Download Gastro43-PhysiologyoftheLiver

Tuesday, March 04, 2003 [10AM]
Dr. Gwirtz
Jack Sun for Shane Ashford
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Physiology of the Liver
Lab practical grades:
 class average = 91.4
 A = 86
 B = 29
 C=6
 <C = 2
Dr. Gwirtz will not cover too much on bilirubin because it has been previously covered during previous
courses and during CIL.
Dr. Gwirtz expects us to know the following during this Lecture: (Pay special attention to these topics)
 Functions of the liver
o Synthesis of plasma protein – Albumin being the most important
o Regulation of blood glucose level, lipids and proteins
o Serves as a blood reservoir ( know how the liver accomplishes this)
o Storage site for iron, vitamins
o Removal of drugs and hormones
Liver Lobule
 plates of hepatocytes synthesize bile and dump
their contents in to the bile canaliculi which will
eventually lead to the bile duct
 portal vein brings blood from splanchnic organs
o supplies liver with nutrients, amino acids,
monosaccharide
Hepatocytes
Features of the Liver:
 liver is 2.5% of body weight
 it receives 25% of cardiac output via hepatic portal vein and hepatic artery
o 70-80% of blood liver receives comes from portal vein (Deoxygenated blood)
o 20-30% comes from hepatic artery (Oxygenated blood)
o If there is a decrease in hepatic artery blood supply, the portal circulation increase and with
increase in portal circulation there will be decrease in hepatic artery circulation
o Importance: the liver has dual circulation to compensate if something goes wrong
 Liver is important in maintenance of blood glucose levels
 regulates blood lipids levels by secreting VLDLs
 synthesizes and secretes many circulating plasma proteins (important in maintaining plasma
osmolarity)
 metabolizes drugs and toxic substances taken up by portal circulation
o liver is one of the first places ingested drugs will hit and from therein it will be quickly
removed from the body by excreting through the bile
o liver also excretes bile pigments, cholesterol and drugs
 performs endocrine functions
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Anatomy of the Liver
 Liver lobule is the basic functional unit of the liver which is comprised of hepatic cellular plates
 It contains central vein, portal vein, hepatic artery – these all make up the Portal Triad
 Liver also has high lymph flow
 Bile canaliculi
o Bile synthesized from the hepatocytes travel down the bile canaliculi to join the bile duct to
be transported outside of the liver
o Lined with hepatocytes with tight junctions among the hepatocytes
o Space of Disse
 Space between sinusoidal plates (cells) and hepatocytes
 Perisinusoid space lined with endothelial cells
 It connects with the lymphatic vessels
 Sinusoidal cells have endothelial lining and large pores
 Kupffer cells are the resident macrophages of the liver – derived from monocytes
 Ito cells are fat storage cells
 liver contains bile ductules and ducts which lead to join the pancreatic duct and together they
empty into the Major duodenal Papilla controlled by the Sphincter of Oddi
o contraction of Sphincter of Oddi inhibits bile and pancreatic juice flow into the small
intestines
o relaxation allows bile and pancreatic juice to flow
Hepatic Cell Types
 Hepatocyte
o located in parenchyma
o intermediary metabolism, detoxification of drugs, synthesis of protein, formation of bile
 Endothelial Cell
o located in sinusoids
o pores keep back formed elements of the blood but permit passage of macromolecules that are
smaller than the elements of the blood
 Kupffer Cell
o Located in intrasinusoidal sites
o Role equal that of macrophages
o phagocytosis of blood elements, pathogens (bacteria, virus) and dead liver cells
 Bile Ductular Epithelial Cell
o secretion of bicarbonate
o Secretin stimulates the Bile Ductular Epithelial cells to secrete bicarbonate
 Ito Cell - fat storage cells
o perisinusoidal sites (space of Disse)
o storage of vitamin A, synthesis of collagen following liver injury, perhaps regulation of
sinusoidal resistance and endothelial permeability
 regulation of capillary filtration in the liver
Blood Supply to the Liver
 High blood flow
 Hepatic portal vein
o 70-80% of blood supply
o poorly oxygenated blood
o branches to form small venules
o empties into sinusoids
 Hepatic artery
o 20-30% of blood supply
o high in oxygen content; this is where the liver receives its oxygen
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o branches to form arterioles, capillaries which also drains into sinusoids
 Hepatic Sinusoids
o very porous (large seivelike plates) for exchange of materials between perisinusoidal space
and sinusoids
o allows material to move through and between them
o empty into central veins, which join to form hepatic vein, which joins inferior vena cava
Liver as Blood Reservoir
 Liver is an expandable organ & large quantities of blood stored in blood vessels
 Normal blood volume of liver = hepatic veins + hepatic sinuses = 450 ml
o 10 % of total blood volume
 During exercise or even severe blood loss, blood in the liver will move into the systemic
circulation to keep blood pressure up
 High pressure in right atrium  back pressure in the liver
o During right heart failure,
 Venous pressure is going to increase;
 Capillary filtration will increase, moving more fluid from systemic circulation into the
liver.
 Edema formation in the liver will soon follow
 The liver gets encapsulated and too much fluid builds up in the liver and the fluid
eventually goes into the abdominal cavity forming an Ascites
o liver expands and 0.5 to 1 liter of extra blood can be stored in the hepatic veins and sinuses
o liver is a large, expandable, venous organ capable of acting as a valuable blood reservoir in
times of excess blood volume and capable of supplying extra blood in times of diminished
blood volume
 liver myoepithelial cells contract in response to norepinephrine and epinephrine
Lymph Flow
 Because pores in the hepatic sinusoids are very permeable and allow ready passage of both fluid
and proteins into the spaces of Disse, the lymph draining from the liver usually has a protein
concentration of about 6 g/dl - only slightly less than the protein concentration of plasma
o allows large quantities of lymph to form
o one half of all the lymph formed in the body under resting conditions arises in the liver
 During high hepatic vascular pressure fluid can easily move into the abdominal cavity forming an
Ascites
o leak through outer surface of liver capsule directly into the abdominal cavity
o fluid is almost pure plasma
 Just a few mm Hg increase in hepatic pressure results in excess transudation into lymph
Metabolic Functions of the Liver
 Converts drugs, their metabolites and xenobiotics (compounds foreign to body) into hydrophilic
compounds
o eg, alcohol metabolism
o inactivation of toxic chemical such as alcohol
 Majority of water-soluble nutrients and vitamins, minerals absorbed from small intestine
transported vial portal blood to liver
o Liver important in maintaining an adequate supply of nutrients for cell metabolism
 Carbohydrate metabolism
 Lipid metabolism
 Protein and amino acid metabolism
 Carbohydrate metabolism
o Glucose buffer function
o Storage of large amounts of glycogen
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o
o
o
o
 Glycogen is broken down during low blood glucose
 glycogen storage occurs during high glucose level
Conversion of galactose and fructose to glucose
Gluconeogenesis
Formation of many chemical compounds from intermediate products of carbohydrate
metabolism
Important role in maintaining a normal blood glucose concentration
Lipid Metabolism
 Oxidation of fatty acids for energy
 Synthesis of fatty acids
 Synthesis of lipoproteins from proteins and CHO
o VLDL, LDL, HDL, cholesterol, phospholipids
o So, if you happen to be on a low fat diet your body can still make fat given the right amount
of proteins and CHOs
 Catabolism of lipoproteins
 Production of ketone bodies
 Regulation of lipid metabolism
 Bile synthesis from cholesterol
o Excess cholesterol can be excreted from the body in the bile
 liver is important in maintaining blood lipid levels
Dr. Gwirtz said you don’t have to specific pathways but know the general idea, such as Acetyl CoA can
be used to make cholesterol that can be stored in the liver or secreted through bile acids
Protein and Amino Acid Metabolism
 Indispensable in amino acid metabolism; synthesizes most of the circulating plasma proteins
 Synthesis of ammonia which is made into urea to be excreted from the body
 Liver forms plasma proteins at rate of 15-20 g/day
 Can replenish 1/2 of plasma proteins in 1-2 weeks
 Chronic liver disease (e.g., cirrhosis) plasma proteins fall it low levels causing generalized edema
and Ascites
o Capillary filtration will increase
o Decrease in plasma oncotic pressure will allow more fluid to leave the capillary forming an
edema and later an ascites
 Albumin (major blood protein: 50%)
o transports fatty acids, steroid hormones, fat-soluble vitamins and drugs, calcium ions,
lipophilic substances
 Glycoprotein transport proteins
o transcortin (corticosteroid-binding globulin), thyroid-binding globulin, sex hormone
(testosterone-estradiol)-binding globulin, transferrin (iron transport)
 Acute phase proteins (of the inflammatory response)
o Inflammatory proteins are synthesized in the liver
o Ceruloplasmin, 1-antitrypsin,  1-acid glycoprotein,  2-macroglobulin
 Dietary proteins can be used to:
o Synthesized tissue proteins
o Formation of ATP through Acetyl CoA
o Formation of urea to get rid of ammonia
Liver as a Storage Organ
 Fat-soluble vitamins
o We have enough supply to last us for a while
o Vitamin A - 10 months supply
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o Vitamin D - 3-4 months “
o Vitamin K - 1 year “
o Vitamin B12 – 1 year “
 Storage and homeostasis of iron
o Important for synthesis of transferring protein for iron absorption in the small intestine
Endocrine Functions
 Modify or amplify hormone action
o Vitamin D
o Thyroxine
o Growth hormone
o These hormones are either modified or amplified in the liver
 Removal of circulating hormones
o Insulin
o Glucagon
o Growth hormone
o GI hormones
o thyroxine
o essentially all the steroid hormones such as estrogen, cortisol, and aldosterone
Removal of Drugs
 Liver removes or excretes drugs, hormones, other substances (especially fat-soluble)
o detoxify drugs or excrete into the bile
o many drugs, including sulfonamides, penicillin, ampicillin, and erythromycin
o major routes for excreting calcium
Bilirubins
 One of the routes for removal dead RBC that is excreted in the bile and eliminated in the stool
 It is a greenish yellow pigment.
 This is a major end product of hemoglobin degradation
 Provides an exceedingly valuable tool for diagnosing both hemolytic blood diseases and various
types of liver diseases
Dr. Gwirtz left out some things she didn’t think was important relating the physiology of the liver. These
include certain enzymes that become predominant in circulation during different types of liver diseases.
For example, hepatocyte diseases and ductal diseases have different types of enzymes that become
elevated during the disease’s course. She will leave this up to the clinician to cover next year.