Pathophysiology Flashcards

Which mechanism primarily drives beta-cell dysfunction in long-standing type 2 diabetes?

Answer: Glucotoxicity and lipotoxicity causing oxidative stress

Chronic hyperglycemia (glucotoxicity) and elevated free fatty acids (lipotoxicity) generate oxidative stress that progressively impairs and destroys beta cells in type 2 diabetes.

In type 1 diabetes, the primary immunological mediators of beta-cell destruction are:

Answer: Autoreactive CD4+ and CD8+ T lymphocytes

Autoreactive CD4+ helper and CD8+ cytotoxic T lymphocytes are the principal mediators of beta-cell destruction in type 1 diabetes through a cell-mediated autoimmune process.

The incretin effect is significantly reduced in type 2 diabetes primarily because:

Answer: Beta-cell responsiveness to GIP is diminished

In type 2 diabetes, GLP-1 secretion may be near-normal but beta-cell responsiveness to glucose-dependent insulinotropic polypeptide (GIP) is markedly reduced, diminishing the incretin effect.

Hepatic insulin resistance in type 2 diabetes primarily leads to:

Answer: Decreased glycogen synthesis and increased gluconeogenesis

Hepatic insulin resistance impairs insulin's ability to suppress gluconeogenesis and promote glycogen synthesis, resulting in inappropriately elevated fasting hepatic glucose output.

Latent autoimmune diabetes in adults (LADA) is best distinguished from type 2 diabetes by:

Answer: Presence of islet autoantibodies such as GAD65

LADA is characterized by the presence of islet autoantibodies (most commonly anti-GAD65) in adults who initially appear to have type 2 diabetes but have underlying autoimmune beta-cell destruction.

During diabetic ketoacidosis, the anion gap increases primarily due to accumulation of:

Answer: Acetoacetate and beta-hydroxybutyrate

The elevated anion gap in DKA results from accumulation of ketoacid anions—acetoacetate and beta-hydroxybutyrate—produced from accelerated fatty acid oxidation in the absence of insulin.

Polydipsia in uncontrolled diabetes mellitus is physiologically triggered by:

Answer: Osmotic diuresis causing intravascular volume depletion and hyperosmolality

Glucosuria exceeds the renal threshold, causing osmotic diuresis with water loss, resulting in hypernatremia and plasma hyperosmolality that stimulates hypothalamic osmoreceptors to trigger thirst.