Download (2026): BIO 4404: Pathophysiology (Chapter 41) and more Lecture notes Advanced Education in PDF only on Docsity!
What is glycolysis? Breakdown of glucose; humans primarily rely on glucose and fats to provide energy for cellular function
What is glycogenesis? excess glucose is stored in the form of glycogen, especially in muscle and liver cells
What is glycogenolysis? breakdown of glycogen to glucose
What is gluconeogenesis? endogenous production from amino acids, glycerol, lactate, and other metabolic intermediates by the liver
What is the function of the GLUT protein system? GLUT 1-4: cells vary in permeability to glucose; most cells use process of facilitated diffusion which utilizes four glucose transporter proteins
Which GLUT proteins are insulin dependent? GLUT-
Which GLUT proteins are insulin independent? GLUT-1,2,
Where are GLUT-1 and GLUT-3 located? (3) - Neural cells
- RBCs
- Pancreatic beta cells
Where is GLUT-2 proteins located? liver cells
Where are GLUT-4 proteins located? (2) - Cardiac and skeletal muscle cells
What is C-peptide? correlates with level of insulin production
How is C-peptide a diagnostic tool for Type 1 versus Type 2 diabetes?
There is less C-peptide in Type 1
What is the role of amylin? (4) - co-secreted with insulin from the pancreas
- targets α-cells in pancreas decrease glucagon secretion
- delays GI emptying to prevent postprandial blood sugar spikes
- promotes satiety
Where is amylin produced? pancreas
What is the role of glucagon in glucose metabolism? (2) - produced by α-cells in pancreas and secreted as plasma glucose levels drop
- targets the liver → stimulates breakdown of stored glycogen and use of FFA & amino acids to form glucose → increase blood glucose level
Where is glucagon produced? alpha cells of pancreas
What is the role of incretins (GLP-1) in glucose metabolism? (2)
- targets the pancreas → increase insulin secretion and decrease glucagon secretion
- delays GI emptying → promotes satiety
Where is incretin (GLP-1) produced? cells in the small intestine
How is DPP-4 related to incretin level? GLP-1 has a very short half-life in circulation; rapidly degraded by enzyme DPP-
What is the role of neuropeptide Y (NPY) in metabolism? creates "hunger" sensation in hypothalamus → increased food intake → weight gain/obesity risk
Where is NPY produced? hypothalamus
What is the role of ghrelin in metabolism? ghrelin levels increase during dieting, and it is ectopically expressed by metastatic cancer cells → promotes hypermetabolic state
Where is ghrelin produced? secreted by cells in the stomach and targets hypothalamus to secrete NPY
What is the role of leptin in metabolism? (2) - inhibits secretion of NPY promoting satiety
Where is leptin produced? adipose tissue
How does growth hormone (GH) contribute to hyperglycemia?
promotes synthesis of IGF
How does cortisol and catecholamines (stress hormones) contribute to hyperglycemia?
↑ production and release of glucose from the liver
How does catecholamines (epinephrine) contribute to hyperglycemia?
↑ production and release of FFA
What are 4 examples of screening methods used for detection of glucose intolerance?
- Fasting blood glucose (FBG)
- Oral glucose tolerance test (OGTT)
- Glycated hemoglobin testing (HBA1c)
- urine test
What evidence is there that Type 2 DM has a genetic component?
40+ SNPs have been identified that appear associated with increased risk
How does increased caloric intake contribute to decreased insulin receptor sensitivity?
decreased insulin receptor sensitivity - ↑ caloric intake promotes chronic hyperinsulinemia → down-regulation of insulin receptors or GLUT on target cells = "insulin resistance"
Why is there a gradual decline in insulin production in the pancreas?
chronic ↑ insulin secretion and hyperglycemia lead to β-cell "exhaustion" and pancreatic fibrosis → destruction of beta cells and gradual decrease in insulin (and amylin) production
What is the etiology of hyperglycemia? excess glucose relative to insulin level
What is the pathogenesis of dawn phenomenon? early morning rise in levels of GH, cortisol, glucagon and catecholamines → increased glucose release occurs between 3:00-8:00 AM
What are the clinical manifestations of dawn phenomenon? (6)
- Nausea
- Fatigue
- Blurred vision
- Feeling of unease
- Thirst
- Nocturia
What is the pathogenesis of Somogyi Phenomenon? nocturnal hypoglycemia with rebound hyperglycemia stimulated by secretion of catecholamines and cortisol from adrenal glands
What are the clinical manifestations of Somogyi Phenomenon? (2)
- Sleep disturbances
- Headache
What is the etiology of acute hypoglycemia? excess insulin level relative to glucose level
What is the pathogenesis of acute hypoglycemia? decreased glucose and/or increased insulin levels increased peripheral glucose uptake → decreased availability of glucose to brain
What are the clinical manifestations of acute hypoglycemia? (7)
- Diaphoresis
- Tachycardia
- Headache
- Visual disturbance
- Weakness
- Paresthesia
- Confusion
What is the etiology of diabetic ketoacidosis (DKA)? acute insulin deficiency, which can be amplified by physical or emotional stress
What is the pathogenesis of diabetic ketoacidosis (DKA)? (2)
- continued insulin deficiency promotes lipolysis to form glycerol and FFA → liver converts FFAs to acetoacetic acid → converted to acetone and ketone bodies (-) and ketoacids → released into bloodstream → ketoacidosis
- ketoacids lower blood pH → metabolic acidosis and elevated anion gap (AG) → Kussmaul respirations = rapid, deep breaths → increased CO2 output to raise blood pH
What are the clinical manifestations of diabetic ketoacidosis (DKA)?
- Kussmaul respirations
- Metabolic acidosis
- Polyuria
- Polydipsia
- Polyphagia
- Hyperkalemia
What is the etiology of non-ketotic hyperglycemic hyperosmolar syndrome (NHHS)?
relative insulin deficiency; usually secondary to illness, surgery or infection
What is the pathogenesis of non-ketotic hyperglycemic hyperosmolar syndrome (NHHS)? (5)
- decrease in insulin secretion → extreme hyperglycemia (BG > 600)
- polyuria (4-12L) with K+ loss → hypovolemia → hyperosmotic plasma
- hypovolemia → extreme dehydration → polydipsia and orthostatic hypotension
- hyperosmotic plasma → electrolyte imbalances → weakness, lethargy, stupor
- enough insulin is present to prevent lipolysis and ketone formation → pH & AG are both WNL, so ketosis rarely occurs
What are the clinical manifestations of non-ketotic hyperglycemic hyperosmolar syndrome (NHHS)? (7)
- Hyperglycemia
- Hypovolemia
- Polydipsia
- Orthostatic Hypotension
- Lethargy
- Stupor
- Weakness
What are Kussmaul respirations and what is their purpose? (2)
- Rapid, deep breaths
- Increased CO2 output to raise blood pH in metabolic acidotic state
What is the etiology of macrovascular complications of diabetes mellitus?
damage to large blood vessels providing circulation to the brain, heart, and extremities
What is the pathogenesis of macrovascular complications of diabetes mellitus? (3)
- chronic hyperglycemia promotes release of pro-inflammatory chemicals → chronic inflammation of vascular → arteriosclerosis
- elevated FFA levels are converted to CHO in the liver and released into circulation → hyperlipidemia → vascular inflammation
- increased blood glucose facilitates platelet adherence hypercoagulability risk → clot formation
What is the etiology of microvascular complications of diabetes mellitus?
damage to small blood vessels (arterioles and capillaries)
What is the pathogenesis of microvascular complications of diabetes mellitus?
- circulating glucose irreversibly binds to plasma proteins resulting in formation of advanced glycation end-products (AGE) that adhere to vasculature walls → abnormal thickening of capillary walls, especially in kidneys
- diabetics also have elevated ketone levels and increased catabolism of protein to form urea by-product; constant filtration of ketones and urea → nephropathy → renal failure
- hyperglycemia promotes increased glucose uptake into insulin-independent cells (neurons, nephrons) where it is metabolized to form sorbitol which draws H2O into those cells → F/E imbalances
