Renal Part3

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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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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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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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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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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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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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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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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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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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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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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