The Kidney

1. The Kidney

2. Definitions Azotemia – Increased BUN and creatinine, usually related to decreased GFR Pre-renal azotemia – hypoperfusion of the kidneys Post-renal azotemia – obstrution to urine flow Uremia – azotemia plus other metabolic and endocrine alterations resulting from renal damage

3. Definitions Nephritic syndrome – glomerular disease, hematuria, RBC casts, mild to moderate proteinuria, hypertension, oliguria, edema Rapidly progressive glomerulonephritis- nephritic syndrome with rapid decline (hours to days) in GFR Nephrotic syndrome – glomerular disease, proteniuria >3.5 gm per day, hypoalbuminenia, severe edema, hyperlipidemia, lipiduria, inreased risk of infection, inreased risk of thrombosis, renal vein thrombosis

4. Definitions Acute renal failure – rapid and frequently reversible onset, oliguria or anuria and recent onset of azotemia Chronic renal failure – Prolonged symptoms and signs of uremia

5. Definitions

6. Chronic Renal Failure

7. Chronic Renal Failure

8. Glomerular Diseases Acute Proliferative Glomerulonephritis- ( poststreptococcal) 1-4 weeks after a strep infection ( pharynx or skin) Most frequently -6-10 years of age Malaise, fever, nausea, oligouria, hematuria, RBC casts, mild proteinuria, periorbital edema, mild to moderate hypertension Immune complex mediated disease Enlarged, hypercellular glomeruli Granular deposits Serum complement is decrease. ASO and other anti-strep antibodies are increased EM – subepithelial humps Adults tend to present with sudden hypertension and/or edema and elevated BUN

10. Glomerular Diseases Rapidly progressive ( crescentic ) GN- Rapid and progressive loss of renal function Formation of crescents- proliferation of parietal cells, infiltration of WBCs into the urinary space, compress the glomerular tuft, obliterate Bowman capsule Rupture of the GBM Type I anti-GBM, e.g. Goodpasture syndrome Type II Immune complex, e.g. Post-infectious GN Type III pauci-immune ANCA, e.g. Wegener granulomatosis

13. Primary Glomerular Membranous Minimal-change Focal segmental glomerulosclerosis Membrano-proliferative Other – e.g. IgA nephropathy Systemic DM Amyloidosis SLE Drugs- NSAIDs, penicillamine, heroin Infections – malaria, syphilis, HBV, HCV,HIV Malignant disease Misc – e.g. hereditary nephritis Causes of Nephrotic Syndrome

14. Minimal Change Disease Most frequent cause of nephrotic syndrome in children Visceral epithelial cells- uniform and diffuse effaement of foot processes Immunoflorescence is negative

15. Membranous Nephropathy Common cause of nephrotic in adults Diffuse, uniform thickening of the glomerular capillary wall Granular immunoflorescence Subepithelial deposits

16. Focal Segmental Glomerulosclerosis Most common form of nephrotic syndrome in adults Collapsing glomerulopathy – HIV associated Loss of foot processes Epithelial damage

17. Membranoproliferative GN Alterations in the GBM Proliferation of glomerular cells Leukocyte infiltration Also called mesangiocapillary GN Type I Immune complexes and activation of both classical and alternative complement pathways, subendothelial deposits Type II dense-deposit disease activation of the alternative complement pathway

18. IgA Nepropathy (Berger Disease) IgA deposits in the mesangial regions Frequent cause of recurrent gross or microscopic hematuria Probably the most common cause of GN worldwide Henoch-Schonlein purpura Secondary- liver disease and gluten enteropathy

19. Alport Syndrome Hereditary nephritis Hematuria with progression to chronic renal failure Nerve deafness Various eye disorders ( e.g. lens dislocation) Abnormalities of alpha chains in type IV collagen

20. Benign Familial Hematuria Hereditary nephritis Asymptomatic hematuria Diffuse thinning of the GBM Renal function is normal Prognosis is excellent

21. Lupus Nephritis Type I – No renal involvement ( mild mesangial) Type II – Mesangial form – granular mesangial deposits of immunoglobulin and complement Type III – Focal-proliferative - Type IV – Diffuse proliferative ( most severe) - crescentic Type V – Membranous – thickening of GBM

22. Diabetic Glomerular Nephropathy Widespread thickening of the GBM Diffuse increase in mesangial matrix- expansion of the mesangium correlates with measures of deteriorating renal function Nodular glomerulosclerosis – Kimmelsteil- Wilson disease

23. AKI ( ATN) Acute diminution of renal failure, and often morphologic evidence of tubular injury Most common cause of Acute renal failure Tubular injury and persistent and severe disturbances in blood flow Causes – Ischemia, direct toxic injury, acute tubulointerstitial nephritis, urinary obstruction Initiation, maintenance, recovery phases Tubulointerstitial nephritis Causes- infections, toxins, metabolic diseases, physical factors, neoplasms, Immunologic reactions,vascular diseases, miscellaneous Tubular and Interstitial Diseases

24. Pyelonephritis and UTI Lower track – frequency, urgency, pyuria, dysuria, hematuria, Upper track ( pyelo) – fever leukocytosis, CVA tenderness, WBC casts in urine patchy interstitial suppurative inflammation, intratubular aggregates ofn neutrophils, tubular necrosis, Papillary necrosis, pyonephrosis, perinephric abscess, pyelonephritic scar-inflammation, fibrosis, deformation of underlying calyx and pelvis E. Coli most common Ascending infection VUR, obstruction, instrumentation, pregnancy, preexisting renal lesions, DM, immunosuppression

25. Vascular Diseases Benign nephrosclerosis- hyaline arteriosclerosis Malignant nephrosclerosis – fibrinoid necrosis and onion-skinning Renal artery stenosis – most common cause is atherosclerosis, fibromuscular dysplasia Renal infarction – white – end-organ

29. Thrombotic Microangiopathies Microangiopathic hemolytic anemia Thrombocytopenia Renal failure ( in many cases) Thrombotic lesions in capillaries and arterioles Endothelial injury Platelet aggregation Typical ( epidemic, classic, diarrhea-positive) HUS- Shiga-like toxins, E. coli 0157:H7 Atypical ( non-epidemic, diarrhea-negative) HUS- genetic mutations in complement-regulatory factors, antiphospholipid syndrome, postpartum, vascular diseases, drugs, irradiation Thrombotic Thrombocytopenia Purpura – ADAMTS13, CNS involvement dominant

30. Cystic Diseases Adult polycystic kidney disease – AD, CRF later in life, berry aneurysms, hepatic cysts,MVP and other valvular lesions Childhood polycytic kidney disease- AR, Death in infancy or childhood, hepatic fibrosis

31. Urinary Tract Obstruction Common causes: Congenital anomalies Urinary calculi BPH Tumors Inflammation Sloughed papillae or blood clots Pregnancy Uterine prolapse and cystocele Functional disorders – neurogenic bladder Hydronephrosis – Dilation of the renal pelvis and calyces associated with progressive atrophy of the kidney due to obstruction to the outflow of urine Obstruction also triggers an interstitial inflammatory reaction, leading eventually to interstitial fibrosis

32. Urolithiasis Calcium stones- oxalate and/or phosphate Triple stones – magnesium ammonium phosphate, infections, staghorn calculi Uric acid stones Cystine

33. Tumors Renal cell carcinoma – adenocarcinoma. Smoking, obesity, unopposed estrogen, Asbestos, petroleum products, heavy metals CRF, acquired cystic disease, tuberous sclerosis von Hippel-Lindau Clear cell- 70-80% CVA pain, palpable mass, hematuria Paraneoplastic syndromes, widespread metastases before local signs and symptoms