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8/8/2019 Renal Part3
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RENAL DISEASE:CHRONIC RENAL FAILURE
Pathophysiology of Disease: Chapter 16 (394Pathophysiology of Disease: Chapter 16 (394--398)398)
JackDeRuiter, PhD
Department of Ph
arm
acalScien
ces
April, 2000
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ETIOLOGY
(page 394)
Diabetes mellitus (28%)
Hypertension (25%)
Glomerulonephritis (21%)
Polycystic Kidney Diease (4%)
Other (23%): Obstruction, infection, etc.
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Pathology and Pathogenesis (page 395)
Chronic vs Acute renal failure pathogenesis: Acute: tubularcell death and regeneration
(reversible)
Chronic: Irreversible nephron loss
Glomerular Hyperfiltration:
Compensatory mechanism with increased
nephron GFR:
Pre-disposition to glomerular sclerosis
Azotemiaat 30-35% GFR
Uremia:
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Pathogenesis of Uremia
Retention of nitrogenous wastes
Increased intracellular Naand water
Decreased intracellular K
Increased levels ofbioactive substances
normally cleared renally (hormones)
Decreased levels of hormones and other
mediators produced by the kidney
Decreased basalbody temperature
Diminished lipoprotein lipase activity
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CHRONICRENAL 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
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CHRONICRENAL FAILURE:
Sodium and Volume Balance (page 395)
Sodium and water retention:
CHF, Hypertension, ascites, edema
Enhanced sensitivity to extra-renal sodium andwaterloss
vomiting, diarrhea, fever, sweating
Symptoms: dry mouth, dizziness, tachycardia, etc.
Recommendations
Avoid excess salt and water intake
Diuretics or dialysis
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CHRONICRENAL FAILURE:
Potassium Balance (pages 395-396)
Hyperkalemia (GFRbelow 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.
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CHRONICRENAL FAILURE:
Potassium Balance and Diabetes (page 396)
Diabetics (majorcause of CRF):
Hyporeninemic hypoaldosteronism Lackof renin - decreased angiotensin II -
impaired aldosterone secretion - loss of
compensation forlow GFr
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CHRONIC RENAL FAILURE:
Metabolic Acidosis (page 396)
Decreased acid excretion and ability to
maintain physiologicbuffering
capacity:
GFR > 20 mL/min: transient moderate
acidosis
Treat with oral sodium bicarbonate
Increased susceptibility to acidosis
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CHRONIC RENAL FAILURE:
Mineral and Bone (page 396-397)
Bone disease (Figure 16-6) from:
Decreased Caabsorption from the gut
Over-production of PTH
Altered Vitamin D metabolism
Chronic metabolicacidosis
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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 metabolicabnormalities
(Caalterations, hyperlipidemia)
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CHRONIC RENAL FAILURE:
Hematological Abnormalities (page 397)
Anemia: lackof erythropoietin production
Bone marrow suppression:
uremic poisons: leukocyte suppression - infection
bone marrow fibrosis: elevated PTH an aluminum
toxicity from dialysis
Increasedbruising,blood loss (surgery) and
hemorrhage
Lab Abnormalities: Prolongedbleeding time,
abnormal platelet aggregation
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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
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CHRONIC RENAL FAILURE:
Gastrointestinal Abnormalities (page 397)
Peptic Ulcer disease: Secondary
hyperparathyrodism? Uremic gastroenteritis: mucosalalterations
Uremic Fetor: bad breath (ammonia)
Non-Specificabnormalities:anorexia, nausea, vomiting, diverticulosis,
hiccoughs
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CHRONIC RENAL FAILURE:
Endocrine Abnormalities (page 398)
Insulin: Prolonged half-life due to reduced
clearance (metabolism)
Amenorrheaand pregnancy failure: low
estrogen levels
Impotence, oligospermiaand geminalcell
dysplasia: Low testosterone levels
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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