Lecture 1: Liver Anatomy and Physiology

Question 1

Describe the general anatomy of the liver… lobules etc

Answer 1

8 Segements made into lobules
Each lobule is represented as a hexagonal cluster of hepatocytes which is connected to a central vein, hepatic portal vein, bile duct, hepatic artery.

Question 2

Draw a diagram of a liver lobule labelled correctly

Answer 2

Lecture slides

Question 3

Describe AND draw a flow diagram of the DUAL blood flow through the liver and Bile flow

Answer 3

Blood is conveyed to the lobules by branches of the hepatic portal vein and the hepatic artery.

It then flows through sinuses, bathing the hepatocytes, to the central vein of the lobule, a branch of the Hepatic vein which drains into the Inferior Vena Cava.

The hepatocytes secrete bile into bile canuliculi running between the hepatocytes, and these drain into branches of the bile duct.

Refer to lecture slides for diagram

Question 4

What is the challenge with liver cells

Answer 4

Lonely cells, very temperamental when outside the body

Cells die immediately and function is lost in order of hours.

Question 5

What are the cells that reside in the liver?

Answer 5

hepatocyte
stellate fat storing cell
Kupffer cell
liver endothelial cell

Question 6

Describe/explain hepatocyte cell functions

Answer 6

Also called parenchymal cells.

Make up 70 to 80 percent of the liver’s cytoplasmic mass.

Are involved in synthesizing protein, cholesterol, bile salts, fibrinogen, phospholipids and glycoproteins.

Question 7

Describe/explain endothelial cell functions

Answer 7

Transportation of WBC and increasing immune tolerance.

Secrete cytokines, which is a forem of cellular communication signal.

Question 8

Describe/explain kupffer cell functions

Answer 8

Reticuloendothelial cells of the liver

Secrete mediators of immune response system

Phagocytize bacteria, foreign material

Blood flowing through intestinal capillaries picks up many bacteria in intestines

Question 9

Describe/explain stellate cell functions

Answer 9

Exist in the space between parenchymal cells and sinusoidal endothelial cells

Vitamin A-storing cells, lipocytes, interstitial cells, fat-storing cells, promote ion movement and proliferation of chemical responses to stress.

Question 10

General functions of liver

Answer 10

Production of bile

Production of cholesterol, carbohydrate, proteins

Regulate blood levels of amino acids

Processing of haemoglobin for use of its iron content

Conversion of ammonia to urea

Detoxification of drugs
Regulate blood clotting

Question 11

What is Carbohydrate Metabolism regulation?

Answer 11

storage of glycogen

gluconeogenesis site

role in glucose homeostasis.

Question 12

What is Fat Metabolism regulation?

Answer 12

The liver is central to the processing of dietary fats to lipoproteins

Question 13

What is Protein Metabolism regulation?

Answer 13

De-animation of amino acids

Question 14

What is the function of protein metabolism?

Answer 14

Deamination of amino acids, conversion of the non-nitrogenous part of those molecules to glucose or lipids.

Formation of urea for removal of ammonia from the body fluids

Formation of plasma proteins – not gamma globulins

Interconversions of the various amino acids and synthesis of other compound from amino acids

Question 15

What is the function of proteins metabolism? IN HEPATIC DISEASE

Answer 15

Ammonia detoxification disorder and failure of urea formation
(ammonia comes from bacterial degradation of nitrogen substances in intestines, from intestine mucosa during glutamine degradation, from degradation of amino acids in kidneys and muscles)

Hyperamonemia
increase of ammonia blood concentration (>50 μmol/l)

Hepatic encephalopathy 
Toxic effect of ammonia in the brain (Binding of ammonia to glutamate = glutamine)
Mental changes (capriciousness, disorientation, sleeping disorders, chaotic speech, personality changes)	
Motoric changes (increased in muscle reactivity, hyperreflexion, tremor) 

Hepatic coma to death
Endogenous = viral hepatitis and poisoning (hepatic cells desintegration)
Exogenous = final status of chronic cirrhosis (ammonia and other toxic substances bypass the liver through the extrahepatic anastomoses)

Question 16

Draw the diagram of Liver and Amino acid metabolism

Answer 16

Lecture slides

Question 17

Function of carbohydrate metabolism

Answer 17

Storage of glycogen
Glucose buffer function = removing excess of glucose from blood, storage, fast return when the blood concentration decreases
Conversion of galactose/fructose to glucose

Question 18

What is glycogenolysis, glycogenesis, gluconeogenesis?

Answer 18

glycogenesis:
Excess glucose entering the blood after a meal is rapidly taken up by the liver and sequestered as the large polymer, glycogen

glycogenolysis:
When blood concentrations of glucose begin to decline, the liver activates other pathways which lead to depolymerization of glycogen to glucose

gluconeogenesis:
Synthesizing glucose out of such things as amino acids and non-hexose carbohydrates

Question 19

Carbohydrate metabolism in hepatic disease

Answer 19

Hyperglycaemia:
in patients with cirrhosis after carbohydrate rich meal.

liver insufficiency → decrease of glucose utilization → hyperglycemia → hyperinsulinemia → down-regulation of insulin receptors → insulin resistance

Hypoglycemia in alcohol abusers – alcohol suppresses citrate cycle and thereby impairs gluconeogenesis from amino acids. After depletion of glycogen storages comes hypoglycemia that threatens the patient’s life

Question 20

Fat metabolism function

Answer 20

Oxidation of fatty acids to supply energy for other body function

Synthesis of large quantities of cholesterol (80% of cholesterol synthesized in the liver is converted into bile salts), phospholipids, and most lipoproteins

Inactivation of steroids and their excretion of the body

Synthesis of lipoproteins, fat from proteins and carbohydrates

Remainder is excreted in bile as cholesterol or after conversion to bile acids.

Question 21

In bile formation there are two stages of secretion.

Answer 21

Initial portion is from hepatocytes (contains bile acids, cholesterol, organic constituents).Mostly bile acids
Additional secretion is a watery solution of sodium and bicarbonate – secreted by secretory epithelial cells lining the ductules and ducts. Neutralising gastric acid

Question 22

Bile composition

Answer 22

Water, electrolytes, cholestrol, phospholipids, bile acids, bilirubin

Question 23

Bile acid purpose

Answer 23

1. Fat emulsifation/absorption

2. Neutralisation of gastric acid

Question 24

what controls bile secretions?

Answer 24

Cholecystokinin (CCK)
Most potent stimulant for bile secretion
Stimulus for release = fat in duodenum

Secretin
Stimulated in response to acid in duodenum
Stimulates bile duct (and pancreas) to secrete bicarb and H20
Expands volume of bile and bile flow increases

Acetylcholine secreting nerve fibers
Not as potent, from vagi and enteric nervous system
ie smell food gastric system kicks in and pH drops, releases bicarbonate

Question 25

Process of Haem elimination

Answer 25

To be eliminated haem is changed to bilirubin in phagocytic cells, bound to albumin
Stripped off albumin in hepatocytes
Conjugated by addition of glucouronic acid
Excreted in stool as sterobilin

Question 26

Purpose of bile acids

Answer 26

Synthesized in the liver from cholesterol

Critical for absorption of fats and vitamins

Composition depends on species, but must be conjugated to taurine or glycine to be excreted

Question 27

Is cholesterol made into bile acids?

Answer 27

Yes.

When fat is consumed this is taken into as bile and this bile goes to the liver. Bile emulsifies the fat. Without Bile acids fat can not be transported to liver or absorbed in the body

Question 28

Bile in enterohepatic recirculation

Answer 28

95% bile acids are reabsorbed in ileum and circulated back to liver

Hepatocytes reabsorb essentially all bile acids in portal vein in healthy situation

In hepatocyte disease – decreased ability of cells to extract bile acids from portal system

Canilicular disease can result in leakage of bile acids back into systemic circulation

In shunting, bypass hepatocytes so don’t get reabsorbed and are elevated in systemic circulation (into blood system)