renal diseases -...
TRANSCRIPT
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Renal diseases
Acute renal failure
Chronic renal failure
Nephrotic syndrome
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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
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Acute renal failure
• a sudden loss of renal function
• reduced production of urine
• oliguria - decrease in the urine flow to the range of :
– 400-500 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
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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%)
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Acute renal failure
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Causes of acute prerenal failure
•1. hypovolemia, hypotentionblood 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
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Hepatorenal Syndrome
Acute, prerenal failure
Patomechanism of renal ischemia in hepatorenal syndrome:
1. Reduction of the effective blood flow due to sequestration offluid 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 -> compressionof renal veins
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ARF due to vascular diseases
1.Renal artery embolioriginate most frequently from heart(mural or valvular thrombi)renal artery thrombosis often results from trauma
2. Atheroembolic Renal Diseaseembolization of material from atheroscleroticplaque - often due to surgery or radiographicinstrumentation on aorta
3. Renal Vein Thrombosis- in infants due to volume depletion- in adults after trauma; oral contraceptives
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Acute renal failureIschemic 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
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ATN due to toxins
-Aminoglycosides-aminoglycosides are cytotoxic to proximaltubules due to accumulation
-Cephalosporins-Amphotericin
-Radiocontrast media: •-volume reduction - osmotic diuresis•-toxicity to proximal tubules•-renal vasoconstriction due to tubuloglomerular reflex -hypoperfusion
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A. Organic solvents-1. carbon tetrachloride
used as cleaning solventcytotoxic to proximal tubules
-2. ethylene glycol-direct toxicity to epithelium and oxalic acid crystals
B. Anesthetic agents1. Methoxyflurane
metabolised to inorganic fluorides-> nephrogenic DI and/or ATN;metabolised to oxalic acid -> crystals
B. Heavy metals1. mercury, bismuth, arsen – very rare cases2. Cisplatin - a cancer chemotherapeutic contains platinium- heavy metal
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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
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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 bloodpressure drops)
- Endothelin> NO2. 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, endothelins3. Damage of tubular epithelium- back leakage of filtrate
tubular obstruction
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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)
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The recovery phase:
- progressive rise in urine volume (200-300 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
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Metabolic complications of ATN
1. Progressive rise in:- BUN of 10-20 mg/dl per day (more in catabolic state )- creatinine 0.5 -1.0 mg/dl per day2. Water and sodium retention3. Hyperkalemia4. Acidosis5. Hypocalcemia due to:- -hyperphosphatemia- -resistance to parathyroid hormone
-abnormalities in vit.D metabolism
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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
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Postrenal ARF
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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
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3. Tubular function
A. Partial obstruction:
decreased ability to concentrate urine
decreased ability to acidify urine
B. After relief of obstruction -> postobstructivediuresis caused by:
- volume overload
- osmotic diuresis
- decreased tubular reabsorption of sodium
(thick ascending limb of the loop of Henle)
- unresponsiveness to ADH
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Chronic renal failure
1. GFR>50 ml/min – functional kidneys reserve - normalfunction
2. 50ml/min> GFR >25ml/min – decreased functionalkidneys 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
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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) ORGFR <60 mL/min/1.73 m2
• 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 m2)
• Stage 2: Mild reduction in GFR (60-89 mL/min/1.73 m2)• Stage 3: Moderate reduction in GFR (30-59 mL/min/1.73 m2)• Stage 4: Severe reduction in GFR (15-29 mL/min/1.73 m2)• Stage 5: Kidney failure (GFR <15 mL/min/1.73 m2 or dialysis)
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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
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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
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Uremia
Metabolic and systemic disorders in chronic renal failure
1.Anemiashortened lifespan of red blood cellsreduced synthesis of erythropoetininhinbition of the erythropoetin effect on bone marrow excessive blood loses
2.Lipids metabolismhipertriglyceridemiaimpaired lipolytic activity of plasma
3.Cardiovascular systemhypervolemia => increased afterload => left ventricle failurehypertensionprecipitation of calcium-phosphatepericarditis
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4.Nervous systemperipheral polyneuropathyimpaired motility of GI tractarrhytmiaslack or excessive stimulation of muscles
5.Gastrointestinal tractdiffusion of toxic compounds into GI lumen
inflammationbleedingmalabsorption
6.Hyperinsulinemiainsulin resistance
7.Bonedemineralisation due to
metabolic acidosishyperparathyroidism
lack of vitamin D3
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8. Impaired renal degradationProlactin => lactation
LH => gynecomastia
Gastrin => gastritis
Glucagon => glucose intolerance
Insulin => hyperinsulinism
PTH => osteitis fibrosa
-Decreased synthesis or activation
Erythropoetin
1,25-dihydroxyvitamin D3
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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
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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
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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
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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 HDL7. Edema- reduced oncotic pressure (starts when total plasma protein concentration decreases to 4g/dL)- primary change in kidney (excessive retention of Na and water)
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Nephritic syndrome
Nephritic syndrome
clinical signs and symptoms caused by
immune-mediated glomerulonephritis
• Symtoms:
• - Proteinuria
• - Hematuria of glomerular origin
• - Oliguria
• - Hypertension
• - Edema