1. Chapter 11 Pathophysiology of Renal disorders. By Dr. Uche Amaefuna-Obasi (MD)

2. THERE ARE MORE TO LECTURES THAN JUST SLIDES

3. Renal Diseases

4. Introduction: 150gm: each kidney 1700 liters of blood filtered  180 L of G. filtrate  1.5 L of urine / day. Kidney is a retro-peritoneal organ Blood supply: Renal Artery & Vein One half of kidney is sufficient – reserve kidney function: Filtration, Excretion, Secretion, Hormone synthesis.

5. Kidney Location:

6. Kidney Anatomy:

7. Renal Pathology Outline Glomerular diseases: Glomerulonephritis Tubular diseases: Acute tubular necrosis interstitial diseases: Pyelonephritis Diseases involving blood vessels: Nephrosclerosis Cystic diseases Tumors

8. Clinical Syndromes: Nephritic syndrome. Oliguria, Haematuria, Proteinuria, Oedema. Nephrotic syndrome. Gross proteinuria, hyperlipidemia, Acute renal failure Oliguria, loss of Kidney function - within weeks Chronic renal failure. Over months and years - Uremia

9. Introduction Functions of the kidney: excretion of waste products regulation of water/salt maintenance of acid/base balance secretion of hormones Diseases of the kidney glomeruli tubules interstitium vessels

10. Kidneys Nephron Working unit of the kidney Consists of Glomerulus: works like a sieve Tubules: fluid reabsorbed or sent to bladder

12. Kidney Functions Regulates extracellular fluid & osmolarity, electrolyte concentrations, & acid-base balance Excretes wastes Secretes renin Produces erythropoietin Converts vitamin D to active form

14. Azotemia:  BUN ( A blood urea nitrogen (BUN) test measures the amount of nitrogen in your blood that comes from the waste product urea. Urea is made when protein is broken down in your body. Urea is made in the liver and passed out of your body in the urine. A BUN test is done to see how well your kidneys are working), creatinine Uremia: azotemia + more problems Acute renal failure: oliguria Chronic renal failure: prolonged uremia Abnormal findings

15. Hematuria Oliguria Azotemia Hypertension Nephritic syndrome Massive proteinuria Hypoalbuminemia Edema Hyperlipidemia/-uria Nephrotic syndrome

19. Glomerular diseases Nephrotic syndrome Minimal change disease Focal segmental glomerulosclerosis Membranous nephropathy Nephritic syndrome Post-infectious GN IgA (immune) nephropathy

20. Nephrotic Syndrome Massive proteinuria Hypoalbuminemia Edema Hyperlipidemia

21. Adults: systemic disease (diabetes) Children: minimal change disease Characterized by loss of foot processes Good prognosis Causes

22. Nephrotic Syndrome Any kidney disorder that results in proteinuria exceeding 3.5 g/day Cause Any damage to glomeruli increasing their permeability to plasma proteins

23. Nephrotic Syndrome Possible causes Infections Chemical damage Immunological & hereditary disorders Diabetes mellitus Clinical findings Proteinuria Low serum albumin Edema Elevated blood lipids Blood coagulation disorders

24. Consequences Disturbances in protein metabolism Edema Loss of albumin Sodium retention Risk of CVD Elevated LDL, VLDL & lipoprotein(a) Loss of blood clotting proteins Loss of antibodies Decreased vitamin D-binding protein Lower D & calcium levels Protein energy malnutrition (PEM)

25. © 2007 Thomson - Wadsworth Consequences of Protein Loss

26. Treatment Medications Anti-inflammatory drugs, ACE inhibitors, antihypertensives, immunosuppressants, lipid-lowering drugs, diuretics Protein & energy 0.8-1.0 grams/day 35 kcalories/kg Fat Low saturated fat, cholesterol, & refined sugars Sodium 2-3 g/day Vitamin D & calcium Multivitamin

27. Nephritic Syndrome Hematuria Oliguria, azotemia Hypertension

28. Post-infectious GN, IgA nephropathy Immunologically-mediated Characterized by proliferative changes and inflammation Causes

29. Post-Infectious Glomerulonephritis Child after streptococcal throat infection Immune complexes Hypercellular glomeruli Subepithelial humps

30. IgA Nephropathy Common! Child with hematuria after (URI) Upper Respiratory Infection IgA in mesangium Variable prognosis

31. Tubular and interstitial diseases Inflammatory lesions pyelonephritis

32. Pyelonephritis Invasive kidney infection Usually ascends from UTI Fever, flank pain Organisms: E. coli, Proteus

33. Women, elderly Patients with catheters or mal-formations Dysuria, frequency Organisms: E. coli, Proteus Urinary Tract Infection

34. Acute pyelonephritis with abscesses

36. Chronic pyelonephritis

37. Drug-Induced Interstitial Nephritis Antibiotics, NSAIDS IgE and T-cell-mediated immune reaction Fever, eosinophilia, hematuria Patient usually recovers Analgesic nephritis is different (bad)

38. Acute Tubular Necrosis The most common cause of ARF! Reversible tubular injury Many causes: ischemic (shock), toxic (drugs) Most patients recover

39. Benign Nephrosclerosis Found in patients with benign hypertension Hyaline thickening of arterial walls Leads to mild functional impairment Rarely fatal

40. Malignant nephrosclerosis Arises in malignant hypertension Hyperplastic vessels Ischemia of kidney Medical emergency

41. 5% of cases of hypertension Super-high blood pressure, encephalopathy, heart abnormalities First sign often headache, scotomas Decreased blood flow to kidney leads to increased renin, which leads to increased BP! 5y survival: 50% Malignant Hypertension

42. Adult Polycystic Kidney Disease Autosomal dominant Huge kidneys full of cysts Usually no symptoms until 30 years Associated with brain aneurysms.

43. Adult polycystic kidney disease

44. Childhood Polycystic Kidney Disease Autosomal recessive Numerous small cortical cysts Associated with liver cysts Patients often die in infancy

45. Childhood polycystic kidney disease

46. Medullary Cystic Kidney Disease Chronic renal failure in children Complex inheritance Kidneys contracted, with many cysts Progresses to end-stage renal disease

47. Tumors Renal cell carcinoma Bladder carcinoma

48. Renal Cell Carcinoma Derived from tubular epithelium Smoking, hypertension, cadmium exposure Hematuria, abdominal mass, flank pain If metastatic, 5y survival = 5%

49. Renal cell carcinoma

50. Bladder Carcinoma Derived from transitional epithelium Present with painless hematuria Prognosis depends on grade and depth of invasion Overall 5y survival = 50%

52. Acute renal failure Acute renal failure represents a rapid decline in renal function leading to increased blood levels of nitrogenous wastes and impaired water and electrolyte balance, and manifesting water intoxication, azotemia, hyperkalemia, and metabolic acidosis.

53. Acute Renal Failure Function rapidly deteriorates Reduced urine output Build up of nitrogenous wastes Mortality rates are high

54. Acute renal failure is reversible if the cause can be identified and corrected before permanent kidney damage has occurred. The most common indicator is azotemia, which is an accumulation of nitrogenous wastes (urea nitrogen, uric acid and creatinine)

55. Etiology and classification Prerenal failure Intrarenal failure Postrenal failure

56. Causes Prerenal Heart failure Shock Blood loss Intrarenal Infections Toxins Drugs Direct trauma Postrenal Factors preventing excretion of urine Urinary tract obstructions

57. Prerenal failure- functional failure Prerenal failure is the most common form of acute renal failure. It is caused by a marked decrease in renal blood flow. Causes Hypovolemia Heart failure Intrarenal vasoconstriction Increased blood vessel bed

58. Intrarenal failure- parenchymal renal failure Intrarenal failure results from conditions that can cause damage to structures within the kidney, glomerular, tubular and interstitial.

59. Causes Acute tubular necrosis (ATN) Prolonged renal ischemia (ischemic ATN) or ischemia-reperfusion injury Toxic insult of tubules by drugs, heavy metals (nephrotoxic ATN) Intratubular obstruction hemoglobin and myoglobin severe hypokalemia, hypercalcemia Acute glomerulonephritis and acute pyelonephritis

60. Postrenal failure – obstructive renal failure Obstruction of urine outflow from the kidneys. (ureter, bladder and urethra) Prostatic hypertrophy (most common)

61. Consequences Oliguria < than 400 mL urine/day Sodium retention Elevated potassium, phosphate, & magnesium Edema Uremia BUN, creatinine & uric acid accumulate in blood Fatigue, lethargy, confusion, headache, anorexia, metallic taste, N & V, diarrhea

62. Treatment Drug therapy Diuretics Potassium exchange resins Insulin, glucose Bicarbonate Protein Depends on kidney function, degree of catabolism, use of dialysis Fluids Measure output and add 500 mL Can increase if on dialysis Electrolytes Restrict potassium, phosphorus, sodium

63. Chronic Renal Failure Is a gradual & irreversible deterioration Usually not diagnosed until 75% of function is lost Causes Diabetes mellitus 43% Hypertension 26% Inflammatory, immunological, or hereditary diseases May follow acute failure

64. Consequences Nephrons enlarge to compensate Overburdened nephrons degenerate End-stage renal disease occurs Evaluation Glomerular filtration rate (GFR) Rate at which kidneys form filtrate

66. Consequences Electrolyte imbalances occur when GFR becomes extremely low Hormonal adaptations are inadequate Intake of water & electrolytes are very restrictive or excessive Renal osteodystrophy Increased parathyroid hormone contributes to bone loss Acidosis may develop Uremic syndrome Mental dysfunctions Neuromuscular changes Muscle cramping, twitching, restless leg syndrome Protein energy malnutrition

67. Complications of Uremic Syndrome Impaired hormone synthesis Impaired hormone degradation Bleeding abnormalities Increased cardiovascular disease risk Reduced immunity

68. Treatment Goal Slow disease progression Prevent or alleviate symptoms Drugs Antihypertensives Erythropoietin Phosphate binders Sodium bicarbonate Cholesterol-lowering medications Active vitamin D supplements

69. Dialysis Removes excess fluid & wastes from blood Blood is circulated though a dialyzer Blood is bathed by dialysate Hemodialysis & peritoneal dialysis

70. Medical Nutrition Therapy Energy Enough to maintain healthy weight & prevent wasting Low-protein diet Can increase when on dialysis Lipids Restrict saturated fat & cholesterol Fluids Not restricted until output decreases Sodium Mild restriction Potassium May need to restrict high- potassium foods

71. Medical Nutrition Therapy Calcium & vitamin D needs increase May need phosphorus restrictions Restrict protein Restrict milk & milk products Dietary supplements Generous folate and B 6 Recommended amounts of water- soluble vitamins except vitamin C IV iron administration Intradialytic parenteral nutrition

73. Kidney Transplants Restores function Allows a more liberal diet Frees patient from dialysis Immunosuppressive drug therapy Many side effects affecting nutrition Protein & energy requirements increase Control CHO & lipids Sodium, potassium, & phosphorus intakes liberalized Calcium supplementation Be alert for potential food borne infection

74. Kidney Stones Affects 12% of men & 5% of women Crystalline mass in urinary tract Severe pain Can obstruct tract Formation is promoted by: Reduced urine volume Blocked urine flow Increased concentrations of stone-forming substances

75. Types of Stones Calcium oxalate stones Most common Reduce intake of oxalate Avoid vitamin C supplements Uric acid stones Abnormally acidic urine Associated with gout Low-purine diet Cystine stones Inherited disorder cystinuria Struvite stones Form in alkaline urine

76. Calcium Oxalate Stone

77. Consequences Renal colic Severe, continuous pain Begins in the back & travels toward bladder Nausea & vomiting Urinary tract complications Urgency Frequency Inability to urinate Obstruction Infection

78. Prevention & Treatment Drink 12-16 cups of fluids/day Tea, coffee, wine, beer No apple or grapefruit juices

79. Other Dietary Measures Consume enough calcium to control oxalate absorption Restrict dietary oxalate & purine Moderate protein intake Sodium restriction

82. Dialysis

83. How Does Dialysis Work? Employs diffusion, osmosis, & ultrafiltration If a substance is lower in dialysate, substance will diffuse out of the blood If substance is higher in the dialysate, substance will diffuse into the blood Ultrafiltration removes fluid from the blood

85. Dialysis Hemodialysis Lasts 3-4 hours 3 times/week Complications Infections Blood clotting Hypotension Muscle cramping Headaches, weakness Nausea & vomiting Agitation Peritoneal dialysis Vascular access not required Fewer dietary restrictions Can be scheduled when convenient Acute failure Continuous renal replacement therapy (CRRT)