Renal diseases. Acute renal failure Chronic renal failure Nephrotic syndrome

Transcription

1 Renal diseases Acute renal failure Chronic renal failure Nephrotic syndrome

2 Acute renal failure Acute renal failure (ARF) is characterized by sudden loss of the ability of the kidneys: to excrete wastes to concentrate urine to conserve electrolytes to maintain fluid balance

3 Acute renal failure a sudden loss of renal function reduced production of urine oliguria - decrease in the urine flow to the range of : ml/day (less than 20mL/hr) anuria - absence of urine or less than 50ml/day - retention of water, H+, and minerals - metabolic acidosis - retention of metabolic waste products in the blood: BUN creatinine

4 Acute renal failure Prerenal ARF (about 70%) Renal ARF (about 25%) -tubular diseases (about 85% of all renal ARF cases) -interstitial diseases -glomerular diseases -vascular diseases Postrenal ARF (about 5%)

5 Acute renal failure

6 Causes of acute prerenal failure 1. hypovolemia, hypotention blood loss fluid loss extensive burns, watery diarrhea, or vomiting 2. left ventricle failure 3. systemic vasodilatation sepsis, anesthesia, anaphylaxis 4. preglomerular vasoconstriction NSAID, hepatorenal syndrome, vasoconstrictors

7 Hepatorenal Syndrome Acute, prerenal failure Patomechanism of renal ischemia in hepatorenal syndrome: 1. Reduction of the effective blood flow due to sequestration of fluid in the third space 2. Reduced peripheral vascular resistance due to presence of false neurotransmitters 3. Renal vasoconstriction - endotoxin reabsorbed from GI tract constrict renal vessels 4. Increased intraabdominal pressure due to ascites -> compression of renal veins

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9 ARF due to vascular diseases 1.Renal artery emboli originate most frequently from heart (mural or valvular thrombi) renal artery thrombosis often results from trauma 2. Atheroembolic Renal Disease embolization of material from atherosclerotic plaque - often due to surgery or radiographic instrumentation on aorta 3. Renal Vein Thrombosis - in infants due to volume depletion - in adults after trauma; oral contraceptives

10 Acute renal failure Ischemic ATN (Acute tubular necrosis) -excessive decrease of ECF -inhibition of prostaglandin synthesis (NSAIDs) Necrosis occures in : - proximal tubules - ascending loop of Henle Reduced ECF volume activates baroreceptors, leading to secretion of: -renin -antidiuretic hormone (ADH) resulting in : oliguria fluid retention azotemia mineral disorders acidosis

11 ATN due to toxins -Aminoglycosides -aminoglycosides are cytotoxic to proximal tubules due to accumulation -Cephalosporins -Amphotericin -Radiocontrast media: -volume reduction - osmotic diuresis -toxicity to proximal tubules -renal vasoconstriction due to tubuloglomerular reflex - hypoperfusion

12 A. Organic solvents -1. carbon tetrachloride used as cleaning solvent cytotoxic to proximal tubules -2. ethylene glycol -direct toxicity to epithelium and oxalic acid crystals B. Anesthetic agents 1. Methoxyflurane metabolised to inorganic fluorides-> nephrogenic DI and/or ATN; metabolised to oxalic acid -> crystals B. Heavy metals 1. mercury, bismuth, arsen very rare cases 2. Cisplatin - a cancer chemotherapeutic contains platinium - heavy metal

13 ATN caused by hemoproteins - myoglobin plasma increase (ATN occurs in 30% of patients with rhabdomyolysis) - hemoglobin plasma increase as the result of hemolysis hemoglobinuria - the cells of proximal tubules are destroyed - capasity of the proximal tubule to absorb heme protein is exceeded - precipitation of protein in the tubules lumen - relase of iron, iron-induced oxidant stress - heme proteins are scavengers of NO - vasoconstriction

14 Oliguria, anuria - pathomechanism 1. Intrarenal vasoconstriction - renal blood volume is reduced to 30-50% of normal (both in ischemic and nephrotoxic ATN) - loss of autoregulation (lack of vasodilation of the afferent arteriole when blood pressure drops) - Endothelin> NO 2. Decreased permeability coefficient in glomerulus - reduction in size and density of the endothelial fenestrae - epithelial swelling, constriction of mesangial cells induced - by angiotensin II, ADH, endothelins 3. Damage of tubular epithelium - back leakage of filtrate tubular obstruction

15 Clinical course of ATN The initiation phase: - hours-days - no morphological changes - time for prevention of ATN - factors : ischaemia, toxins and inflamation The maintenance phase: - GFR is low <5 ml/min - lasts 1-2 weeks up to 6-8 weeks - oliguria (<400 ml/day) - or non-oliguric patients (>400 ml/day)

16 The recovery phase: - progressive rise in urine volume ( ml/hour) - dysfunction of tubules (polyuria and osmotic diuresis) - renal function improves within weeks up to 1 year - in one/third of patients GFR remains 20-30% below normal - minor but persistent defect in maximum concentration ability and urinary acidification occurs in many patients

17 Metabolic complications of ATN 1. Progressive rise in: - BUN of mg/dl per day (more in catabolic state ) - creatinine mg/dl per day 2. Water and sodium retention 3. Hyperkalemia 4. Acidosis 5. Hypocalcemia due to: - -hyperphosphatemia - -resistance to parathyroid hormone -abnormalities in vit.d metabolism

18 Systemic complications of ATN 1. Gastrointestinal -erosive gastrointestinal disorders (bleeding, anorexia, nausea, vomiting) 2. Cardiovascular -congestive heart failure due to fluid overload, arrhytmias 3. Neurological -lethargy, coma 4. Hematologic -anemia -bleeding disorders 5. Immunologic -increased sensitivity to infections

19 Postrenal ARF

20 Obstructive uropathy patomechanisms 1. Renal Blood Flow - decrease in afferent arterioral resistance 2. GFR - reduced due to increased pressure in Bowman s space - reduced blood flow

21 3. Tubular function A. Partial obstruction: decreased ability to concentrate urine decreased ability to acidify urine B. After relief of obstruction -> postobstructive diuresis caused by: - volume overload - osmotic diuresis - decreased tubular reabsorption of sodium (thick ascending limb of the loop of Henle) - unresponsiveness to ADH

22 Chronic renal failure 1. GFR>50 ml/min functional kidneys reserve - normal function 2. 50ml/min> GFR >25ml/min decreased functional kidneys reserve polyuria not destroyed nephrons adaptive changes - enhanced function osmotic diuresis 3. 25ml/min> GFR > 5 ml/min renal insufficiency; metabolic and systemic disorders 4. GFR< 5 ml/min - uremia

23 Progressive loss of renal function Progressive loss of renal function over time; based on a gradual decline in the GFR and creatinine clearance. The diagnosis of CKD requires the following: Decline of kidney function for 3 months or more AND Evidence of kidney damage (e.g. albuminuria or abnormal biopsy) OR GFR <60 ml/min/1.73 m 2 Each patient is classified into one of the following 5 stages of CKD because management and prognosis varies according to the progression of damage. Stage 1: Kidney damage with normal or increased GFR (>90 ml/min/1.73 m 2 ) Stage 2: Mild reduction in GFR (60-89 ml/min/1.73 m 2 ) Stage 3: Moderate reduction in GFR (30-59 ml/min/1.73 m 2 ) Stage 4: Severe reduction in GFR (15-29 ml/min/1.73 m 2 ) Stage 5: Kidney failure (GFR <15 ml/min/1.73 m 2 or dialysis)

24 Chronic renal failure Causes of chronic renal failure: 1. Diabetic nephropathy about 50% 2. Hypertension about 25% 3. Glomerulonephritis about 15% 4. Other : interstitial nephritis, obstructive uropathy, inborn defects ie. polycystic kidney disease

25 Mechanisms of metabolic and 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) Excessive activation of compensatory mechanisms leads to pathology

26 Uremia Metabolic and systemic disorders in chronic renal failure 1.Anemia shortened lifespan of red blood cells reduced synthesis of erythropoetin inhinbition of the erythropoetin effect on bone marrow excessive blood loses 2.Lipids metabolism hipertriglyceridemia impaired lipolytic activity of plasma 3.Cardiovascular system hypervolemia => increased afterload => left ventricle failure hypertension precipitation of calcium-phosphate pericarditis

27 4.Nervous system peripheral polyneuropathy impaired motility of GI tract arrhytmias lack or excessive stimulation of muscles 5.Gastrointestinal tract diffusion of toxic compounds into GI lumen inflammation bleeding malabsorption 6.Hyperinsulinemia insulin resistance 7.Bone demineralisation due to metabolic acidosis hyperparathyroidism lack of vitamin D3

28 8. Impaired renal degradation Prolactin => lactation LH => gynecomastia Gastrin => gastritis Glucagon => glucose intolerance Insulin => hyperinsulinism PTH => osteitis fibrosa -Decreased synthesis or activation Erythropoetin 1,25-dihydroxyvitamin D3

29 Nephrotic syndrome - proteinuria > 3.5 g/day - hypoalbuminemia - hyperlipidemia - edema Nephrotic syndrome I. primary renal disease II.secondary nephrotic syndrome I. Primary nephrotic syndrome results from primary renal diseases most of which are of unknown origin

30 II. Secondary nephrotic syndrome a renal complication of multisystemic disease - immune-mediated - SLE - metabolic - diabetes mellitus - neoplastic - amyloidosis of multiple myeloma - infectious - membranous nephropathy - focal glomerulosclerosis - HIV infection

31 Metabolism of proteins in the nephrotic syndrome 1. Hypoalbuminemia- albumin synthesis is increased - synthesis does not compensate for urinary losses 2. Immunoglobulins - hypogammaglobulinemia is present in nephrotic syndrome; immunoglobulin synthesis does not compensate for urinary losses 3. Hormone binding proteins - plasma concentration of thyroxin binding globulin and corticosteroids binding globulin are decreased - urinary loss of vitamin D binding protein => decreased calcium absorption in gastrointestinal tract 4. Decreased serum transferrin and ceruloplasmin concentration

32 5. High molecular weight serum proteins - increased of hepatic synthesis of these proteins => increased plasma concentration - reduced plasma concentration of antithrombin III (inhibitor of coagulation) and increase of fibrinogen concentration => thrombosis 6. Hyperlipidemia - reduced plasma albumin => stimulation of LDL and VLDL synthesis - increase of plasma LDL and VLDL - reduced catabolism of VLDL - no change or decrease of HDL 7. Edema - reduced oncotic pressure (starts when total plasma protein concentration decreases to 4g/dL) - primary change in kidney (excessive retention of Na and water)

33 Nephritic syndrome Nephritic syndrome clinical signs and symptoms caused by immune-mediated glomerulonephritis Symtoms: - Proteinuria - Hematuria of glomerular origin - Oliguria - Hypertension - Edema