The liver performs many essential functions including metabolism, synthesis of proteins and clotting factors, and storage of vitamins and minerals. It receives approximately 1.5 L of blood per minute, regulated through intrinsic and extrinsic mechanisms. The basic structural and functional unit of the liver is the lobule, containing hepatocytes arranged in plates around a central vein. Anaesthetic agents can impact hepatic blood flow and metabolism. Tests of liver function include albumin and clotting factors to assess synthesis, and AST, ALT, alkaline phosphatase and bilirubin to detect cellular injury.

1. HEPATIC
PHYSIOLOGY AND
EFFECT OF
ANAESTHETIC
AGENTS

2. HEPATIC
PHYSIOLOGY
Presenter:
Dr.Waquas Ahmed
Junior Resident-1
Department of Anaesthesiology
& Critical Care Medicine
Moderator:
Dr. Bibha
Assistant Professor
Department of Anaesthesiology &
Critical Care Medicine

3. INTRODUCTION
■ Liver is the largest internal organ.
■ Weighs 1.5 kg or about 2% of the total body weight in an adult.
■ Hepatic blood flow is 1.5L/min (25% of the Cardiac Output)
■ Right lobe: Left lobe = 6:1
■ In the right mid axillary line, the liver spans from the 7th to the 11th ribs.
■ It is covered by the peritoneum (Glisson’s capsule), except for the gall bladder
bed, the inferior venacava, the bare area, and the porta hepatis.
■ Nerve plexus fibres: Sympathetic gangliaT7-T10, Right & LeftVagi & Phrenic
nerve
■ Lypmhatic vessels: glands around porta hepatis, coeliac glands, diaphragm,
mediastinal, thoracicVC

5. FUNCTIONAL UNIT OF LIVER: LOBULE
■ Described by Kiernan in 1833 as functional and structural unit of liver
■ Roughly 1 X 2 mm
■ Hexagonal structure
■ Human liver contains 50,000 to 100,000 lobules
■ Plates of hepatocytes located in a radial distribution about a central vein
■ Afferent blood supply from portal vein and hepatic arterioles enters at the
periphery of the lobule.
■ Bile formed in the hepatocytes flows into canaliculi located between the
plates of hepatocytes.

6. Fig: A sketch over the liver and
the hepatic microstructures

7. Hepatic Lobule
■ Central:
Tributary of hepatic vein
■ Periphery:
A triad of branches of the
 hepatic artery
 the portal vein
 the bile duct

8. The concept of the Liver Acinus
■ Functional microvascular unit of the liver.
■ This concept was first defined by Rappaport et al. in 1954
■ Important in describing some structural-functional relationships of the
hepatic lobule
■ There exists a gradient of oxygen and nutrition concentration along the
sinusoids

10. Fig: The concept of the liver
acinus

11. ■ The activity of each hepatocyte is determined by its position
along this oxygen-nutrient gradient, which gives rise to three
zones; zone 1, zone 2 and zone 3.
■ Zone 1 is the most oxygen- and nutrient-rich zone which has a
metabolic activity different from the one in zone 3.
■ Zone 3 is exposed to the lowest concentrations of oxygen and
nutrition

12. TYPES OF LIVER CELLS
SINUSOIDAL ENDOTHELIAL CELLS:
 These are different form the endothelium in the rest of the body
 Large pores in between the cells are called fenestrae
 The fenestrae allow passage of relatively large particles out of the blood
like albumin, lipds and lipoproteins
 They lack the basement membrane thus have increased endothelium
permeability

13. TYPES OF LIVER CELLS
HEPATIC EPITHELIAL CELLS:
 Liver parenchymal cells referred to as Hepatocyte commonly.
 Highly polarized epithelial cells and serve as metabolic factories of the
liver.
 Heterogenous plasma membranes with three distinct specialized
domains.
 Ability to regenerate.

16. HEPATIC BLOOD FLOW

17. REGULATION OF HEPATIC BLOOD
FLOW
INTRINSIC MECHANISM
 HEPATIC ARTERIAL
BUFFER RESPONSE
(HABR)
 METABOLIC CONTROL
 PRESSURE-FLOW
AURTOREGULATION
EXTRINSIC MECHANISM
 NEURAL CONTROL
 HUMORAL CONTROL

18. INTRINSIC
MECHANISM

19. HEPATIC ARTERIAL BUFFER RESPONSE
■ Most important intrinsic buffer response.
■ Changes in portal venous flow cause reciprocal changes in hepatic
arterial flow.
■ When portal venous flow decreases, the HABR compensates by
increasing hepatic arterial flow and vice versa.
■ Mechanism involves the synthesis and washout of adenosine (i.e., a
vasodilator) from periportal regions.
■ HABR can nearly double the hepatic flow.

20. METABOLIC CONTROL
■ Decrease oxygen tension or the pH of portal venous blood increase
hepatic arterial flow.
■ Postprandial hyperosmolarity increases both hepatic and portal venous
flow.

21. PRESSURE-FLOW AUTOREGULATION
■ Enables tissue-specific regulators to govern organ blood flow despite
fluctuations in systemic arterial pressure.
■ Mechanism involves myogenic responses of vascular smooth muscle to
stretch.

22. EXTRINSIC MECHANISM

23. NEURAL CONTROL
■ Fibres of the vagus, phrenic and splanchnic nerves (post ganglionic
sympathetic fibers fromT5 throughT11) enter the liver at the hilum.
■ When sympathetic tone decreases, splanchnic reservoir volume
increases.
■ Sympathetic nerve stimulation may reduce hepatic blood volume by up
to 50 per cent.

24. HUMORAL CONTROL
■ Glucagon induces dose-dependent relaxation of hepatic arterial smooth
muscles.
■ Hence blocks the effects of physiologic vasoconstrictors on the hepatic
artery.
■ Angiotensin-II constricts the hepatic arterial and portal venous beds.

26. ■ High blood flow of liver is due to low vascular resistance in
portal vein.
■ Average PortalVein Pressure (PVP) is 8 to 10 mm of Hg.
■ PVP exceeds hepatic venous pressure by 4 to 5 mm of Hg.
■ Hepatic venous pressure gradient > 5mm of Hg is
abnormal and called Portal Hypertension

27. Venous drainage of the liver:
Hepatic Sinusoids
CentralVeins
Interlobular & Supralobular veins
3 Hepatic veins
InferiorVena Cava

28. LYMPHATICS
■ The liver has a high blood flow and a highly permeable microcirculation.
The consequent production of interstitial fluid, intrahepatic lymph, is
formed in the perisinusoidal space of Disse between the hepatocytes
and sinusoidal lining endothelium.
■ Lymphatic vessels drain via the portal tracts, closely applied to the
hepatic arterial branches, to the hilum and thence to the thoracic duct.
■ Some interstitial fluid drains through Glisson's capsule into the
peritoneum.
■ The lymph flow rate in liver is approximately 0.5 ml/kg of liver per
minute making up 25 to 50 per cent of thoracic duct lymph flow.

29. Lymphatic drainage:
SUPERFICIAL DEEP
CAVAL
HEPATIC
COELIAC
PARACARDIAL
NODES AROUND
IVC & HEPATIC NODES

30. Liver Functions:
■ SYNTHESIS
■ METABOLISM
■ STORAGE

31. SYNTHESIS
■ Carrier/modulator proteins such as albumin, complement,
coagulation factors, transferrin, ceruloplasmin, thyroid-binding
globulin, haptoglobin, globulins & alpha-1-antitripsin
■ Enzymes, i.e pseudocholinesteraze
■ Bile acids
■ Lymph (50%)
■ Erythropoesis, mainly in the foetus

32. METABOLISM
■ Carbohydrate, protein, lipids
■ Bilirubin via conjugation
■ Hormones (cortisol, oestrogens, vasopressin, aldosteron,
thyroxine)
■ Drugs via oxidation, reduction, hydrolysis, methylation,
acetylation.
■ Old erythrocytes
■ Antigens and bacteria

33. STORAGE
■ Glycogen
■ Vitamins A, D, K, B12 and folate
■ Blood-approximately 10-15% of the total blood volume

34. LIVER STORES
■ 1 L of Blood
■ Vitamin B12 (1 year supply)
■ Vitamin D (3 month supply)
■ Vitamin A (10 month supply)
■ Iron (Ferritin)

35. METABOLIC FUNCTIONS
■ Carbohydrate metabolism-glucose buffer function
■ Protein metabolism
– deamination
– urea cycle
– interconversions between nonessential amino acids
■ Lipid metabolism
– β oxidation of FA→AcetylCoA→ketone bodies
– FFA esterified to formTAG.
– lipoprotein synthesis
– phospholipids & cholesterol synthesis
Glycogenesis Gloconeogenesis
EUGLYCEMIA
Glycogenolysis SURGICAL STRESS

36. SYNTHETIC FUNCTIONS:
■ PLASMA PROTEINS
 Albumin (12-15g/day)
 Globulins
■ CLOTTING FACTORS- all coagulation factors except factor III (tissue thromboplastin),
IV (Calcium) &VIII (vonWillebrand factor)
■ ANTITHROMBIN III, PROTEINC & S, Plasminogen activator inhibitor (PAI)
■ ENZYMES-ALP,AST (SGOT),ALT (SGPT)
■ PSEUDOCHOLINESTERASE
■ CHOLESTEROL, LIPOPROTEINS ,PHOSPHOLIPIDS
■ ACUTE PHASE REACTANTS

37. BILE SYNTHESIS
■ BILE EXCRETION: 600-1200ml/day
CHOLESTEROL
BILE ACIDS & BILE SALTS
ACTIVATION OF LIPASE EMULSIFICATIONOF FAT

38. ASSESSMENT OF HEPATIC FUNCTION

39. AST (Aspartate aminotransferase) &
ALT (Alanine aminotransferase)
■ Assess cellular injury & not function
■ AST is also found in nonhepatic tissues like heart, skeletal
muscle, kidney, and brain.
■ ALT is primarily localized to liver.
■ The AST/ALT ratio is helpful in differentiating aloholic liver
disease (ratio is >2) from viral hepatitis (ratio <1)

40. Indices of Bile Flow Obstruction
■ Alkaline Phosphatase (AP)
■ 5’-Nucleotidase (5’-NT)
■ 𝝲-glutamyl transferase (GGT)
■ Bilirubin

41. Tests of hepatic synthetic functioning
Serum Proteins:
Albumin, Globulin
Serum albumin is not a reliable marker
of acute liver disease as its half-life is 3
weeks.
Coagulation testing:
PT & INR
■ Sensitive indicators of hepatic
disease because of the short half-life
of factorVII.
■ The PT depends on sufficient intake
ofVitamin K, which in turn depends
on adequate biliary secretion of bile
salts.