RENAL DISEASE: OVERVIEW AND ACUTE RENAL FAILURE Pathophysiology of Disease: Chapter 16 (388-394)

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RENAL DISEASE OVERVIEW AND ACUTE RENAL FAILURE
Pathophysiology of Disease Chapter 16 (388-394)

• Jack DeRuiter, PhD
• Department of Pharmacal Sciences
• April, 2000

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Kidney Sites Susceptible to Renal Disease (page
388)

• General Renal medulla
• Low oxygen environment Ischemia
• Glomerulus
• Structure predisposes it to immune complex
  deposition and complement fixation
• Tubules
• Post-Renal Structures (ureters, bladder)
• Malformations, Obstruction, Masses (i.e. cancer)

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CATEGORIZATION

• Generalized Site of Disease
• Prerenal Inadequate renal blood flow
• Intrarenal Nephron damae
• Postrenal Obstruction, Structural defects
• Site of Renal Lesion (Intrarenal)
• Glomerulopathy
• Nephritic
• Nephrotic
• Tubulointerstitial Disease
• Etiologic Factors Infection, Diabetes, etc.

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Glomerular Capillary Normal versus Pathology
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Glomerular Capillary Pathology(see previous
slide)

• 1. Membranous nephropathy Subepithelial deposits
• 2. Post-infectious glomerulonephritis
  Subepithelial
• 3. Lupus glomerulonephritis Subendothelial
  deposits
• 4. IgA Nephropathy Mesangial deposits
• 5. Goodpastures Syndrome Antibody binding to
  GBM
• 6. Glomerular injury with proteinuria Podocyte
  effacement

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Nephrotic vs Nephritic Disorders

• Nephrotic
• profound proteinuria
• Immune complex deposits Epithelial
• NO cellular inflammatory reaction
• Nephritic
• Variable proteinuria
• Immune complex deposits Subendothelial or GBM
• Cellular inflammatory reaction

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ACUTE RENAL FAILUREClinical Presentation (pages
389-390)

• Heterogeneous group of disorders characterized by
  rapid deterioration in renal function (Decreased
  GFR)
• Rapid elevation of BUN and serum creatinine
• Oliguria Variable
• Other Henaturia, proteinuria, edema,
  hypertension

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ACUTE RENAL FAILUREEtiology (page 390 and Table
16-3)

• Prerenal
• CV and volume depletion
• Drug-induced or related (NSAIDs, ACEIs,
  diuretics)
• Intrarenal
• Inflammatory disease Vasculitis,
  glomerulo-nephritis, drug-induced
• Acute tubular necrosis
• Postrenal Obstruction, Cancer, congenital
  abnormalities

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ACUTE RENAL FAILUREPathology (pages 390-392)

• Acute tubular necrosis (ATN)
• Tubular cell sloughing
• Reversibility/Irreversibility Dependent on time
  of intervention
• ATN Pathogenesis
• Tubular occlusion theory and cast formation
• Vascular hypoperfusion theory Afferent
  vasoconstriction with Efferent vasodilation
• Role of renal mediators?

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ACUTE RENAL FAILUREEarly Clinical
Manifestations (pages 392-394)

• Symptoms depend on degree and cause of renal
  failure (See Table 16-5)
• Initial Symptoms Fatigue and malaise
• Loss of excretory capacity and accumulation of
  water, electrolytes and nitrogenous wastes
• Prerenal azotemia Elevated BUN/SrCr (20-301)
  with normal SrCr
• Urinalysis No casts detected
• Maximal urinary concentration 1500 mosm/L
• Fractional Na Excretion (99)
• May progress to ATN without proper treatment

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ACUTE RENAL FAILURELater Clinical
Manifestations (pages 392-394)

• Later Symptoms (frank ATN) dyspnea, orthopnea,
  heart (sound S3), edema
• Normal BUN/SrCr, profressive elevation of SrCr
• Casts (protein, RBC, epithelial cells)
• Urine osmolality
• Fractional excretion of Na (as low as 1)