There are two main types of renal failure - acute and chronic. Acute renal failure is a sudden onset condition characterized by oliguria/anuria and a rapid rise in BUN and creatinine levels. Chronic renal failure is a long-term condition that impairs homeostasis due to structural kidney damage and leads to metabolic complications like acidosis, hypocalcemia, and hyperphosphatemia. The causes and stages of both acute and chronic renal failure are described.

1. Renal Failure

2. Types Acute Chronic

3. Acute renal failure Sudden onset with oliguria/anuria Rapid rise in BUN and S Creatinine

4. RENAL DISEASE – CLINICAL FEATURES Azotaemia = BUN , Creatinine - biochemical abnormality Pre renal - due to renal hypoperfusion ( shock, haemorrhage, CCF). No parenchymal renal disease. Renal – due to renal parenchymal disease. Post renal – due to obstruction to urine outflow below kidney. Uraemia = azotemia + S/S of renal failure

6. Types Pre-renal Intra-renal Post-renal

8. Pre-renal Inadequate blood flow to kidney Hypovolemia Renal artery stenosis Congestive cardiac failure Intrarenal small vessel disease Drugs ( NSAIDs, ACE inhibitors )

10. Intra-renal Glomerulonephritis Interstitial nephritis Toxin induced Pigment induced

12. Post-renal Intra – renal obstruction Extra – renal obstruction

14. Pathogenesis ARF leads to acute tubular necrosis Hypoxic injury

16. Renal Tubular Injury in ATN Loss of polarity and brush border Normal epithelium with brush border

17. Cell death -apoptosis and necrosis Sloughing of dead and viable cells - luminal obstruction

19. Spread and de-differentiation of viable cells Proliferation, differentiation and reestablishment of polarity Normal epithelium with brush border

20. Urinary abnormalities ATN – Granular, epithelial casts, urine osmolality < 350 mOsm/L

21. Other abnormalities Hyperkalemia Azotemia Metabolic acidosis Hyponatremia and hypervolemia

22. Prevention and treatment Supportive care Fluid and sodium restriction Treat the hyperkalemia, acidosis Dialysis

23. Dialysis Increased intravascular volume leading to CHF, Pulmonary edema, intractable hypertension Non-responsive hyperkalemia Symptomatic uremia – lethargy, neurologic changes, seizures

24. Chronic Renal Failure Impaired homeostasis due to structural damage to kidney Metabolic acidosis Hypocalcemia Hyperphosphatemia Altered Vit D metabolism Toxemia

26. present absent Metabolic bone disease present absent Anemia small normal to large Kidney size polyuria oliguria Urine output polyuria, polydipsia recent drug administration, toxin exposure,surgery/hypovolemia History Chronic Renal failure Acute renal failure

27. Etiology Diabetes Mellitus Hypertension Glomerulonephritis PKD Obstruction Infection

28. Stages Decreased renal reserve Renal insufficiency Renal failure Uremia

29. Stages Decreased renal reserve GFR 50-75% S. creatinine, BUN : normal

30. Stages Renal insufficiency GFR < 50% S. creatinine, BUN : start to rise Mild anemia, hyposthenuria, nocturia Increase in serum PTH Azotemia/metabolic acidosis may occur

31. Stages Renal failure ( GFR 10-25%) GFR < 10-25% Marked anemia, severe acidosis Hypocalcemia, hyperphosphatemia

32. Stages Uremia >90% nephron mass destroyed S. creatinine, BUN : sharp rise Severe symptoms

33. Pathogenesis Intact nephron hypothesis Trade off hypothesis Glomerular hyperfiltration hypothesis

34. Intact nephron hypothesis GFR is reduced, number of functional nephrons is reduced, but amount of solutes excreted remains same When >75% nephron mass is destroyed – BUN and S. creatinine begin to rise

35. Trade off hypothesis Increased blood conc. of some solutes stimulate secretion of other factors Retention of phosphate – release of PTH – increased Ca levels & reduced phosphate, reduced bicarbonate absorption – acidosis ,osteomalacia, calcification

36. Glomerular hyperfiltration hypothesis With progressive loss of some nephrons, hyperfiltration occurs in the remaining – leads to fibrosis and scarring Any added stress precipitates Uremia

37. Alterations of metabolism and function Disorders of Urine Disorders of Water and Sodium balance Disorders of Potassium balance Metabolic Acidosis Renal Azotemia Renal Hypertension Calcium, Phosphate and bone metabolism Renal anemia and bleeding tendency

38. Disorders of Urine Initial nocturia, polyuria, later oliguria, anuria Isosthenuria – s.g. : 1.010, 285mOsm/L Urinary sediment contains cells and casts

39. Disorders of Water and Sodium balance Continued ingestion of salt – CHF, Hypertension, edema Excess water ingestion – Hyponatremia, hypervolemia, weight gain ECF depletion - shock

40. Disorders of Potassium balance Hyperkalemia if GFR < 5% by potassium sparing diuretics and in Diabetes mellitus(hyporeninemic hypoaldosteronism) ->reduced angiotensin II & impairs aldosterone secretion.

41. Metabolic Acidosis Metabolic acidosis Impaired ability to excrete H + Decreased NH 4 + excretion Retention of phosphate

43. Renal Azotemia Increase of non-protein-nitrogen Urea, creatinine, phenols, amines, urates, guanidines

44. Renal Hypertension Fluid and Na overload(usual cause) Hyper-reninemia(less often) by failing kidney in response to falling renal perfusion.

45. Calcium, Phosphate and bone metabolism Diminished absorption of calcium from the gut Overproduction of parathormone Disordered Vit D metabolism Chronic metabolic acidosis Hypophospatemia

46. Renal anemia and bleeding tendency Lack of erythropoietin Bone marrow suppression Bone marrow fibrosis due to PTH Aluminum toxicity Dialysis related blood loss Coagulation defects – mainly platelet related

48. Uremia End stage of renal failure

49. Etiology & Pathogenesis Urea & other small m.w. molecules Middle molecules Polypeptide hormones

50. Urea & other small m.w. molecules When Blood urea > 300mg/dL – anorexia, weakness, headache, vomiting and bleeding Phenol, cresol, catechol, hydroquinone Methylguanidine Polyamines – putrescine, cadaverine, spermidine

51. Middle molecules Mol wt – 300 to 5000 Greater morbidity In vitro – neurotoxicity, inhibits hemopoiesis, lymphoblast transformation, glucose utilization, fibroblast proliferation, leukocyte phagocytic activity and platelet aggregation

52. Polypeptide hormones Insulin, Glucagon, PTH, gastrin, calcitonin Trade off hypothesis

53. Alterations of metabolism and function Neuromuscular Cardiovascular and pulmonary Hematological Gastrointestinal Endocrine and metabolic Dermatologic Immunologic

54. Neuromuscular CNS – mild insomnia to seizures, coma PNS – restless legs syndrome, foot drop Aluminum toxicity, disequilibrium syndrome

55. Cardiovascular and pulmonary CHF, Pulmonary edema Uremic pericarditis Arrhythmias Accelerated atherosclerosis

56. Hematological Lack of erythropoietin Bone marrow suppression Bone marrow fibrosis due to PTH Aluminum toxicity Dialysis related blood loss Coagulation defects – mainly platelet related

57. Gastro intestinal Nausea, vomiting When GFR<10%, anorexia Uremic colitis, peptic ulcer Uremic gastroenteritis

58. Endocrine and metabolic Low estrogen in women – amenorrhoea, infertility Low testosterone in men – impotence, oligospermia, germ cell dysplasia Increased half life of insulin

59. Dermatologic Pallor due to anemia Gray discoloration due to hemochromatosis Ecchymosis & hematomas Pruritis & excoriations Uremic frost

60. Immunologic Immune suppression

61. Prevention & treatment Conservative Dialysis Peritoneal / hemodialysis Renal transplantation

62. dialysate out dialysate in Process of CAPD