Metabolism And Excretion Lecture 3- Structure And Function Of The Liver Part 2

Front 1

liver stores

Back 1

glycogen, lipid, vitamin b12, vitamin A, copper and iron

Front 2

Metabolism of steroid hormones
by the liver

Back 2

Cortisol, estrogen, progesterone, testosterone

Front 3

Biotransformation of endogenous waste products by the liver

Back 3

Site of degradation of most soluble proteins
Most incoming ammonia (largely derived from bacterial deamination of dietary amino acids in the gastrointestinal tract) converted by hepatocellular urea cycle enzymes into urea and is excreted in urine.

Front 4

Synthesis of albumin by the liver

Back 4

Largely responsible for the oncotic (osmotic) property of blood that retains body water in circulation

Front 5

Synthesis of anti-coagulation factors by the liver

Back 5

Necessary to prevent clotting of blood in circulation
Plasminigoen
Antithrombin III
Protein C and S

Front 6

Gluconeogensis

Back 6

Gluconeogensis
Formation of glucose from non-carbohydrate precursors
Takes place in hepatocytes

Front 7

Central to lipid metabolism and storage by the liver

Back 7

Hepatocytes esterify incoming fatty acids to triglycerides
Triglycerides are then packaged by hepatocytes with apoprotiens to from very low density lipoproteins
They are then exported to the sinusoids as readily viable energy source for other proteins

Front 8

Immune surveillance by the liver

Back 8

Liver contains resident population of large granular lymphocytes (pit cells, with natural killer activity) that target foreign antigens and antigenically abnormal host cells that enter sinusoids

Front 9

Site of extramedullary haematpoiesis in the liver

Back 9

Normally takes place in mammalian foetal liver especially in the persinusoidal spaces
Declines post-natally but may return if there is a sustained demand for erythrocytes, leukocytes and/or platelets.

Front 10

Hepatic circulation

Back 10

Dual blood supply in mammals
70-75% of afferent hepatic blood flow is via the portal vein draining the splanchnic viscera
Allows rapid (first pass) hepatic clearance of ingested nutrients, xneobiotics, infectious agent and antigens absorbed from the gastrointestinal tract

Front 11

Portal venous blood supplies hepatocytes with

Back 11

trophic factors
Amino acids
Insulin
Glucagon

Front 12

25-30% of afferent hepatic blood flow is via

Back 12

the hepatic artery
Branch of celiac artery that arises from abdominal aorta

Front 13

IF PROTAL VENOUS FLOW INCREASES HEPATIC ARTERIAL....
REGULATORY MECHANISM CONTROLLED BY ...

Back 13

FLOW DECREASES
SYMPATHETIC NERVOUS SYSTEM

Front 14

Hepatic artery and portal vein enter the liver at the....where the ...exits

Back 14

hilus (porta haptis)
major bile duct

Front 15

Blood that passes through the sinusoids is collected into ... which drains into... and then into... and the...to return to the ... side of the heart

Back 15

central veins
sub lobular veins
hepatic vein
caudal vena cava
right

Front 16

Health of the liver is dependent on

Back 16

adequate blood supply and flow in and out of and on adequate biliary drainage.

Front 17

MOST NOXIOUS STIMULI ENTER THE LIVER VIA THE

Back 17

PORTAL VEIN, HEPATIC ATERY OR BILE DUCTS.

Front 18

Microscopically the hepatic parenchyma appears

Back 18

uniform

Front 19

liver is subdivided into hexagonal units call

Back 19

hepatic lobule

Front 20

zone 1

Back 20

PERIPORTAL HEPATOCYTES
young cells
rich in rough endoplasmic reticulum
closest to incoming portal vein and hepatic arterial branches
best supply of oxygen, nutrients and other trophic factors
greatest site of mitotic activity and aerobic metabolism
main site of protein synthesis
main site of gluconeogensis and glycogen storage
main site of urea cycle enzyme activity
main site of lipid and cholesterol metabolism

Front 21

zone 2-

Back 21

MIDZONAL HEPATOCYTES
share functions with hepatocytes of zones 1 and 3

Front 22

zone 3-

Back 22

PERIACINAR (CENTRILOBAR) HEPATOCYTES
closest to the venous outflow route from the liver
poorest supply of oxygen and therefore very susceptible to hypoxia
relatively old cells that contain litter rough endoplasmic reticulum
rich is smooth endoplasmic reticulum
Rich in CYTROCHROME P450, GLUCURONUL TRANFERASE AND GLUTHIONE S-TRANFERATE which are involved in biotransformation of lipid soluble drugs and toxins, endogenous steroid hormones, etc.

Front 23

basic pattern of blood flow within sinusoids is form

Back 23

the portal vein and hepatic artery branches to the central vein

Front 24

sinusoidal system is ...pressure
lined by

Back 24

low

specialized fenestrated endothelial cells that lack a typical basement membrane

Front 25

kupffer cell

Back 25

fixed cells of the monocyte-machrophage system
lie in sinusoidal lumen anchored to endothelium
Less readily activated than other macrophages but play an important role on phagocytosis of dead and dying cells, circulating particulate matter, micro organisms, and microbacterial toxins and circulating immune complexes.
Responsible for filtering function of liver
Can release large amount of potent mediators- nitric oxide, interleukin 6 and tumor necrosis factor alpha- which ahs effects on other cells in the liver and beyond

Front 26

Persinusoidal space= space of DISSE

Back 26

Cannot be discerned in healthy liver using a light microscope
Microvilli of hepatocytes extend into this space to increase the hepatocellular surface area and promote exchange of substances with sinusoal blood
Contains loose extracellular protein matrix, Stellate cells, nerve fibers and pit cells
Site of hepatic lymph formation
Hepatic lymph is a filtrate of plasma and contains 70% of total plasma proteins
Hepatic lymph drains form the space is Disse to the lymphatics in portal area to the liver hilus to the lymphatics of hepatic ligaments to hepatic lymph nodes to thoracic duct.

Front 27

Stellate cells= Ito cells

Back 27

Look like adipocytes in health
Specialized lipocytes located in the persinusiodal space
Produce and maintain delicate extracellular matrix that supports the sinusoidal endothelium

Front 28

Matrix is composed

Back 28

of type IV collagen

Front 29

IN HEALTH Stellate cells store

Back 29

lipid droplets that are rich in vitamin A

Front 30

HEPATIC INJURY CAN LEAD TO LOCAL RELASE OF

Back 30

CYTOKINES FROM ACTIVATED KUPFFER CELLS OR INJURED HAPTOCYTES, which leads to stimulation of Stellate cells and the mitotic division and transformation of fat into collagen producing myofibers which cause fiberplasia and often permanent fibrosis

Front 31

NEW COLLAGEN ESPECIALLY TYPE I AND III IS LARGELY DEPOSITED

Back 31

IN THE PERISINUSOIDAL SPACE

Front 32

IMMATURE COLLAGEN MAY BE DEGRADED IF

Back 32

HEPATIC INJURY IS MILD AND TRANSIENT

Front 33

If insult is severe, persistent or repetitive the progressive fibrosis that results is...This leads to capilirisation of sinusoid

Back 33

irreversible
(sealing of fenestrated endothelium and filing in of the persionusoidal space by collagen), increased resistance to blow flow and impaired perfusion of hepatocytes and compromised section of hepatocelluar products into the sinusoidal space

Front 34

Mature hepatocytes are usually in most mitotic or G0 phase but can enter cell cycle and undergo mitotic division under the influence of growth factors- from

Back 34

kupffer cells or Stellate cells

Front 35

Regeneration ability does not involve formation of new lobules but rather

Back 35

mitotic division of surviving hepatocytes on the existing connective tissue scaffold

Front 36

Restoration of normal mass therefore requires

Back 36

retention of scaffold, adequate blood supply and biliary drainage

Front 37

In chronic or repetitive hepatic insults the parenchyma regeneration tends to be

Back 37

nodular

Front 38

Oval cells (ductual precursor cells)

Back 38

Small bipolar epithelial stem cells located in the lining of terminal bile ducts located in zone 1parenchyma adjacent to the portal areas
Can divide and differentiate into either chloangiogal cells or heaptocytes

Front 39

Biliary hyperplasia

Back 39

Proliferation of new biliary channels in the portal areas and in periportal parenchyma
After parenchymal necrosis biliary hyperplasia is thought to be due to mitotic division of oval cells and therefore formation of new cholangioles and replacement of lost hepatocytes

Front 40

Periductular liver progenitor cells

Back 40

Derived from circulating bone marrow stem cells
Putative multipotent