FPGEE Pathophysiology 1 — Questions and Answers
Question 1: Which pathophysiological mechanism primarily underlies the development of type 2 diabetes mellitus?
- Autoimmune destruction of beta cells
- Insulin resistance combined with progressive beta-cell dysfunction (Correct answer)
- Absolute insulin deficiency due to pancreatectomy
- Excessive glucagon secretion without insulin resistance
Correct answer: Insulin resistance combined with progressive beta-cell dysfunction
Type 2 DM is characterized by peripheral insulin resistance and gradual decline in pancreatic beta-cell secretory capacity, unlike the autoimmune destruction seen in type 1 DM.
Question 2: In heart failure with reduced ejection fraction (HFrEF), which compensatory mechanism initially helps maintain cardiac output but ultimately worsens cardiac remodeling?
- Decreased renin release
- Activation of the renin-angiotensin-aldosterone system (RAAS) (Correct answer)
- Parasympathetic nervous system activation
- Decreased antidiuretic hormone secretion
Correct answer: Activation of the renin-angiotensin-aldosterone system (RAAS)
RAAS activation causes fluid retention and vasoconstriction that initially compensates for low output, but chronic activation promotes maladaptive cardiac hypertrophy and fibrosis.
Question 3: A patient with chronic kidney disease develops anemia. What is the primary pathophysiological reason?
- Iron deficiency due to poor dietary intake
- Decreased erythropoietin production by the diseased kidneys (Correct answer)
- Hemolysis caused by uremic toxins primarily
- Vitamin B12 malabsorption secondary to renal tubular damage
Correct answer: Decreased erythropoietin production by the diseased kidneys
The peritubular interstitial cells of the kidney are the primary source of erythropoietin; CKD destroys these cells, reducing EPO production and thereby red cell production.
Question 4: Which of the following best describes the pathophysiology of asthma?
- Irreversible destruction of alveolar walls leading to air trapping
- Reversible airway inflammation and bronchospasm driven by Th2-mediated hypersensitivity (Correct answer)
- Neutrophilic inflammation causing permanent airway remodeling
- Mucus plug obstruction without underlying inflammation
Correct answer: Reversible airway inflammation and bronchospasm driven by Th2-mediated hypersensitivity
Asthma involves a Th2 lymphocyte-driven inflammatory response with eosinophil recruitment, mast cell degranulation, and reversible bronchoconstriction, distinguishing it from COPD.
Question 5: In atherosclerosis, which event is considered the earliest pathological change in the arterial wall?
- Calcification of the tunica media
- Accumulation of oxidized LDL and foam cell formation in the intima (Correct answer)
- Smooth muscle cell proliferation into the lumen
- Thrombosis over a ruptured plaque
Correct answer: Accumulation of oxidized LDL and foam cell formation in the intima
The fatty streak, formed by oxidized LDL being engulfed by macrophages to form foam cells in the subintimal space, is the earliest lesion in atherosclerosis.
Question 6: A patient presents with polyuria, polydipsia, and hyponatremia. MRI shows a pituitary tumor. Which pathophysiological defect best explains the polyuria?
- Excess ADH production causing water retention and dilutional hyponatremia
- Deficient ADH secretion leading to inability to concentrate urine (Correct answer)
- Primary polydipsia resetting the osmotic threshold
- Aldosterone excess causing potassium wasting and water loss
Correct answer: Deficient ADH secretion leading to inability to concentrate urine
A pituitary lesion can disrupt ADH (vasopressin) synthesis or secretion, causing central diabetes insipidus with hypotonic polyuria and compensatory polydipsia.
Question 7: Which mechanism explains the hypercalcemia seen in primary hyperparathyroidism?
- Decreased calcitonin secretion by thyroid C-cells
- Excess PTH stimulating osteoclast activity, renal calcium reabsorption, and calcitriol synthesis (Correct answer)
- Vitamin D toxicity causing excessive intestinal calcium absorption
- Thiazide diuretic-induced reduction of renal calcium excretion
Correct answer: Excess PTH stimulating osteoclast activity, renal calcium reabsorption, and calcitriol synthesis
Excess PTH acts on bone to release calcium via osteoclasts, on the kidney to reabsorb calcium, and induces 1-alpha hydroxylase to increase calcitriol, collectively raising serum calcium.
FPGEE Pathophysiology 1
Which pathophysiological mechanism primarily underlies the development of type 2 diabetes mellitus?