renal disease chronic renal failure pathophysiology of disease chapter 16 394 398 n.
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RENAL DISEASE: CHRONIC RENAL FAILURE Pathophysiology of Disease: Chapter 16 (394-398) PowerPoint Presentation
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RENAL DISEASE: CHRONIC RENAL FAILURE Pathophysiology of Disease: Chapter 16 (394-398)

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RENAL DISEASE: CHRONIC RENAL FAILURE Pathophysiology of Disease: Chapter 16 (394-398)

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RENAL DISEASE: CHRONIC RENAL FAILURE Pathophysiology of Disease: Chapter 16 (394-398)

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  1. RENAL DISEASE:CHRONIC RENAL FAILUREPathophysiology of Disease: Chapter 16 (394-398) Jack DeRuiter, PhD Department of Pharmacal Sciences April, 2000

  2. ETIOLOGY (page 394) • Diabetes mellitus (28%) • Hypertension (25%) • Glomerulonephritis (21%) • Polycystic Kidney Diease (4%) • Other (23%): Obstruction, infection, etc.

  3. 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

  4. 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

  5. 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

  6. 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

  7. CHRONIC RENAL FAILURE:Potassium Balance (pages 395-396) • Hyperkalemia (GFR below 5 mL/min) • GFRs >5 mL/min: compensatory aldosterone-mediated 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.

  8. 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

  9. 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

  10. 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

  11. 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)

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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