Renal Disease

Renal Disease

RENAL DISEASE: CHRONIC RENAL FAILURE Pathophysiology of Disease: Chapter 16 (394-398) Jack DeRuiter, PhD Department of Pharmacal Sciences April, 2000 ETIOLOGY (page 394)

Diabetes mellitus (28%) Hypertension (25%) Glomerulonephritis (21%) Polycystic Kidney Diease (4%) Other (23%): Obstruction, infection, etc. Pathology and Pathogenesis (page 395) Chronic vs Acute renal failure pathogenesis: Acute: tubular cell death and regeneration

(reversible) Chronic: Irreversible nephron loss Glomerular Hyperfiltration: Compensatory mechanism with increased nephron GFR: Pre-disposition to glomerular sclerosis Azotemia at 30-35% GFR Uremia: <20% normal excretory capacity Pathogenesis of Uremia

Retention of nitrogenous wastes Increased intracellular Na and water Decreased intracellular K Increased levels of bioactive substances normally cleared renally (hormones) Decreased levels of hormones and other mediators produced by the kidney Decreased basal body temperature Diminished lipoprotein lipase activity

CHRONIC RENAL FAILURE: CLINICAL MANIFESTATIONS (pages 395-398)

Sodium and water retention Hyperkalemia Metabolic Acidosis Mineral and Bone metabolism Cardiovascular and Pulmonary Disorders Hematologic Abnormalities Neuromuscular Abnormalities Gastrointestinal Abnormalities Endocrine Abnormalities Dermatologic Abnormalities

CHRONIC RENAL FAILURE: Sodium and Volume Balance (page 395) Sodium and water retention: CHF, Hypertension, ascites, edema Enhanced sensitivity to extra-renal sodium and water loss vomiting, diarrhea, fever, sweating Symptoms: dry mouth, dizziness, tachycardia, etc. Recommendations Avoid excess salt and water intake Diuretics or dialysis

CHRONIC RENAL FAILURE: Potassium Balance (pages 395-396) Hyperkalemia (GFR below 5 mL/min) GFRs >5 mL/min: compensatory aldosteronemediated K transport in the DCT K-sparing diuretics, ACEis, beta-blockers impair Aldosterone-mediated actions Exacerbation of hyperkalenia: Exogenous factors: K-rich diet, etc. Endogenous factors: infection, trauma, etc. CHRONIC RENAL FAILURE:

Potassium Balance and Diabetes (page 396) Diabetics (major cause of CRF): Hyporeninemic hypoaldosteronism Lack of renin - decreased angiotensin II impaired aldosterone secretion - loss of compensation for low GFr CHRONIC RENAL FAILURE: Metabolic Acidosis (page 396) Decreased acid excretion and ability to maintain physiologic buffering capacity: GFR > 20 mL/min: transient moderate

acidosis Treat with oral sodium bicarbonate Increased susceptibility to acidosis CHRONIC RENAL FAILURE: Mineral and Bone (page 396-397) Bone disease (Figure 16-6) from: Decreased Ca absorption from the gut Over-production of PTH Altered Vitamin D metabolism Chronic metabolic acidosis CHRONIC RENAL FAILURE:

Cardiovascular and Pulmonary Abnormalities (page 397) Volume and salt overload CHF and pulmonary edema Hypertension Hyperreninemia: Hypertension Pericarditis: Remic toxin accumulation Accelerated atherosclerosis: linked to factors above and metabolic abnormalities (Ca alterations, hyperlipidemia) CHRONIC RENAL FAILURE:

Hematological Abnormalities (page 397) Anemia: lack of erythropoietin production Bone marrow suppression: uremic poisons: leukocyte suppression - infection bone marrow fibrosis: elevated PTH an aluminum toxicity from dialysis Increased bruising, blood loss (surgery) and hemorrhage Lab Abnormalities: Prolonged bleeding time, abnormal platelet aggregation CHRONIC RENAL FAILURE:

Neuromuscular Abnormalites (page 397) CNS Abnormalities: Mild-Moderate: Sleep disorders, impaired concentration and memory, irritability Severe: Asterixis, myoclonus, stupor, seizures and coma Peripheral neuropathies: restless legs syndrome Hemodialysis-related neuropathies CHRONIC RENAL FAILURE:

Gastrointestinal Abnormalities (page 397) Peptic Ulcer disease: Secondary hyperparathyrodism? Uremic gastroenteritis: mucosal alterations Uremic Fetor: bad breath (ammonia) Non-Specific abnormalities: anorexia, nausea, vomiting, diverticulosis, hiccoughs CHRONIC RENAL FAILURE: Endocrine Abnormalities (page 398) Insulin: Prolonged half-life due to reduced clearance (metabolism)

Amenorrhea and pregnancy failure: low estrogen levels Impotence, oligospermia and geminal cell dysplasia: Low testosterone levels CHRONIC RENAL FAILURE: Dermatologic Abnormalities (page 398) Pallor: anemia Skin color changes: accumulation of pigments Ecchymoses and hematomas: clotting abnormalities Pruritus and Excoriations: Ca deposits from secondary hyperparathyroidism

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