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chronic renal failure

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  2. 2. Dr. Abdur Rahman Emoo Medical Officer Department of CardiologyDhaka National Medical College Hospital 2
  3. 3. Chronic renal failure (CRF) refers to an irreversable deterioration in renal function classically develops over a period of yearsInitially it is manifest only as a biochemical abnormality, loss of excretory, metabolic & endocrine function of kidney leads to development of symptoms & signs of CRF. 3
  4. 4. Factor 2002 2003 2004 2005 New ESRD cases 86 82 85 93 Incidence (pmp) 150 143 149 163 Age-adjusted 232 186 317 181 incidence (pmp) Sex ratio 55/45 63/37 65/35 52/48 (male/female) Mean age (years), Diabetic nephropathy 46+/-15 47 50+/-10 43 47+/-13 40 46+/-12 46 6SD (%)ESRD=end-stage renal disease, pmp=per million population, SD = standarddeviation. 4
  5. 5.  CRF is a permanent, usually progressive, diminution in renal function to a degree that has damaging consequences for the patient. It is characterized by an increasing inability of the kidney to maintain normal low levels of the products of protein metabolism(such as urea), normal blood pressure and hematocrit, and sodium, water, potassium, and acid-base balance. 5
  6. 6.  Congenital & inherited : 5% Renal artery stenosis : 5% Hypertension : 5-25% Glomerular disease (IgA nephropathy is common) : 10-20% Interstitial disease : 5-15% Systemic inflammatory disease : 5% ( SLE, Vasculitis)Diabetes mellitus : 20-40% Unknown : 5-20% 6
  7. 7.  Hypertension Reduced renal perfusion : Renal artery stenosis Hypotension due to drug treatment Na & water depletion Poor cardiac function Urinary tract obstruction Urinary tract infection Nephrotoxic medication Other infection : increased catabolism & urea production 7
  8. 8. Stages Description GFR(ml/min/1.73 Action m2 ) 1 Kidney damage > 90 Investigate with normal or (Haematuria & high GFR proteinurea) 2 Kidney damage 60-89 Renoprotection- with slightly low BP control, GFR dietary modification 3 Kidney damage 30-59 with low GFR 4 Severe low GFR 15-29 Prepare for renal replacement therapy 8 5 Kidney failure <15 or dialysis
  9. 9.  Hypothesis Glomerular hyperfiltration/hyperperfusion Glomerular hypertension Nephrotoxicity of lipids Similarities with atherosclerosis Glomerular hypertrophy Nephrotoxicity of proteinuria Growth factors Platelet-derived growth factor Transforming growth factor β Mesangial/myofibroblast differentiation Podocyte injury 9
  10. 10. glom vasc dis tubu-inters dis dis Ca × P ↑ loss of nephron nephroarte PTH↑ riolosclero sis adaption of remaining nephrons HBP + hyperlip glom hypertrophy idemia hyperperfusion atheros GCP↑ clerosis mes.proliferation, focal GS, proteinuria ↑Renovascular renal tubu-inters. atrophyfailure ESRD Aquired renal cystic disease 10
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  12. 12. Early Late(GFR < 15 ml/min, BUN > 60 mg/dL) hypertension  cardiac failure  anemia proteinuria,elevated  serositis BUN or sCr  confusion, coma nephrotic syndrome  anorexia recurrent nephritic  vomiting syndrome  peripheral gross hematuria neuropathy  hyperkalemia  metabolic acidosis 12
  13. 13. en al ni cr ? h ro ive is c re ss hy progW refailu 13
  14. 14. ° Persistence of initial disease process that caused renal injury or presence of additional factors that promote renal injury (mineralization, infection, drugs, toxins, etc.)z Hyperfiltration theory: progression of renal disease despite resolution of primary insult. a. Premise A reduction in number of nephrons past some critical threshold leads to failure of the remaining nephrons. CRF has been recognized as a progressive disease. b. Mechanism Renal afferent arteriole vasodilation promotes glomerular hypertension which causes further glomerular injury and perpetuation of renal decline. 14
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  16. 16. ical lin fc F o i s n CR es s i en e og om th drPa yn s 16
  17. 17. A. Lethargy, fatigue, nausea and depression The magnitude of BUN increase is usually proportional to uremic signs and estimates degree of other retained uremic toxins. Additional uremic factors: include PTH, by-products of protein catabolism, and other metabolic derangementsB. Polyuria and compensatory polydipsia1. Hyperfiltration Remnant nephrons are operating under conditions of osmotic diuresis (increased SNGFR).2. Disruption of renal medullary gradient Tubulointerstitial disease as well as high tubular flow rates may prevent maintenance of hypertonic interstitium.3. Impaired nephron response to ADH. 17
  18. 18. C. Gastrointestinal signs1. Uremic stomatitis High blood levels of urea diffuse into oral cavity, bacteria convert to ammonia = locally toxic = oral ulceration.2. Vomiting: more common a. Central (CNS) causes: uremic toxins stimulate chemoreceptor trigger zone. b. Uremic gastroenteritis i. Local effects: urea and ammonia are locally toxic. ii. Increased gastrin (reduced renal clearance) results in increased gastric acid production and gastric mucosal injury. iii. Other factors: ischemia, altered gastric mucosa turnover, and other likely contribute to gastric injury.3. Diarrhea: uremic enterocolitis (less common) - may occur in part due to high ammonia levels. 18
  19. 19. D. Anemia: normocytic, normochromic, non-regenerative.1. Decreased erythropoietin (EPO) production: predominant cause of anemia in CRF. Intrinsic renal disease = decreased synthesis of EPO = decreased BM production of RBCs. Unidentified circulating uremic inhibitors may also play a role in inhibiting erythropoiesis.2. Reduced RBC survival: uremic toxins decrease lifespan of circulating RBCs.3. Blood loss a. Bleeding tendency: often noted in uremic patients. Characterized by prolonged mucosal bleeding time. Circulating uremic toxins may cause platelet defects. b. Gastrointestinal bleeding: may occur in association with GI ulceration and platelet defects. 19
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  21. 21. E. Hypertension1. Common complication: with chronic renal disease the incidence of HT is 50 – 93%2. Etiology: pathogenesis not fully understood - likely multifactoriala. BP = cardiac output X peripheral resistanceb. Possible contributory factorsi. Sodium retention from decreased renal excretion (= increased ECF)ii. Activation of RAS (= vasoconstriction and ECF expansion)iii. Sympathetic activation and endothelial factors 21
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  23. 23. 3. Clinical signs: often clinically silent.a. Vasculature: sustained arterial HT = muscular occlusion of small arteries = decreased perfusion (especially heart, eyes, kidneys, and brain).b. Heart: sustained HT may result in LVH (usually subclinical).c. Ocular lesions: dilated, tortuous retinal vessels, retinal hemorrhage, detachments, and blindness. 23
  24. 24. 1. RSHP develops in patients with CRF as a result of the bodys attempt to maintain calcium and phosphorus homeostasis.2. Sequela of RSHPa. Phosphorus: compensatory increases in PTH act to decrease Pi and increase serum Ca levels. When GFR declines to < 20%, renal adaptive mechanisms have been maximized and hyperphosphatemia occurs.b. Calcitriol (vitamin D3)i. Early in CRF, retained Pi = increased PTH = increased calcitriol production.ii. Later in CRF, loss of ability to make calcitriol = elevated set- pt for Ca-induced suppression of PTH = PTH secretion despite normal to high iCa. 24
  25. 25. c. Renal osteodystrophyi. Increased PTH = mobilization of Ca/Pi from bone; if prolonged = ROD (demineralization and replacement with fibrous tissue)ii. Clinically evident ROD is uncommon - occurs most often in the immature animal due to metabolically more active bone.d. Soft tissue mineralization: most often affects the lungs, kidneys, heart, arteries, and stomach. Common in cases of advanced CRF. When Ca X Pi > 70 = soft tissue mineralization may occur.e. Other sequela of RSHP PTH has been implicated as a "uremic toxin": malaise, anemia, neurologic signs. Mechanism of toxicity: increase PTH = increased Ca into cells = cell dysfunction or death. 25
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  27. 27. 1. Normal function of the kidney in acid - base regulation. The kidney works in concert with the lungs and the blood buffer system to maintain normal acid-base homeostasis within the body.a. The proximal renal tubule excretes majority of acid (reabsorbs HCO3, makes NH3).b. The distal renal tubule excretes H+ (under influence of aldosterone), and also makes NH3.2. The kidney in CRFa. Development of acidosis Compensatory mechanisms maintain acid - base status until GFR has decreased to < 5 - 20% of normal.b. Role of ammoniai. H+ excretion is sustained mostly by increasing production of NH3 (H+ trapped in urine as NH4+).ii. Even with compensatory increase in NH3 production/nephron there is a total decrease in NH3 production due to the overall loss of functional 27 nephrons in advanced RF.
  28. 28. H. Hypokalemia: serum K+ < 3.5 mEq/L. Chronic acidosis promotes hypokalemia (increase H+ = increase aldosterone = increase K+/H+ excretion).I. ProteinuriaUrinary protein excretion typically is increased (1.5 - 2X normal) with CRF.Proteinuria in CRF is likely due to changes in glomerular hemodynamics rather than structural glomerular lesions. 28
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  32. 32. 1. Infection Uremia is associated with impaired CMI and neutrophil function - bacterial infections are common complications of the patient with CRF.2. Dyslipoproteinemias: common in people with CRF.a. Pathogenesis: not completely understood May be associated with increased PTH levels (suppresses insulin release = decreased lipoprotein lipase = increased lipoproteins).b. Clinical consequences Lipoproteins are entrapped in mesangium of glomeruli = taken up by macrophages = foam cells = increased production of PGs and toxic by- products = glomerular injury = glomerulosclerosis.3. Neurological abnormalities May note mental dullness, lethargy, tremors, peripheral neuropathies and uremic encephalopathy. Likely due to effects of PTH, hypertension, electrolyte disturbances or other uremic toxins. 32
  33. 33. Acute Renal Failure Chronic Renal Failure1. Hematocrit to increased (dehydration) Decreased (chronic anemia)2. Azotemia/PO4 Elevated Elevated3. Potassium Usually increased to decreased4. Calcium Low to normal Low, normal, or high5. Urinalysis Active sediment Inactive sediment6. Urination Oliguria, anuria Polyuria7. Weight Good nutritional status Weight loss8. Kidneys to increased size Small, irregular 33
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  35. 35.  1. CBC : May note a normocytic, normochromic, non-regenerative anemia and variable leukocytosis (secondary to associated stress, infection or inflammation). 2. Haematinics : supplementation if deficient to optimise response to erythropoietin. 35
  36. 36.  Serum biochemistry profile : Characteristic findings may include *azotemia, *hyperphosphatemia, *metabolic acidosis, *hypokalemia, variable calcium levels, and elevations in serum amylase and lipase (usually not greater than 2 - 4X normal). *Indicates the four most common findings on serum biochemistry profile. Parathyroid hormone Lipid profile S. Glucose level 36
  37. 37.  Ultrasonography : to confirm/refute two equal-sized unobstructed kidneys. Chest X-ray : heart size, pulmonary oedema. ECG : if >40 yrs or risk factors for cardiac disease Renal artery imagingMicrobiology : Hepatitis & HIV serology—if dialysis is needed. 37
  38. 38.  Group & save Tissue typing Cytomegalovirus if transplantation is needed Epstein-Barr virus Varicella zoster virus 38
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  42. 42. Treatment 42
  43. 43.  Aim of treatment :- Primary disease and reversible factors treatment Conservative treatment Treatment of complications of uremia Blood purification Renal transplantation 43
  44. 44.  Enough calorie intake: 126-147KJ Low protein diet: 0.6-0.8g/kg/d,60% high quality protein Essential amino acid supplement α-ketoacid supplement Vitamin supplement: folic acid, Vit C, Vit B6, Vit D Fluid intake—3 lt/day associated with 5-10 g/day of NaCl & 70 mmol/day. 44
  45. 45.  Control of Blood Pressure :-ACE inhibitor is more effective than other therapies. Angiotensin-II receptor antagonists also reduce glomerular perfusion pressure. Correction of Anaemia :- Recombinant human erythropoietin is effective in correcting anaemia . Atherosclerosis :- Atherosclerosis is common & treated by anti-lipidemic drugs. Hypocalcaemia :- is corrected by 1α hydroxylated synthetic analogues of vitamin-D. Hyperphosphataemia :- is controlled by dietary restriction of foods (milk, cheese, eggs etc). Acidosis :- is controlled by calcium carbonate (upto 3gm/day). Infection :- it must be recognised & treated promptly. 45
  46. 46.  GI manifestation :- to reduced by using H2 receptor or proton-pump inhibitor. Neuropathy :- results from demyelination of medulated fibres. Amitriptyline & Gabapentine used to symptom relief. Myopathy :- Generalised myopathy due to combination of poor nutrition , hyperparathyroidism , vit-D deficiency.Muscle cramp are common & quinine- sulphate may be helpful. Patient ‘s legs are jumpy during night & is often improved by clonazepam. 46
  47. 47.  Hemodialysis Peritoneal dialysis 47
  48. 48. Superior Vena Cava Lung Heart Liver Aorta Spleen Right Kidney Left Kidney Large Intestine Small Intestine Right Ureter Left Ureter Bladder Healthy Kidney Diseased Kidney Physical Basis Renal Replacement 48
  49. 49. Erythrocyte, Red Blood Cell Bacteria Albumin, asExample of a BigProtein Molecule Medium sized Molecules, e.g. β2-Microglobulin Electrolytes Water Flow is Easily Possible The semipermeable membrane functions similar to a fine sieve, only molecules that are small enough can pass. Healthy Kidney Diseased Kidney Physical Basis Renal Replacement 49
  50. 50. Anti-Coagulation Blood Pump Dialyzer Blood to the Patient Fresh Dialysate Used Blood from Dialysate the PatientHealthy Kidney Diseased Kidney Physical Basis Renal Replacement 50
  51. 51. Dialysate Bundle of InflowCapillaries in the Housing Blood Outflow Dialysate Outflow Solute Transfer across the Capillary Walls Blood Inflow The dialysate flows outside of the capillaries, blood within the capillaries countercurrently. Healthy Kidney Diseased Kidney Physical Basis Renal Replacement 51
  52. 52. Bag with Fresh Solution Peritoneal dialysis is done by filling Peritoneum specially composed peritoneal dialysis solution into the abdominal cavity. The solute transfer Implanted between blood and Catheterthe solution happens by diffusion. The water removal from the patient is Peritonealan osmotic process. Dialysis Solution Bag for Used Solution Healthy Kidney Diseased Kidney Physical Basis Renal Replacement 52
  53. 53. Liver Aorta Kidney Transplantin the Fossa Iliaca,Not at the Positionof Healthy Kidneys Connection of Renal Artery and Vein to the Pelvic Connection of Vessels the Ureter to the Bladder of the Recipient Healthy Kidney Diseased Kidney Physical Basis Renal Replacement 53
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