Renal failure

RENAL FAILURE

1. RENAL FAILURE DR. M.MOUNIKA 1 ST YEAR PG PATHOLOGY MODERATOR: DR KR. GOPALAKRISHNAN MD., READER OF PATHOLOGY

2. RENAL FAILURE • It happens when the kidneys cannot remove the body’s metabolic wastes or perform their regulatory function. • It is a systemic disease and is a final common pathway of many different kidney and urinary tract diseases.

3. ACUTE RENAL FAILURE Is a syndrome characterized by rapid onset of renal dysfunction, chiefly oliguria or anuria , and sudden increase in metabolic waste products [urea and creatinine ] in the blood with consequent development of uraemia .

4. ETIOPATHOGENESIS A. PRERENAL Hypovolemia . Altered renal hemodynamics resulting in hypoperfusion . Inadequate cardiac output.

5. B. INTRARENAL Vascular disease. Diseases of the glomeruli . Acute tubular necrosis. Tubulointerstitial nephritis. Pyelonephritis . Nephrotoxicity .

6. C. POSTRENAL Ureteric . Bladder neck. Urethra.

7. PHASES OF ACUTE TUBULAR NECROSIS 3 PHASES: Oliguric phase. Diuretic phase. Phase of recovery. PRERENAL SYNDROME:

8. CHRONIC KIDNEY DISEASE Is a syndrome characterized by progressive and irreversible deterioration of renal function due to slow destruction of renal parenchyma, eventually terminating in death when sufficient number of nephrons have been damaged.

9. ETIOPATHOGENESIS Glomerular pathology: Primary - Membranous glomerulonephritis Membrano -proliferative glomerulonephritis . Lipoid nephrosis . Anti- glomerular basement membrane nephritis. Systemic- Systemic lupus erythematosus . Diabetic nephropathy.

10. ETIOPATHOGENESIS CONT.. Tubulointerstitial pathology: Vascular causes. Infectious causes. Toxic causes. Obstructive causes

11. PATHOPHYSIOLOGY Two mechanisms Initiating mechanisms specific to the underlying etiology. A set of progressive mechanisms, involving hyper-filtration and hypertrophy of the remaining viable nephrons . Stages of CRF: are based on the GFR .

12. STAGES OF CHRONIC RENAL FAILURE Decreased renal reserve. Renal insufficiency. Renal failure. End stage kidney[ chronic kidney disease]

13. PATHOGENESIS OF GLOMERULAR INJURY Immune mechanisms underlie most forms of primary glomerulopathy and many of secondary glomerular disorders. Antibody mediated Cell mediated Activation of alternative complement pathway.

14. ANTIBODY MEDIATED Two mechanisms: Antibodies reacting in situ within the glomerulus . [fixed intrinsic tissue antigens, planted antigens] Deposition of circulating antigen-antibody complexes in the glomerulus . [exogenous and endogenous antigens]

15. ACUTE TUBULAR NECROSIS 2 Types. Ischaemic ATN- shock, crush injuries, non-traumatic rhabdomyolysis , mismatched blood transfusions, black water fever. Toxic ATN- general poisons, heavy metals, drugs, radiographic contrast material.

16. Nephritic syndrome: It is a clinical syndrome characterized by: Hematuria with RBCs casts. Proteinuria (<3 gm). Hypertension. Mild edema. Oliguria .

17. PATHOGENESIS It is an acute glomerular injury. Lesions causing nephritic syndrome have in common proliferation of endocapillary cellularity ( Mesangial and endothelial cells) and associated with leukocytic infiltration. Inflammatory reaction injures the capillary wall, permitting escape of RBCs and proteins in urine ( hematuria and proteinuria ). At the same time increased Mesangial cellularity compress capillary Lumina and inducing hemodynamic changes that lead to reduction of GFR that manifested clinically by oliguria with fluid retention and azotemia . Hypertension results from fluid retention and renin release from such ischemic kidney.

18. Rapidly progressive glomerulonephritis [RPGN] Presents with an acute reduction in renal function resulting in acute renal failure in a few weeks or months. It is characterized by formation of crescents outside the glomerular capillaries.

19. PATHOGENESIS Injury of capillary wall leads to escape of plasma proteins, fibrin and inflammatory cells to Bowman's capsule. This will lead to proliferation of parietal cells with infiltration of macrophages and interstitial fibroblasts leading to crescent formation. Crescents eventually obliterate Bowman's space and compress the glomeruli .

20. TYPES Type 1 RPGN: anti-GBM nephritis Type 2 RPGN: any immune complex GN may lead to RPGN. Type 3 RPGN: pauci -immune

21. CHRONIC GLOMERULONEPHRITIS: It is the end-stage of a variety of glomerular diseases which result in irreversible impairment of renal functions. It constitutes 35-50% of end-stage renal disease that require chronic dialysis or renal transplantation.

22. FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS) Characterized histologically by: focal and segmental obliteration of capillary loops by increased collagen (sclerosis) and accumulation of lipid and proteinaceous material Types: Idiopathic. Superimposed with primary glomerular disease. Secondary.

23. PATHOGENESIS Injury to visceral epithelial cells is its hallmark that leads to focal hyper-permeable foci leading to entrapment of plasma proteins and lipids. This results into mesangial cell reaction with increased mesangial matrix.

24. MEMBRANOUS NEPHROPATHY Diffuse thickening of the glomerular capillary wall due to the accumulation of deposits containing Ig along the subepithelial side of the basement membrane. 75% primary and remaining secondary. Drugs[ penicillamine , gold, captopril , NSAIDS], underlying malignant tumours , SLE, infections, autoimmune disorders. Chronic immune complex mediated disease.

25. MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS Immune mediated injury rather than a specific disease.[hepatitis C and B] 2 types Pathogenesis: Evidence of immune complex in the glomerulus and activation of both classical and alternative complement pathways.

26. DIABETIC NEPHROPATHY Glomerular lesions. Capillary basement membrane thickening. Diffuse mesangial sclerosis. Nodular glomerulosclerosis . Renal vascular lesions . Renal atherosclerosis and arteriosclerosis. Pyelonephritis .

27. DIABETIC NEPHROPATHY

28. IGA NEPHROPATHY/BERGER DISEASE Etiopathogenesis : Hereditary or acquired[respiratory or gastrointestinal exposure to environmental antigens] defect leading to aberrantly glycosylated IgA1 which form immune complexes deposited in the mesangium .

29. IMMUNOFLUORESCENCE LOCATION: Subendothelial deposit. Subepithelial deposit. Intramembranous deposit. Mesangial deposit. STAINING PATTERN: Diffuse linear staining. Granular lumpy bumpy deposits. Irregular fluffy deposits.

30. ELECTRON MICROSCOPY Effacement of podocytes . Electron dense immune complex. GBM thickening. GBM replication. Collagen matrix deposition. Fibrillary deposit.

31. URINE ANALYSIS Pre-renal ARF : Specific gravity>1.018. Hyaline casts. Intrinsic ARF: Renal artery thrombosis: Mild proteinuria . Occasional hematuria .

32. 2. Athero -embolic disease : Eosinophiluria . 3. Renal vein thrombosis: Mild proteinuria . Occasional hematuria . 4. Glomerulonephritis / vasculitis : Hematuria with red cell casts/ dysmorphic red cells. Granular casts. Proteinuria [<1g/dl]

33. 5. Hemolytic-uremic syndrome/ thrombotic thrombocytopenic purpura : Hematuria . Mild proteinuria . Red cell casts[rare]. 6. Malignant hypertension . Hematuria with red cell casts/ proteinuria . 7. Acute tubular necrosis : Muddy brown granular or tubular epithelial cell casts. Specific gravity<1.015.

34. 8. Allergic interstitial nephritis : White cell casts. Eosinophiluria . 9. Acute bilateral pyelonephritis : Leucocytes. Proteinuia . Positive urine culture Postrenal ARF: Usually normal. Hematuria if due to stones.

35. CHRONIC GLOMERULONEPHRITIS Fixed specific gravity. Proteinuria Waxy casts

36. HEMOTOLOGY

37. THANK YOU