APPLIED ANATOMY AND HISTOLOGY OF LIVER, HEPATIC CIRCULATION AND FACTORS AFFECTING HEPATIC BLOOD FLOW

DR KAVITHA LAKSHMAN

University College of Medical Science & GTB Hospital, Delhi

ANATOMY OF THE LIVER

Largest gland, largest reticuloendothelial organ Weighs around 1.2 to 1.6 Kg Occupies the right upper quadrant of the abdomen Invested in peritoneum except gallbladder bed, IVC, bare area of liver Ligaments- duplication of peritoneum over the liver

EXTERNAL FEATURES OF LIVER

DIVISIONS OF THE LIVER

Falciform ligamentoversimplified,anatomically incorrect Cantlie's line- a plane running from the gallbladder to the left side of the IVC Couinads segments- 8 functional segments, each supplied by a pedicle Bismuths classification- 4 sectors separated by scissurae containing the three main Hepatic vein

SEGMENTS OF LIVER

SECTORS OF LIVER

BILE DUCT

NERVE SUPPLY AND LYMPHATIC

Sympathetic nerve fibers Parasympathetic fibers T6T11 Rt&Lt vagus Rt Phenic.N Superficial lymphatics:Surface of organ and terminate in Caval ,Hepatic,Celiac lymph nodes

Deep lymphatics: IVC and Hepatic nodes

HISTOLOGY OF THE LIVER

HEPATOCYTES

HEPATOCYTES
Hepatocytes - polyhedral , with a central spherical nucleus. Single-cell-layer plates Lined on either sides by sinusoids. Every hepatocyte has contact with adjacent hepatocytes, the biliary space (bile canaliculus), and the sinusoidal space, allowing its broad range of functions

SINUSOIDS
Sinusoids are blood filled spaces 10um in diameter Hepatic and Portal blood mixes here Endothelial cells -lack intercellular junctions -Absence of basement membrane -Contain multiple and large fenestrations. Maximal contact of hepatocyte membrane(space of Disse) and blood in the sinusoidal space. Permits free bidirectional movement of solutes

KUFFER CELLS
Resident macrophages line sinusoids Partly derived from bone marrow monocytes Clearance of gut derived toxins Engulf debris and dead rbcs Secrete cytokines IL-1,IL-6,TNF alfa Express class II MHC- antigen presentation

KUFFER CELL

ITO CELLS
Found in the space of Disse. They have dendritic processes which are in contact with hepatocyte microvilli and endothelial cells. Vitamin A storage Synthesis of extracellular collagen. Play a central role in the development and progression of hepatic fibrosis

HEPATIC LOBULE
50,000-100000 lobules Functional unit of the liver

PORTAL TRIAD

HEPATIC ARCHITECTURE

FUNCTIONS OF HEPATOCYTES
Metabolism of proteins, carbohydrates, lipids Metabolism of heme, bile Synthesis of coagulants-2,7,9,10,protein S,C Drug metabolism Immune defense

DRUG METABOLISM
Phase 1 Metabolism e.g. oxidations, reductions, hydrolysis convert drugs to more polar compounds The products of phase 1 metabolism are -Readily excreted in bile or urine than their precursors are. -These products may also be substrates for phase 2 conjugations.

Phase 2 metabolism Conjugate xenobiotics or their metabolites with endogenous hydrophilic molecules such as glucuronic acid, acetate, sulfates, amino acids, and glutathione, glucuronic acid etc When compared with their precursors, conjugated xenobiotics are usually less efficacious, less toxic, more hydrophilic, and more readily excreted in bile or urine.

Phase 3 Elimination Involve specific molecular transportersknown as ATP-binding cassette (ABC) transport proteinsthat facilitate the excretion of xenobiotics and endogenous compounds. These proteins use ATP hydrolysis to drive molecular transport. Major ABC transport proteins include cystic fibrosis transmembrane conductance regulator (CFTR), canalicular copper transporters, and multidrug resistance protein (MDR).

 dysfunction of ABC transport proteins can disrupt the flow of bile, impair excretion of xenobiotics and endogenous compounds, and induce cholestatic liver injury.

Blood supply of liver

The liver is at the hub of the splanchnic circulation. Receives 25% of the total cardiac output via a dual vascular supply. Arterial blood is supplied via the hepatic arterya branch of the common hepatic artery that has its origin at the celiac trunk of the abdominal aorta On the other hand, the portal vein has as its tributaries the superior mesenteric and splenic veins, which carry the entire venous drainage of the preportal splanchnic beds.

HEPATIC ARTERY
% BLOOD FLOW %O2 SUPPLY 25-30% 45-55%

PORTAL VEIN

70-75% 50-60%

OXY SAT
PRESSURE AUTOREGULATION

98%
90 mmHg PRESENT

60-75%
5-13mm Hg ABSENT

HA+PV HEPATIC ARTERIOLE+PORTAL VENULE

SINUSOIDS(FENESTERATED ENOTHELIUM)
HEPATOCYTES SINUSOIDS SPACE OF DISSE CENTRAL VEIN(TERMINALHEPATIC VENULE) LOBULE MAIN HEPATIC VEIN IVC

PORTAL VEIN
Begins and ends in a network of capillaries lack of valves - accommodate high flow at low pressure because of the low resistance 75% of hepatic blood flow Postcapillary and largely deoxygenated large-volume flow rate provides 50% to 70% of the liver's oxygenation.

 Numerous connections exists between the portal venous system and the systemic venous system. Provide collateral supply under conditions of high portal venous pressure 1. Submucosal veins of the proximal stomach and distal esophagus, which receive portal flow from the short gastric veins and the left gastric vein 2.Umbilical and abdominal wall veins, which recanalize from flow through the umbilical vein in the ligamentum teres 3.Superior hemorrhoidal plexus, which receives portal flow from inferior mesenteric vein tributaries

FACTORS AFFECTING THE HEPATIC BLOOD FLOW

INTRINSIC REGULATION HEPATIC ARTERIAL BUFFER RESPONSE METABOLIC CONTROL PRESSURE FLOW AUTO REGULATION EXTRINSIC REGULATION NEURAL CONTROL HUMORAL CONTROL

HEPATIC ARTERIAL BUFFER RESPONSE

Change in portal venous flow-reciprocal change in hepatic arterial flow Adenosine in periportal region Can double hepatic arterial flow Disrupted in endotoxemia , splancnic hypoperfusion, portal inflow falls by >50%

PRESSURE FLOW AUTOREGULATION

Myogenic response vascular smooth muscle Transmural pressure-myogenic tone-vessel caliber-dec blood flow Hepatic artery-present Fed state- active Is of minimal significance intraoperatively

METABOLIC CONTROL
Low pH and oxygen tension portal blood increases hepatic blood flow Postprandial hyperosmolarity increases both hepatic and portal blood flow

NEURAL CONTROL
Post ganglionic sym. T6-T11 Vagus ,Phrenic nerve Sympathoadrenal stimulation (hypercarbia,hypoxia,pain) vasoconstrictiondecrease in hbf With in sec, splanchnic stimulation autotransfuse 400500 ml (80% total hepatic blood vol)into central circulation in healthy euvolemic individuals

HUMORAL CONTROL
EPINEPHRINE
Hepatic a. vasoconstriction followed by vasodilation Portal v--- vasoconstriction

DOPAMINE

-vasodilation

Glucagon

-vasodilation

Angitention II -vasoconstriction

Vasopressin constricts splanchic arterial bed decreases portal venous resistance

FACTORS INCREASING HEPATIC BLOOD FLOW HYPERCAPNIA AC.HEPATITIS VIRAL,ALCOHOLIC SUPINE POSTION FOOD DRUGS B-AGONIST PHENOBARBITONE

FACTORS DECREASING HEPATIC BLOOD FLOW IPPV+PEEP SURGERY HYPOCAPNIA;HYPOXIA UPRIGHT POSTURE CIRRHOSIS DRUGS A-AGONIST B-BLOCKERS H2 BLOCKERS CIMETIDINE,RANITIDINE,VASO PRESSIN ANESTHETICS-VOLATILE AND INTRAVENOUS

EFFECT OF ANAESTHESIA ON HEPATIC BLOOD FLOW

Hepatic blood flow usually decreases during regional and general anesthesia All volatile anesthetic agents reduce portal hepatic blood flow- halothane Indution agents- ketamine increases flow GA-decrease in map, co, reflex sympathetic stimulation Spinal and epidural anesthesia decrease hepatic blood flow primarily by lowering arterial blood pressure.

Ventilation- IPPV, PEEP Surgery direct vascular compression, local reflexes, reflex sympathetic stimulation

REFERENCES
PHILIP SM, SIMON G, HEPATIC PHYSIOLOGY AND PATHOLOGY,MILLERS 7TH EDITION,411-435 BRAIN S, DAVID ROCCAFORTE. HEPATIC ANATOMY, FUNCTION AND PHYSIOLOGY. CLINICAL ANAESTHESIA,6TH EDITION,1247-78 EDWARD MORGAN . HEPATIC PHYSIOLOGY AND ANAESTHESIA.CLINICAL ANAESTHESIOLOGY, 4TH EDITION INTERNATIONAL PRACTICE OF ANAESTHESIA, PRYS ROBERTS MICHAEL A, YUMNG F, ANATOMY AND PHYSIOLOGY OF THE LIVER,SABISTON TEXT BOOK OF SURGERY, 18TH EDITION NEIL R B,ANATOMY OF THE LIVER .GRAYS ANATOMY 39TH EDITION HEPATIC PHYSIOLOGY,GANONG 22ND EDITION STOELTING R, HILLIER S, LIVER AND GASTROINTESTINAL TRACT PHARMACOLOGY AND PHYSIOLOGY IN ANAESTHETIC PRACTICE, 4TH EDITION

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