Ch31. Renal Physiology

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Ch31. Renal Physiology Anesthesia

• R1 ???

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• Kidney ? ??
• volume ? ??? ??? ??
• Toxins ??
• Hormones?? (renin, erythropoietin, active form of
  vit.D)

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THE NEPHRON

• 6?? specialized segment ? ??
• - The Glomerular Capillaries
• - The Proximal Tubule
• - The Loop of Henle
• - The Distal Tubule
• - The Collecting Tubule
• - The Juxtaglomerular Apparatus

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The Glomerular Capillaries

• Glomerulus Bowmans capsule ?? ???? ??? ??
• - Single afferent arteriole, single efferent
  arteriole
• Mesangial cells glomerular filtration?
  regulation?? ??
• Contractile protein vasoactive substances? ??
• Mesangial cell? ???? glomerular filtration ??
• - angiotensin II, vasopressin, norepinephrine,
  histamine, endothelins,
• thromboxzne A2, leukotrienes, prostaglandin
  F2, platelet-activating factor
• Mesangial cell? ???? filtration ???
• -Response to atrial natriuretic peptide(ANP),
  prostaglandin E2,
• dopamine
• Filtration pr. ??? afferent efferent arteriolar
  tone? ??
• Filtration pr. ? efferent arteriolar tone? ????
  ???? afferent arteriolar tone? ???

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The proximal tubule

• Bowmans capsule?? ultrafiltrate ?? 65-75?
  reabsorbed
• Proximal tubule? ?? ??? Na? ???

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The Proximal Tubule

• Na-K-ATPase? ?? tubular cell?? capillary? Na?
  active transport
• Tubular fluid??? Na? passive movement ??
• Angiotensin II, norepinephrine? Na ??? ??
• Dopamine, fenoldopam? ???? ????
• Na ???? ?? solute? ???, H ???
• ???
• chloride ? tight junction ?? ??
• ???? ?? passive ?? ???
• ?? ???? ???? ?? ??
• ??? creatinine, cimetidine, quinidine
• ??? urate, ketoacids, penicillins,
  cephalosporins, diuretics, salicylates, most
  x-ray dyes

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The Loop of Henle

• ?? Hypertonic medullary interstitium ??,
• urine ??
• Filtered sodium load? 15-20 ???
• Ascending thick segment ???? water? solute? ???
  ????? ?? 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 ??
• Calcium? magnesium ???? ??
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  

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The Distal Tubule

• Filtered sodium load ? 5 ???? ??
• parathyroid hormone- vitamin D- mediated
  calcium ???? Major site
• Aldosterone-mediated Na ???

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The Collecting Tubule a.
cortical collecting tubule

• 2?? cell type
• Principal cells (P cells)
• -Potassium??
• -Participate in aldosterone-mediated Na ???
• 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

• ADH(antidiuretic hormone)? ???? ?? ??
• Dehydration? ADH ??? ???? luminal memb.?
  water? permeable?? ??? urine? ??
• C. hypertonic medulla ???? ?? collecting tubule?
  ??
• Cortical collecting tubule? urea? ?? ???? ???? ??
• 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 ??, ?????? ?? innervation
• ß1-adrenergic sympathetic stimulation? ?? renin?
  Release?? afferent arteriolar wall pr.? ????
• Renin? Liver?? angiotensin I?? ???
• ?? Lung?? ACE(angiotensin-converting enz.)? ??
  angiotensin II? ??
• ? BP ??? aldosterone ??? ?? ??? ?

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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 ??
• ??? filtered??? ????? ??? ?? ??
• GFR? ???
• ?? 120 25 ?/min
• ?? 95 20 ?/min
• Creatinine clearance? ?? ???? ?? ??
• Overestimation ?? ?? ??

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Control Mechanisms

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

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Control Mechanisms

• C. Hormonal regulation
• -Afferent arteriolar pressure? ??? renin
  release? angiotensin II? ??? ??
• ?Angiotensin II? ???? ????? ??? 2???? RBF? ????
• Afferent, efferent arteriole? ?? ?????
  efferent arteriole? ?? ?? ??? ??? ? ?? GFR? ???
  ???
• -Vasodilating prostaglandin(PGD2,PGE2,PGI2)?
  systemic hypotension? renal ischemia? ???
  protective mechanism? ??
• -ANP direct smooth muscle dilator
• norepinephrine angiotensin II ?
  vasoconstrictive action ? antagonize
• Afferent arteriole? dilation??? efferent
  arteriole? constriction ?? ????? GFR? ????

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Control Mechanisms

• D. Neuronal regulation
• - a1-adrenergic recepter?proximal tubule??
  sodium? ???? ??
• - a2 recepter? sodium? ???? ????? water
  excretion? ?? ??
• -Dopamine fenoldopam? D1-receptor activation?
  ?? afferent efferent arteriole? dilation ???,
  norepinephrine-induced renal vasoconstriction?
  reverse?? ? ??

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EFFECTS OF ANESTHESIA SURGERY ON RENAL FUNCTION

• 1. ?? ?? RBF, GFR, urinary flow, sodium
  excretion? reversible? ??
• 2. ??? ??? Regional anesthesia? ? ????
• 3. ??? ??? ???? indirect?? autonomic and
  hormonal ???
• ???
• 4. ??? intravascular volume? ?? ?? ?? ? ??? ??? ?
  ??
• 5. High dose? methoxyflurane, enflurane,
  sevoflurane ? renal toxicity
• ? ?? ? ? ??.

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INDIRECT EFFECTS

• (1) Cardiovascular effects
• ??? ????? cardiac depression ?? vasodilation ???
  ????? ???? ? ??
• Regional anesthesia? sympathetic blockade? ??
  hypotension ?? ??
• BP? autoregulation ??? ?? ???? RBF, GFR, urinary
  flow, sodium excretion ???
• IV fluid??? hypotension ????? ?? ???? renal
  function? ????? ??
• (2) Neural effects
• Light anesthesia, intense surgical stimulation,
  tissue trauma, anesthetic-induced circulatory
  depression??? sympathetic activation ? ??
• Sympathetic overactivity? renal vascular
  resistance? ?? ???,
• ?? ???? ??? ?? RBF, GFR, urinary output? ??
  ???.

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• (3) Endocrine effects
• ???? endocrine change? stress response? ???
• Catecholamines,renin, angiotensin II,
  Aldosterone, ADH, adrenocorticotrophic Hormone,
  cortisol?? ??
• Catecholamines, ADH, angiotensin II? renal a.
  constriction? ?? RBF? ????
• Aldosterone sodium ???? ???? sodium retention,
  ECF ?? ? ??
• ADH? water retention ??? ? ??, ?? ??
  hyponatremia? ??

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DIRECT ANESTHETIC EFFECTS

• (1) Volatile agents
• - Halothane, enflurane, isoflurane renal
  vascular resistance ????
• - enflurane, Sevoflurane? ?? ??? fluoride ???
  ???? renal toxicity? ??? ? ??
• - Compound A
• Sevoflurane? ?? ?? low flow? ???
• ??????? renal damage? ????? ?????? ????
• ??
• Sevoflurane ??? fresh gas flow? ?? 2L/min ?? ??? ?

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• (2) Intravenous agents
• Opioid,barbiturate ?? ??? ?? minor effect
• nitrous oxide ? ?? ? ?????? ?? ??? ??? ? ??
  
• ?-adrenergic blocker (droperidol ?)
• RBF? redistribution ??
• Antidopaminergic agents (MXL, phenothiazines,
  droperidol ?)
• Dopamine? ?? renal response ?? ??? ??
• ACE inhibitors
• Renal perfusion? ?? ????? ???? ?? ?? ? ??

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DIRECT SURGICAL EFFECTS

• laparoscopy??? pneumoperitoneum? oligouria ??
• -Central venous compression (renal vein vena
  cava)
• -Renal parenchymal ??
• -cardiac output? ??
• -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

• Diuretics Sodium water???? ???? 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?? water ???? ????
• ?? ??? 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 ?? ??? ?

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• Uses
• 1. high-risk ???? ?? ???? ??
• 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
• 2. acute oliguria? Evaluation
• Hypovolemia ??? urinary output ????
• Severe glomerular or tubular injury ??? ?? ??
• 3. oliguric renal failure ? nonoliguric renal
  failure?? ??
• ? controversial
• 4. intracranial pressure and cerebral edema ??
• 5. ?? ? intraocular pressure ??

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• Intravenous dosage
• Mannitol, 0.25-1 g/kg
• Side effects
• Plasma extracellular osmolality? ??? ??
• ? Water? ?? ??? ?? ??? ??? ??
• ? ???? intravascular volume ??, cardiac
  decompensation, pulm. edema ?? ?? ??
• ???? hyponatremia, hemoglobin concentration ??
• ???? 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) ?
• thick ascending limb ?? Na Cl- ????
  inhibition
• -Na-K-2Cl- luminal carrier protein?? Cl-? ??
• urinary calcium magnesium excrection ??
• Ethacrynic acid? ???? sulfonamide derivative? ??
• ? sulfonamide drug? allergy ?? ???? diuretic of
  choice
• Torsemide antihypertensive action

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• Uses
• 1. Edematous states ( sodium overload)
• Heart failure, cirrhosis, nephrotic syndrome,
  renal insufficiency
• IV ??? ??? cardiac pulmonay ????? ???? ?
• 2. Hypertension
• 3. Evaluation of acute oliguria
• Small dose (10-20 mg)
• Little or no response hypovolemia
• 4. oliguric renal failure ? nonoliguric renal
  failure ? ??
• Controversial
• Mannitol? ?? ???
• 5. Hypercalcemia? ??
• 6. Hyponatremia ?? ??

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• 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
  ??
• 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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• 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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• 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
  ?? ??