RENAL DISEASE OVERVIEW AND ACUTE RENAL FAILURE Pathophysiology

RENAL DISEASE: OVERVIEW AND ACUTE RENAL FAILURE Pathophysiology of Disease: Chapter 16 (388 -394) Jack De. Ruiter, Ph. D 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. Ig. A 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 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

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 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?

ACUTE RENAL FAILURE: Early 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/Sr. Cr (20 -30: 1) with normal Sr. Cr – 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 392 -394) • Later Symptoms (frank ATN): dyspnea, orthopnea, heart (sound S 3), edema – – Normal BUN/Sr. Cr, profressive elevation of Sr. Cr Casts (protein, RBC, epithelial cells) Urine osmolality Fractional excretion of Na (as low as 1%)