A Review of Liver Anatomy and Physiology

By, Dr. Arun Kumar B.S.

PG, Dept of AnesthesiologyYMC

Moderator: Dr. Mallikarjun

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).

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 Rappaport’s 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 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.

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 flow.

• 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 GlycogenesisGlycogenolysis Gluconeogenesis

Fat metabolism - ketogenesis

Protein metabolism anabolism deamination urea formation

Secretion of bileDetoxificationMetabolism of

vitamins A,D,K,E & Clotting factors,

esp prothrombinStorage 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 5-

aminolevulinic 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 6- glucuronide 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/DRUGS N/+ ++ N

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.• Davidson’s textbook of medicine 21st ed.• www.slideshare.org• Image courtesy: google image search.

THANK YOU