U10C6 CKD And Diabetes Flashcards

Question

What is the Pathophysiology of type 2 diabetes?

Answer 1

• Reduction in peripheral insulin sensitivity or insulin resistance (hyperinsulinaemia) of skeletal muscle and adipose tissues • Current hypotheses suggest that insulin resistance might be mediated by either: • i) Intracellular accumulation of free fatty acids in skeletal muscle and hepatocytes (possibly via activation of PKC’s which inhibit normal insulin signalling pathways) or • ii) Endocrine functions of adipocytes- Altered release of resistin, adiponectin and leptin all favour a reduced sensitivity of target tissues to insulin • Secondary beta cell failure also seen. Beta cell hyperplasia and hypertrophy occur in the attempt to make more insulin to reduce blood glucose. Beta cells also secrete amylin which builds and aggregates in the islets and causes hypoplasia and hypotrophy of beta cells • Glucose transporter (GLUT4) not moved to cell membrane in response to insulin (insulin resistance) preventing cells from taking up glucose from the bloodstream as well as failing to inhibit hepatic gluconeogenesis– therefore hyperglycaemia results • hyperglycaemia leads to symptoms of diabetes

Answer 2

Overview: Insulin deficiency can result in hyperglycaemia which can lead to hypertension and kidney disfunction. Hypertension further exacerbates kidney disfunction and can lead to kidney failure. For additional information: Three mechanisms contributing to diabetic nephropathy caused by underlying hyperglycaemia: 1) Increased pressure state. Hypertension = increased pressure throughout arteriovascular system = increased pressure in afferent arteriole which in turn increases the filtration rate of the glomerulus. Efferent vasoconstriction due to activation of RAAS builds up pressure in the glomerulus, increasing filtration rate. Hyperglycaemia also activates RAAS, increasing glomerulus filtration rate 2) Increased pressure results in mesangial expansion – in response to damage, the mesangial cells response by secretion of cytokines that produce inflammation and oxygen free radicals that results in endothelial disfunction. This leads to decreased surface area in the glomerulus for filtration. Dilation of the fenestrations allows larger molecules e.g. proteins to leak out 3) Combination of the above factors lead to nephron ischemia and atrophy of the vasculature which will reduce the kidney’s ability to filter blood, ultimately leading to kidney failure in diabetic nephropathy

Answer 3

- Diabetic nephropathy (DN) is a chronic kidney disease defined by structural and functional changes that develop as a result of microvascular complications associated with long-standing or poorly controlled diabetes - Diabetic nephropathy is the leading cause of chronic kidney disease (CKD) - Major risk factor is hypertension - Diabetic nephropathy is a clinical syndrome characterized by: ✓ Persistent albuminuria ✓ Decline in GFR ✓ Raised arterial blood pressure - Albuminuria is the first sign and peripheral edema is the first symptom of diabetic nephropathy

Answer 4

- Hyperglycaemia leads to the production of reactive oxygen species and activation of pathways (protein kinase C, polyol, hexosamine, and advanced glycation end products (AGE)). - Marked inflammation by an increase in cytokines and chemokines, including IL-6, MCP-1, TGF-beta, and VEGF = inflammation fibrosis and increased vascular permeability. - Causes podocytopathy, resulting in albuminuria. - The resulting systemic and intraglomerular hypertension results in proteinuria. - Proteinuria causes epithelial-mesenchymal cell transformation leading to fibroblasts and chronic tubular injury

Answer 5

❖ Stage 1 (Very early diabetes/Hyperfiltration) • Hyperfiltration with increased capillary glomerular pressure • Above normal Glomerular Filtration Rate (GFR) • Glomerular hypertrophy / Increase Renal size ❖ Stage 2 (developing/silent stage) • Continued hyperfiltration and hypertrophy • GFR remain elevated or return to normal • No evidence of albuminuria • Glomerular damage in the form of basement membrane thickening and mesangial expansion ❖ Stage 3 (Microalbuminuria) • Urinary albumin excretion rate becomes abnormal (e.g., 30–300 mg/24 hr) • Renal functions could be normal or reduced • Hypertension develop during this stage ❖ Stage 4 (Overt nephropathy) • Urinary albumin excretion is more than 300 mg, and creatinine levels in the blood rise • Majority of patients at this stage have systemic hypertension • If untreated a vicious cycle of progressive renal impairment develop leading to end stage renal disease ❖ Stage 5 (Uremia) • GFR has fallen to <15ml/min • Renal replacement therapy

Answer 6

**HbA1c high** - HBA1c = glycated haemoglobin (non-enzymatic glycation of Hb - glucose binds to RBCs) - so used as measure of glycaemic control (over previous 3-4 months) - Normal = <42mmmol/mol (< 5.7%) - Prediabetic = 42-47mmol/mol (5.7-6.4%) - Diabetic = >48mmol/mol (> 6.5%) - Insulin resistance - of liver, skeletal muscle, adipose tissue = no/little response to insulin → dec insulin secretion → cannot respond to hyperglycaemia - do have excess glucose in blood - so get excess binding of glucose to Hb = excess HBA1c **Cholesterol high** - HDL holds the cholesterol it 'carries' very strongly - so cholesterol is less able to become loose & attach to arterial walls - LDL holds the cholesterol it 'carries' less strongly - so cholesterol is more able to become loose & attach to arterial walls (so LDL deposits its cholesterol on arterial walls) = forms plaques which can occlude lumen- limiting blood flow = atherosclerosis if partially occludes coronary artery = angina OR fully occludes = MI) - Dyslipidaemia -> present in diabetics - characterised by hypertriglyceridemia, low HDL, high LDL, high total cholesterol → So is linked to higher risk of cardiovascular complications in diabetics → So TDs are prescribed statins e.g., atorvastatin - to lower cholesterol synthesis **EGFR low** - Measure of creatinine in blood as it is excreted as a waste product from muscles- amount made should equal amount excreted - Hyperglycaemia - More NA+ reabsorption to absorb excess glucose - Less NaCl detected by macula densa in DCT - RAAS activated - Increase in BP and renal perfusion - Angiotensin 2 will cause efferent arteriole constriction - Pressure increase causes damage to glomerulus **Albumin/creatinine ratio high** - Don’t want albumin in urine but want creatinine - Ratio is high as there is more albumin and less creatinine **Potassium, urea, phosphate high** - Decreased GFR - Decreased renal excretion - Increased resorption **Calcium and 1,25-dihydroxy vitamin D3 low** - Decreased conversion of calcidiol to calcitriol - Decreased levels of calcitriol in the blood - Decreased calcium absorption from the small intestine **PTH high** - Hypocalcemia - Decreased inhibition of PTH release - Increased PTH in blood

U10C6 CKD And Diabetes Flashcards

(41 cards)