This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
1. Anatomy Of The Liver And Effect Of Anaesthetic Drugs On
LiverPresented by:Dr. Rajat DadheechModerator:Dr. Rama
Chatterjee
2. Anatomy of the liverThe liver is the largest gland of the
body, weighing 1200 -1600 g, it is wedge- shaped, and covered by a
network of connective tissue (Glissons capsule).
3. It is connected to the diaphragm and abdominal walls by five
ligaments: the membranous falciform (also separates the right and
left lobes), coronary, right and left triangular ligaments, and the
fibrous round ligament (which is derived from the embryonic
umbilical vein).
4. Lobes Of The LiverAnatomically the liver is divided into a
Right and a Left lobe by the falciform ligamentThe Right lobe also
has two minor lobes- The caudate lobe and The quadrate lobe
5. Blood Supply: The Liver receives around 1500 ml of blood/min
The blood supply of the Liver is derived from The Portal Vein (80%)
and The Hepatic Artery (20%) Terminal branches of the hepatic
portal vein and hepatic artery empty together and mix as they enter
sinusoids in the liver. Sinusoids are distensible vascular channels
lined with highly fenestrated endothelial cells and bounded
circumferentially by hepatocytes.
6. The bloodleaves thesinusoids via acentral vein ,which drains
inthe hepatic vein.
7. Claude Couinad A french surgeon & anatomist who made
significant contribution in the field of hepatobiliary surgery ,he
was the first to describe segmental anatomy of the liver
8. Functional divisions of Liver Middle hepatic vein divides
the liver into right and left lobes (or right and left hemiliver).
This plane runs from the inferior vena cava to the gallbladder
fossa (Cantlies line) Right hepatic vein divides the right lobe
into anterior and posterior segments Left hepatic vein divides the
left lobe into a medial and lateral part.
9. Histology Liver lobules hexagonal structuresconsisting
ofhepatocytes At each of the sixcorners of a lobule is aportal
triad
10. Portal Triads: Branches of two vessels: portal vein,hepatic
artery, along with bile drainage ductules all runtogether to
infiltrate all parts of liver. Zonal Flow of Blood
11. Zone 1- Rich in Oxygen, mitochondria Concerned with
Oxidative metabolism and synthesis of glycogenZone 2-
transitionZone 3- lowest in Oxygen, anaerobic
metabolism,Biotransformation of drugs, chemicals, and toxinsMost
sensitive to damage due to ischemia, hypoxia, congestion
12. Hepatic Micro Circulatory Cone
13. Biliary Tract:
14. Regulation of Hepatic Blood FlowIntrinsic Regulation
Hepatic Arterial Buffer Response -HABR Pressure flow Autoregulation
Metabolic controlExtrinsic Regulation Neural Control Humoral
Control
15. Hepatic arterial buffer system With an intact HABR, changes
in portal venous flow cause reciprocal changes in hepatic arterial
flow. The HABR mechanism involves the synthesis and washout of
adenosine from periportal regions. Various disorders (e.g.,
endotoxemia, splanchnic hypo perfusion) may decrease or even
abolish the HABR and render the liver more vulnerable to hypoxic
injury.
16. PRESSURE FLOW AUTO REGULATION- Hepatic pressure
auto-regulation keeps constant blood flow despite wide fluctuation
in systemic BP. The mechanism involves myogenic responses of
vascular smooth muscle to stretch. The hepatic artery exhibits
pressure-flow auto regulation in metabolically active liver
(postprandial) but not in the fasting state. Thus, hepatic flow
autoregulation is not likely to be an important mechanism during
anesthesia. Pressure-flow autoregulation is nonexistent in the
portal circulation.Thus, decrease in systemic blood pressureas
often occurs during anesthesiatypically lead to proportional
decrease in portal venous flow
17. Metabolic Control Decrease in oxygen tension or the pH ,
Pco2 of portal venous blood ,typically lead to increase in hepatic
arterial flow. Postprandial hyperosmolarity increases hepatic
arterial and portal venous flow but not in the fasting state. The
underlying metabolic and respiratory status (e.g., hypercapnia,
alkalosis, arterial hypoxemia) also modulates the distribution of
blood flow within the liver.
18. NEURAL CONTROL Fibres of the vagus,phrenic and splanchnic
nerves(postganglionic sympathetic fibres from T6 to T11)enter the
liver at the hilum When sympathetic tone decreases,splanchnic
reservoir increases whereas sympathetic stimulation,translocates
blood volume from the splanchanic reservoir to the central
circulation. Vagal stimulation alters the tone of the presinusoidal
sphincters,the net effect is a redistribution of intrahepatic blood
flow without changing total hepatic blood flow.
19. Humoral Control Gastrin, Glucagon, Secretin, Bile
salts,Angiotensin II, Vasopressin, Catecholamines. Cytokines,
Interleukins, and other inflammatory mediators have been implicated
in the alteration of normal splanchnic and hepatic blood flow.
21. Liver and Anaesthesia Anesthesia & anaesthetic drugs
affects the hepatic function by following mechanisms : Alteration
in the hepatic blood flow n HABR. Metabolic function. Drug
metabolism. Billiary function.
22. Effect of volatile agents on hepaticblood flow Halothane:
Causes hepatic arterial constincton, microvascular vasoconstriction
Enflurane: Increase in hepatic vascular resistance Isoflurane:
Increase in microvascular blood velocity Sevoflurane &
Desflurane: Preservation of hepatic blood flow & function
23. EFFECT OF INTRAVENOUS AGENTSON HEPATIC BLOOD FLOW KETAMINE:
Little effect on hepatic blood flow PROPOFOL: Significant
splanchnic vasodilator increases both hepatic arterial & portal
venous blood flow THIOPENTONE & ETOMIDATE: Hepatic arterial
blood flow reduction, reducedf cardiac output
24. NEUROMUSCULAR BLOCKINGDRUGSVecuronium, rocuronium,
mivacurium: Reduced elimination and Prolong duration of action
specially with infusion & repeated dosesAtracurium &
cisatracrium: Nondependant of hepatic metabolism and can be used
without modification of doses in end stage liver disease
25. REGIONAL ANESHESIA & HEPATICBLOOD FLOW Reduction in
hepatic blood flow in high spinal & epidural anesthesia
Secondary to hypotension Reversed by vasopressors like dopamine,
ephedrine
26. Halothane Hepatitis It is immunologically mediated,as it
induces both neoantigens & auto antigens. The incidence of
fulminant hepatic necrosis terminating in death associated with
halothane was found to be 1 per 35,000. Demographic factors ; Its a
idiosyncratic reaction, susceptible population include Mexican
Americans ,Obese women, , Age >50 yrs, , Familial
predisposition,Severe hepatic dysfunction while Children are
resistant. Prior exposure to halothane is a important risk factor
& multiple exposure increases the chance of hepatitis.
27. ISOFLURANE. Isoflurane metabolism yields highly
reactiveintermediates (TF-acetyl chloride; acyl ester) that
bindcovalently to hepatic proteins. For this isoflurane most
likelycauses hepatitis.It undergoes minimal biodegradation,
preservesmicrovascular blood flow & oxygen delivery more
thanhalothane or enflurane .DESFLURANE-it is similarly
biotransformed totrifluoroacyl metabolites, appears even less
likely thanisoflurane to cause immune injury because only 0.02 to
0.2%of this agent is metabolized (1/1,000th that of
halothane).Desflurane metabolites are usually undetectable in
plasma,except after prolonged administration.
28. Desflurane hepatic blood flow ,it markedly reduce
oxygendelivery to the liver and small intestine without
producingcomparable reductions of hepatic oxygen uptake or hepatic
andmesenteric metabolism. Therefore, desflurane anesthesia
maydecrease the oxygen reserve capacity of both the liver and the
smallintestine.SEVOFLURANE It is metabolized more extensively than
isofluraneor desflurane,but slightly less than enflurane, and much
less thanhalothane. The metabolism of sevoflurane is rapid (1.5 to
2 timesfaster than enflurane), and produces detectable
plasmaconcentrations of fluoride and hexafluoroisopropanol
(HFIP)within minutes of initiating the anesthesia. The liver
conjugates most of the HFIP with glucuronic acid, whichis then
excreted by the kidney.
29. NITROUS OXIDE- it produces a mildincrease in sympathetic
nervous systemtone leads to mild vasoconstriction of thesplanchnic
vasculature, leading to adecrease in portal blood flow, and
mildvasoconstriction of the hepatic arterialsystem. N2O is a known
inhibitor of theenzyme methionine synthase, whichcould potentially
produce toxic hepaticeffects.
30. Intravenous Anesthetics- Etomidate and thiopental at larger
doses (>750 mg) may cause hepatic dysfunction by hepatic blood
flow, either from hepatic arterial vascular resistance or from
reduced cardiac output and blood pressure. Ketamine has little
impact on hepatic blood flow, even with large doses Propofol
increases Blood Flow in both the hepatic arterial and portal venous
circulation, suggesting a significant splanchnic vasodilator
effect
31. OPIOIDS Opioids have little effect on hepatic function,
provided they do not impair hepatic blood flow and oxygen supply.
All opioids increase tone of the common bile duct and the sphincter
of Oddi, as well as the frequency of phasic contractions, leading
to increases in biliary tract pressure and biliary spasm. Morphine
undergoes conjugation with glucoronic acid at hepatic & extra
hepatic site (kidney). The significantly reduced metabolism of
morphine in patients with advanced cirrhosis leads to a prolonged
elimination half-life, markedly increased bioavailability of orally
administered morphine, decreased plasma protein binding, and
potentially exaggerated sedative and respiratory-depressant
effects. The oral dose of the drug should be reduced because of
increased bioavailability
32. Neuromuscular Blocking Drugs The volume of distribution of
muscle relaxants, may increase due to albumin an increase in
-globulin or the presence of edema.so the initial dose requirements
of these medications are increased in cirrhotic patients and
subsequent dose requirements may be , and drug effects prolonged,
owing to in hepatic blood flow and impaired hepatic clearance, and
possible concurrent renal dysfunction.
33. Neuromuscular Blocking DrugsVecuronium-it is a steroidal
muscle relaxant It undergoes hepatic elimination by acetylation.
Decreased clearance, a prolonged elimination half-life, and
prolonged neuromuscular blockade in patients with cirrhosis .
Rocuronium- another steroidal muscle relaxant with a faster onset
of action than vecuronium, also undergoes hepatic metabolism and
elimination. Hepatic dysfunction can increase the volume of
distribution of rocuronium, thereby prolonging its elimination
half-life and producing a longer clinical recovery profile and
return of normal twitch tension.
34. Neuromuscular Blocking DrugsAtracurium & Cisatracurium
Elimination half-lives and clinical durations of action are similar
in cirrhotic.82%to Bound albumin they undergo clearance by
organ-independent elimination i.e. spontaneous non-enzymatic
degradation (Hoffmanns elimination). Laudanosine, a metabolite of
both atracurium and cisatracurium, is eliminated primarily by the
liver; and although its concentration may increase in patients
undergoing liver transplantation, clinically relevant neurotoxicity
has not been reported
35. EFFECTS OF HEPATIC DYSFUNCTIONOF ANESTHETIC DRUGS Altered
protein binding Altered volume of distribution Altered drug
metabolism due to hepatocyte dysfuction
36. EFFECTS OF HEPATIC DYSFUNCTIONON ANESTHETIC DRUGS Opioids:
exaggerated sedative & respiratory depressant effect and Half
life is almost doubled Benzodiazepines : Duration of action
increased Thiopentone, Etomidate, Propofol, Ketamine: Repeated
doses & prolong infusion causes accumulation of drugs Increases
risk of hepatic encephalopathy
37. TAKE HOME MESSAGES Liver major organ of metabolism Live
dysfuction affects pharmacokinetics of anesthetic drugs Anesthetic
drugs affects liver function Neuroaxial blocks: reduction in
hepatic blood flow due to hypotension Intropetative hypotension,
hypoxia, hypocapnia, use of hepatotoxic drugs in perioperative
period can cause postoperative hepatic dysfunction