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Usmle Fast Facts

Usmle Fast Facts


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Published by Qasim Chaudhry

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Published by: Qasim Chaudhry on May 14, 2011
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  • Creatinine
  • Urea
  • Distal Nephron
  • Atrial Natriuretic Hormone
  • Prostaglandins
  • Indications
  • Mechanism of Renal Action
  • Antihypertensive Action
  • Clinical Toxicity
  • Mechanism of Action
  • Clinical Uses & Dosage
  • Other Potassium Sparing Agents
  • Carbonic Anhydrase InhibitorsAcetazolamide
  • Osmotic Agents Mannitol
  • Common
  • Uncommon
  • Diagnosis
  • Common Causes
  • Aetiology
  • Investigation
  • Management
  • Classification
  • Causes of Acute Renal Failure
  • Risk Factors
  • Ischaemia
  • Nephrotoxins
  • Mechanism of Oliguria
  • Drugs
  • Uric Acid Nephropathy
  • ATNRisk Factors
  • Histological Lesion
  • Causes of Pulmonary Infiltrates in ARF
  • Causes of Acidosis in ARF
  • Biochemistry
  • Abnormal Urea/Creatinine Ratio
  • Urinary Sediment
  • Imaging
  • Renal Biopsy
  • Beneficial Effects
  • Deleterious Effects
  • Klienknecht et al.Nephron 1976
  • Lucas et al. Surgery 1977
  • Methods
  • Physiological Defence
  • Diuretics
  • Other Agents
  • Essential Features
  • NB: alternate pathway activation seen in membranoproliferative GN
  • Aetiology Common
  • Essential Features →Leaky Glomeruli
  • Techniques
  • 4.haemodiafiltration*CAV or CVV+ HDF
  • Filter Membranes
  • Membrane Selection
  • Advantages
  • Problems
  • Methods to Improve Clearance
  • Dialysate
  • Gambro Solution #1
  • Disequilibrium
  • Hypoxaemia
  • Compounds Removed by Haemodialysis
  • Advantages CAVHD
  • Problems Conventional Haemodialysis
  • Efficiency
  • Problems Peritoneal Dialysis
  • Other Complications
  • Retained Potentially Toxic Metabolites
  • Clinical Effects
  • Clinical Features
  • Metabolic Effects
  • Immunosuppression
  • Coagulopathy
  • Indications for Dialysis
  • Clinical Presentation
  • Histological Presentation
  • Implicated Antigens
  • Pathogenesis
  • Laboratory
  • Treatment Modalities
  • Prognosis
  • Precipitating Factors
  • Arteriolar Vasodilatation Hypothesis1988
  • Secondary Tubular Dysfunction
  • Mediator Imbalance
  • Intra-Abdominal Hypertension
  • High SNS Tone & Reversible Cortical Ischaemia
  • Investigations
  • Crush Injuries & Renal Failure
  • Management Israel (Nephron 1990)
  • Treatment
  • Type III - RTA
  • Type IV - RTA
  • Proximal
  • Distal
  • Hyperkalaemic RTA
  • Renin
  • Angiotensinogen
  • Angiotensin II
  • Angiotensin III

ICU - Genitourinary

lie opposite the L1-L2 vertebral bodies, right being ~ 1 cm lower a. b. c. d. length nephrons renal blood flow GFR ~ 11.5-12.5 cm ~ 1.3 x 106 ~ 15% being long-looped ~ 1.25 l/min ~ 25% of resting CO

~ 125 ml/min or 180 l/day ~ 20% of ERPF (625 ml/min) GFR estimated by creatinine clearance inulin would be ideal, however requires infusion to steady state & cumbersome ~ 18 ml/min ~ 7% of basal VO2 → global ERO2 < 10%

e. f.

renal VO2

hydrostatic pressure i. glomerular capillary ~ 45 mmHg ii. glomerular oncotic ~ 25-35 mmHg iii. Bowman's capsule ~ 10 mmHg filtration pressure equilibrium is reached ~ 2/3 along the glomerular capillary

Renal - Physiology
Na+ excretion K+ excretion osmolar load urine osmolarity obligate urine volume urine SG pH urea protein WBC's RBC's normal minimum normal minimum ~ 100-200 ~ 5-10 ~ 30-100 ~ 20 ~ 8-12 ~ 600 ~ 40-1200 ~ 0.3-0.5 ~ 500 ~ 1003-1030 ~ 4.5-8.0 ~ 5-10 < 0.7 mean ~ 6 mmol/kg/d g/l < 1/HPF < 1/HPF mmol/d mmol/d mmol/d mmol/d mosm/kg/d mosm/d mosm/l ml/kg/hr ml/d

< 3/µl | 3000/ml < 1/µl | 1000/ml

ICU - Genitourinary
Creatinine creatine is an amino acid, derived from, 1. 2. exogenous ingestion synthesis in the liver - small amount - from glycine & arginine ? ornithine

creatine is taken-up by skeletal muscle ~ 150 mg / 100 g muscle regularly turned-over, nonenzymatically, between,

CPK ←  →

creatine ←  →


creatinine is an anhydride, cyclised degradation product of creatine daily production / excretion is relatively constant ~ 8-25 mmol/d (15-20 mg/day) this rate of production varies ~ 10% for a given individual, largely ∝ skeletal muscle mass muscle content is low ~ 0.3 mmol/l, due to rapid diffusion out of the sarcolemma serum levels rise when the GFR is reduced by ~ 50%,

δ [creatinine](%) ~ 1 / δ GFR(%)
ie., plasma creatinine → ~ doubles for each 50% reduction in nephron mass normal serum level ~ 0.06-0.11 mmol/l (see table following) this is elevated to a greater extent in renal or post-renal failure, than in pre-renal failure levels fall in pregnancy due to dilution & ↑ GFR the normal urea:creatinine ratio ~ 70-150:1 varies 10-25% in normal adults, decreasing with age,

ClCR ≈ 133 - (0.64 x Age)
serum creatinine is a poor reflection of GFR because, a. b. c. excretion is by filtration and tubular secretion with a fall in GFR


- tubular secretion increases - VdSS increases

production varies with - muscle mass - age - catabolic state - muscle damage (myositis, rhabdomyolysis, myopathies) false increase with non-creatinine chromogens ketones - acetoacetate cephalosporins flucytosine (Jaffe colour absorption)



creatinine excretion impaired by cimetidine, cotrimoxazole


ICU - Genitourinary

Normal Values
GFR premature at birth at 1 month Maximum Urine Concentration Plasma Creatinine

10-20 0.7-0.8 1-2 50 ml/min/m2 ml/min/m2 ml/min/m2 ml/min/m2

60-80 ml/min/m2

75-185 ml/min/1.73m2
(95%CI | 70kg → 1.7m2)

450-600 mosmol/l maternal at birth1 infant ~ 18-35 µmol/l child ~ 30-60 µmol/l youth ~ 45-90 µmol/l 7.35 20 mmol/l



male ~ 55-120 µmol/l female ~ 45-95 µmol/l

pH [HCO3-]

7.4 25 mmol/l

decreases due to low muscle mass and high rate of anabolism

Urea clearance varies with GFR → reabsorption ~ 40-60% handled by simple diffusion, both secreted & reabsorbed in different regions of nephron Distal Nephron basolateral Na/K-ATPase is mineralocorticoid sensitive responsible for reabsorption of ~ 5% of filtered Na+ in absence of aldosterone ~ 50% of distal Na+ is reabsorbed → maximal Na+ excretion ~ 750 mmol/d (~ 1500 mmol/d enters DT)


CCF iii. 4. increased ANP levels are found in. natriuresis & modest kaluresis ↓ MAP ∝ vasodilatation inhibition of renal salt/H2O retaining systems i. 7. 2. plasma levels respond to Na+ intake in disease. 3. ↓ renal renin release ii. hypervolaemic disorders i. 152 AA preprohormone 1. CRF essential hypertension pre-eclampsia SIADH hyperthyroidism cirrhosis PAT . levels decline modestly .urinary [Na+] > 20 mmol/l 2. not PG mediated) effects at physiological levels.ICU . PG inhibitors → 1. hyperaldosteronism ii. increased incidence of ARF papillary necrosis & CRF hyporeninaemic hypoaldosteronism → hyperkalaemic RTA (type IV) acute interstitial nephritis & nephrotic syndrome 4 .Genitourinary Atrial Natriuretic Hormone → 126 AA prohormone (atriopeptigen) → 19-28 AA bilogically active peptides the predominant circulating hormone is the 28 AA atriopeptin specific ANH receptors located in vascular. 5. renal and adrenal tissue → ↑ cGMP does not inhibit NaK-ATPase & effects are not inhibited by NSAIDs (ie. 6. 1. ↓ ADH release in health. 3. 3. 2. ↓ aldosterone synthesis & release iii.with onset of HRS. 4. Prostaglandins major proportion is PGE2 synthesised in the medulla inhibition by NSAIDs does little to GFR/RBF in normal individuals in hypovolaemic states.

they are secreted by the pars recta PT and act from within the lumen Indications 1. carbonic anhydrase agents 5.renal failure .nephrotic syndrome .cerebral oedema .CCF .metabolic alkalosis .hypertension .bromide or iodide intoxication .high altitude disease .ICU .RTA . and in this regard they are superior to loop agents 5 . their main action in chronic therapy appears to be vasodilatation this is maximal at the lower dose range. having equivalent maximal chloruretic effects with the closely related phthalimidine derivates (chlorthalidone) used mainly for hypertension although termed diuretics. hypermagnesaemia . all agents → oedematous states .hypercalcaemia. 6.cerebral oedema 2. loop agents 4.hypercalcuria . ∴ ceiling effect → parallel dose-response curves.renal tubular toxins 3. potassium sparing agents osmotic agents Benzothiazides synthesised as an extension of studies into carbonic anhydrase inhibitors inhibit chloride transport in the cortical portion of the thick ascending limb of the loop of Henle only ~ 10% of the filtered load of Na+ is handled by this segment.diabetes insipidus . hyperkalaemia. diluting segment agents .hyperaldosteronism.glaucoma .hyponatraemia . 1° or 2° .ascites .Genitourinary DIURETICS except for the osmotic agents they are all extensively protein bound except for spironolactone.

1. 3. noradrenaline and aldosterone all rise as compensatory mechanisms. 5.ICU . fluid leaving the early DT is not as dilute acute increases in potassium excretion variable potency as carbonic anhydrase inhibitors GFR may be reduced decreased excretion of calcium decreased excretion of magnesium . increase excretion of chloride & sodium accompanying loss of free water in patients with diabetes insipidus. the doses required for antihypertensive efficacy is far less than that required for saluresis. however they are unlikely to be effective alone in severe hypertension the exact mechanism of their antihypertensive action is unclear & effects are probably multiple as plasma renin.direct vasodilatation of renal vasculature . 7. enhanced reabsorption of urate in PT & decreased active secretion Antihypertensive Action given acutely in moderately large doses they result in decreased. plasma volume & cardiac output GFR & renal blood flow mean arterial pressure chronically. as infusion of saline but not dextran. 2.direct action on DT + volume contraction with ↑ PT reabsorption 3.Genitourinary Mechanism of Renal Action 1. kaluresis and loss of free water the urinary filtration fraction. 2. they decrease urinary water excretion ie. therefore reduction in these is not involved saluresis appears to be the critical factor. 6. 8. returns BP to pretreatment values 6 . renal vascular resistance and plasma renin activity rise modestly some of the initial reduction in plasma volume is recovered. 4.clinically insignificant . with a mean reduction of ~ 5% CO & GFR return to pretreatment values potentiate the antihypertensive action of agents acting via other mechanisms antihypertensive effect in any given patient is unpredictable.

ICU .rarely with hyperparathyroidism hyperuricaemia hypercalcaemia & hypophosphataemia hyperlipidaemia purpura. photosensitivity reactions . 7. 3. 2.↑ glycogenolysis . vi. ± contraction alkalosis . 6.thrombocytopaenia 7 .Genitourinary Clinical Toxicity 1. dermatitis.erythema multiforme depression of the formed elements of blood interstitial nephritis necrotizing vasculitis cholestatic hepatitis pancreatitis .↓ insulin secretion & ↓ glycogenesis . azotaemia iv. 5. biochemical side-effects i. metabolic alkalosis iii. 4. hypokalaemia ii. hyperglycaemia v. vii.

depression of the formed elements of blood iv.frusemide only ix. skin rashes . abnormalities of fluid & electrolyte balance are most common i. deafness .usually biochemical. frusemide. hypomagnesaemia ↑ excretion of both Ca++ and Mg++ in proportion to the naturesis side-effects unrelated to the primary action of these agents are rare i. mild carbohydrate intolerance . bumetanide and ethacrynic acid these are structurally quite distinct and do not form a chemical class. 8 . hypocalcaemia. and a loop agent will be more efficacious the site of action is at the luminal membrane. hyponatraemia iv.ICU . 1. GIT disturbances . only a pharmacological one Mechanism of Action inhibit chloride reabsorption in both medullary and cortical portions of the thick ascending limb of the LOH → ~ 15% + 10% of total Na+ reabsorption when GFR is reduced by > 50% the thiazides lose most of their diuretic & antihypertensive action. 1. allergic interstitial nephritis . liver dysfunction vii. urticarial v. hypokalaemia ii.bullous.reversible renal failure viii. metabolic alkalosis ↑ excretion of ammonia and titratable acid iii. 3.possibly via production of prostacycline ↓ pulmonary oedema enhanced interstitial → intravascular fluid movement tends to maintain intravascular volume during diuresis Clinical Toxicity two important generalisations.with or without ulceration iii. hyperuricaemia . to inhibit the Na+-K+-2Cl.ethacrynic acid >> frusemide >> bumetanide . 2. ↓ PAOP . clinical gout rare ii. paraesthesias vi.Genitourinary High-Ceiling / Loop Diuretics three commonly used agents.synergistic with aminoglycosides 2.cotransport mechanism frusemide & bumetanide are both sulphonamides → carbonic anhydrase inhibitors *only in very high doses frusemide also increases venous capacitance.

ICU . c. prevent it from assuming the active conformation are effective only in the presence of endogenous or exogenous aldosterone may be overcome by increasing concentrations of mineralocorticoid the urinary Na+:K+ ratio serves as a direct index of aldosterone activity only ~ 5% of filtered Na+ is handled in the DT. 50 and 100 mg average daily doses ~ 100 mg/d in adults. hypertension refractory oedema . and may therefore have a direct diuretic action. however this is not observed clinically Clinical Toxicity a. 3.3 mg/kg for children 9 . principal toxic effects relate to hyperkalaemia gynaecomastia minor GIT symptoms . c.due to androgen-like activity Clinical Uses & Dosage a. it also inhibits the biosynthesis of aldosterone. 2.Genitourinary Spironolactone a 17-spirolactone steroid which is a competitive antagonist of mineralocorticoids (aldosterone) the receptor is a cytoplasmic protein which appears to exist in two allosteric forms spironolactone (± its metabolite canrenone) bind to this protein. therefore 1. and 3.especially states of secondary hyperaldosteronism diagnosis & management of primary hyperaldosterone states oral tablets as 25.usually in conjunction with another diuretic . b. b. ∴ maximal diuresis is small often used to offset the kaluric/magnesuric effects of loop agents spironolactone also increases calcium excretion via a direct effect on tubular transport at very high concentrations.

d. concomitant use of a potassium wasting diuretic iii.vasodilatation 2° hyperosmolality factitious hyponatraemia not truely "factitious". except possibly post-transplantation majority of action is due to inhibition of NaCl & H2O reabsorption in the ascending LOH side effects. ii. e. a. modest natriuresis . b. i. c. non-metabolised carbohydrate with MW ~ 182 in controlled studies. excessive mineralocorticoid activity these agents result in a marked decrease in potassium excretion NB: their action is similar to that of spironolactone. a. at the luminal brush border the reduction in pulmonary CO2 excretion is transient & clinically unimportant diuretic action is weak due to compensation by later tubular segments increases urinary excretion of Na+.without altering chloride produce a clinical type II RTA Osmotic Agents Mannitol non-absorbable. or reduction in duration or mortality of ARF has not been demonstrated. c. initial ECF overload hypotension .mainly accompanied by chloride under normal conditions. iii. prevention of ARF. they are not antagonists of aldosterone their principal effect appears to be to inhibit the luminal electrogenic entry of sodium in the distal tubule → decreased electrochemical gradient they also inhibit distal secretion of hydrogen ion → resulting in alkalinisation of the urine Carbonic Anhydrase Inhibitors Acetazolamide major effects in the proximal tubule. there is little change in potassium excretion when potassium excretion is high. actually hyperosmolar hyponatraemia hyperosmolality acute renal failure 10 . however.exacerbation of CCF . i.Genitourinary Other Potassium Sparing Agents amiloride and triamterene appear to have identical mechanisms of action interfere with transport in the late segments of the nephron.late volume depletion . increased dietary intake ii.ICU . b. K+ and HCO3.

stricture . not anuria 3. 4.surgical misadventure .urethral . 3. 5.Genitourinary Anuria Common a. acute renal failure congenital GUS anomalies 11 .papillary necrosis .retroperitoneal tumour . 5. b.parenchymal diseases * usually oliguria. bilateral vascular obstruction 4.bladder acute renal disease in patient with one functioning kidney Uncommon 1.ICU .benign / malignant . "apparent" anuria 2° to dehydration blocked catheter bladder neck obstruction trauma . 2.calculi .renal vein thrombosis . urethral obstruction bilateral ureteric obstruction .aortic dissection .renal artery thrombosis .bladder calculus .retroperitoneal fibrosis .

creatinine .place | flush | replace catheter . investigations i.kidney size & morphology b. haematuria.calcification aorta/renal .bladder shadow .prostate .infection. dehydration hypotension sepsis acute tubular necrosis mechanical . electrolytes iii.hydronephrosis . urinary symptoms .kidney position/size .surgery .Na+.catheter problems < 0.Genitourinary Diagnosis a. hypovolaemia. LDH .drugs . anaemia.5 ml/kg/hr → ARF ≤479 ≥ 36 ≥ 270 ml/24 hr or ≤158 ml/8 hr mmol/l µmol/l < 400 < 16 ml/d ml/hr urine output urea creatinine 12 .fluid status .eosinophilia .urea.ICU . 2.palpate bladder & kidneys . HCO3. FBE ii. history .3-0. abdominal U/S perfusion scan Oliguria Def'n: urine output Knaus.LFT's. thrombocytopaenia . K+. 2.ESR . AXR plain iv. 3. 3. examination c. Common Causes 1. 5. OSF 1. WCC .pain. v.lower limb ischaemia . 4.haemolysis.

volume status. postrenal 3.nephrotoxins .emboli . b.haemorrhage .C&S .fibrosis . hypovolaemia .abdominal hypertension 2.fibrosis raised intra-abdominal pressure 4.pancreatitis iii. urethral damage .CT scan . intrinsic renal disease i.technetium DPTA scan 13 . hepatorenal syndrome v. Investigation a. shock .trauma.renal biopsy .APKD.sepsis.dehydration. medullary sponge kidney ii.catheter flush . glomerulonephritis iv. e. ATN . vascular events . prerenal . casts c.sediment microscopy. preceding renal function .Genitourinary Aetiology 1. surgery . protein. uninalysis d. perfusion .M.renal U/S .obstruction. history examination .thrombosis .burns .IVP .CRF. sepsis . congenital .sepsis . calculi .hypotension .trauma.plain AXR .cardiac failure .cardiac output. Hb .SG. plasma / urine electrolytes and osmolality specific investigations .ICU .

post-obstruction . fluid status .supine posture .drugs. HPO4= . < 200 ml/hr.CXR. glucose . etc. iii.urea and creatinine b. K+.theophylline . Ca++.mannitol. diuretics osmotic agents hypothermia diabetes insipidus Management a. v.fluid status . acute renal failure ii. iv. etc.polyuric renal failure (Cr > 0.M.C&S.excessive oral fluids.ICU . SG.reabsorption of 3rd space losses .return of bowel function . c. d.mental state.Na+.central | nephrogenic .ADH assay (DDAVP challenge) 14 .fluid intake . hyperglycaemia . . Na+ intake . is common and usually benign → seen in the recovery phase of many illnesses or postoperatively severe polyuria is less common and usually implies DI or polyuric renal failure Common Causes 1. ↓ tubular reabsorption i. history .surgery.relief of raised intra-abdominal pressure.Genitourinary Polyuria Def'n: urine output > 5000 > 200 > 500 ml/d ml/hr ml/hr in severe cases mild polyuria. f.PHX renal disease .2) . e. trauma . ↑ ECFV . examination uninalysis plasma/urine plasma biochemistry specific investigations . ↑ RBF 3. .inotropes .hypokalaemia.recovery phase of ATN .glucose. K+ and osmolality . hypercalcaemia 2.

hyperviscosity syndrome . hypokalaemic . drug induced polydipsia . ? Bartter's iv. reabsorption of 3rd space losses iii.transplantation . water / saline excess i.polycystic disease v.pyelonephritis . chlorpromazine osmotic diuresis i. traumatic ~ 30% iii.Conn's syndrome. Fvi. demeclocycline . uraemia iii.post-partum necrosis . drugs . sarcoidosis nephrogenic DI i.lithium. systemic disease . drugs b.aneurysm .ATN recovery .Genitourinary Classification a. hyperglycaemia ii. congenital and familial ii. psychogenic polydipsia v.methoxyflurane.diuretics .sickle cell disease . iv.diuretic abuse .1° & 2° . hypercalcaemic . IV fluids ii. idiopathic ~ 30% ii. vi. dextrans . renal failure .anticholinergics .hyperparathyroidism. hypothalamic thirst disorder iv.myeloma 15 .post-obstructive .IV contrast media c.mannitol .CHI .hypertonic dextrose. central DI i. .surgery . d. especially breast & lung . nephrocalcinosis iii.ICU .thioridazine. chronic inflammatory hypoxic brain damage .amyloid .TB. neoplastic vascular lesions v.

oliguric or non-oliguric d. prolonged pre/post-renal disease will result in structural renal damage a.U/P creatinine < 20 "filtration failure" < 15-20 ml/min < 10-15 ml/min/m2 . infection vi.2 mmol/l . tubular dysfunction iii.Genitourinary ACUTE RENAL FAILURE Def'n: any reduction in renal excretory function sufficient to result in retention of nitrogenous waste: 1. 16 . cardiac failure iv. and not included in the causes of ARF. persistent GFR urinary indices urine output Causes of Acute Renal Failure LIGW states.3-0. . ischaemic tubular disease iv.Na+ & osmolality → tubular dysfunction < 0.ICU . biochemistry .urea > 20 mmol/l . nephrotoxic tubular disease iii. TB c. hepatorenal disease intrinsic renal disease i. 3. 4. as they do not indicate intrinsic renal disease however. surgical.bacteria. glomerulonephritis ii. calculi. trauma. intra-abdominal hypertension vi. dehydration ii. interstitial nephritis v. hypovolaemia. filtration failure ii.5 ml/kg/hr * but "oliguria" ≠ ARF 2. stricture ii. 'prerenal' and 'postrenal' failure should be considered as respective azotaemia syndromes. hypotension iii. obstructive renal disease i. prostatic. infiltration vii. retroperitoneal fibrosis alternative classification i.creatinine > 0. trauma b. prolonged impairment of renal blood flow i.ATN ? ATN . renovascular disease v.

cephalosporins . impaired RBF 17 .hepatorenal failure . thermal burn.jaundice. DIC . malignant hypertension . IABP.hyperuricaemia . chronic drug therapy acute drug therapy i. cyclosporin.ICU . polyuria. physiologic changes 4. SIRS . chronic disease states 3. rifampicin . oedema . ATN ii.endotoxaemia . hypotension .diabetes mellitus .lithium.aminoglycosides. NSAID's . radiocontrast agents. PAN. soft tissue trauma . electrocution . DIC 2.frusemide. TTP.advancing age . renal cross-clamping . liver dysfunction . thoracic. osmolar diuresis . captopril .high or low CO. rifampicin .HUS.renal artery occlusion . ↓ RVPP . cephalosporins. triamterene . SVR . interstitial nephritis 6.renal vein thrombosis . cisplatin.abnormal O2 extraction ratio .anaphylaxis.abnormal urine indices ± fluid balance.tachycardia.renal trauma.NSAID's. major abdominal/orthopaedic) .aspirin. ABx .muscle injury.oliguria.hypotension. anaphylactoid reactions .cimetidine. acute disease states .renal venous hypertension (CVP.advancing age .transfusion reaction.penicillins. thiazides. amphotericin.renal disease . diuretics.diuretics. mithramycin . sulphonamides.raised intra-abdominal pressure . 5.high or low protein intake .sepsis.vascular disease .↑ CVP.aortic. abdo surgery) .transfusion .surgery (CNS.Genitourinary Risk Factors 1. procedures 7.

toxins CCl4. urethral trauma . HgCl2. organophosphates.hyper-Ca++. mannitol. electrolytes ii.hyperphosphataemia metabolites .Genitourinary h.bladder rupture.bilateral ureteral obstruction . . rifampicin.papillary necrosis .stones. radiocontrast media. chemotherapeutic agents. heroin. EDTA.surgical ligation . hypo-K+ . thiazides. cephalosporins. vit.ICU . sulphonamides. iii. allopurinol. post-renal 18 . drugs aminoglycosides. heavy metals.pigments (bilirubin. hydrallazine. toxic causes i. amphotericin. methoxyflurane. clot.retroperitoneal fibrosis . propylthiouracil. toluene. procainamide. methanol. probenecid. j. tumour . Hb) high plasma oncotic pressure . ethylene glycol.urethral/bladder neck obstruction .hyperuricaemia . paracetamol. D ii. uranyl nitrate metabolic causes i. penicillamine. lithium.renal pelvic trauma i. myoglobin.

dehydration iii. cardiogenic shock . 2. cf. thiazides. lithium. . penicillamine. D toxins: CCl4. postoperative sepsis underlying poor medical condition elderly those at lower risk are associated with. scleorderma. pancreatitis. TTP. polyuria nephrotoxic obstetric → mortality ~ 26%. cephalosporins. methoxyflurane. methanol. prolonged aortic cross-clamping nephrotoxic agents i. HgCl2. urate b. DIC. burns iv. intra-abdominal hypertension ix. 2. arrhythmia. heavy metals. haemoglobin. rhabdomyolysis. hydrallazine. 4. toluene. heroin. myopathy ii. eclampsia v. exogenous antibiotics . 3.Genitourinary Acute Tubular Necrosis the most common cause of ARF in ICU (~ 70%).ischaemia. 1. severe hypercalcaemia. 1. severe sepsis. organophosphates.myoglobin. paracetamol.cyclosporin. cisplatin. allopurinol. oliguria trauma. SIRS. ethylene glycol. severe renovascular disease vi. endogenous ii. hypotension.ICU . haemolysis vii. 5. sulphonamides . EDTA. mechanical ventilation x. probenecid. methotrexate. procainamide.aminoglycosides. 3. 50% in oliguric ARF Aetiology a.amphotericin. rifampicin cytotoxics . uranyl nitrate 19 . hepatorenal syndrome viii. malignant hypertension. mithramycin radiocontrast media other drugs: ACE inhibitors. propylthiouracil. factors which interfere with renal blood flow i. hypovolaemia. most are multifactorial the associated mortality ~ 30-60% those at high risk (50-70%) are those associated with. severe pre-eclampsia. mannitol. vit.

3. cf.minor decreased glomerular membrane permeability . 7. 4. Nephrotoxins prerenal hypoperfusion markedly increases susceptibility to ATN from nephrotoxic agents presumably due to increased tubular concentration (∴ tubular cell []'n) & transit time protection from toxic agents is afforded by saline loading (± mannitol) which increase proximal tubular flow. 2. 1.Genitourinary Initiation Phase Ischaemia initiation phase of both ischaemic and nephrotoxic ATN is thought to relate to renal ischaemia ↓ GFR being secondary to afferent arteriolar constriction. 6.unlikely. 2. tubular obstruction micropuncture studies have often (not always) shown increased pressure tubular backleak probably only a minor role in overall reduction in GFR vasodilatation of the efferent arteriole . frusemide which inhibits TGF does not protect against ATN interruption of the renin-angiotensin axis does not protect against ATN inhibition of renal synthesis of PGE2 ↓ ANH ↑ ADH ↑ adenosine ↑ endothelin *vasoconstrictor in renal vasculature ATN 3. 4. frusemide which only increases distal flow studies with radiocontrast agents show no benefit from mannitol. and in the presence of background disease (IDDM) actually enhances toxicity Maintenance Phase ATN GFR commonly < 5% RBF is usually ~ 25-50% of normal factors acting to maintain filtration failure. 5. sympathetic stimulation intra-renal renin-angiotensin activation tubuloglomerular feedback prevents large losses of Na+ which would otherwise occur with failure of reabsorption ("acute renal success") however. no structural defect 20 . 1.ICU .

d. Drugs 1. 2. low osmolality contrast media glomerulo-tubular balance decreased glomerular permeability intratubular obstruction interstitial oedema cortical ischaemia 2. 4. interstitial parenchymal urate deposition & CRF nephrolithiasis ATN especially if plasma level rises acutely eg. treatment of haematological malignancy 21 . magnesium & potassium wasting similar pattern seen with cisplatin NSAIDs interfere with renal PG synthesis and increase incidence of ATN in hypoperfusion radiocontrast media potentiate ARF with hypoperfusion. i. 1. 3. c. Uric Acid Nephropathy three types of renal lesion. e.ICU . nephrogenic DI ii. 3. shock states & sepsis appear to be little difference between older agents & newer non-ionic. aminoglycosides peak levels correlate with bactericidal activity trough levels correlate more closely with clinical toxicity toxicity less with single daily doses. tumour lysis syndrome. due to saturable uptake mechanism for aminoglycosides amphotericin B toxicity increases with a cumulative dose > 2-3g average dose 0.Genitourinary Mechanism of Oliguria a. b. greater with infusions. distal RTA iii.5 mg/kg/d for 70 kg → 70 days initial disorder is distal tubular dysfunction with.

rhabdomyolysis. patient factors ii. hepatic failure c. sepsis v. haemorrhage ii. surgery . anaesthesia .cardiothoracic .biliary tract sepsis. prolonged hypovolaemia. delayed resuscitation disease factors . pigmenturia . jaundice .drugs (as above) .ICU . haemolysis iv. hypotension ii.GA > LA . drugs . hypertension .major trauma b. hypotension. d. iii. Risk Factors preoperative i.site and duration . intraoperative i.major intra-abdominal. dehydration.prolonged dehydration . hypovolaemia.Genitourinary ATN a. pancreatitis iv.other sepsis .age > 50 .major trauma postoperative i.hypoxia. 22 . hypotension . prolonged hypovolaemia. mechanical ventilation vi. vascular .as above non-surgical ATN i. hypotension ii.PH X renal disease.mechanical ventilation iii. hypovolaemia. intra-abdominal hypertension ≥ 30 mmHg iii. aminoglycoside excess iii.diabetes .

nephrotoxic lesion tubular epithelial necrosis with BM sparing epithelial regeneration takes days frequently non-oliguric ischaemic lesion → tubulorrhexis loss of tubular epithelium and BM epithelial regeneration takes weeks found in most cases of ATN b. 23 .Genitourinary Histological Lesion a.ICU .

~ 1-2 mmol/l/d non-volatile acid production is much higher → ~ 1 mmol/kg/d of SO4= & PO4=. steroids.5 mmol/l/d (non-catabolic) if initially 3.relative. 24 .rarely > 23 haematological i. lymphoid atrophy reduced IgG. thrombocytopaenia & platelet dysfunction iii. complement impaired PMN chemotaxis. ↑ [uric acid] vii. ↑ [Mg++] .5 mmol/l and symptoms at ~ 6. b. metabolic acidosis → ↓ HCO3.15 mmol/l/d azotaemia normal solute load maximum [urine] in catabolic states ARF maximum [urine] δ [urea] / d δ [Cr] / d c. biochemical i. blood loss impaired synthesis. excluding lactate [HCO3-] .Genitourinary Complications of ARF/ATN a.5 mmol/l. cyclosporin infections → 30-70%. higher if present in dialysate or antacids vi.mechanism unclear ? [Ca++].hypertension.ICU . ↑ NaCl / H2O . decreased erythropoietin ii. haemolysis.5-2. ↑ [HPO 4=] ~ 2-2.production usually normal ± leukocytosis immunosuppression lymphopaenia. oliguria . ↑ [K+] ~ 0. wound.05-0.[PO4=] < 5 v. non-catabolic) ~ 0. normochromic normocytic anaemia → Hct ~ 20-30% haemodilution.↑ cellular release & catabolism / ↓ renal excretion ++ iv. urine. hypo-Na+.rarely < 12 mmol/l anion gap . lung. normal number impaired acute inflammatory response and delayed hypersensitivity drug effects.absolute < 400 ml/d ~ 80% . e. ↓ [Ca ] ~ 1. leukocyte dysfunction . line d. then will take 6-10 days iii. non-oliguric ~ 20% ~ 600 mosm/d ~ 1200 mosm/l → ~ 500 ml/d obligatory volume ~ 1000-1500 mosm/d ~ 350 mosm/l → ~ 3-4 l/d required urine volume ~ 5-10 mmol/l/d (lower in afebrile.mild.2 mmol/l .3-0. oedema ii.5 mmol/l .

hypertension. f. g.ICU . ileus . d.Genitourinary f. myoclonic twitches.lethargy. polyarteritis nodosa. vomiting. pericarditis. LVF / CCF bacterial pneumonia atypical pneumonia septicaemia ARDS autoimmune diseases . systemic sclerosis . b.anorexia.viral. c. cardiovascular .CCF. disseminated TB recent paper stating cANCA +'ve patients more common cause of renal dysfunction & pulmonary haemorrhage cf. somnolence. usually mild . effusion . mycoplasma.arrhythmias.asterixis. e.increased sensitivity to anaesthetic agents g. nausea. seizures . GIT neurological Causes of Pulmonary Infiltrates in ARF a.SLE. Legionaire's disease. confusion . AIM 1996) 25 . 25% after 2 weeks . hypervolaemia . Goodpasture's syndrome (Niles. h.Goodpasture's .Wegener's granulomatosis .haemorrhage ~ 10-30%. etc.

ii. iii.< 12 mmol/l b. hyperkalaemia & high AG acidosis NB: non-volatile acid production ~ 1 mmol/kg/day HCO3. HPO4=) high anion gap acidosis rarely → AG > 23 / HCO3.ICU . early i. c. tubular dysfunction. normal anion gap later i. iv. reduced H+ secretion ii. accumulation of organic acids.falls 1-2 mmol/l/day in ARF 26 .Genitourinary Causes of Acidosis in ARF a. hyperchloraemic metabolic acidosis iii. glomerular dysfunction accumulation of organic acids (HSO4=. other causes ARF 2° low cardiac output → lactic acidosis respiratory failure → respiratory acidosis starvation in RF → ketoacidosis rhabdomyolysis.

8 > 1. low muscle mass .ICU .hyperalimentation .2 ~ 1. ↑ creatinine 27 . cephalosporins (factitious) ii.010-1.ketones.rhabdomyolysis . ↓ creatinine low ratio i.015 > 40 > 20 ≤3 < 20 >1 >1 mosm/l mosm/l rarely ≤8 ATN mosm/l Def'n: RFI FENa = renal failure index = % fractional excretion Na+ = urine [Na+] / [U/P creatinine] = [U/P Na+].020 < 20 < 20 >8 > 40 <1 <1 < 350 ~ 0. high ratio i. ↑ urea ∼ 100:1 (R: 70-150) > 200:1 is indicative of pre-renal disease . hypovolaemia .hepatorenal syndrome .8-1.elderly.dehydration.catabolic states.liver failure.GIT bleeding . 2. steroids . protein malnutrition .100 / [U/P creatinine] Abnormal Urea/Creatinine Ratio Def'n: normal U:C ratio 1.drugs: tetracyclines. ↓ urea ii.acute muscular diseases .Genitourinary Investigations Biochemistry Urinary Indices of Renal Failure Parameter urine osmolality U/P osmolality urine SG urine [Na+] urine [Cl-] U/P urea U/P creatinine RFI FENa Pre-renal ARF > 500 > 1. sepsis .

cortex/medullary morphology CT scan IV pyelogram radio-isotope perfusion scan renal angiogram 2. 5. cast types i. WC-casts. iii. 6.epithelial cells .pyelonephritis .fever. 7.eosinophils. diuretics. protein and lipid clinical syndromes i. hyaline casts ii. iv.granular. epithelial cells. 3. 5. 3.WBC's. exercise .RBC's. iii.Genitourinary Urinary Sediment 1. 2. cellular & pigmented casts . proteinuria. GN pyelonephritis interstitial nephritis Imaging 1. NB: 2-5 may effectively assess renal perfusion.renal diseases . vascular supply Renal Biopsy 1. WC-casts. ultrasound 93-98% sensitivity for detection of renal tract obstruction also assesses renal size. RC-casts.ICU . iv. lipid . cellular casts . proteinuria . glomerulonephritis vasculitis SLE Goodpasture's syndrome TTP interstitial nephritis oliguria lasting > 8 weeks 28 . 4.WBC's.chronic renal disease .glomerulonephritis . 4. ATN ii. 2. red cell casts white cell casts waxy casts .

d. a. c. ↑ tubular and urine flow ↑ Na+ and osmolar clearance ↓ tubular O2 demand decreases GFR ∝ → tubuloglomerular feedback (TGF) ↓ O2 demand ?? conversion of oliguric to non-oliguric renal failure Deleterious Effects a. or retrospective controls variability in drug dosages small numbers 29 . hyponatraemia direct nephrotoxicity ototoxicity . b. d. c.ICU .↓ O2 demand . b.idiosyncratic interstitial nephritis > 4 mg/min. e. a. hypovolaemia hypokalaemia. f.Genitourinary Renal Failure .absolute & relative (CCF) problems with most frusemide studies. b. c. c. aminoglycosides decreased GFR . e. or > 80-100 µg/ml (250 mg → 60 mins) additive toxicity with other drugs. esp. e. b.TGF (↑ Na+ excretion → ↓ GFR) beneficial uses in non-renal failure. fluid overload states cerebral oedema hyperkalaemia hypercalcaemia ?? renal protection ? this is no longer recommended . d. diagnosis of ARF unclear especially distinction of ATN from pre-renal ARF different risk groups obstetric & medical have better prognosis than surgical and post-traumatic uncontrolled. e. d.Frusemide Beneficial Effects a.

1 ± 3 g/day predominantly surgical and post-traumatic renal failure. nor the oliguric period Lucas et al.5 mg/kg given to 45 post-traumatic (incipient) renal failure patients after volume loading. high dose frusemide. RBF iii. 22% obstetric no difference in the number of dialysis runs required. non-oliguric converted to polyuric renal failure ~ 80% or polyuria maintained ~ 100% no difference in.5-6 mg/kg q4h 50% surgical or traumatic. the number of dialysis runs required ii.Genitourinary Brown. mortality iii. adequacy of the volume loading used would results have been the same if volume status was maintained 30 . 1. i. Ogg. 1. 1. intrarenal distribution of blood flow 10% developed hypotension 2-10 hrs following administration 3. ie. 2.ICU . GFR ii. resulted in an increase in Na+ and osmolar clearance no change in. i. Surgery 1977 NB: "frusemide does not protect against renal failure" frusemide 0. Cameron Clin. high risk continuous frusemide infusion. questions ?? 1. 2. 2. 1981 randomised controlled trial of high dose frusemide. Klienknecht et al. Nephrol. biochemical renal recovery 2 patients suffered ototoxicity Nephron 1976 → 7 vs 6 3. randomised controlled trail.

avoid nephrotoxins .IV fluids . ii. defence of blood volume maintenance of CO ± MAP . Physiological Defence 1.euvolaemia or mild hypervolaemia .antibiotics. pigments. 4.ICU . 5. diuretics iv. other agents .↓ tubular reabsorption → ↓ renal VO2 . 5. O2 delivery iv. physiological i. avoidance of embolisation v. etc.free radical scavengers . cardiac output → iii.Genitourinary Renal Failure .IV fluids (Na+ containing§) .normal [Hb]. 2. high sodium excretion§ maintain DO2 nutrition . limitation of aortic clamp times iv. not absolute 31 . physical i.RX of arrhythmias . sodium excretion v. minimise direct trauma pharmacological i. renodilators v. dialytic therapies monitoring ?? improvement in outcome 3. SpO2 and avoidance of hypercarbia/acidosis ? probable benefit in outcome.inotropes .NSAID's iii.Ca++-channel blockers. contrast dyes. nutrition RBF/GFR 2.theoretical. 4. volume more important 3. etc.Prophylaxis & Protection Methods 1. detection / management of intra-abdominal hypertension ii. avoid inhibitors of autoregulation . blood volume ii. detection / management of post-renal obstruction iii.

most uncontrolled → reversal of oliguria but not renal function proposed mechanisms of action. AJKD 1996. possibly detrimental in radiocontrast studies" frusemide animal studies variable some benefit in ischaemic. ii. no good RCT looking at 'prevention' 32 . in this study. NB: Brown. "anti-sludging" tubular cytoprotection iii. i. Nephrology. Ogg & Cameron (Clin. "possible benefit post-transplantation. iv. iii. osmotic diuresis ii. the controls received 1g of frusemide over 4 hrs there were only 50 patients total. ~ 25 in each group if we accept that non-oliguric renal failure has a better prognosis than oliguric renal failure. ↑ renal vasodilatory PG synthesis iv. but not in nephrotoxic injury conflicting results for prophylactic use in surgical patients effects are negligible once volume is aggressively controlled no overall benefit in established oliguric renal failure theoretical benefit in critical ischaemic lesion (↓ O2-demand) → 2. then why didn't conversion to the former improve prognosis ?? all patients were in established ARF. non-oliguric converted to polyuric renal failure ~ 80% polyuric renal failure maintained ~ 100% no difference in the number of dialysis runs required (7 vs 6) no difference in mortality no difference in biochemical renal recovery however. no controlled trials. no proven benefit in any other scenario.Genitourinary Diuretics 1. free-radical scavenger LIGW states.ICU . mannitol found to be protective in many animal studies both for ischaemic (NA & renal artery clamping) and nehprotoxic models few human studies. ∴ "not recommended as a renal protective agent" Conger. 1980) i.

blood volume. then greater attention must be paid to the basic elements of critical care . extrarenal side-effects . ATP-MgCl2 inosine clonidine chlorpromazine 33 . or other diuretics are used in the setting of ARF. Bersten AIC 1992) Other Agents Ca++ entry blockers. but ?? not in septic patients conflicting animal evidence regarding protective effect known diuretic effect → demonstrated in uncontrolled human studies no controlled human studies looking at long term renal function or mortality adverse effects include. AJKD) agents investigated but inadequate studies. proven lack of benefit in ARF may be of some benefit post-transplantation (Conger. RV & LV afterload . diuresis may mask. and usually an ↑ RBF potential ↓ renal VO2 due to inhibition of Na+ reabsorption potential renal vasodilator in normal man. or augment hypovolaemia & renal hypoperfusion similar ↑ RBF achievable with inotropes not affecting tubular function tubular & DA1-receptor effects blocked by commonly used drugs NB: "if dopamine. 3.ICU .tachyarrhythmias .↑ shunt fraction & ↓ P aO2 . 1.↑ PCWP. 4. renal perfusion pressure (MAP) and cardiac output .Genitourinary 1. thereby may worsen regional O2 supply/demand iii. 2. i.↓ central respiratory drive . low dose dopamine ↑ DO2 via modest ↑ CO (~ 20% on low dose).as urine output can no longer be used as a guide to the adequacy of RBF" (Duke.↓ TSH release & ? other anterior pituitary function ii. the induced diuresis is not always associated with an increase RBF iv. impairs TGF mechanism.

effusion ii. 6. Ca++ chanel blockers adenosine receptor antagonists oxypentifylline chlorpromazine clonidine ATP-MgCl2 ANF * except transplants . dialysis indications i.Genitourinary Management ARF 1. NB: maintenance of volume status & biochemical normality during polyuric recovery phase other therapies of little or no use. uraemic symptoms | complications (Ur > 50 mmol/l) v. thrombocytopaenia. infections | sepsis biochemical homeostasis nutrition some poorly controlled studies suggest improved survival with use of TPN monitor drug therapy / avoid nephrotoxic agents normalise intra-abdominal pressure . 4. anaemia. pericarditis. 7. 3.creatinine ~ 200-400 µmol/l . metabolic acidosis. 1. bleeding tendency iii. 4. encephalopathy. 3.urea ~ 20-40 mmol/l management of uraemic complications i. refractory to RX iv. hyperkalaemia iii. 2. 5. hyperuricaemia aim in maintenance phase for . neuropathy iv.ICU .aim for < 20 cmH2O 2. 6. fluid overload | pulmonary oedema ii. peptic ulcer disease v.aminophylline 34 . 5. myopathy.

rarely generalized <3 g/d NB: alternate pathway activation seen in membranoproliferative GN Aetiology a.usually facial . e. 2.14 ii. 4. i. ↑ creatinine > 0.Genitourinary Nephritic Syndrome Essential Features 1. b. d. low C3. low C3 / normal C4 → → "classical" pathway activation "alternative" pathway 5. .4 ii. uraemia > 20 mild oedema mild proteinuria ↑ ESR hypergammaglobulinaemia low complement levels. 9. 8. usually sudden onset haematuria and RBC casts hypertension > 140/90 mmHg mmol/l mmol/l (or > 20% increase) biochemical renal insufficiency i. 7. Common post-streptococcal GN Goodpasture's syndrome SLE Henoch-Schönlein purpura polyarteritis nodosa 35 . 6. c.ICU . 3.

minimal change GN iii. i. f.Genitourinary Nephrotic Syndrome Essential Features → a. c. d. b. e. h. g. focal glomerulosclerosis iv.crescentic. membranous GN ii. proliferative GN membranoproliferative mesangioproliferative other ~ 75% ~ 40% ~ 15% adult / 80% children ~ 15% ~ 7% ~ 5% . primary glomerular lesions i.5 g/d < 20 g/l hyperlipidaemia / lipiduria Aetiology a. focal 36 .ICU . Leaky Glomeruli ↑ creatinine and urea generalized oedema heavy proteinuria hypoalbuminaemia ± hypertension no haematuria oliguria usually insidious onset > 3.

collagen-vascular disease SLE. syphilis. malignancy Hodgkin's & NH lymphomas. secondary glomerular lesions ~ 25% i. renovascular hypertension thyroiditis. multiple myeloma vi. antivenoms / antitoxins contrast media. Henoch-Schönlein purpura.Genitourinary b. leukaemia. schistosomiasis. melanoma Wilm's tumour. bacterial endocarditis. street heroin iv. diabetes mellitus ii. captopril. familial sickle cell disease. Wegener's). shunt infections leprosy. infections post-streptococcal. GIT). Alport's syndrome (sensorineural deafness) vii. probenecid. filariasis iii. myxoedema. carcinoma (breast. drugs gold.ICU . dermatomyositis v. miscellaneous sarcoidosis. morbid obesity renal transplant rejection vesico-ureteric reflux 37 . EBV. malaria. penicillamine. HBV. Goodpastures' necrotising vasculitis (inc. amyloidosis pre-eclampsia. PAN.

acute reversible renal failure .especially in critically ill i. rarely .ICU . lithium ii. uraemic symptoms / complications v. hyperuricaemia fluid overload states . refractory metabolic acidosis iv. 6. isopropanol iii.theophylline. barbiturates plasmapheresis i. methanol. 4. myasthenia haemoperfusion theoretical advantages for lipid soluble / highly protein bound molecules studies have not shown improved morbidity/mortality severe thrombycytopaenia is a common side-effect recently developed polystyrene resins (Amberlite XAD-4) have high affinity for lipid soluble compounds and have a clearance ~ 2x charcoal research i. hepatic encephalopathy ii.refractory to conventional therapy drug overdosage i. salicylates iv. GB syndrome iii. 3. hyperkalaemia ii. ethylene glycol. 5. septicaemia / SIRS 2.Genitourinary DIALYTIC THERAPIES Indications 1. fluid overload | pulmonary oedema iii. 38 . hyperviscosity syndromes ii.

4.75m2 for maximal solute clearance .regenerated cellulose. driven by the electrochemical activity gradient for each molecular species ultrafiltration: solvent & solute transfer through a semipermeable membrane.ICU . intermittent conventional haemodialysis ii.cuprophane . polycarbonate . SCUF . plate 39 .Genitourinary Techniques Def'n: dialysis: solute diffusion through a semipermeable membrane. no requirement for dialysate solution major disadvantages are potential fluid imbalance due to large volumes filtered *CAV or CVV haemodialysis i. 5. is only 50 ml/min haemofiltration *CAV or CVV + HF uses ultrafiltration only to remove solvent & solute filtrate replacement either pre/post-filter pre-filter dilution may increase urea clearance up to 20% results in better CVS stability.minimize extracorporeal blood volume c. b. synthetic ≥ BSA x 0.slow continuous ultrafiltration usually only used for excess fluid removal clearance of urea. with 3000 ml/hr filtrate. 3. surface area material i. continuous most commonly used in ICU haemodiafiltration peritoneal dialysis *CAV or CVV + HD = dialysis + ultrafiltration → CVVHD 2. + HDF Filter Membranes a. cellulose acetate . geometry i. see later major advantages are simplicity.polymethylmethacrylate (PMMA) . driven by the hypdrostatic & osmotic pressure difference across the membrane 1. cellulose ii.polysulphone.polyacrylnitrile (PAN) . hollow fibre ii. polyamide.

fluid overload creation of "fluid space" for TPN.A. slow electrolyte removal large volumes removed systemic anticoagulation thrombocytopaenia technical difficulties i.. 3. 2. i. J.albumin replacement avoids rises in ICP with haemodialysis 3. 6. thrombosis iii. 4. ABP. g.ICU . haemorrhage. 5. renal and hepatic failure metabolites ii. electrolyte & acid-base abnormalities ii. → ↓ platelet sequestration ↓ neutrophil activation ↓ IL-1 production from monocytes higher hydraulic permeability. infection iv. 4. access ii. 5. c. Problems 1. drugs. b. more effective solute clearance longer filter life more rapid resolution of ARF & lower mortality (Hakim et al. d.Neph.potential for hypo/hypervolaemia 40 .Genitourinary Membrane Selection synthetic membranes a. e. mediators of systemic inflammatory response syndrome maintenance of oncotic pressure . cardiovascular stability correction of.Soc. 2. etc low & middle MW molecule clearance i. f. 1994) ∴ preferred for HF Haemofiltration Advantages 1. other complications .

82 mmol/l 10. 6. ∴ solutions should be avoided in hepatic failure bicarbonate solutions result in fewer problems.pumped . increase filter blood pressure / flow pre-dilution ultrafiltrate "suction" counter-current dialysate plate filter . however Ca++ & Mg++ cannot be added directly Gambro Solution #1 1. d. Na+ ClK+ Ca++ Mg++ lactate glucose 140 mmol/l 102 mmol/l 1. intermittent vs continuous CAV vs CVV anticoagulation *vascular access Dialysate acetate or lactate are added due to poor stability of bicarbonate in solution normal individuals can metabolise up to 300 mmol/hr of acetate. headache. 3. c. e.ICU . haemodialfiltration . 8.ie. dizziness. b.short. ∴ predominantly ionized * both D & L-lactate 0.0 1. c. 4.6 45 mmol/l mmol/l mmol/l * no protein. 2. nausea hypoxia hypotension NB: ∴ lactate often used in critically ill lactate metabolised mainly in the liver. largely in skeletal muscle this is significantly reduced in critically ill patients high acetate levels → a. wide-bore lines . 3. 7. 5.9 mmol/l osmolality 285 mosmol/kg 41 .Genitourinary Methods to Improve Clearance a.non-classical haemoperfusion Haemodialysis 1. fatigue. 2. b.

antibiotics aminoglycosides most cephalosporins & penicillins . c. e. meprobamate .aspirin. quinidine.procainamide.methyldopa . d.lactic acid.from lactate/acetate subsequent hypoventilation membrane dependent mechanisms . uric acid.ICU . agitation.phenobarbitone . etc.Genitourinary Disequilibrium usually patients with moderate to severe azotaemia dialysed too rapidly results in cerebral oedema due to rapid reduction in ECF urea with insufficient time for diffusion causes headache. d. f. cimetidine b.diazoxide. nitroprusside .alcohols.not cefamandole or cloxacillins metronidazole.C' activation. sulphonamides some anti-TB drugs acyclovir hypnosedatives antiarrhythmics antihypertensives . dizziness. seizures and coma Hypoxaemia occurs during the first 1-2 hrs. b. theophylline (?). Compounds Removed by Haemodialysis a. chloramphenicol. paraquat . others 42 . N&V.lithium. platelet activation. endogenous metabolites. usually more marked with acetate ? because greater capacity for metabolism a. disopyramide . c.immunosuppressive agents . loss of CO2 in the dialysate consumption of CO2 with regeneration of HCO3. etc.

neutrophil activation . Conventional Dialysis Techniques Advantages 1.↑ shunt fraction . 3.500 < 40. 5. disequilibrium syndrome blood loss vascular access equipment trained personnel Dialytic Therapies Mode Blood Flow ml/min 1250 200-300 100-200 150-250 150-250 15-30 15-30 500 Dialysate Flow ml/min Cl-MW D < 50.000 < 5.rapid electrolyte shifts 3. 2. CAVHD cardiovascular stability better middle molecule clearance no disequilibrium syndromes technical .platelet margination . haemodynamic instability hypoxia .less expensive . 4.000 < 1. 2.5 2-7 20-30 2-12 2-12 Kidney HD1 CAVHF CVVHD CVVHDF 1 conventional 4 hr haemodialysis averaged over 24 hours 43 .training of personnel Conventional Haemodialysis Problems 1. 7.Genitourinary CAVH vs.000 < 40.000 Cl-urea ml/min > 60 150 7-15 15-30 15-30 Fluid loss litres 1. 6. 4.ICU . less equipment .simpler.rapid fluid shifts .

abdominal drains. 3.intra-abdominal infection . drains .recent surgery .peritonitis .markedly hyperosmolar dialysate fluids Problems 1. c. 2. 4. e.ICU . . difficult insertion haemorrhage bowel perforation drainage failure difficult/contraindicated with . slow fluid and solute removal less predictable effect catheter related infection drainage failure respiratory embarrassment hyperglycaemia protein loss difficult/relatively contraindicated with .previous surgery.peritonitis Other Complications a. c. etc. a.especially in children 44 . b. 6.Genitourinary Peritoneal Dialysis used for both acute and chronic renal supplementation technical difficulties.↓ FRC .abscess . catheter related infection respiratory embarrassment . b. 7. adhesions Efficiency a.recent surgery. d.pleural effusion . 5. slow fluid and solute removal less predictable effect than other dialytic therapies hyperglycaemia protein loss Peritoneal Dialysis . b. 8. d.

3.↑ glucose. urate. TG . GFR ~ 15-20% 45 .K+. tyrosine.probably only a "marker" in CRF . b. 4. phenylalanine d.MW's ~ 300-3500 . creatinine . 2. PRL Clinical Effects a. insulin .mild elevation of creatinine (∝ 1/GFR) . HPO4= & urate rise as GFR < 25% c.asymptomatic . urea polypeptide "middle molecules" guanine derivatives . LH.PTH .Genitourinary CHRONIC RENAL FAILURE Common Causes 1. CVS.↑ creatinine.guanidine.creatine. nocturia . CNS complications . c. methyl/dimethyl-guanidine .tryptophan. e.polyuria.anaemia .metabolic acidosis .guanidosuccinic acid . diabetic nephropathy hypertension glomerulonephritis polycystic kidney disease analgesic nephropathy ~ 28% ~ 24% ~ 21% Retained Potentially Toxic Metabolites a. urea .glucagon. g.fluid overload .GH. 5.ICU . b.GIT. f. nucleotide metabolites aromatic amino acid derivatives aliphatic amines elevated hormone levels .overt renal failure .hypertension . GFR ~ 50% GFR ~ 25-30% .

anaemia.ICU . growth and sexual dysfunction v. fatigue. GIT haemorrhage vii. hypocalcaemia glucose intolerance ii. dialysis dementia ? aluminium toxicity from older filters v. muscle cramps iii. splenomegaly. seizures vii. coma iv. hyperuricaemia. accelerated atherosclerosis viii. ecchymoses x. CCF. hypertension. ascites viii. protein. hypotension ii. 2° hyperparathyroidism ii. fluids & electrolytes Na+ & fluid overload metabolic acidosis hyperkalaemia. uraemic lung v. cardiomyopathy ix.Genitourinary Clinical Features 1. low complement 2. hyperlipidaemia iii. paralysis. coagulopathy. anorexia. myoclonus. nausea. gastroenteritis vi. atherosclerosis vi. peptic ulcers xii. hypothermia. renal osteodystrophy. immunosuppression xi. calorie malnutrition iv. lymphopaenia. restless leg syndrome those "exacerbated" by haemodialysis i. pallor. muscle irritability. hepatitis. those corrected by dialysis i. vomiting. asterixis. peripheral neuropathy vi. hypersplenism xiii. disequilibrium syndrome (cerebral oedema) iv. platelet dysfunction those which may be unchanged by dialysis i. pericarditis. pruritus. intracellular potassium deficit hyperphosphataemia. 46 . neutropaenia. c. lethargy iii.

impaired Na+/K+-ATP'ase activity hypothermia. d. c.steroids. c. lymphopaenia. lymphoid atrophy normal neutrophil number but impaired chemotaxis decrease in acute inflammatory response & delayed hypersensitivity ↓ IgG and complement levels drug immunosuppression . e. normal cholesterol . b. b. b. insulin resistance protein intolerance high TG. e.ICU . d.hyperglycaemia. occasionally ketosis Immunosuppression a. cyclosporin Coagulopathy a.Genitourinary Metabolic Effects a. c. ↓ BMR glucose intolerance. impaired platelet function low levels of PAF III impaired prothrombin activity ? guanidosuccinic acid 47 .

pericarditis .neuropathy .barbiturates. c.6-0. methanol . ethanol. progression of CNS disease . drug intoxication iii.or rapidly increasing pH < 7. hypertension . short term dialysis i. awaiting transplantation 48 .uraemic symptoms ii.salicylates. other therapy i.uncontrolled hyper-Ca++/K+ b. failed conservative management ii.6 mmol/l [urea] > 40 mmol/l.ICU . creatinine > 0. symptomatic renal failure .or associated with arrhythmias . progression of bone disease v. biochemical chronic dialysis i. fluid overload ii.Genitourinary Indications for Dialysis a.8 mmol/l iii. uraemic pericarditis vii.metabolic acidosis . or rapidly increasing .theophylline . GFR < 3 ml/min iv.15 [Cr] > 0. lithium .encephalopathy vi.CCF.0 mmol/l . acute biochemical alterations [K+] > 7.

bacterial .EBV.SLE. drugs 49 . 6.heroin b.diffuse .β-haemolytic Streptococci. minimal lesion membranous focal glomerulosclerosis proliferative GN . viral c.heavy proteinuria. 4.very rarely . acute nephritic syndrome nephrotic syndrome chronic renal failure loin pain constitutional features of CRF acute oliguric renal failure . mumps .shistosomiasis .no cellular proliferation Implicated Antigens a.varicella.rapidly progressive . presentation may be fulminant or indolent Histological Presentation a.malaria .chronic endothelial .penicillamine . 2. c.HBV .Genitourinary GLOMERULONEPHRITIS Clinical Presentation 1.ICU ."normal" LM presentation . b. rbc casts . d. PAN. oedema . SS . hypoalbuminaemia.syphilis .hypertension. oedema * ie.mesangial . protozoal d.TB . Coxsackie B .proteinuria. haematuria. Staphlococci . 3.toxoplasmosis .Salmonella .focal .cryoglobulins . autoimmune e. 5.thyroiditis .

ICU - Genitourinary
Def'n: disease of unknown aetiology with target organ dysfunction secondary to marked platelet aggregation in the microcirculation (Dabrow & Wilkins 1993) TTP first described by Moschocowitz in 1925 HUS first described by Gasser et al. in 1955 now considered different expressions of the same underlying disease process known associations, a. infection, septicaemia * feces for pathogens i. children - especially Shigella sp., Salmonella ii. adults - enterohaemorrhagic E. coli - VTEC 0157:H7 produces vero cytotoxin - pneumococcal infection iii. viruses - Coxsackie, echoviruses drugs pregnancy radiation autoimmune disorders - SLE, scleroderma - OCP, cisplatin, mitomicin C, cyclosporin A malignant hypertension

b. c. d. e. f.

Pathogenesis plasma contains a transmissible factor which aggregates platelets this is not complement or antibodies unknown mechanism results in widespread endothelial damage (key lesion) → release of HMW-vWF → platelet aggregation excess ULvWF, possible due to missing enzyme in its processing, eg protease inhibitor multi-organ infarction / ischaemia, mainly renal in HUS arterioles filled with hyaline thrombosis(fibrin & platelets) diarrhoea negative HUS, frequently associated with severe pneumococcal infection characteristically become far more ill than the E.coli associated HUS mechanism is felt to be due to exposure by neuraminidase producing strains of pneumococcus of a usually hidden T antigen (Thomsen-Friendenreich antigen) found on platelets, red cells and endothelial cell surfaces most people have naturally occuring antibodies to this T "cryptantigen", which rapidly leads to the damage associated with HUS. avoid transfusing serum in any form (no FFP/cryo) unless exsanguinating, and wash all RBC's this will avoid giving the patient a fresh new supply of IgM to bind and damage the cells with T antigen still available


ICU - Genitourinary
Clinical Features a. b. c. d. e. f. g. h. fever nausea, vomiting, diarrhoea, abdominal pain arthralgia bleeding, petechiae renal failure & uraemia jaundice rarely hepato/splenomegaly cerebrovascular events → → - especially in TTP children & more severe renal failure fever & CNS signs are usually absent young female, adults & more thrombotic events, especially CNS

NB: HUS usually TTP usually

Laboratory a. microangiopathic haemolytic anaemia anaemia, fragmented rbc's, reticulocytosis thrombocytopenia ↓ haptoglobin, ↑ haemopexin, haemalbumin present normal coagulation profile hyperbilirubinaemia, ↑ LDH ANA ~ 20% +'ve biopsy → characteristic vascular changes skin, mucous membranes, gingiva, renal - c.f. DIC - isolated deficiencies may occur

b. c. d. e.

Diagnosis 1. 2. 3. 4. 5. anaemia - microangiopathic picture

evidence of haemolysis severe thrombocytopaenia uraemia normal coagulation profile and absence of FDP's


ICU - Genitourinary
Treatment Modalities 1. routine management of, i. anaemia ii. renal failure iii. hypertension iv. electrolyte & fluid balance early, uncomplicated disease → prednisolone severe disease i. plasmapheresis ii. plasma transfusion iii. vincristine for refractory TTP/HUS iv. high dose IgG inhibits platelet aggregation v. splenectomy antiplatelet drugs not effective

2. 3.


Prognosis usually lasts days → weeks, rarely months fatal if left untreated, but treatment is effective in most Hayward et al. 1994, a. b. c. d. remission late TTP/HUS related problems ESRF relapse ~ 96% ~ 50% ~ 8% ~ 21%


angiotensin II. g. c. 3. without obvious other cause. hypotension hypervolaemia decreased response to vasopressors high circulating renin. 5. intrarenal PG's protect GFR against high circulating angiotensin/aldosterone Precipitating Factors 1. 3.ICU . i. low cardiac output. aldosterone these may decrease with the onset of HRS increased renal excretion of noradrenaline & TBXB2 decreased renal production / urinary excretion of PGE2 normally increased in cirrhosis with ascites ie. i. where both liver and kidneys are primarily affected by the underlying disease process Clinical Features a. 4. usually occurs with. fulminant hepatic failure paracentesis diuretics NSAIDs sepsis . e. b. 1. mortality ~ 95% * recovery associated with improvement of liver function oliguric renal failure with H2O/Na+ retention high urine osmolality with [Na+] < 10 mmol/l low SVR. h. characterised by. syndrome associated with ascites! ? intravascular volume depletion ? impaired renal PG synthesis ? relative hypovolaemia ? chronic endotoxaemia 53 . chronic alcoholic cirrhosis ii. ? probably marker only. f.any cause 2.Genitourinary HEPATORENAL SYNDROME Def'n: potentially reversible renal failure associated with severe liver failure. d. 2. oliguria with low urine Na+ high urine osmolality but unresponsive to fluids / inotropes may progress to ATN NB: this is distinct from pseudohepatorenal syndrome.

improved filtration with FFP or AII infusion ? opposite of arteriolar vasodilatory mechanism . ↓ "glomerulopressin" Intra-Abdominal Hypertension increased renal vein pressure improved filtration with paracentesis + colloid or peritovenous shunt 54 . synthesised in the liver . ADH → intense renal vasoconstriction Na+ & H2O retention worsen oedema and ascites the kidneys respond with ↑ PG synthesis (vasodilatory) which delays the onset of ARF this accounts for the marked sensitivity to NSAID's and other PG inhibitors Secondary Tubular Dysfunction the disorder is completely reversible with return of liver function successful transplantation of HRS kidneys the enzymuria & β2-microglobinuria seen in HRS is not seen in ATN or pre-renal failure however.low renin substrate in HRS .reduces afferent aa. MW ~ 500. absence of histological tubular damage in some studies other studies show ATN-like changes. b.cf.fall in substrate & enzyme activity .synthesis blocked by NSAID's ↓ renin-angiotensin activity d. c.hormone . bile vacuoles in tubular cells and hypertrophied JGA Mediator Imbalance xenon studies show maldistribution of RBF a. normal in ATN ? 1° or 2° to hypovolaemia & high circulating catecholamines * little evidence to support this (Maxwell & Kleeman) . tone and increases GFR .increased by AA infusion & glucagon . ↓ PGE2 ↑ TBXA2 → renal cortical hypoperfusion .ICU .Genitourinary Proposed Mechanisms Arteriolar Vasodilatation Hypothesis 1988 intense arteriolar vasodilatation 2° to hepatic failure → arterial underfilling distinct from hypovolaemia → ↑ PRA / AI&II / aldosterone ↑ NA.

levels are only marginally reduced . g.levels correlate poorly with the degree of Na+ retention high renin-angiotensin II ? aldosterone chronic endotoxaemia Treatment a. c. c. 1.dopamine . f.infusion does not improve filtration .Genitourinary High SNS Tone & Reversible Cortical Ischaemia probably not involved. fall in ANF . 2.marked hypotension . 3. i. b.no increase in GFR * no lasting effect lumbar sympathectomy 55 . optimise volume status ii. largely supportive → prevention i.ICU . j. treat septicaemia iii. e. a. avoid nephrotoxic agents paracentesis + FFP | Albuminex-20% peritoneovenous (LeVeen) shunt ↑ preload. vasodilators vasopressors A-II inhibitors Ca++ entry blockers PGE2 infusion TBXB2 inhibitors water immersion dialysis plasma exchange .increases venous pressure . other modalities tried with little or no success. h. d. cardiac output ↑ RBF.transient improvement . 4. GFR high operative mortality may result in marked thrombocytopaenia no improved survival liver transplant b. d.

crush injuries | compartment syndromes ii. LSD. associated with the excretion of myoglobin in the urine Aetiology 1. 3. trauma / ischaemia / exhaustion i. hypokalaemia. 4. McArdle's syndrome familial myoglobinuria 2.Genitourinary RHABDOMYOLYSIS Def'n: the disintegration or dissolution of muscle. overuse prolonged exercise. myxoedema. heroin overdose of any sedative agent & pressure effects vii. electric shock v. Legionaires' disease metabolic defects i. gas gangrene iii. burns iv.alcohol.ICU . arterial embolism | thrombosis. NB: systemic release of myoglobin by itself is not nephrotoxic. drug induced suxamethonium in myopathic disorders myopathy . however when combined with hypotension and renal hypoperfusion may result in ATN 56 . severe hypophosphataemia.aminophylline. viral myositis ii. thyrotoxicosis iii. pretibial syndrome status epilepticus tetanus delerium tremens infection / inflammation i. acute polymyositis iv. amphetamines . phencyclidine. envenomation viii. salicylates. torniquets. antishock trousers iii. hyperthermic syndromes heat stroke malignant hyperthermia malignant neurolept syndrome vi. hyperosmolality ii.

2.Genitourinary Investigations 1. 4. hyperkalaemia hyperuricaemia ↑ LDH. activation of renin-angiotensin system.30 mmHg → fasciotomy 2.ICU . Management 1. muscle compartment pressures normal < 10 mmHg if > 30-40 mmHg. AST CK-MM > 5x or greater metabolic acidosis thrombocytopaenia & haemoconcentration myoglobinuria false negative tests may occur in up to 36% of cases both haemoglobin & myoglobin test positive to urine "dipstick" 3. or > BPDias . 4. hyperphosphataemia. 2. ∴ reducing cast formation animal studies showing reduction in ATN like mannitol. Crush Injuries & Renal Failure 1. aggressive IVT to support intravascular volume & urine output saline loading → prevent hypovolaemia / dehydration mannitol theoretically increases proximal tubular flow & reduces effects of pigmenturia supported by some animal data on nephrotoxic models supported by the "Israeli" school but no controlled trials to support use human trials in prevention of angiographic dye ARF worsen outcome bicarbonate alkalinisation of urine improves solubility of myglobin. ↑ catechoamines & ADH nephrotoxicity of myoglobinuria & uricosuria potentiated by acidifcation & concentration in tubules acute increase in plasma Ca++-PO4= product may result in suppression of renal function microthrombi in renal vasculature 57 . no controlled trials to support use acetazolamide 3. 3. early. biochemistry hypocalcaemia.

ICU . Israel (Nephron 1990) early aggressive volume replacement.if plasma pH > 7.due to enhancement of metastatic calcification claimed improvement in survival against historical controls no prospective randomised study to support this protocol almost certainly associated with electrolyte disturbances 58 .4% @ 500 ml/hr 12 l/day → 600g dextrose = 840 mmol NaCl + 120 g mannitol acetazolamide 2.Genitourinary Management 1. .45 .saline or Ringer's lactate @ 1500 ml/hr adult @ 20 ml/kg/hr child forced mannitol-alkaline diuresis 5% Dextrose + NaCl 70 mmol + mannitol 20% + bicarbonate 8. preferrably at the scene of injury immediate resuscitation N. 50 ml 50 ml = 10g = 50 mmol 2400 kcal 600 mmol NaHCO3 3.

d.0 mmol/kg/day → ↓ CO2 production in GIT or.RTA a combination of type I & type II RTA (very rare. chronic acidaemia → ↑ Ca++ excretion ii. nephrocalcinosis.ICU . b. c. vit.reabsorption (reduced TM) mild low anion gap acidosis. impaired HCO3. Na+/K+-citrate large K+ supplement usually not required Type II Proximal RTA generalized tubular disorder.Genitourinary RENAL TUBULAR ACIDOSIS Type I Distal RTA inherited as an autosomal dominant.D deficiency. also have amino aciduria and phosphaturia treatment need only be commenced when the [HCO3-] < 18 mmol/l → NaHCO3 ~ 5-10 mmol/kg/d + K+ supplement Type III . rickets . low anion gap acidaemia hyperchloraemia and hypokalaemia urine pH > 5. c. or excrete daily acid load Clinical Features a. even after acid load absence of urinary infection . b.4. calculi ~ 60-70% iv. possibly doesn't exist!) 59 .especially children Treatment a. NaHCO3 ~ 0.pH < 7.35 complications i. "classic" RTA inability to maximally acidfy the urine.5-2.NH4Cl ~ 100 mg/kg . osteomalacia. may be congenital or acquired reduced H+ secretion. 2° hyperparathyroidism iii.

diabetic nephropathy hypertensive nephrosclerosis chronic tubulointerstitial nephropathies also seen in Addison's disease & advanced age NB: hyperkalaemia inhibits renal tubular generation of ammonia.5 < 10% high no no low low for pH < 4 mmol/kg 60 . thereby reducing urinary buffer and worsening the acidosis Renal Tubular Acidosis Type I "site" of lesion low anion gap acidosis minimum urine pH % filtered HCO3.ICU .excreted plasma K+ Fanconi syndrome nephrocalcinosis / stones daily H+ excretion ammonium excretion daily HCO3.replacement distal yes > 5.RTA the urine acidifies during periods of marked acidaemia.5 < 10% low no yes low high for pH < 4 mmol/kg Type II proximal yes < 5. 3.Genitourinary Type IV . however there is hyperkalaemia metabolic acidosis may be associated with hypotension usually seen with hyporeninaemic hypoaldosteronism. 1. 2.5 > 15% low yes no normal normal > 4 mmol/kg Type IV distal yes < 5.

D Distal 1. isolated HCO3.amphoterecin B. 2. analgesic nephropathy. hyperparathyroidism .drug induced. amyloidosis. 1° hyperparathyroidism drugs . hereditary defects . toxic damage heavy metals . immunologic autoimmunopathy .myeloma. MGUS iv. paraquat iii. GI disorders . defect in NH3 generation ↓ ATP synthesis inhibition of glutamine metabolism decreased availability of glutamine fuel competition ii. cf ospeoporosis hyperkalaemia generalised proximal tubular defect i. dysproteinaemias .m.Fanconi-like syndromes ii.wasting i. RA renal transplantation interstitial nephritis v. Hg drugs . or produce the disease medullary sponge kidney.Genitourinary Causes of RTA Proximal 1. idiopathic nephrocalcinosis chronic hydronephrosis.sporadic low carbonic anhydrase activity . . 6-mercaptopurine.deficiency. iii. acetazolamide .Pb.ketoacidosis.ICU . As. lithium low NH3 availability i.CAH. idiopathic nephrocalcinosis *may be a result of. defect in NH3 transfer interstitial nephritis hyperkalaemia 3. idiopathic ii. or resistance to Vit. renal transplantation hyperthyroidism.deficiency of.hyperkalaemia . 2.1° hyperparathyroidism . . TPN 61 .genetic / hereditary .aminoglycosides. 4. SLE.malnutrition.

combined with cortisol Addison's disease. drugs mineralocorticoid resistant hyperkalaemia i. idiopathic bilateral adrenalectomy bilateral adrenal destruction . isolated aldosterone deficiency cortisone methoxidase .haemorrhage. familial transient hypoaldosteronism of infancy chronic idiopathic hypoaldosteronism heparin induced secondary hyporeninaemic hypoaldosteronism i.usually results in hyperkalaemia ii.Genitourinary 5. drugs spironolactone amiloride. primary aldosterone deficiency i. triamterene 2. chloride shunt .ICU . pseudohypoaldosteronism . H backleak hereditary disorders drugs . infection. tubulointerstitial nephritis iii.hypervolaemic iv.amphoterecin B Hyperkalaemic RTA 1. generalised DT dysfunction obstructive nephropathy sickle cell disease. diabetes mellitus ii. 3. tumour. amyloid interstitial nephritis ii. nephrosclerosis iv. 62 . infiltration congenital enzyme defects ii. low H+ secretion i. H+-pump defect interstitial renal disease low aldosterone activity . voltage defect low Na+ delivery inhibitors of Na+ reabsorption low aldosterone activity + iii.hypovolaemic iii.types I & II.

antagonise aldosterone . b. angiotensin I/II & aldosterone secretion normal BP decreased vascular response to noradrenaline & angiotensin II§ hypokalaemia ± alkalosis ± hypomagnesaemia weakness & periodic paralysis polyuria ∝ nephrogenic DI overproduction of prostaglandins → altered Na+/K+ handling NB: the principal defect is reduced NaCl absorption in the thick ascending LOH → volume depletion & TGF → ↑ renin-angiotensin-aldosterone increased NaCl delivery to the late DT. ↓ vasopressor activity of angiotensin-II .↓ angiotensin II .ICU . e. b.↓ renin release . c. d. 2. ibuprofen .indomethacin. with raised aldosterone. 4. a.? diminished by downregulation vasodepressor actions of PGE2 & bradykinin → → ↑ renal kallikrien ↑ plasma bradykinin Treatment a. 3. oral K+ / Mg++ supplementation propranolol / atenolol captopril spironolactone PG synthesis inhibition ~ opposite to RTA . autosomal recessive .frequently symptomatic in childhood renal juxtaglomerular apparatus hyperplasia high plasma renin activity. produces severe K+ wasting defective function of TA-LOH results in hypomagnesaemia & exacerbation of K+ wasting hypokalaemia → ↑ PGE2.aspirin NB: → 63 .Genitourinary Bartter's Syndrome 1. PGI2 → further increase in renin secretion angiotensin-II & aldosterone normal BP reflects. 5.

ICU .chlorpromazine .CCF.Bartter's syndrome . drugs Angiotensinogen an α 2-globulin. glycoprotein. enalpril. steroids with glucocorticoid effect oestrogens. c. a.captopril.diuretics . b.α/β-adrenergic blockers . 3. acts to cleave the Leu-Leu bond in angiotensinogen to form angiotensin I plasma elimination half life.pre-renal ARF .renovascular disease . synthesised by the liver ? also synthesized locally by the macula densa for local release angiotensin I is formed from the 10AA at the amino terminus production is increased by.β1-agonists .tubuloglomerular balance .chronic liver disease . a.at the macula densa low angiotensin II level .most anaesthetic agents . saralasin . total body Na+ deficit upright posture disease states .OCP d. hypovolaemia. 2. 4.Angiotensin System Renin a glycoprotein acid protease released by the juxtaglomerular apparatus MW ~ 40000. b. t½β ~ 15-30 min stimuli to release include. increased sympathetic tone increased Cl.theophylline .Genitourinary Renin . 1.reduced -'ve feedback on JGA reduced hydrostatic pressure in the afferent arteriole common clinical stimuli include. pregnancy effectively "renin substrate" levels may be derranged in hepatorenal syndrome 64 .vasodilators . hypotension .

Genitourinary Angiotensin II produced by cleavage of 2AA from angiotensin I by ACE in the lung. ie. d. t½β ~ 1-2 min inactivated by many different enzymes in many tissues including RBC's actions include. c. ∴ ↑ GFR/RBF ratio ↑ renal PGI2 production counteracts adverse renal effects and maintains RBF negative feedback on renin release at JGA aldosterone release from ZG of adrenal cortex facilitation of SNS via presynaptic AII receptors weak direct inotropic and chronotropic effects hypothalamic CNS effects i. i. and splanchnic circulation less effect on cerebral. 8AA peptide hormone ? ACE also present in the kidney plasma elimination half life. ↑ SNS discharge ii. ↑ ADH release Angiotensin III produced by cleavage of 1AA from angiotensin II more potent aldosterone release than angiotensin II vasoconstrictor effects more potent on the arterial beds of the kidney. muscle. e. b. f.inhibited by saralasin ↑ efferent > afferent arteriolar tone in the kidney ↓ GFR and ↑ Na+ reabsorption through GTB → → ↓ RBF > GFR. thirst stimulation iii. potent vasoconstrictor (2nd to endothelin). g. a. h.ICU . skin. coronary and pulmonary circulations 65 .

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