Patfis GGA Kel.10

7/30/2019 Patfis GGA Kel.10

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Definition:

A syndrome characterized by rapid

decline in glomerular filtration rate(hours to days), retention ofnitrogenous waste products, and

perturbation of extracellular fluidvolume and electrolyte and acid-base homeostasis


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ARF complicates approximately 5% ofhospital admissions and up to 30% of

admissions to ICU Oliguria (urine output 400 mL/d) is a

frequent but not invariable clinicalfeature (50%)

Asymptomatic, diagnosedbloodurea and creatinine concentrations

Most ARF reversible


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ARF may complicate a wide range ofdiseases, which for purposes of diagnosisand management are conveniently

divided into:(1) Prerenal ARF, prerenal azotemia) (55%)

cause renal hypoperfusion withoutcompromising the integrity of renalparenchyma

(2) Intrinsic renal ARF, renal azotemia (40%) directly involve renal parenchyma

(3) Postrenal ARF, postrenal azotemia (5%) associated with urinary tract obstruction


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Penelitian Definiside Medonca et al

(2000)7,

Tepel et al (2000) 9

SCr 0,5 mg/dl in 24 hours

Brivet et al (1996) 10 SCr > 2.0 mg/dl = (ARF)SCr >3.5 mg/dl and/orBUN > 100 mg/dl(Severe ARF)

Agrawal and Swartz

(2000) 1SCr > 0,5 mg/dl/day with UO < 400 ml/day

(complete renal shutdown)Ricci dkk (2006) 11 SCr between 1,5 10 mg/dl

UO between 0-900 cc/dayGFR >50 % with UO (hours to days)


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Most common form of ARF

Represents a physiologic response to

mild to moderate renal hypoperfusion Prerenal ARF reversible upon

restoration of renal blood flow and

glomerular ultrafiltration pressure Renal parenchymal tissue is not

damaged


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More severe hypoperfusion ischemicinjury of renal parenchyma intrinsic

renal ARF Can complicate any disease that

induces hypovolemia, low cardiacoutput, systemic vasodilatation, orselective intrarenal vasoconstriction


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Hypovolemia systemic MAP activated baroreceptors trigger acoordinated series of neural and humoral

responses designed to restore bloodvolume and arterial pressure:

Activation of the sympathetic nervoussystem

Activation of renin-angiotensin-aldosterone system

Release of arginine vasopressin (AVP;formerly called antidiuretic hormone)


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Norepinephrine, angiotensin II, and AVPact in concert preserve cardiac and

cerebral perfusion by stimulatingvasoconstriction

inhibiting salt loss through sweat glands

stimulating thirst and salt appetite promoting renal salt and water retention


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Glomerular perfusion, ultrafiltrationpressure, and filtration rate are preserved

during mild hypoperfusion throughseveral compensatory mechanisms

Stretch receptors in afferent arteriolestrigger afferent arteriolar vasodilatationthrough a local myogenic reflex(autoregulation)


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Biosynthesis of vasodilator prostaglandins(prostaglandin E2 and prostacyclin)

dilation of afferent arterioles

Angiotensin II induces constriction ofefferent arterioles

intraglomerular pressure is maintained

the fraction of plasma flowing throughglomerular capillaries that is filtered

(filtration fraction)GFR is preserved


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More severe hypoperfusion

compensatory responses areoverwhelmedGFR

Prerenal ARF


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NSAIDs do not compromise GFR inhealthy individuals but may precipitate

prerenal ARF in patients with volumedepletion or in those with chronic renalinsufficiency in whom GFR is maintainedthrough prostaglandin-mediated

hyperfiltration by the remainingfunctional nephrons


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Angiotensin II preserves glomerular filtrationpressure distal to stenoses by

elevating systemic arterial pressure triggering selective constriction of

efferent arterioles

ACE inhibitors blunt these responses andprecipitate ARF (usually reversible)


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Causes:

(1) diseases of larger renal vessels,

(2) diseases of the renal microcirculationand glomeruli

(3) ischemic and nephrotoxic ARF

(4) tubulointerstitial inflammation


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Most intrinsic renal ARF is triggered by

1. Ischemia (ischemic ARF)

2. Nephrotoxins (nephrotoxic ARF)


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Patients undergoing

Major cardiovascular surgery

Suffering severe trauma Hemorrhage

Sepsis

Volume depletion


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Hypoperfusion

ischemic injury to renal parenchymal

cells, particularly tubular epitheliumbilateral renal cortical necrosis

irreversible renal failure


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The course of ischemic ARF is typicallycharacterized by three phases:

Initiation phase Maintenance phase

Recovery phase


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Hours to days The initial period of renal hypoperfusion during

which ischemic injury is evolving

GFR declines because(1) glomerular ultrafiltration pressure as a

consequence of renal blood flow(2) the flow of glomerular filtrate within tubules

is obstructed by casts comprised ofepithelial cells and necrotic debris derivedfrom ischemic tubule epithelium

(3) there is backleak of glomerular filtratethrough injured tubular epithelium


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12 weeks renal cell injury is established GFR stabilizes at its nadir (typically 5 to 10

mL/min)

urine output is lowest uremic complications arise persistent intrarenal vasoconstriction medullary ischemia triggered by dysregulated

release of vasoactive mediators from injuredendothelial cells congestion of medullary blood vessels reperfusion injury


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Renal parenchymal cell, particularlytubule epithelial cell, repair and

regeneration and a gradual return ofGFR to or towards premorbid levels


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Intrarenal vasoconstriction:

Radiocontrast agents (contrast

nephropathy) Cyclosporine

Tacrolimus (FK506)

acute fall in renal blood flow and GFR a relatively benign urine sediment

a low fractional excretion of sodium


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Direct toxicity to tubule epithelial cells

and/or intratubular obstruction are major

pathophysiologic events in ARF induced by:

Antibiotics + antivirus Anticancer drugs

- Acyclovir - Cisplatin

- Foscarnet - Carboplatin

- Aminoglycosides - Ifosfamide

- Amphotericin B

- Pentamidine


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Amphotericin B dose-related ARF

intrarenal vasoconstriction and directtoxicity to proximal tubule epithelium

Cisplatin and carboplatin accumulatedby proximal tubule cells provoke ARFafter 7 to 10 days of exposure by: Inducing mitochondrial injury

Inhibition of ATPase activity Free radicalmediated injury to cell membranes Apoptosis Necrosis


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Endogenous nephrotoxins:

Calcium intrarenal vasoconstriction

Myoglobin Hemoglobin

Urate

Oxalate Myeloma light chains


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Urinary tract obstruction


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Obstruction to urine flow:

Between the external urethral meatus andbladder neck

Bilateral ureteric obstruction

Unilateral ureteric obstruction in a patientwith one functioning kidney or with

preexisting chronic renal insufficiency


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The most common cause of postrenalARF

Usually due to: Prostatic disease (e.g., hypertrophy,

neoplasia, or infection)

Neurogenic bladder

Therapy with anticholinergic drugs


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Less common causes of acute lowerurinary tract obstruction:

Blood clots Calculi

Urethritis with spasm


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Ureteric obstruction may result from

intraluminal obstruction calculi

blood clots infiltration of the ureteric wall

neoplasia

external compression

retroperitoneal fibrosis neoplasia

abscess

inadvertent surgical ligature)


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Early stages of obstruction (hours to days)

Continued glomerular filtration

increased intraluminal pressure upstreamto the site of obstruction

gradual distention of the proximal

ureter, renal pelvis, and calyces a fall in GFR


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Patfis GGA Kel.10