability), prostaglandins (pain, fever, vasodilation), leukotrienes (chemotaxis, bronchoconstriction), bradykinin (pain), and cytokines TNF/IL-1 (systemic effects).

What are the steps of leukocyte extravasation in acute inflammation?

Margination, rolling (selectins), adhesion (integrins/ICAM), transmigration (diapedesis), and chemotaxis toward the injury site.

Differentiate acute from chronic inflammation by cell type and duration.

Acute: rapid onset, short duration, neutrophil predominance, exudate. Chronic: prolonged, dominated by macrophages, lymphocytes, and plasma cells, with tissue destruction and fibrosis.

What is granulomatous inflammation and name two causes.

Chronic inflammation with collections of activated epithelioid macrophages (granulomas), often with giant cells. Causes: tuberculosis and sarcoidosis.

Differentiate healing by primary intention from secondary intention.

Primary intention: clean, apposed wound edges (surgical incision), minimal scar. Secondary intention: large gaping wounds healing by granulation tissue, wound contraction, and a larger scar.

What are the phases of wound healing?

Hemostasis, inflammation, proliferation (granulation tissue, angiogenesis, re-epithelialization), and remodeling/maturation (collagen reorganization).

What is the difference between regeneration and repair (fibrosis)?

Regeneration restores normal tissue by proliferation of parenchymal cells (in labile/stable tissues). Repair replaces lost tissue with connective tissue (scar) when cells cannot regenerate or the framework is damaged.

Differentiate transudate from exudate.

Transudate: low protein, low specific gravity (<1.012), few cells, from hydrostatic/osmotic imbalance (e.g., heart failure). Exudate: high protein, high specific gravity (>1.020), many cells, from inflammation/increased permeability.

What is edema and list its main mechanisms.

Abnormal accumulation of fluid in interstitial spaces. Mechanisms: increased hydrostatic pressure, decreased plasma oncotic pressure (hypoalbuminemia), lymphatic obstruction, sodium retention, and increased vascular permeability.

Define hypernatremia and hyponatremia with their normal serum sodium range.

Normal serum Na+ is 135-145 mEq/L. Hyponatremia <135 mEq/L (causes confusion, seizures); hypernatremia >145 mEq/L (causes thirst, neurological signs).

What are the ECG and clinical features of hyperkalemia?

Serum K+ >5.0 mEq/L; ECG shows peaked T waves, widened QRS, and flattened P waves; can cause cardiac arrhythmias and arrest. Muscle weakness occurs.

State the normal serum potassium and calcium ranges.

Serum potassium: 3.5-5.0 mEq/L. Serum total calcium: 8.5-10.5 mg/dL (about 9-11 mg/dL).

What clinical sign is associated with hypocalcemia?

Neuromuscular irritability with tetany, including Chvostek sign (facial twitch on tapping) and Trousseau sign (carpal spasm with BP cuff inflation).

Give the Henderson-Hasselbalch equation for blood pH.

pH = 6.1 + log([HCO3-] / (0.03 x PaCO2)). Normal pH 7.35-7.45, with HCO3- ~24 mEq/L and PaCO2 ~40 mmHg.

Differentiate the four primary acid-base disorders by pH, PaCO2, and HCO3-.

Metabolic acidosis: low pH, low HCO3-. Metabolic alkalosis: high pH, high HCO3-. Respiratory acidosis: low pH, high PaCO2. Respiratory alkalosis: high pH, low PaCO2.

How is the anion gap calculated and what does a high value indicate?

Anion gap = Na+ - (Cl- + HCO3-); normal ~8-12 mEq/L. A high anion gap indicates metabolic acidosis from added acids (e.g., lactic acidosis, ketoacidosis, renal failure, toxins).

Differentiate leukocytosis from leukopenia.

Leukocytosis is an elevated WBC count (>11,000/microL), often from infection or inflammation. Leukopenia is a low WBC count (<4,000/microL), e.g., from bone marrow suppression.

Differentiate acute from chronic leukemia.

Acute leukemia: rapid onset, proliferation of immature blasts, aggressive (AML, ALL). Chronic leukemia: slow onset, accumulation of more mature cells (CML, CLL).

What genetic abnormality is the hallmark of chronic myeloid leukemia (CML)?

The Philadelphia chromosome, t(9;22), producing the BCR-ABL fusion gene with constitutive tyrosine kinase activity.

Differentiate Hodgkin from non-Hodgkin lymphoma.

Hodgkin lymphoma: contiguous nodal spread, Reed-Sternberg cells present, often localized, better prognosis. Non-Hodgkin: noncontiguous/extranodal spread, no Reed-Sternberg cells, more variable.

What is the diagnostic cell of Hodgkin lymphoma?

The Reed-Sternberg cell, a large binucleate ('owl-eye') cell of B-cell origin.

What is multiple myeloma?

A malignant plasma cell neoplasm producing monoclonal immunoglobulin (M protein), causing lytic bone lesions, hypercalcemia, renal failure, anemia, and Bence Jones proteinuria.

Classify anemias based on red cell size (MCV).

Microcytic (MCV <80 fL): iron deficiency, thalassemia. Normocytic (80-100 fL): acute blood loss, anemia of chronic disease. Macrocytic (MCV >100 fL): B12/folate deficiency.

What causes sickle cell anemia and its key feature?

A point mutation (glutamate to valine) in the beta-globin gene producing HbS, which polymerizes when deoxygenated, causing sickling, vaso-occlusion, and hemolytic anemia.

Differentiate the bacterial structures targeted by Gram staining.

Gram-positive bacteria have a thick peptidoglycan wall and retain crystal violet (appear purple). Gram-negative bacteria have a thin peptidoglycan layer with an outer membrane and stain with safranin (appear pink).

What is the difference between an exotoxin and an endotoxin?

Exotoxins are secreted proteins from gram-positive and gram-negative bacteria, highly potent and specific. Endotoxin is lipopolysaccharide (LPS) in the gram-negative outer membrane, released on lysis, causing fever, shock, and DIC.

What general features distinguish viral from bacterial infections pathologically?

Viruses are obligate intracellular pathogens causing cytopathic effects, inclusion bodies, and a predominantly lymphocytic/mononuclear response; bacterial infections typically provoke a neutrophilic (pus-forming) response.

What is the pathophysiology of HIV/AIDS?

HIV infects and depletes CD4+ T-helper cells (binding via gp120 to CD4 and CCR5/CXCR4), progressively destroying cell-mediated immunity and predisposing to opportunistic infections and malignancies when CD4 count falls (AIDS defined at CD4 <200/microL).