Renal Pathology I

Review gross/microscopic anatomy of the kidney Clinical Manifestations of Renal Diseases Pathology of Selected Renal Diseases

Gross Anatomy
150 grams each (5-6 oz.) cortex (1.2-1.5 cm), columns of Bertin medulla (pyramids & papillae) ureters, pelvis, calyces

Histology
Glomeruli: cortical and juxtamedullary Tubules: proximal & distal Interstitium: space between the tubules and the glomeruli Vasculature all 4 compartments are affected by most disease processes

Glomerular Histology
network of capillaries

fenestrated endothelial cells (70-100 nm) GBM avg. thickness 3500 angstroms
type IV collagen, proteoglycans (heparin)

visceral & parietal epithelium

podocytes (visceral) form the foot processes 20-30 nm filtration slit

mesangium supporting structure

Tubules
Many subdivisions Proximal & distal tubules Collecting ducts Major function reabsorb specific portions of the filtrate Na+, water, glucose, amino acids, K+, phosphates, and proteins

Vasculature
receives ~ 25% cardiac output renal cortex receives ~ 90% of this flow main-segmental-interlobar-arcuate branches, afferent/efferent arterioles peritubular capillaries & vasa recta diseases that affect the vessels of the glomeruli will also affect the tubules (!)

Clinical Manifestations of Renal Diseases

Azotemia: biochemical problem elevated BUN & creatinine

decreased GFR prerenal, renal or postrenal causes gastroenteritis, dermatitis, metabolic acidosis, pericarditis, peripheral neuropathy, hyperkalemia

Uremia: azotemia with clinical symptoms

Major Clinical Renal Syndromes

Acute Nephritic syndrome: glomerular syndrome with acute onset of hematuria, mild to moderate proteinuria and hypertension Nephrotic syndrome: heavy proteinuria, hypoalbuminemia, edema, hyperlipidemia and lipiduria

Major Clinical Renal Syndromes

Renal tubular defects: polyuria, nocturia, and electrolyte problems (metabolic acidosis) Chronic renal failure: prolonged uremia Urinary tract infections: bacteria and pyuria Nephrolithiasis (stones): renal colic, hematuria, recurrent stone formation

Diagnosis of Renal Disease

Renal Biopsy Light microscopy

H&E, PAS, Jones and Trichrome stains immune complexes, fibrin, light chains basement membranes and location of ICs

Immunofluorescence microscopy

Electron microscopy

Autosomal Dominant (Adult) Polycystic Kidney Disease

fairly common, 1 in 1000 persons affected autosomal dominant, 95-100% penetrance gene is (APKD1) on chromosome 16 (90%) polycystin (cell membrane protein) 1st symptoms usually not until 30-40s
Renal insufficiency by then Hemorrhage & pain in many

chronic renal failure

Autosomal Dominant Polycystic Kidney Disease

enlarged bilaterally (can be marked!) numerous cysts, filled with clear to redbrown fluid cysts arise from various segments, thus the epithelial lining varies too 40% have cysts elsewhere (liver) 10% of pts will require dialysis or transplantation

Autosomal Recessive (Childhood) Polycystic Kidney Disease

rare, with many subcategories mutation on chromosome 6p renal failure develops shortly after birth cysts are bilateral in the cortex & medulla liver cysts, progressive liver fibrosis later (cirrhosis)

Glomerular Diseases
Primary Glomerular Diseases

kidney is the primary organ involved e.g. IgA Nephropathy kidney is one of multiple organs involved by a systemic disease process SLE, Diabetes mellitus, Amyloidosis

Secondary Glomerular Diseases

Glomerular Diseases
some of the most common causes of chronic renal failure Glomeruli may be injured by many processes immunologic, vascular Mechanisms
Immune complexes deposited in glom BM Auto-antibodies directed to the BM Injury to the glomerular epithelial cells (podocytes)

Diabetes Mellitus
thickened capillary basement membranes diffuse glomerular sclerosis

thickened GBM increased mesangial matrix Kimmelsteil-Wilson disease pathognomonic lesion for DM

nodular glomerular sclerosis

Diabetes Mellitus
Two processes play role in the lesions Defect leading to glycosylation

Thickened basement membranes

Hemodynamic effects lead to sclerosis May also have HTN Tight glucose control, ACE-inhibitors

Minimal Change Disease

lipoid nephrosis, common in ages 2-6 yrs nephrotic syndrome (selective - albumin) EM shows fusion of foot processes > 90% respond to steroids (kids) by light & IF normal, no ICs