ACUTE RENAL FAILURE oliguria anuria

Transcription

1 ACUTE RENAL FAILURE acute inability of kidneys to regulate water and solutes balance oliguria decrease in urine flow (less than 20ml/h) ml/day anuria urine output <50 ml/day

2 ACUTE PRERENAL FAILURE About 70% of all ARF cases Patomechanisms intravascular depletion cardiac failure systemic vasodilatation (sepsis, anesthesia, anaphylaxis) preglomerular vasoconstriction nonsteroidal antiinflammatory drugs vasoconstrictors

3 Hypovolemia Afferent Glomerular Arteriole CONSTRICTION VASODILATION GFR Mild Hypovolemia Angiotensin II Sympathethic system ADH < Myogenic reaction TG feedback NO Prostaglandins Unchanged Moderate hypovolemia Angiotensin II Sympathethic system ADH = Myogenic reaction TG feedback NO Prostaglandins Unchanged or slightly decreased Severe hypovolemia Angiotensin II Sympathethic system ADH > Myogenic reaction TG feedback NO Prostaglandins Decreased Acute Prerenal Failure

4 TOXIC NEPHROPATHY 1. Aminoglycosides - aminoglycosides are filtered - part of the filtered load is reabsorpbed in proximal tubule and accumulates within cells => toxicity 2. Cephalosporins - synergistic toxicity with aminoglycosides 3. Radiocontrast agents - induce osmotic diuresis => volume depletion - direct tubular toxicity (proximal tubules) - renal vasocontriction due to tubuloglomerular feedback - population with increased risk: - aged people - heart failure - volume depletion

5 TOXIC NEPHROPATHY 4. Organic solvents: - carbon tetrachloride (proximal tubules) - ethylene glycol: direct toxicity to epithelial cells + oxalic acid crystals 5. Pigment induced ATN - myoglobin (ATN occurs in 30% of pts with rhabdomyolysis) - hemoglobin: intravascular hemolysis hemoglobinuria - cytotoxicity towards proximal tubules - precipitation of protein within the tubules - heme proteins scavenge NO vasocontriction 6. Heavy metals - mercury, bismuth,arsen rare nowadays

6 PATHOMECHANISM OF OLIGURIA - ANURIA 1. Intrarenal vasoconstriction - in humans RBF by 30-50% - loss of autoregulation - endothelin > NO 2. Decreased permeability coefficient in glomerulus - reduction in size and density of the endothelial fenestrae - epithelial swelling - constriction of mesangial cells (ANG II, ADH, endothelins) 3. Damage to tubular epithelium - back leakage of filtrate - tubular obstruction

7 ACUTE OBSTRUCTIVE UROPATHY 1. Types of obstructive uropathy Partial or complete Unilateral or bilateral Acute or chronic 2. Changes in GFR Intitially unchanged Decreased ( after few hours) 3. Tubular function Partial obstruction Decreased ability to concentrate urine Decreased ability to acidify urine After relief of obstruction postobstructive diuresis: Volume overload Osmotic diuresis Decreased tubular Na + reabsorption (TALH) Reduced rersponsiveness to ADH

8 ACUTE OBSTRUCTIVE UROPATHY James M. Gloor & Vicente E. Torres

9 CLINICAL COURSE OF ATN 1. The initiation phase - hours days - no morphological changes - time for prevention of ATN 2. The maintenance phase - GFR is low < 5mL/min - lasts 1-2 weeks up to 6-8 weeks - patient is oliguric (<400mL/day) or non-oliguric (>400 ml/day) 3. The recovery phase - progressive rise in urine volume (up to ml/h) - dysfunction of tubules (polyuria + osmotic diuresis) - renal function improves within weeks up to 1 year - in 1/3 of pts GFR remains 20-30% below normal - minor but persistent defect in maximum urine concentration ability and in urine acidification

10 METABOLIC COMPLICATIONS OF ATN 1. Progressive rise in metabolites which are not excreted via kidney: - BUN of mg/dl per day (more in catabolic pts) - creatinine mg/dl per day 2. Water and sodium retention 3. Hyperkalemia - serum K + rises <0.5 meq/l/day 4. Acidosis - plasma HCO 3- falls 1-2 meq/l/day (more in catabolic pts) 5. Hypocalcemia due to: - hyperphosphatemia - resistance to PTH - lack of viatmin D hydroxylation in kidney - malabsorption

11 CHRONIC RENAL FAILURE CAUSES 1. Diabetic nephropathy 2. Hypertension 3. Glomerulonephritis 4. Other interstitial nephritis obstructive uropathy polycystic kidney disease

12 DIABETIC NEPHROPATHY

13 DIABETIC NEPHROPATHY- HYPERFILTRATION Increased filtered glucose load Increased proximal glucose-sodium rebasorption Decreased amount of sodium in distal nephron Decreased amount of sodium reabsorbed at macula densa Reduced release of adenosine from macula densa Reduced resistance of the glomerular afferent arteriole HYPERFILTRAFION

14 HYPERFILTRATION => GLOMERULOSCLEROSIS

15 DECREASE OF GFR vs. PLASMA CREATININE

16 STAGES OF RENAL FAILURE 1. GFR>50 ml/min no disorders 2. 50ml/min> GFR >25ml/min decreased functional kidneys reserve; polyuria 3. 25ml/min> GFR > 5 ml/min renal insufficiency; metabolic & systemic disorders 4. GFR< 5 ml/min - uremia

17 CRF - METABOLIC & SYSTEMIC DISORDERS Accumulation of toxic compounds organic (urea, guanidine, guanidinosuccinic acid, methylguanidine... β2-microglobulin deposition in connective tissue, joints middle molecules Advanced Glycation End Products inorganic compounds (phosphate) Hormonal alterations Impaired renal degradation Prolactin => lactation LH => gynecomastia Gastrin => gastritis Glucagon => glucose intolerance Insulin => hyperinsulinism PTH => osteitis fibrosa Decreased synthesis or activation Erythropoietin 1,25-dihydroxyvitamin D3 Trade-off hypothesis Excessive activation of compensatory mechanisms leads to pathology

18 CRF - METABOLIC & SYSTEMIC DISORDERS (I) Acid-base and water balance metabolic acidosis ( muscle degradation) hypervolemia hyperkalemia (rare) Anemia shortened lifespan of red blood cells reduced synthesis of erythropoetin inhibition of the erythropoetin effect on bone marrow excessive blood loses Lipids metabolism hipertriglyceridemia impaired lipolytic activity of plasma Cardiovascular system hypervolemia => increased afterload => left ventricle failure hypertension pericarditis

19 CRF - METABOLIC & SYSTEMIC DISORDERS (II) Nervous system peripheral polyneuropathy (organic toxic compounds and middle molecules) reduced activity of baroreceptors impaired motility of GI tract arrhytmias lack or excessive stimulation of muscles ( paralysis; restless legs syndrome) Gastrointestinal tract diffusion of toxic compounds into GI lumen inflammation bleeding malabsorption Bone demineralisation due to metabolic acidosis demineralisation ( hyperparathyroidism, lack of vitamin D 3 )

20 PROTEINURIA NEPHROTIC SYNDROME

21 GLOMERULAR PERMEABILITY proteins with a radius <20 A and neutral electric charge are filtered without hindrance proteins with a radius > 50A and neutral electric charge are not filtered

22 PROTEINURIA 1. Overflow proteinuria Excessive filtration of proteins which cannot be reabsorbed (myeloma, hemoglobinuria, myoglobinuria) 2. Tubular proteinuria inability of proximal tubules to reabsorb proteins filtered in normal amounts Fanconi syndrome, aminoglycosides nephropathy, heavy metal toxicity 3. Glomerular proteinuria glomerular hemodynamics glomerular endothelial cells glomerular basement membrane podocytes

23 NEPHROTIC SYNDROME Proteinuria > 3.5 g/day Hypoalbuminemia Hyperlipidemia Edema

24 REGULATION OF BLOOD PRESSURE BLOOD PRESSURE = CARDIAC OUTPUT x VASCULAR RESISTANCE A. Acute mechanisms fast, not precise,adaptation after hours-days B. Long term mechanism slow, precise, steady correction pressure diuresis adaptation of water & sodium excretion via kidney to maintain steady ECF volume => blood volume => BP

25 HYPERTENSION BLOOD PRESSURE BP systolic [mm Hg] BP diastolis [mm Hg] Normal <120 <80 Prehypertension Hypertension I o Hypertension II o > >100 95% of hypertension = primary, essential hypertension 5% of hypertension = secondary hypertension

26 PATHOGENESIS OF HYPERTENSION 1. Hypertension due to excessive ECF volume Initially hypervolemic hypertension which changes into vasoconstrictive hypertension 2. Vasoconstrictive hypertension The primary defect: increased peripheral ( renal) arterial resistance 3. Mixed hypertension

27 INHIBITORS of Na + -K + -ATPase SODIUM RETENTION Endogenous inhibitors of Na + -K + -ATPase Inhibition of Na + -K + -ATPase in renal tubules Inhibition of Na + -K + -ATPase in other cells Increased urinary Na + excretion Increased Ca ++ in cytosol Contraction of vascular smooth muscles Increased release of cathecholamines from presynaptic bulb Endothelium increased endothelins decreased NO INCREASED PERIPHERAL RESISTANCE

28 Renal failure Retention of sodium Hypervolemia Formation of natriuretic hormones (Inhibitors of Na + -K + ATPase) Hypertension Increased sodium excretion via surviving nephrons PATHOLOGY COMPENSATION

29 SODIUM & POTASSIUM DIET RECOMENDATIONS GENERAL: reduction of Na + intake and supplemetation of K + Na + intake of 65 mmol/day for 50 year old or younger Na + intake of 55 mmol/day for 50years< adult <70 years Na + intake of 50 mmol/day for older than 70 years K + intake higher than 120 mmol/day Dietary K + /Na + ratio should be increased from to approx. 2.0

30 SODIUM & POTASSIUM - DIET Sodium [ mmoll] Potassium [mmol] Two slices of ham Cup of canned chicken noodle soup Orange Cup of boiled pea Natural food 20-40/day >150/day Western civilisation /day 30-70/day Natural food K + /Na + ratio >3 => hypertension in less than 1% Western civilisation - K + /Na + ratio <0.4 => hypertension in 30% Only 12-15% of Na+ originates from natural food and about 80% is the result of food processing

31 ESSENTIAL PRIMARY HYPERTENSION 1. Abnormalities in CNS Increased basal sympathetic activity Abnormal stress response 2. Abnormalities in kidney Increased RAA activity Deficiency of vasodilators Excessive Na + reabsorption Age dependent decrease of the kidneys ability to excrete sodium 3. Abnormalities in blood vessels Decreased NO and/or increased endothelins production Excessive sensitivity to catecholamines

32 SECONDARY HYPERTENSION 1. Renal failure (2-4%) Hypervolemic mechanism 2. Stenosis of the renal artery (1%) Vasoconstrictive and hypervolemic mechanism 3. Pheochromocytoma Excessive synthesis of catecholamines => increased sympathetic activity Positive inotropic and chronotropic effect on the heart=> increased cardiac output Constriction of large veins =>increased preload=>increased cardiac output Stimulation of RAA &stimulation of Na + reabsorption in kidney=> ECF volume Constriction of arteries => increased BP

33 SECONDARY HYPERTENSION 4. Glucocorticoids Hypervolemic mechanism Stimulation of angiotensinogen synthesis in liver Sensitization of the vascular wall to catecholamines 5. Hyperthyroidism ( Systolic BP and Diastolic BP) reduced peripheral resistance increased sensitivity of the cardiovascular system to catecholamines cardiac hypertrophy ( thyroid hormones & hyperdynamic circulation) stimulation of angiotensinogen synthesis in liver stimulation of sympathetic system => increased release of renin increase in blood volume & erythrocyte mass)

34 SECONDARY HYPERTENSION 6. Obesity More frequent in abdominal obesity Release of FFA from adipocytes (catecholamines)=> FFA inhibit insulin uptake into hepatocytes=> peripheral hyperinsulinism Adipocytes produce: Leptin => stimulation of sympathetic system Angiotensin II Hormones decreasing tissue sensitivity to insulin => hyperinsulinism Increased intraabdominal pressure => increased pressure applied to renal veins=> reduced renal blood flow => reduced pressure natriuresis

35 HYPERTENSION SYSTEMIC CONSEQUENCES 1. Heart Increased afterload => concentric hypertrophy of the left ventricle Hypertrophy of the ventricle => decreased compliance of the ventricle => diastolic failure of heart Acceleration of atherosclerosis=>ischemic heart disease => systolic and diastolic heart failure 2. Arteries & microvessels Eccentric hypertrophy of the large arteries Concentric hypertrophy of the medium and small vessels Reduction of the microvascular network 3. Cerebral circulation Impaired autoregulation of the cerebral blood flow Shift of physiological autoregulation range (60 150mm Hg) towards higher values High blood pressure is better tolerated than lowered blood pressure