Renal Pathology I

1. Renal Pathology I • Review gross/microscopic anatomy of the kidney • Clinical Manifestations of Renal Diseases • Pathology of Selected Renal Diseases

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

4. 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

6. 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

10. 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

11. 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 (!)

13. Clinical Manifestations of Renal Diseases • Azotemia: biochemical problem elevated BUN & creatinine • decreased GFR • prerenal, renal or postrenal causes • Uremia: azotemia with clinical symptoms • gastroenteritis, dermatitis, metabolic acidosis, pericarditis, peripheral neuropathy, hyperkalemia

14. 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

15. Major Renal Syndromes • Acute renal failure: sudden onset of azotemia with oliguria (or anuria) • rapid glomerular injury, acute tubular necrosis, interstitial injury • Asymptomatic hematuria or proteinuria • detected by lab studies • mild glomerular abnormalities

16. 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

17. Diagnosis of Renal Disease • Renal Biopsy • Light microscopy • H&E, PAS, Jones and Trichrome stains • Immunofluorescence microscopy • immune complexes, fibrin, light chains • Electron microscopy • basement membranes and location of IC’s

21. Congenital Anomalies of the Kidney • affects 10% of the population • cause of chronic renal failure in 20% of kids • Polycystic kidney disease is responsible for 10% of CRF in adults • Other anomalies - Agenesis, hypoplasia, ectopic, horseshoe kidneys

22. 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 30-40’s • Renal insufficiency by then • Hemorrhage & pain in many • chronic renal failure

23. Autosomal Dominant Polycystic Kidney Disease • enlarged bilaterally (can be marked!) • numerous cysts, filled with clear to red-brown 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

26. 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)

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

28. 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)

30. Diabetes Mellitus • Systemic disease that causes Nephrotic Syndrome • major cause of renal morbidity/mortality • Proteinuria develops 12-20 yrs after the clinical onset • Progressive loss of GFR • ESRD in almost 30% of IDDM pts • also affects the arterioles & tubules too

31. Diabetes Mellitus • thickened capillary basement membranes • diffuse glomerular sclerosis • thickened GBM • increased mesangial matrix • nodular glomerular sclerosis • Kimmelsteil-Wilson disease • pathognomonic lesion for DM

33. 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

34. 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 IC’s

36. Membranous Glomerulonephritis • Primary GN causing Nephrotic syndrome • IF: granular deposits of Ig & C’ • 85% of MGN are idiopathic • secondary MGN may be seen in pt with: • tumors, SLE, gold/mercury exposure, drugs, infections, DM, thyroiditis • 10% die or develop renal failure in 10 yrs • course is variable

40. Focal Segmental Glomerulosclerosis (FSG) • 10-15% of nephrotic syndrome • Some glomeruli are normal • Idiopathic and secondary FSG • HIV infection, heroin abuse • poor response to steroids • 20% have a rapid course • 50% develop ESRD in 10 yrs

42. Let’s Take a Break…back in 10 minutes