A Review of Liver Anatomy

and Physiology
By,
Dr. Arun Kumar B.S.
PG, Dept of Anesthesiology
YMC
Moderator: Dr. Mallikarjun

TRIVIA
Largest internal organ weighing approx 1.21.5kg 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).

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.

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 Rappaports
acinus: the parenchymal mass in
between two centrilobular veins.
Centre formed by portal triad( PV,
HA, BC, nerves and lymphatics).

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.

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

Hepatic blood supply

Dual supply of Portal vein and
Hepatic artery.
Portal vein 55-60% of the total blood,
45% oxygenation, hepatic artery 4450% 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

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.

 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.

 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

 Effect of intravenous agents:

thiopentone, etomidate, propofol
produces dose dependant reduction
in the hepatic blood flow.

REVIEW OF ANATOMY AND

PHYSIOLOGY
FUNCTIONS OF THE
LIVER:
Carbohydrate
metabolism
Glycogenesis
Glycogenolysis
Gluconeogenesis

Fat metabolism ketogenesis

Protein metabolism
anabolism
deamination
urea formation

Secretion of bile
Detoxification
Metabolism of
vitamins A,D,K,E
&
Clotting factors,
esp prothrombin
Storage
Blood store

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 5aminolevulinic acid catalysed by ALA
synthetase.

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.

Xenobiotic
Biotransformation

It is divided into
Phase I reaction.
Phase II reaction.
Phase III reaction.

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.

CYP 450 inhibitors

Grapefruit juice.
erythromycin,
isoniazid,
sulfonamides,
ketoconazole

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.

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 6glucuronide a potent byproduct which is
responsible for some of the analgesia
produced by morphine.

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.

Factors affecting Drug

Biotransformation

Genetic factors
Diet
Environment
Age
Enzyme Induction/Inhibition
Liver disease
Cardiac disease

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.

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.

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.

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).

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

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.

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

INTERPRETATION
SGOT/SGPT

BILIRUBIN

ALKPO4

BILIARY OBS

++

+++

HEPATITIS

+++

++

ALCOHOL/DRUG N/+
S

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.

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.

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.

 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.

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

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