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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.
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.
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.
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.
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.
Genetic factors
Diet
Environment
Age
Enzyme Induction/Inhibition
Liver disease
Cardiac disease
LFT contd
This group of tests include serum
bilirubin, SGOT, SGPT, AlkPO4, total
protiens including Albumin, globulin
and A/G ratio.
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.
GRATITUDE
Millers Anesthesia 7th edition vol 1.
Prys- Roberts textbook of Anesthesia
2nd edition.
Davidsons textbook of medicine 21st
ed.
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