Download - Renal failure
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Renal Failure
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Types
• Acute
• Chronic
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Acute renal failure
• Sudden onset with oliguria/anuria
• Rapid rise in BUN and S Creatinine
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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
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Types
• Pre-renal
• Intra-renal
• Post-renal
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Pre-renal
• Inadequate blood flow to kidney– Hypovolemia– Renal artery stenosis– Congestive cardiac failure– Intrarenal small vessel disease– Drugs ( NSAIDs, ACE inhibitors )
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Intra-renal
• Glomerulonephritis
• Interstitial nephritis
• Toxin induced
• Pigment induced
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Post-renal
• Intra – renal obstruction
• Extra – renal obstruction
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Pathogenesis
• ARF leads to acute tubular necrosis
• Hypoxic injury
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Renal Tubular Injury in ATN
Loss of polarity and brush border
Normal epithelium with brush border
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Cell death -apoptosis and necrosis
Sloughing of dead and viable cells - luminal obstruction
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Spread and de-differentiation of viable cells
Proliferation, differentiation and reestablishment of polarity
Normal epithelium with brush border
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Urinary abnormalities
• ATN – Granular, epithelial casts, urine osmolality < 350 mOsm/L
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Other abnormalities
• Hyperkalemia
• Azotemia
• Metabolic acidosis
• Hyponatremia and hypervolemia
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Prevention and treatment
• Supportive care
• Fluid and sodium restriction
• Treat the hyperkalemia, acidosis
• Dialysis
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Dialysis
• Increased intravascular volume leading to CHF, Pulmonary edema, intractable hypertension
• Non-responsive hyperkalemia
• Symptomatic uremia – lethargy, neurologic changes, seizures
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Chronic Renal Failure
• Impaired homeostasis due to structural damage to kidney– Metabolic acidosis– Hypocalcemia– Hyperphosphatemia– Altered Vit D metabolism– Toxemia
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Acute renal failure Chronic Renal failure
History recent drug administration, toxin exposure,surgery/hypovolemia
polyuria, polydipsia
Urine output oliguria polyuria
Kidney size normal to large small
Anemia absent present
Metabolic bone disease
absent present
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Etiology
• Diabetes Mellitus
• Hypertension
• Glomerulonephritis
• PKD
• Obstruction
• Infection
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Stages
• Decreased renal reserve
• Renal insufficiency
• Renal failure
• Uremia
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Stages
• Decreased renal reserve – GFR 50-75%– S. creatinine, BUN : normal
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Stages
• Renal insufficiency – GFR < 50%– S. creatinine, BUN : start to rise– Mild anemia, hyposthenuria, nocturia– Increase in serum PTH– Azotemia/metabolic acidosis may occur
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Stages
• Renal failure ( GFR 10-25%)– GFR < 10-25%– Marked anemia, severe acidosis– Hypocalcemia, hyperphosphatemia
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Stages
• Uremia– >90% nephron mass destroyed– S. creatinine, BUN : sharp rise– Severe symptoms
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Pathogenesis
• Intact nephron hypothesis
• Trade off hypothesis
• Glomerular hyperfiltration hypothesis
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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
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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
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Glomerular hyperfiltration hypothesis
• With progressive loss of some nephrons, hyperfiltration occurs in the remaining – leads to fibrosis and scarring
• Any added stress precipitates Uremia
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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
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Disorders of Urine
• Initial nocturia, polyuria, later oliguria, anuria
• Isosthenuria – s.g. : 1.010, 285mOsm/L
• Urinary sediment contains cells and casts
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Disorders of Water and Sodium balance
• Continued ingestion of salt – CHF, Hypertension, edema
• Excess water ingestion – Hyponatremia, hypervolemia, weight gain
• ECF depletion - shock
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Disorders of Potassium balance
• Hyperkalemia if GFR < 5%
by potassium sparing diuretics and in Diabetes mellitus(hyporeninemic hypoaldosteronism)→reduced angiotensin II & impairs aldosterone secretion.
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Metabolic Acidosis
• Metabolic acidosis
– Impaired ability to excrete H+
– Decreased NH4 + excretion
– Retention of phosphate
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Renal Azotemia
• Increase of non-protein-nitrogen
• Urea, creatinine, phenols, amines, urates, guanidines
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Renal Hypertension
• Fluid and Na overload(usual cause)
• Hyper-reninemia(less often) by failing kidney in response to falling renal perfusion.
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Calcium, Phosphate and bone metabolism
• Diminished absorption of calcium from the gut
• Overproduction of parathormone
• Disordered Vit D metabolism
• Chronic metabolic acidosis
• Hypophospatemia
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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
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Uremia
• End stage of renal failure
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Etiology & Pathogenesis
• Urea & other small m.w. molecules
• Middle molecules
• Polypeptide hormones
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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
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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
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Polypeptide hormones
• Insulin, Glucagon, PTH, gastrin, calcitonin
• Trade off hypothesis
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Alterations of metabolism and function
• Neuromuscular
• Cardiovascular and pulmonary
• Hematological
• Gastrointestinal
• Endocrine and metabolic
• Dermatologic
• Immunologic
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Neuromuscular
• CNS – mild insomnia to seizures, coma
• PNS – restless legs syndrome, foot drop
• Aluminum toxicity, disequilibrium syndrome
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Cardiovascular and pulmonary
• CHF, Pulmonary edema
• Uremic pericarditis
• Arrhythmias
• Accelerated atherosclerosis
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Hematological
• Lack of erythropoietin
• Bone marrow suppression
• Bone marrow fibrosis due to PTH
• Aluminum toxicity
• Dialysis related blood loss
• Coagulation defects – mainly platelet related
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Gastro intestinal
• Nausea, vomiting
• When GFR<10%, anorexia
• Uremic colitis, peptic ulcer
• Uremic gastroenteritis
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Endocrine and metabolic
• Low estrogen in women – amenorrhoea, infertility
• Low testosterone in men – impotence, oligospermia, germ cell dysplasia
• Increased half life of insulin
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Dermatologic
• Pallor due to anemia
• Gray discoloration due to hemochromatosis
• Ecchymosis & hematomas
• Pruritis & excoriations
• Uremic frost
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Immunologic
• Immune suppression
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Prevention & treatment
• Conservative
• Dialysis – Peritoneal / hemodialysis
• Renal transplantation
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dialysate out dialysate in
Process of CAPD
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