Pathophysiology Flashcards

Advanced glycation end products (AGEs) contribute to diabetic complications primarily by:

Answer: Cross-linking proteins and activating RAGE receptors to cause inflammation

AGEs accumulate on long-lived proteins causing cross-linking that stiffens vessels and tissues, and activate RAGE receptors triggering inflammatory cascades that damage endothelium and other structures.

The polyol pathway contributes to diabetic complications through which primary mechanism?

Answer: Sorbitol accumulation and osmotic stress combined with NADPH depletion

Excess glucose is converted to sorbitol by aldose reductase (consuming NADPH), then to fructose (generating NADH), causing osmotic damage and depleting antioxidant capacity via reduced glutathione regeneration.

Diabetic nephropathy progresses from microalbuminuria to overt proteinuria primarily because of:

Answer: Intraglomerular hypertension causing progressive podocyte injury and loss

Intraglomerular hypertension driven by efferent arteriolar constriction causes mechanical stress on podocytes, leading to their detachment and foot process effacement, allowing increasing protein filtration.

In diabetic peripheral neuropathy, which nerve fiber type is typically affected earliest?

Answer: Small unmyelinated C fibers and thinly myelinated A-delta fibers

Small unmyelinated C fibers (pain, temperature) and A-delta fibers are most vulnerable to the metabolic insults of hyperglycemia, explaining why burning pain and temperature loss typically precede vibration loss.

Nonproliferative diabetic retinopathy progresses to the proliferative stage primarily driven by:

Answer: Retinal ischemia triggering VEGF-mediated neovascularization

Pericyte loss and capillary occlusion cause retinal ischemia, which upregulates VEGF secretion; this drives growth of fragile new blood vessels that can bleed and cause traction retinal detachment.

Charcot neuroarthropathy (Charcot foot) in diabetes develops through which pathophysiologic sequence?

Answer: Peripheral neuropathy → repetitive unperceived trauma → hyperemic bone resorption → fracture and deformity

Loss of protective sensation allows repetitive microtrauma; neurogenic inflammation and autonomic vasodilation then cause hyperemia and osteoclast-mediated bone resorption, leading to fracture and progressive joint destruction.

Protein kinase C (PKC) activation in diabetic vasculopathy results primarily from:

Answer: Increased diacylglycerol synthesis from elevated intracellular glucose

High intracellular glucose increases de novo diacylglycerol (DAG) synthesis, which activates PKC (especially beta isoform), impairing NO production, increasing VEGF, and promoting vascular dysfunction.