Anesthesia w/ Hepatic/Renal disease

Question 1

What is the physiologic function of the kidneys?

Answer 1

• Body fluid homeostasis: extracellular & total body water
• Blood pressure regulation (RAAS)
• Electrolyte balance: calcium & phosphate
• Acid-base balance: bicarbonate & hydrogen ions
• Excretion
  
  • Metabolic by-products: urea, uric acid, ammonia, bilirubin
  • Water soluble toxins and drugs
• Reabsorption:
  
  • Water, electrolytes, Glucose, Active form of vit D
• Endocrine
  
  • Secretes vasoactive hormones: renin, bradykinins, prostaglandins
  • Primary source of erythropoietin

Question 2

What is a nephron? what types of nephrons are there?

Answer 2

• Nephron = functional unit
• Type I - Outer cortical nephron
  
  • present in the superficial portion of the cortex
  • Short loops of Henle that reach the outer medulla
• Type II - Juxtamedullary nephron
  
  • Present in deep regions of the cortex
  • Birds and mammals
  • Long LOH extend to the inner medulla
  • Larger glomeruli & higher GFR

Question 3

What is different about avian and reptile kidneys?

Answer 3

• Only a few thousand nephrons
• Cannot concentrate urine in the kidneys be instead in the cloaca
• secrete uric acid, not urea

Question 4

What is the blood supply of the kidneys?

Answer 4

• Capillary Networks:
  
  • Glomerular capillaries under high pressure for filtration
  • Peritubular capillaries under low pressure
    
    • Secretion & reabsorption
    • Facilitate countercurrent mechanism
• Countercurrent Mechanisms:
  
  • Process of using energy to generate an osmotic gradient that enables water reabsorption from the tubular fluid and production of concentrated urine

Question 5

What is the Blood flow to the kidney? % received?

Answer 5

• Receive 20-25% of total CO
  
  • Renal blood flow is dispersed unevenly
  • 80-90% RBF goes to the renal cortex
  • 10% goes to the outer medulla
  • 1-3% goes to the inner medulla
    
    • Low flow helps maintain hypertonicity of filtrate
• Kidneys account for 10% of total Oxygen consumption (VO₂)
  
  • 75% of renal VO₂ is due to active sodium excretion
  • Medulla has highest VO₂ but receives the lowest fraction of RBF
    
    • Extracts 79% of delivered oxygen
    • Medullary cells function at borderline hypoxia
    • Acute tubular necrosis occurs when >40% reduction in RBF

Question 6

How is renal blood flow controlled?

Answer 6

• Autoregulation
  
  • Maintenance of constant RBF and GFR in range of blood pressures of 80-180 mmHg
  • Goal is to maintain stable GFR despite fluctuations in systemic blood pressure
  • Can be over-ridden extrinsically so there is variation in RBF within the range of autoregulation
    
    • Disruption in the normal physiological state (e.g. hemorrhagic shock, sepsis)

Question 7

What are the types of autoregulation of renal blood flow?

Answer 7

• Myogenic
  
  • Arterial smooth muscle relaxes and contracts in response to changes in arterial vascular wall tension
  • Rapid: occurs within 3-10 seconds
  • Property of pre-glomerular resistance vessels
    
    • Efferent arteriole does not respond to this mechanism
  • Process:
    
    • Increased blood pressure
    • Increased arterial wall stretch
    • Activation of myogenic stretch receptors
    • Open voltage gated calcium channels and inward calcium influx
    • Contraction of vascular smooth muscle cells
    • Minimal changes in RBF and GFR
• Tubuloglomerular feedback
  
  • Feedback mechanism that links sodium & chloride concentrations at the macula densa with control of renal arteriolar resistance

Question 8

Why is renin released?

Answer 8

• Decreased renal perfusion
• Sympathetic stimulation; mediated via B₁ receptors
• Decreased tubular delivery of sodium & chloride to the macula densa

Question 9

What is the Extrinsic Neural Control of the Renal Blood Flow

Answer 9

• Sympathoadrenal axis
  
  • Renal blood vessels supplied almost exclusively with sympathetic vasoconstrictive fibers
  • Little to no basal sympathetic tone
  • Vasoconstriction occurs in response to physiological stress
    
    • I.e. excess sympathetic stimulation such as hemorrhage is ischemia
  • Vasoconstriction occurs to maintain blood volume at the expense of RBF & GFR
  • Minor contribution of parasympathetic fibers, which release NO to cause vasodilation

Question 10

What is the extrinsic hormonal control of renal blood flow

Answer 10

• Circulating catecholamines
  
  • Released in response to physiologic stress
  • Norepinephrine and epinephrine primarily acting at alpha₁ receptors
  • Vasoconstrictors

Question 11

What are the vasoconstrictors that affect renal blood flow?

Answer 11

• Arginine vasopressin
• Adenosine, endothelin, serotonin

Question 12

What are the vasodilators that effect renal blood flow

Answer 12

• Intrarenal prostaglandins
• Atrial natriuretic peptide
• Nitric oxide

Question 13

How does filtration occur across the glomerular capillary wall?

Answer 13

• Separation of an ultrafiltrate of plasm across the glomerular capillary wall
  
  • Charge and size selection
    
    • MW 15000 freely permeable
    • MW 15000-70000 is primarily charge dependent
      
      • more restriction to negatively charged particles
    • MW 70000+ NOT filtered

Question 14

What is the Staging of Renal Disease?

Answer 14

Question 15

How do Anesthetic drugs affect renal physiology?

Answer 15

• Acepromazine
  
  • Maintains autoregulation
  • Maintains RBF/GFR
• Alpha₂ agonists (dexmedetomidine, dotomadine, etc)
  
  • Reduce cardiac output & RBF/GFR
  • Cause diuresis and hyperglycemia ⇢ avoid with post-renal obstruction
• Benzodiazepines (Midazolam, Diazepam, etc)
  
  • Maintains RBF/GFR
• Opioids
  
  • Morphine has active metabolites that are renally excreted
  • Possible prolonged effect?
• Propofol
  
  • Transient reduction in RBF/GFR
• Ketamine
  
  • Maintain RBF/GFR
  • Active metabolite norketamine renally excreted in dogs
  • excreted unchanged in urine of cats ⇢ prolonged action possible
• Inhalants (Sevo, Iso, etc)
  
  • Reduce RBF/GFR

Question 16

What are the effects of NSAIDS on renal physiology?

Answer 16

• COX-2 derived prostaglandins promote vasodilation of afferent arterioles to preserve RBF during low blood flow or hypotensive states

Question 17

What are the functions of the liver?

Answer 17

• Metabolism & Storage of carbohydrates, fats, & proteins
  
  • Carbohydrates:
    
    • Gluconeogenesis & glucose oxidation
    • Glycogenesis, glycogenolysis, glycogen store
  • Lipids:
    
    • Lipogenesis, lipolysis
    • Fatty acid oxidation
    • Ketogeneis
    • Cholesterol & triglyceride synthesis & breakdown
    • Lipoprotein synthesis & breakdown
  • Proteins:
    
    • Albumin synthesis
    • 75-90% alpha globulin synthesis
    • 50% beta globulin synthesis
    • Clotting factor synthesis: II, V, VII, IX, X, fibrinogen factor I, antithrombin III, plasminogen
    • Syntesis and degradation of Amino Acids
    • Converts ammonia to urea
    • Synthesis of multiple enzymes & structural proteins
• Vitamin absorption, storage, & activation
• Bile acid & bilirubin metabolism
• Reticuloendothelial functions (phagocytic Kupffer cells)
• Endocrine functions (immunoglobulin synthesis)
• Drug & toxic metabolism
• Iron, copper & red blood cell storage

Question 18

What is the anatomy of the liver?

Answer 18

• Classically 4 lobes and their subdivisions:
  
  • Right and Left lobes
    
    • can be divided into medial & lateral components
  • Quadrate lobe
  • Caudate lobe (caudate and papillary processes)
• Each lobe has its own arterial supply, venous drainage, & biliary system

Question 19

What is the classical functional unit of the liver

Answer 19

• Hepatic lobule
  
  • Comprised of hepatocytes radiating out from a central vein
  • Hepatic Arteriole, portal venule & bile duct comprise the portal or hepatic triad
    
    • define the perimeter of the lobule
  • Cords of hepatocytes are separated by sinusoids & bile canaliculi

Question 20

What is an acinus?

Answer 20

• Newer functional unit classification
• Cluster of hepatocytes grouped around the terminal branches of hepatic arterioles, hepatic venules, & bile ducts
  
  • I.e. hepatocytes served by each portal triad
• In this model of the subunit, the portal triads are central
• All drainage occurs at the peripheral central vein producing a strong gradient for oxygen

Question 21

What is the blood flow of the liver?

Answer 21

• Receives 25% of CO
• ~12% of total blood volume being received at any given time
• 65% of hepatic blood flow is from the hepatic portal vein
  
  • Portal blood supplies 50-60% of O₂ used by the liver
• 35% of HBF is supplied by the hepatic artery
  
  • Supplies 40-50% of O₂ used by the liver
• Regulation of blood flow largely depends on pre-portal factors affecting portal vein blood flow
• Blood flow is usually maintained constantly and homogenously due to a semi-reciprocal relationship between portal and arterial blood flow
• Decrease in portal flow will cause arterial vasodilation
• Homogeneity flow is important because of the liver’s role in clearance and maintaining venous return

Question 22

What factors increase HBF?

Answer 22

• Post-prandial, glucagon
• Beta-agonists
• Hypercapnia
• P450 enzyme induction (eg. barbituates)
• Hepatitis

Question 23

What factors decrease HBF?

Answer 23

• Upper abdominal surgery
• β-blockade; alpha₁ agonism
• Hypocapnia
• Hypoxia
• P450 enzyme inhibition (H₂ blockers)
• Cirrhosis
• IPPV/PEEP

Question 24

How are exogenous substances hepatically metabolized?

Answer 24

• Microsomal enzyme biotransform lipid soluble substances to water soluble substances
• May or may not be a stepped reaction
• Phase 1: Oxidation, reduction or hydrolysis
  
  • Oxidation occurs via cytochrome P450 enzyme complexes
  • Can be induced or inhibited
    
    • eg. chronic barbiturate use leading to upregulation of P450 enzyme
  • Can render substance more or less active/toxic
• Phase II: Conjugation
  
  • Primary mechanism is glucuronidation
  • Makes substances water soluble for renal or fecal excretion
  • Limited glucuronyl transferases in cats
    
    • Unable to metabolize phenolic compounds as effectively as dogs (NSAIDS, acetaminophen)

Question 25

What enzymes can be evaluated to check the hepatic functionality?

Answer 25

* Alanine aminotransferase (ALT) * Liver specific cytosolic enzyme * Small amount in hear, kidney, muscle * Increased by anticonvulsants & corticosteroids in dos * Aspartate aminotransferase (AST) * Cytosolic enzyme in side variety of tissues such as muscle, heart, kidney, brain, plasma * Increased AST with normal CK suggestive of hepatic insult * Mild elevations from steroids in dogs * Other: * Bile acids * Albumin - decreased at 80% loss of function * Blood urea nitrogen * Ammonia * Glucose * Choesterol * Clotting factors, II, VII, IX, X, and Vit K

Question 26

What effect do anesthetic drugs have a hepatic physiology?

Answer 26

* Acepromazine * Vasodilatory * Careful considerations if hypoproteinemic * Alpha₂ agonists * Reduction in cardiac output ⇢ can cause reduced HBF * Hepatic metabolism (⇣ met with ⇣Hepatic function) * reversible * Benzodiazepines * Contraindicated in hepatic encephalopathy - flumazenil used for treatment * Opioids * Most are hepatically biotransformed so prolonged duration possible * Cause contraction of the Sphincter of Oddi so can increase biliary pressure * Induction agents: * Propofol has extrahepatic metabolism * Ketamine acceptable * Inhalants * HBF reduced secondary to systemic hypotension * Worsened if already hypotensive/hypovolemic

Question 27

What affect do NSAIDS have on hepatic physiology?

Answer 27

idiosyncratic damage through oxidative stress