Ch31. Renal Physiology

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Ch31. Renal Physiology Anesthesia

• R1 ???

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• Play a vital role
• Regulating the volume composition of body
  fluids
• Eliminating toxins
• Elaboratine hormones (renin, erythropoietin,
  active form of vit.D)
• Major causes of postop. morbidity mortality
• Fluid overload
• Hypovolemia
• Postop. renal failure

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THE NEPHRON
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The Glomerular Capillaries

• Glomerulus Bowmans capsule ?? tufts of
  capillaries? ??
• Single afferent arteriole, single efferent
  arteriole
• Mesangial cells regulation of glomerular
  filtration
• Contractile prot. vasoactive substances? ??
• Mesangial cell? ???? glomerular filtration ??
• Response to angiotensin II, vasopressin,
  norepinephrine, histamine, endothelins,
  thromboxzne A2, leukotrienes, prostaglandin F2,
  platelet-activating factor
• Relax ?? filtration ???
• Response to atrial natriuretic peptide(ANP),
  prostaglandin E2, dopamine
• Secrete various substances
• Take up immune complexes
• Filtration pr. ??? afferent efferent arteriolar
  tone? ??
• ?? plasma? 20? filter?

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Sodium reabsorption in the nephron

• Bowmans capsule?? ultrafiltrate ?? 65-75?
  reabsorbed

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The Proximal Tubule

• Na-K-ATPase? ?? tubular cell??
  capillaryf?actively transported out
• Tubular fluid??? Na? passive movement ??
• Angiotensin II, norepinephrine? Na reabsorption
  ??
• Dopamine, fenoldopam? proximal reabsorption ????
• Na reabsorption? ?? solute? reabsorption? H
  secretion ???
• Chloride reabsorption? tight junction ?? ?? ??
  passive ?? concentration gradient ??
• Secreting organic cations and anions
• Cations creatinine, cimetidine, quinidine
• Anions urate, ketoacids, penicillins,
  cephalosporins, diuretics, salicylates, most
  x-ray dyes
• ??? secretory mechanism? ??
• Major role in elimination of many circulating
  toxins

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The Loop of Henle

• Hypertonic medullary interstitium ??, ability to
  concentrate urine
• Filtered sodium load? 15-20 reabsorb
• Ascending thick segment ???? ??? ????? ??
  passive?? ????
• Ascending thick segment
• Na ???? K Cl- ???? directly coupled
• Tubular fluid? Cl-? rate-limiting factor
• ?? ??? ?? water impermeable
• Loop of Henle ??? tubular fluid?
  hypotonic(100-200mOsm/L), interstitium?
  hypertonic ??
• Countercurrent multiplier mechanism

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The Distal Tubule

• Only minor modifications of tubular fluid
• Major site of parathyroid hormone- vitamin
  D-mediated calcium reabsorption

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The Collecting Tubulea. cortical collecting
tubule

• Principal cells (P cells)
• Secrete potassium
• Participate in aldosterone-mediated Na
  reabsorption
• Na? ????? Cl-? ?????? K? ????? ?
• Aldosterone? Na-K-ATPase? H-secreting ATPase?
  enhance ??
• Intercalated cells (I cells)
• Acid-base regulation

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b. medullary collecting tubule

• Principal site of action for ADH(antidiuretic
  hormone)
• Luminal memb.? water permeability? ADH ????? ????
  ????
• Dehydration? ADH ??? ???? luminal memb.? water
  permeable?? ??
• ? Concentrated urine is produced
• Maintaining a hypertonic medulla
• Cortical collecting tubule? urea? ?? freely
  permeable
• Medullary collecting tubule? ????? impermeable
• ADH??? medullary collecting tubule? innermost
  part? urea? ?? permeable ??
• Water? collecting tubule?? ????? urea? highly
  concentrated ?
• Urea? medullary interstitium ??? diffuse out??
  tonicity? ???

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The Juxtaglomerular Apparatus

• Specialized segment of afferent arteriole
• Juxtaglomerular cell
• Renin ??, sympathetic nervous system? ???
• Release of renin? ß1-adrenergic sympathetic
  stimulation? afferent arteriolar wall pr. ???
  ????
• Liver?? angiotensin I?? ???
• ?? Lung?? ACE(angiotensin-converting enz.)? ??
  angiotensin II? ??
• BP ??? aldosterone secretion? major role
• End of thick, ascending cortical segment of loop
  of Henle (macula densa)

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THE RENAL CIRCULATION
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THE RENAL CIRCULATION

• Renal function? ?? renal blood flow? ???
• ????? ???? ?? ???? ??? ??
• Total cardiac output? 20-25? ??
• RBF? ? 80? cortical nephron?? ?? 10-15??
  juxtamedullary nephron?? ?
• Medulla? oxygen tension? 15?Hg? ??? ischemia ???
  ??

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RENAL BLOOD FLOW GLOMERULAR FILTRATION

• Clearance
• ?????? completely cleared?? ???
• Renal blood flow
• PAH(p-aminohippurate) one passage through
  kidney ??? ??? cleared ?
• Glomerular filtration rate
• GFR? ????? RPF? ? 20
• Clearance of inulin ??
• ??? filteredehl?? secret? reabsorb ?? ??
• GFR? ???
• ?? 120 25 ?/min
• ?? 95 20 ?/min
• Creatinine clearancefh ?? ???? ?? ??
• Overestimation ?? ?? ??

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Control Mechanisms

• Intrinsic regulation
• BP 80-180?Hg ???? RBF? autoregulation ??
• BP ??? ?? afferent arteriole? intrinsic myogenic
  response
• Mean systemic arterial pr.? 40-50?Hg ??? ??
  glomerular filtration? ??
• Tubuloglomerular balance feedback
• Renal tubular flow rate? ???? GFR? ??
• Macula densa? afferent arteriolar tone?
  glomerular capillary permeability? ????
• Angiotensin II? ??? ??
• Pressure natriuresis, BP ??? ?? sodium
  reabsorption? ?? ?? tubuloglomerular feedback?
  ???? ??

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Control Mechanisms (2)

• Hormonal regulation
• Afferent arteriolar pressure? ??? renin release?
  angiotensin II? ??? ??
• Angiotensin II? ???? ????? ??? 2???? RBF? ????
• Afferent, efferent arteriole? ?? ????? efferent
  arteriole? ?? ??? ??? GFR? ??? ???
• Vasodilating prostaglandin(PGD2, PGE2, PGI2)?
  renal sysnthesis? systemic hypotension? renal
  ischemia? ??? protective mechanism
• ANP direct smooth muscle dilator
• Antagonize the vasoconstrictive action of
  norepinephrine angiotensin II
• Afferent arteriole? dilation??? efferent
  arteriole? constriction ?? ????? GFR? ????
• Neuronal regulation
• Dopamine fenoldopam? D1-receptor activation? ??
  afferent efferent arteriole? dilation
• Fenoldopam low-dose dopamine infusion?
  norepinephrine-induced renal vasoconstriction?
  reverse

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EFFECTS OF ANESTHESIA SURGERY ON RENAL FUNCTION
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1. RBF, GFR, urinary flow, sodium excretion?
   reversible decrease ??
2. Regional anesthesia? ? ????
3. ??? ??? ???? indirectgka (by autonomic and
   hormonal influence)
4. ??? intravascular volumer? ?? ?? ??? ??? ??? ? ??

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INDIRECT EFFECTS

• Cardiovascular effects
• ??? ????? cardiac depression or vasodilation ???
  ????? ???? ? ??
• Regional anesthesia? sympathetic blockade? ??
  hypotension ?? ??
• BP? autoregulation ??? ?? ???? RBF, GFR, urinary
  flow, sodium excretion ???
• IV fluid? hypotension?? ?? ??
• Neural effects
• Light anesthesia, intense surgical stimulation,
  tissue trauma, anesthetic-induced circulatory
  depression??? sympathetic activation ?? ??
• Endocrine effects
• ???? endocrine change? stress response? ???
• Catecholamines, ADH, angiotensin II? ?? RBF? ????
• Aldosterone sodium reabsorption ???? sodium
  retention, ECF ?? ? ??
• ADH? water retention ??? ? ??

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DIRECT ANESTHETIC EFFECTS

• Volatile agents
• Halothane, enflurane, isoflurane renal vascular
  resistance ????
• Methoxyflurane
• Syndrome of polyuric renal failure? ??
• Metabolic degradation? fluoride ions release ??
  dose related
• Plasma fluoride concentration? 50µ?/L ??? ??
• 1 MAC ???? 2?? ??? high incidence
• Defect in urinary concentrating ability
• Enflurane, possibly sevoflurane? ??? ??? ????
• Preexisting renal impairment may be more
  susceptible
• Obese Pt., isoniazid ???? Pt. ?? enflurane ???
  ??? high plasma fluoride concentration ?? ??
• Renal dysfunction? incidence ??? ???? ??
• Compound A
• Breakdown product of sevoflurane low flow? ???
• ??????? renal damage? ????? ?????? ???? ??
• Sevoflurane ??? fresh gas flow? ?? 2L/min ?? ??? ?

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DIRECT ANESTHETIC EFFECTS (2)

• Intravenous agents
• ?-adrenergic blocker (droperidol ?)
• Catecholamine-induced redistribution of RBF ???
• Antidopaminergic agents (MXL, phenothiazines,
  droperidol ?)
• Dopamine? ?? renal response ?? ??
• Analgesic ?? prostaglandin ?? ??
• Angiotensin II, norepinephrine ??? ??
  vasodilatory prostaglandin? renal production ??
• GFR ??, renal dysfunction ??
• ACE inhibitors
• Renal perfusion? ?? ????? ???? ?? ??

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DIRECT ANESTHETIC EFFECTS (3)

• Other drugs
• Preexisting renal dysfunction? ?? drugs dyes ??
  renal function? ?? ?? ? ??
• Antibiotics aminoglycosides, amphotericin B
• Immunosuppressive agents cyclosporin,
  tacrolimus
• Radiocontrast dyes
• Mechanisms renal arterial vasospasm, direct
  cytotoxic properties, renal microvascular or
  tubular obstruction ?
• Pretreatment with acetylcysteine
• Preexisting renal dysfunction ?? ????
  radiocontrast dye-induced renal failure??? ?? ??
• Calcium channel agents (diltiazem)
• Cyclosporine induced nephrotoxicity??? ??

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DIRECT SURGICAL EFFECTS

• Neuroendocrine stress
• Pneumoperitoneum during laparoscopy
• abd. compartment syndrome-like state ??
• Central venous compression (renal vein vena
  cava)
• Renal parenchymal compression
• Decreased cardiac output
• Increases in plasma levels of renin, aldosterone,
  ADH
• Other surgical procedures
• Cardiopulmonary bypass
• Cross-clamping of the aorta
• Dissection near the renal arteries

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DIURETICS
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• Diuretics Sodium water reabsorption? ????
  urinary output ????
• Diuretics? ?? ????? renal tubule ?? luminal cell
  membrane
• ???? diuretics? highly prot. Bound ?? ??? free
  drug ?? filtration ?? tubule? ???
• ??? proximal tubule?? secreted ??? ? (?? organic
  anion pump ??)
• Impaired renal function ?? ???? diuretics?
  resistance ??? ??

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OSMOTIC DIURETICS (MANNITOL)

• Osmotically active diuretics
• Glomerulus?? filter ?? proximal tubule??
  reabsorption?? ??
• Proximal tubule?? passive water reabsorption?
  ????
• ?? ??? water excretion?? ?????? osmotically
  active diuretics? ???? electrolyte (sodium
  potassium) excretion? ????
• Mannitol
• Little or no reabsorption
• Increase RBF
• Medullary hypertonicity? wash out?? renal
  concentrating ability? ???
• Intrarenal synthesis of vasodilationg
  prostaglandin? ?????
• Free radical scavenger ??? ?

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OSMOTIC DIURETICS (MANNITOL) (2)

• Uses
• Prophylaxis against acute renal failure in
  high-risk patients
• High-risk Pt massive trauma, major hemolytic
  reaction, rhabdomyolysis, severe jaundice,
  cardiac or aortic operations
• Efficacy dilution of nephrotoxic substances,
  prevention of sludging obx, maintenance of RBF,
  reduction of cellular swelling, preservation of
  cellular architecture
• Evaluation of acute oliguria
• Hypovolemia ??? urinary output ????
• Severe glomerular or tubular injury ??? ?? ??
• Conversion of oliguric renal failure to
  nonoliguric renal failure ? controversial
• Acute reduction of intracranial pressure and
  cerebral edema
• Acute reduction of intraocular pressure in the
  perioperative period

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OSMOTIC DIURETICS (MANNITOL) (3)

• Intravenous dosage
• Mannitol, 0.25-1 g/kg
• Side effects
• Plasma extracellular osmolality? ??? ??
• ? rapid intracellular to extracellular shift of
  water
• ? ???? intravascular volume ??, cardiac
  decompensation, pulm. edema ?? ?? ??
• Transient hyponatremia, reductions in hemoglobin
  concentration
• Transient increase in plasma potassium
  concentration
• Diuresis ? Fluid electrolyte losses? ??? ????
  ??? hypovolemia, hypokalemia, hypernatremia ?? ??

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LOOP DIURETICS

• Furosemide(Lasix), bumetanide(Bumex), ethacrynic
  acid(Edecrin), torsemide(Demadex) ?
• Inhibit Na Cl- reabsorption in thick ascending
  limb
• Na-K-2Cl- luminal carrier protein?? Cl-? ??
• Large amounts of Na Cl-? distal nephron?? ?
  reabsorptive capability? ???? ? ? urine remains
  hypotonic
• Increase urinary calcium magnesium excrection
• Ethacrynic acid? ???? sulfonamide derivativerk ??
  ? sulfonamide drug? allergy ?? ???? diuretic of
  choice

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LOOP DIURETICS (2)

• Uses
• Edematous states ( sodium overload)
• Heart failure, cirrhosis, nephrotic syndrome,
  renal insufficiency
• IV ??? ??? cardiac pulm manifestation ????
• Hypertension
• Evaluation of acute oliguria
• Small dose (10-20 mg)
• Little or no response hypovolemia
• ?? ??? ?? redistribution of RBF to
  juxtamedullary nephrons
• Conversion of oliguric renal failure to
  nonoliguric renal failure
• Controversial
• Mannitol? ?? ???
• Treatment of hypercalcemia
• Rapid correction of hyponatremia

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LOOP DIURETICS (3)

• Intravenous dosages
• Furosemide, 20-100 ? bumetanide, 0.5-1 ?
  ethacrynic acid, 50-100 ? and torsemide 10-100 ?
• Side effects
• Distal collecting tubules? Na? ?? ???? K, H
  secretion? ??? hypokalemia, metabolic alkalosis
  ??
• Secondary hyperaldosteronism? ?? accentuate?
• Marked Na losses ? hypovolemia, prerenal
  azotemia
• Hypercalciuria ? stone formation, hypocalcemia
• Hypomagnesemia long-term therapy ??
• Hyperuricemia
• Reversible hearing loss ethacrynic acid gt
  furosemide

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THIAZIDE-TYPE DIURETICS

• Thiazides, chlorthalidone(Thalitone),
  quinethazone(Hydromox), metolazone(Zaroxolyn),
  indapamide(Lozol)
• Distal tubule?? ??
• Inhibition of sodium reabsorption
• Compete for Cl- site on luminal Na-Cl- carrier
  protein
• When given alone, increase Na excretion to only
  3-5 of filtered load
• Enhanced compensatory Na reabsorption in
  collecting tubule ??
• Some carbonic anhydrase inhibiting activity in
  proximal tubule
• ?????? loop of Henle??? sodium reabsorption??
  masked ?? ??
• Loop diuretics? ?? ?? ?? high ceiling diuresis
  ??? ??
• Augment Ca reabsorption in distal tubule

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THIAZIDE-TYPE DIURETICS (2)

• Uses
• Hypertension
• Edematous disorders (sodium overload)
• Hypercalciuria
• Nephrogenic diabetes insipidus
• Ability to impair diluting capacity increase
  urine osmolality
• Only given orally
• Side effects
• Enhance K secretion ? hypokalemia
• Enhance H secretion ? metabolic alkalosis
• Impairment of renal diluting capacity ?
  hyponatremia
• Hyperuricemia, hyperglycemia, hypercalcemia,
  hyperlipidemia

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POTASSIUM-SPARING DIURETICS

• Weak agents, do not increase potassium excretion
• Inhibit Na reabsorption in collecting tubules
• Maximally excrete only 1-2 of filtered Na load
• Aldosterone antagonists
• Spironolactone (Aldactone)
• Effective only in hyperaldosteronism
• Some antiandrogenic properties
• Uses
• Primary and secondary hyperaldosteronism
• Adjuvant in Tx of refractory edematous states
  associated with secondary hyperaldosteronism
• Hirsutism
• Only given orally
• Side effects
• Hyperkalemia, metabolic acidosis
• Diarrhea, lethargy ataxia, gynecomastia, sexual
  dysfunction

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POTASSIUM-SPARING DIURETICS (2)

• Noncompetitive potassium-sparing diuretics
• Tramterene (Dyrenium), amiloride (Midamor)
• Collecting tubule? luminal memb.? open sodium
  channel ?? ??
• ? Inhibit Na reabsorption, K secretion
• Uses
• hypertension, congestive heart failure
• Only given orally
• Side effects
• Hyperkalemia, metabolic acidosis
• Nausea, vomiting, diarrhea
• Amiloride fewer side effects
• paresthesias, depression, muscle weakness,
  cramping
• Triamterene rare occasions
• Renal stones, potentially nephrotoxic (?? NSAIDs?
  ???)

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CARBONIC ANHYDRASE INHIBITORS

• Acetazolamide (Diamox)
• Interfere with Na reabsorption, H secretion in
  proximal tubules
• Weak diuretics
• Uses
• Correction of metabolic alkalosis in edematous
  patients
• Alkalinization of urine
• Reduction of intraocular pressure
• Ciliary process? ???? aqueous humor ??? ????
• Acetazolamide, iv dose is 250-500 ?
• Side effects
• Mild hyperchloremic metabolic acidosis
• Large doses drowsiness, paresthesias, confusion
• Alkalinization of urine quinidine ? amine drug
  ?? ??