The liver is a critical organ in the human body responsible for an array of functions that help support metabolism, immunity, digestion, detoxification, and vitamin storage, among other functions. It comprises around 2% of an adult's body weight.

1. Liver Physiology and functions
Presenter-Dr.B M Arun Kumar
Moderator-Dr.Saraswathi Devi

2. • Second largest organ in the human body
• In newborns – 5% of TBW
• In adults – 2 to 2.5% of TBW
• Weight range is about 1.2 – 1.5 kgs in adults
• Situated in right hypochondrium,part of
epigastrium and extending into left
hypochondriac region

3. COUINAUD MODEL

4. CELLULAR ANATOMY
• LIVER LOBULE :
• Basic structural unit of hepatic parenchyma
• Hexagonal in shape with portal canal at each
corner and a hepatic venule located in center
( central vein )
• Portal canal : lymphatics, nerve fibers and
portal triad (bile ductule,hepatic arteriole and
portal venule )

5. • Array of anastomosing
cords of cuboidal
hepatocytes separated
by lacunae radiate from
portal areas and
converge on central
vein

6. LIVER ACINUS
• Acinus – smallest unit of liver and also
functional unit
• Portal triad at centre and central vein at
periphery
• Oxygenated and nutrient rich blood flows
from portal triad to central vein by hepatic
sinusoids

8. Micro circulation in acinus
• Zone 1 : periportal ( o2 rich
60-65 mmhg), rich in
mitochondrion , kreb’s and
urea cycle
• Zone 2: mid zone
• Zone 3 : centrilobular (30 –
35 mmhg o2), rich in smooth
endoplasmic reticulum ,
glycolysis, lipogenesis , bio
transformation,
glucuronidation

9. VASCULATURE OF LIVER
• Most vascular organ - 25% or 1/3rd
of cardiac
output is received
• Total blood flow is 1100 to 1800 ml /min
(100ml/100gm of tissue)
• Hepatic artery 25- 30 % of blood supply( br of
celiac trunk from aorta)
• Portal vein – 70-75 % of blood supply
(valveless vein formed by union of sup.
Mesenteric vein and splenic vein )

10. HEPATIC BLOOD FLOW
HEPATIC ARTERY PORTAL VEIN
% of total hepatic
blood supply
25-30% 70-75%
% of oxygen supply 45-50% 50-55%
Oxygen saturation 98 % 60-75%
Pressure 100mmhg 6-10mmhg

12. HEPATIC BLOOD FLOW REGULATION
INTRINSIC MECHANISM EXTRINSIC MECHANISM
Hepatic arterial buffer
response
Neural control
Metabolic control Humoral control
Pressure flow auto
regulation

13. Hepatic Arterial Buffer Response
• Changes in portal vein flow cause reciprocal
changes in hepatic artery flow
• Mediated through adenosine(potent vasodilator)
from periportal system
• When portal venous flow decreases , adenosine
accumulates causing arteriolar vasodilation
increasing HABF and vice versa
• HABR can double hepatic arterial flow at its
maximum response
• Hence,cannot fully restore hepatic blood flow
when portal venous flow falls more than 50%

14. DECREASE IN PORTAL VENOUS BLOOD FLOW
INCREASED ADENOSINE PRODUCTION IN
PERIPORTAL SYSTEM
HEPATIC ARTERY DILATION CAUSING
INCREASED BLOOD FLOW
At Maximum can double the flow
HEPATIC ARTERIAL BUFFER RESPONSE

15. Anaesthetic implication
• Halothane inhibits HABR. Hence despite
decrease in portal blood flow ( cardiac output)
hepatic artery doesn’t dilate
• Decreased o2 delivery- zone 3/ centrilobular
necrosis
• Other volatile anaesthetic do not inhibit HABR
at less than or at 1 MAC
• Endotoxemia and splanchic hypoperfusion
inhibits HABR

16. Metabolic control
• Caused by changes in ph and pO2 of portal
venous blood
• HABF increased by decreased portal venous
o2 tension and pH ( acidosis – arterial dilation)
• Post prandial state increases hepatic arterial
and portal venous blood flow

17. Pressure flow autoregulation
• Tendency for local blood flow to remain constant
in spite of changes in arterial pressure
• Mediated by myogenic response of vascular
smooth muscle to stretch
• Hypertension increases myogenic tone( increase
in trans mural pressure), decreases hepatic blood
flow and vice versa in hypotension
• Autoregulation is non existant in in portal
circulation

18. INCREASED BLOOD PRESSURE
PRESSURE OF MYOCYTES
INCREASES IN HEPATIC ARTERY
VESSEL CONTRACTILITY INCREASES
BLOOD FLOW DECREASES
PRESSURE FLOW AUTOREGULATION

19. Anaesthetic implication
• Active only in metabolically active liver
(postprandial) not in fasting state (NPO)
• Hence no role in intra op regulation of HABF
• Systemic hypotension under Anesthesia
decrease blood flow to liver

20. Neural control
• Mediated through vagus nerve, right phrenic
nerve and splanchic nerve ( post ganglionic
sympathetic fibers from T6 – T11)
• Decrease in sympathetic tone increases
splanchic reservoir volume
• Hepatic arterial system - alpha 1,2,beta 2 and
dopamine 1 receptors
• Portal venous system – alpha 1 and dopamine
1 receptors only
• Vagal stimulation causes redistribution of intra
hepatic BF without changing total BF

21. Humoral control
• Glucagon – relaxation of hepatic arterial smooth
muscle
• Angiotensin 2 – constriction of hepatic and portal
beds
• Vasopressin – increases hepatic arterial and
decreases portal venous resistance
• Epinephrine – in portal vein only vasoconstriction
and in hepatic artery gives biphasic response
(induces vasoconstriction via alpha followed by
vasodilation via beta receptors)

22. FACTORS AFFECTING HBF
INCREASE IN HBF
• Feeding
• Glucagon
• Beta agonist
• Hepercapnia,acidosis
• Recumbent position
• Low dose dopamine
• Enzyme inducing drugs
DECREASE IN HBF
• Most of the anaesthetic
agents
• IPPV( decreased CO)
• PEEP
• Alpha agonist
• Beta blocker
• Hypocapnia ,alkalosis
• Hypoxia ( symp
stimulatn)

23. Effect of volatile agents on HBF
• Halothane : inhibit HABR, decrease HABF
• Enflurane : decrease HABF vascular resistance
• Isoflurane : preserves HABR.Vasodialation of
hepatic vasculature . Agent of choice in liver
disease patients
• Sevoflurane and desflurane : preserve HBF and
function
• Nitrous oxide : decreases HBF alpha
adrenoreceptor stimulation

24. Effect of intravenous agents on HBF
• Propofol : reduces HBF in dose dependant
manner
• Ketamine : no much change
• Thiopentone : any decrease in CO decreases
HBF
• Etomidate : decreases HBF

25. Others
• OPIODS : Fentanyl – better o2 supply
• Morphine at smaller dose dilates splanchic
vasculature but at higher dose cause
vasoconstriction
• Regional anaesthesia : decreased HBF d/t
hypotension
• General anaesthesia : decreased HBF d/ t
decreased cardiac output and sympathetic
blockade by various drugs used

26. Functions of liver
• STORAGE
 800 – 1000ml of blood
Fat soluble vitamins
VIT B 12 up to 1 year storage
Vit A upto 12 weeks
Vit D upto 6months
Vit K only upto 1 week
Glycogen

27. • SYNTHESIS :
15%of albumin
Produces about 15-50 gm of plasma protein /day
Clotting factors
Erythropoietin in fetuses and neonate upto 2
days
Thrombopoietin
Angiotensinogen and conversion to AT 1
Pseudocholinesterase
Urea production

28. • METABOLISM :
 Glycogenolysis and gluconeogenesis
Lipogenesis and lipolysis
Synthesis of non essential amino acids
 Lipid and lipoprotein metabolism
Bilirubin metabolism
Elimination of drugs
Harmones and harmone binding protein
regulation

29. Effect of hepatic dysfunction on anaesthesia
• Decreased albumin – increased free fraction of
drugs, hence dosage of the drug should be
reduced
• Increased volume of distribution due to
decreased oncotic pressure intra vascularly
• Decreased drug metabolism - prolong duration of
action of drugs mainly sedatives and hypnotics
• Reduced elimination and prolong duration of
action of vec, rocuronium specially with infusion
and repeated doses

30. • Prolonged opioid action can increase resp.
Depression and sedation
• Since morphine mainly metabolised in liver by
glucuronidation ,any liver disease prolongs it’s
action
• Prolonged DMR action d/t decreased pseudo
cholinesterase production
• But atracurium and cis atracurium can be given
in end stage liver diseases d/t it’s Hoffman’s
elimination

31. LIVER FUNCTION TEST
• Tests for hepatocellular injury ( serum
aminotransferases, LDH ,GST)
• Tests for obstructed bile flow ( alkaline phosphates
,GGT ,5’ nucleotidase)
• Tests based on detoxification and excretory
functions( s. bilirubin)
• Tests that measure biosynthetic functions of liver (
S.Albumin,coagulation profile , prothrombin time,
INR )
• Tests of hepatic blood flow and metabolic capacity

33. Serum aminotransferases
• Hepatocytes contain high levels of enzymes
that can leak into the plasma when there is
liver injury
• Enzymes found in hepatocytes are :
Cytoplasmic – LDH,AST,ALT
Mitochondrial – ASTm
Canalicular – ALP,GGT

34. ALT/SGPT
• Normal 5- 45 IU/L
• Cytosolic enzyme
• Liver specific ,primarily
synthesised in liver
• T1/2 is 18 hrs
AST/SGOT
• Normal 5-30 IU/L
• Mitochondrial enzyme
• Present in
liver ,heart,skeletal
muscles, kidney and
adipose tissue
• T1/2 – 36hrs

35. AST to ALT ratio
• < 1 – non alcoholic steatohepatitis
• 2-4 – alcoholic liver disease ( as alcohol affects
mitochondria ,SGOT/AST levels raise )
• >4 – wilsons disease

36. Lactate Dehydrogenase
• Elevation may be due to hepatocellular injury
or extrahepatic disorder or both
• Extrahepatic involves – hemolysis ,
rhabdomyolysis, MI , CVA , renal infarction

37. ALKALINE PHOSPHATASE
• Normal value : male – 35- 115 IU/L
female – 25 -95IU/L
• Circulating half life 7days
• Present in the biliary canaliculi and sinusoidal
surface of hepatocytes and hence elevated in
cholestatic disorders ( intra or extra hepatic
obstruction)
• Lacks specifity as isoforms are present in bone
osteoblast, intestine, placenta , kidney

38. • Major rise is seen in primary biliary cirrhosis,
choledocholithiasis, malignancy (primary or
metastatic) compressing bile ducts
• ALT : AP >5 hepatocellular injury from
cholestatic disease
• ALT : AP <2 hepatocellular injury from mixed
picture

39. SERUM BILIRUBIN
• It is determined by van den Bergh reaction which
separates bilirubin in to two fractions
• A water soluble ,direct reacting form
representing conjugated bilirubin and a lipid
soluble ,indirect reacting form representing
unconjugated bilirubin
• Indirect positive – hemolytic jaundice
• Direct positive – obstructive jaundice
• Biphasic – hepatic jaundice

40. SERUM ALBUMIN
• Synthesised exclusively by hepatocytes and is the
main constituent of total body protein
• Normal – 3.9 – 5.0 gm/dl
• Long T1/2 of 15 -20 days with 4% degraded/day
• Because of this slow turn over , it is a better
indicator of chronic liver disease such as cirrhosis
and reflects severe liver damage
• Hypoalbuminaemia is not specific for liver disease
and may occur in protein malnutrition of any cause
as well as protein losing enteropathies , nephrotic
syndrome

41. COAGULATION PROFILE
• With exception of factor Vlll and vWF ,blood
clotting factors are made exclusively in
hepatocytes
• Their serum T1/2 are shorter than albumin ,
ranging from 4hrs for factors Vll to 4 days for
fibrinogen
• Rapid turn over – measuring clotting factors is
single best acute measure of hepatic synthetic
function and helpful in both diagnosing &
assesing prognosis of acute parenchymal liver
disease

42. • Coagulation factors 2,7,9,10 as well as protein C
& S undergo post translational modification with
Vit K to become active
• Coagulation profile assessment is necessary for
planning neuraxial anaesthesia ,especially when
patient is on anticoagulants

43. PROTHROMBIN TIME
• Normal 11-14 sec
• Prolongation of PT greater than 3-4 sec from
control are considered significant
• Usually corresponds to INR greater than 1.5

44. INR
• It is used to decrease inter laboratory variations
in values of PT
• INR = PT(patient )/ PT (control) ISI , where ISI is
international sensitivity index of thromboplastin
used by the lab
• Collectively measures extrinsic pathway
coagulation factors (2,5,7,9 & fibrinogen)
• Biosynthesis ( gamma carboxylation ) of these
factors depends on vit k

45. • PT is elevated in hepatitis & cirrhosis as well as
disorders that lead to Vit K deficiency such as
obstructive jaundice /fat malabsorption of any
kind

46. THANK YOU