Pathophysiology of Disease: Chapter 16 ( ) RENAL DISEASE: OVERVIEW AND ACUTE RENAL FAILURE Pathophysiology of Disease: Chapter 16 ( ) Jack DeRuiter, PhD Department of Pharmacal Sciences April, 2000

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)

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.

Glomerular Capillary: Normal versus Pathology

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. Goodpasture’s Syndrome: Antibody binding to GBM 6. Glomerular injury with proteinuria: Podocyte effacement

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

ACUTE RENAL FAILURE: Clinical Presentation (pages ) 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

ACUTE RENAL FAILURE: Etiology (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

ACUTE RENAL FAILURE: Pathology (pages ) 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?

ACUTE RENAL FAILURE: Early Clinical Manifestations (pages ) 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 (20-30:1) with normal SrCr –Urinalysis: No casts detected –Maximal urinary concentration: 1500 mosm/L –Fractional Na Excretion (99%) –May progress to ATN without proper treatment

ACUTE RENAL FAILURE: Later Clinical Manifestations (pages ) 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%)