1. Anatomy Of The Liver And
Effect Of Anaesthetic Drugs
On Liver
Presented by:
Dr. Rajat Dadheech
Moderator:
Dr. Rama Chatterjee

2. Anatomy of the liver
The liver is the largest gland of the body,
weighing 1200 -1600 g, it is wedge-
shaped, and covered by a network of
connective tissue (Glisson's 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 Liver
Anatomically the liver is divided into a Right
and a Left lobe by the falciform ligament
The Right lobe also has two minor lobes-
The caudate lobe and The quadrate lobe

7. 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.

8.  The blood
leaves the
sinusoids via a
central vein ,
which drains in
the hepatic vein.

9. 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

10. 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 (Cantlie's 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.

11. Histology
 Liver lobules –
hexagonal structures
consisting of
hepatocytes
 At each of the six
corners of a lobule is a
portal triad

12. Portal Triads: Branches of two vessels: portal vein,
hepatic artery, along with bile drainage ductules all run
together to infiltrate all parts of liver.
Zonal Flow of Blood

13. Zone 1-
Rich in Oxygen, mitochondria
•Concerned with Oxidative metabolism and synthesis of
glycogen
Zone 2- transition
Zone 3-
• lowest in Oxygen, anaerobic metabolism,
•Biotransformation of drugs, chemicals, and toxins
•Most sensitive to damage due to ischemia, hypoxia, congestion

14. Hepatic Micro Circulatory Cone

16. Biliary Tract:

17. Regulation of Hepatic Blood Flow
Intrinsic Regulation
• Hepatic Arterial Buffer Response -HABR
• Pressure flow Autoregulation
• Metabolic control
Extrinsic Regulation
• Neural Control
• Humoral Control

18. 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.

19. 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 pressure—as often
occurs during anesthesia—typically lead to proportional decrease
in portal venous flow

20. 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.

21. 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.

22. 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.

23. FACTORS AFFECTING HEPATIC
BLOOD FLOW
INCREASE IN HEPATIC DECREASE IN HEPATIC
BLOOD FLOW BLOOD FLOW
 Hypercapnia  IPPV
 Acute hepatitis  Hypocapnia
 Supine posture  Hyhpoxia
 Food intake  Cirrhosis
 Drug: Beta Agonist  alpha Stimulation
Phenobaritone  Beta blocker
 Enzyme inducers  Halothane, volatile &
anesthetics
 Vasopressin

24. 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.

25. Effect of volatile agents on hepatic
blood 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

26. EFFECT OF INTRAVENOUS AGENTS
ON 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

27. NEUROMUSCULAR BLOCKING
DRUGS
Vecuronium, rocuronium,
mivacurium:
• Reduced elimination and Prolong duration of action
specially with infusion & repeated doses
Atracurium & cisatracrium:
• Nondependant of hepatic metabolism and can be used
without modification of doses in end stage liver disease

28. REGIONAL ANESHESIA & HEPATIC
BLOOD FLOW
 Reduction in hepatic blood flow in high spinal &
epidural anesthesia
 Secondary to hypotension
 Reversed by vasopressors like dopamine, ephedrine

29. 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 ; It’s 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.

30. ISOFLURANE. Isoflurane metabolism yields highly reactive
intermediates (TF-acetyl chloride; acyl ester) that bind
covalently to hepatic proteins. For this isoflurane most likely
causes hepatitis.
It undergoes minimal biodegradation, preserves
microvascular blood flow & oxygen delivery more than
halothane or enflurane .
DESFLURANE-it is similarly biotransformed to
trifluoroacyl metabolites, appears even less likely than
isoflurane 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.

31. Desflurane ↓hepatic blood flow ,it markedly reduce oxygen
delivery to the liver and small intestine without producing
comparable reductions of hepatic oxygen uptake or hepatic and
mesenteric metabolism. Therefore, desflurane anesthesia may
decrease the oxygen reserve capacity of both the liver and the small
intestine.
SEVOFLURANE It is metabolized more extensively than isoflurane
or desflurane,but slightly less than enflurane, and much less than
halothane. The metabolism of sevoflurane is rapid (1.5 to 2 times
faster than enflurane), and produces detectable plasma
concentrations of fluoride and hexafluoroisopropanol (HFIP)
within minutes of initiating the anesthesia.
The liver conjugates most of the HFIP with glucuronic acid, which
is then excreted by the kidney.

32. NITROUS OXIDE- it produces a mild
increase in sympathetic nervous system
tone leads to mild vasoconstriction of the
splanchnic vasculature, leading to a
decrease in portal blood flow, and mild
vasoconstriction of the hepatic arterial
system. N2O is a known inhibitor of the
enzyme methionine synthase, which
could potentially produce toxic hepatic
effects.

33. 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

34. 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

35. Neuromuscular Blocking Drugs
 The volume of distribution of muscle relaxants, may
increase due to ↓ albumin an increase in γ-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.

36. Neuromuscular Blocking Drugs
Vecuronium-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.

37. Neuromuscular Blocking Drugs
Atracurium & 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 (Hoffmann's 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

38. EFFECTS OF HEPATIC DYSFUNCTION
OF ANESTHETIC DRUGS
 Altered protein binding
 Altered volume of distribution
 Altered drug metabolism due to hepatocyte dysfuction

39. EFFECTS OF HEPATIC DYSFUNCTION
ON 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

40. 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