1. A Review of Liver Anatomy and
Physiology
By,
Dr. Arun Kumar B.S.
PG, Dept of Anesthesiology
YMC
Moderator: Dr. Mallikarjun

2. TRIVIA
• Largest internal organ weighing approx 1.2-
1.5kg adult i.e 2% TBW, 5% in neonates.
• Reddish brown triangular pyramid shaped, in
rt. Hypochondrium and most of epigastrium.
• Held to place by ligaments (folds of
peritoneum),hepatogastric, hepatoduodenal,
lateral, falciform ligs, obliterated vessels like
ligamentum teres(umbilical vein), ligamentum
venosus(ductus venosum).

3. Macro Anatomy
• For anatomically divided into 2 left and right
lobes with right being bigger.
• Functionally divided into lobes by the portal vein
into 8 lobes.
• Each lobe having a portal vein, branch of hepatic
artery and a bile canaliculi.
• The biliary system rt and lt hepatic ducts which
combine to form common hepatic duct drains to
the gall bladder by cystic ducts.
• Gall 9cm in length, capacity of 50ml, bld supply
from cystic artery, branch of hepatic artery.
• Sphincter of ODDI is at the duodenal opening.

4. Functional units- Micro Anatomy
• Described in classic lobule structure by
Kiernan as early as 1833. as hexagonal str.
With portal triads forming angle joints.
• now its described as Rappaport’s acinus: the
parenchymal mass in between two
centrilobular veins.
• Centre formed by portal triad( PV, HA, BC,
nerves and lymphatics).

5. Microanatomy contd….
• Functionality is based on the flow of blood
from the vessels towards the centrilobular
veins.
• Three zones with zone 1 high oxygenation and
zone 3 prone for hypoxic injury.
• It is here all reactions in the liver taking place.
• Zone 1 periportal region, all reactions in
biotransformation is here esp. cyt P450
enzyme based.

7. Hepatic ultrastructure
• Cells like Kuppfer cells, floating macrophages,
• Stellate cells.

8. Hepatic blood supply
• Dual supply of Portal vein and Hepatic artery.
• Portal vein 55-60% of the total blood, 45%
oxygenation, hepatic artery 44-50% of total
blood but 60% oxygenation.
• Hepatic artery buffer response(hemireciprocal
reflex).
• Middle, right and left hepatic veins take the
blood away from the liver and joins the IVC.

9. HABR
• Also called hemireciprocal response
• Pressure- flow relationship between portal
vein and hepatic artery.
• Portal venous flow reduced then there is
reduction in hepatic artery resistance.
• But not vice versa.
• Adenosine is suggested to be the mediator of
this response.

10. • Factors increasing hepatic blood flow: feeding,
glucagon, hypercapnia, recumbent position,
hepatocellular enzyme induction, ac.
Hepatitis.
• Factors decreasing: Anesthetic agents, surgical
trauma, IPPV, PEEP, bet adrenergic blockade,
Hypocapnia, Vasopressin.

11. • Effect of regional Anesthesia: reduction in the
blood flow parallels reduction in the systemic
MAP.
• Kennedy et al : T5 blockade reduced flow by
23% of the control.
• Inhalational: Halothane greatest reduction in
portal, arterial and total hep blood flow.
• Attenuates HABR.
• Des, sevoflurane maintained blood flow.

12. • Effect of intravenous agents: thiopentone,
etomidate, propofol produces dose
dependant reduction in the hepatic blood
flow.

13. REVIEW OF ANATOMY AND
PHYSIOLOGY
FUNCTIONS OF THE
LIVER:
Carbohydrate
metabolism Secretion of bile
Glycogenesis Detoxification
Glycogenolysis Metabolism of
Gluconeogenesis vitamins A,D,K,E &
Fat metabolism - Clotting factors, esp
ketogenesis
prothrombin
Protein metabolism
anabolism Storage
deamination Blood store
urea formation

14. Heme metabolism
• Main site.
• Hemoglobin is heme and globulin, with heme
containing ferrous and porphyrin IX.
• 20% approx, heme synthesised in the liver.
• Rate limiting step is synthesis of 5-
aminolevulinic acid catalysed by ALA
synthetase.

15. Bilirubin metabolism
• Source is from the Heme metabolism.
• Approx 300mg of bilirubin formed everyday.
• 80% by the phagosytosis of scenecent RBCs by the RE
cells.
• The extracted heme is converted to bilirubin, this is the
rate limiting step.
• This is then bound to albumin and liver processes the
molecules into conjugated bilirubin in 2 steps, and then
excreted.
• Enterohepatic circulation ensures some of these
products to return to the liver.

16. Xenobiotic Biotransformation
• It is divided into
• Phase I reaction.
• Phase II reaction.
• Phase III reaction.

17. PHASE I REACTION
• It is oxidative, hydrolysis,
• reduction reactions.
• It is mainly microsomal oxidases, CYP isozymes
super family.
• These CYP isozymes are concentrated in the
centrilobular zone.
• It needs NADPH for its reactions and hence
formation of superoxides and reactive free
radicals, more chance of injury to these cells,
necrosis.

21. CYP 450 inhibitors
• Grapefruit juice.
• erythromycin,
• isoniazid,
• sulfonamides,
• ketoconazole

22. PHASE II REACTION
• Conjugation with the endogenous hydrophilic
molecules.
• It involves several processes such as
glucuronidation, sulphation, methylation,
acetylation.
• Glucuronidation is the common type.
• Hepatic microsomal uridine diphosphate
glucuronyl transferase mediates the reaction.

23. PHASE II contd…
• These are susceptible to enzyme induction.
• Heavy smoking, phenytoin admistration seen
to increase glucuronidation in humans.
• In some drugs the conjugation ends up with a
metabolite more potent than the parent drug.
Eg: morphine- becomes morpine 6-
glucuronide a potent byproduct which is
responsible for some of the analgesia
produced by morphine.

24. PHASE III REACTION
• It is a energy mediated transport/ elimination.
• by ATP- binding cassette transport proteins.
• Facilitates excretion of xenobiotics and
endogenous compounds.
• These proteins use ATP hydrolysis to drive
molecular transport.
• These resides on the canalicular surfaces of
hepatocytes and enables biliary excretion of
cationic compounds, including anticancer drugs.

26. Factors affecting Drug
Biotransformation
• Genetic factors
• Diet
• Environment
• Age
• Enzyme Induction/Inhibition
• Liver disease
• Cardiac disease

27. Hepatic drug clearance
• Factors : rate of hepatic blood flow, protein
binding, hepatic intrinsic clearance.
• Extraction ratio(E): amt of drug removed from
the blood during a simple pass through the
liver.
• Anesthetics significantly alter extraction by
reducing hepatic blood flow. Esp inhalational
agents.
• Also inhibition of CYP and Phase ii reactions.

29. LIVER FUNCTION TESTS
• AIM: to identify hepatic abnormality
• to differentiate hepatic
• obs/cholestatic disease.
• Assess the severity of hepatic abnormality.
• Identify the specific cause.
• Investigate the possible complications.

30. LFT contd…
• This group of tests include serum bilirubin,
SGOT, SGPT, AlkPO4, total protiens including
Albumin, globulin and A/G ratio.
• These are the biochemical
markers.

31. Serum Bilirubin
• It comprises of total bilirubin, indirect bilirubin
and direct bilirubin.
• Indirect is also unconjugated bilirubin normal
value is: 0.1-0.5mg/dl
• Direct is conjugated or water soluble bilirubin,
normal value: 0.1-0.5mg/dl
• Total bilirubin normal value:0.2-1.2mg/dl
• It is increased more rapidly in primary biliary
disease than hepatic disease(cirrhosis).

32. Albumin
• Produced in the liver.
• Plasma half life is 2 weeks.
• Hence may not be seen in acute liver failure
but definitely seen in chronic liver failure.
• Normal value: 3.2-5g/dl

33. SGPT/SGOT(AST/ALP)
• These are the enzymes in the hepatic cells
mainly the mitochondria.
• Hence when these enzymes are seen in the
circulation they denote hepatocellular
damage.
• Normal value <40.

34. Alkaline phosphate
• This is a collection of enzymes which cleave
phosphate esters in the alkaline environment.
• It is present in liver, bones, GIT etc..
• Undergo post transcriptional modifications in the
liver.
• Present in the biliary canaliculi and cell
membranes of hepatic sinusoids.
• Hence the raise indicates pathology in the
intra/extra hepatic biliary obs., and sinusoid obs.
• Normal value: 60-120mg/dl

35. INTERPRETATION
SGOT/SGPT BILIRUBIN ALKPO4
BILIARY OBS + ++ +++
HEPATITIS +++ + +
ALCOHOL/DRUGS N/+ ++ N

36. Other tests
• CBC- Hb may show anemia esp with the target
cells in jaundiced patients due to
macrocytosis.
• Leucopenia- complicates portal HTN and
hypersplenism.
• Leucocytosis- in hepatic abscess, alcoholic
hepatitis, cholangitis.
• Thrombocytopenia- in cirrhosis, due to dec in
thrombopoetin in liver, and hypersplenism.

37. Other tests… contd…
• Coagulation: K dependent factors.
• Normal half life is 5-72 hrs, hence can be seen
in chr.liver diseases, prothrombin time, INR
raised.

38. Take home msg
• Liver is a important organ, which as an
anesthesiologist should know as a whole.
• Upto 30% normal liver is essential for normal
function.
• Dual blood supply, upto 2l of blood pumped
into it.
• Numerous functions, which can be hampered
by various processes, drugs.

39. • Tests to confirm these disorders should be
asked for in patients with chronic diseases,
and habits.
• And based on which the anesthetic drugs
should be titrated, either reduce the dosage
or increase the time interval of adminstration.

40. GRATITUDE
• Millers Anesthesia 7th edition vol 1.
• Prys- Roberts textbook of Anesthesia 2nd
edition.
• Davidson’s textbook of medicine 21st ed.
• www.slideshare.org
• Image courtesy: google image search.

41. THANK YOU