Histology of The Liver and Gall Bladder

By

Hanaa Said

Under Supervision of

Prof.Dr. Fadia Khalid

The Liver

Anatomy of the liver� The liver is the

second-largest organ of the body and the largest gland, weighing about 1-1.5 kg.

� It is situated in the abdominal cavity beneath the diaphragm.

�

�It is divided anatomically by deep grooves into:

� Two large lobes (the right and left lobes)and

� Two smaller lobes ( the quadrate

and caudate lobes).

Anatomy of the liver

�Exocrine function

�Endocrine function

• It produces most of the circulating plasma proteins (albumins,VLDL,glycoproteins,

• prothrombin and fibrinogen).

• It stores and converts several vitamins(A,D and K) and iron.

• It degrades drugs and toxins byoxidation then conjugation.

�It secretes bile.

�It modifies structure and function

of many hormones:

-Thyroxine

-Growth hormone.

-Insulin and glucagon.

Liver Physiology

Vascular Supply

•The liver has a dual blood supply, receiving oxygenated blood from the left hepatic artery and the right hepatic artery (25%) and nutrient-rich blood via the portal vein (75%).

Both vessels enter the liver at the

porta hepatis.

•Along the length of each slender

branch of the hepatic artery within the portal area, fine branches, known as distributing arterioles,arise; like outstretched arms, they reach toward their counterparts in the neighboring portal areas. Smaller vessels,

Vascular Supply

known as inlet arterioles, branch from

the distributing arterioles (or from the

parent vessel).

•In addition, the interlobular bile ducts

are vascularized by a peribiliary capillary plexus.•Venules are of two sizes: the larger distributing veins and

Vascular Supply

the smaller inlet venules.

•The longitudinal axis of each classical

lobule is occupied by the central vein,

Hepatocytes radiate, from the central vein, forming anastomosing, plates of hepatocytes, separated from each other by as hepatic sinusoids. Inlet arterioles,

Vascular Supply

inlet venules, and branches from the peribiliary capillary plexus pierce the limiting plate to join the hepatic sinusoids. As blood enters the sinusoids, its flow slows considerably and it slowly percolates into the central vein.•As the central vein leaves the lobule,

Vascular Supply

it terminates in the sublobular vein.

Numerous central veins deliver their blood into a single sublobular vein;• Sublobolar veins join each other to form collecting veins, which in turn form the right and left hepatic veins.

Vascular Supply

•Blood leaves the liver at the posterior aspect of the organ through the hepatic veins, which deliver their

contents into the inferior vena cava.

Vascular Supply

Portal area(Portal triad)

Histology of the liverHistological

structure

of

the liver

Stroma Parenchyma

Connective

tissue

capsule

TrabeculaeReticular

networkHepatocytes Blood vessels Bile ducts

Liver, Silver impregnation

Liver lobules

The three types of liver lobules are the classical lobules, portal lobules, and the hepatic acinus (acinus of Rappaport).

I.Classical liver lobule:In this concept, blood flows from the periphery to the center of the lobule into the central vein. Bile, manufactured by

Liver lobules

liver cells, enters into small intercellular

spaces, bile canaliculi, located between hepatocytes, and flows to

the periphery of the lobule to the interlobular bile ducts of the portal areas.

II.Portal lobules

all hepatocytes that deliver their bile to a particular interlobular bile duct.

III.Hepatic acinus (acinus of Rappaport) :It is viewed as three poorly defined, concentric regions of hepatic parenchyma

surrounding a distributing artery in the

Liver lobules

center. The outermost layer, zone 3,

extends as far as the central vein and is

the most oxygen-poor of the three zones.

The remaining region is divided into two equal zones (1 and 2); zone 1 is the richest in oxygen.

Liver lobules

The Three Concepts of Liver lobules

Hepatic Sinusoids and Hepatocyte Plates

Anastomosing plates of hepatocytes, no more than two cells thick prior to the age of 7 years and one cell thick after that age, radiate from the central vein toward the periphery of the classical lobule.The spaces between the plates of hepatocytes are occupied by hepatic

sinusoids, and the blood flowing in these wide vessels is prevented from coming in contact with the hepatocytes by the presence of an endothelial lining composed of sinusoidal lining cells.•sinusoidal lining cells have gaps of 0.5

Hepatic Sinusoids and Hepatocyte Plates

µm between them and fenestrae that are present in clusters, known as sieve plates.

Hepatic Sinusoids and Hepatocyte Plates

Fenenstrations in hepatic blood sinusoids

Hepatic lobule, human

Perisinusoidal space (Space of Disse´ )

•It lies between the basal surfaces of hepatocytes and the basal surfaces of endothelial cells and Kupffer cells.•Small irregular microvilli project from the basal surfaces of hepatocytes into this space to increase surface area for exchange of materials between hepatocytes and plasma found in this space.

•This space contains also Ito cells and reticular fibers supporting endothelial capillaries.•In the fetal liver, it contains islands of blood-forming cells.

Perisinusoidal space (Space of Disse´ )

Kupffer cell(Stellate macrophages)

•Member of the mononuclear phagocytic

system.•They form part of the lining of the sinusoid.•Processes of Kupffer cells often seem to span the sinusoidal lumen and may partially occlude it.•Their cytoplasm contains red cell fragments and ferritin.

Kupffer cell(Stellate macrophages

Functions:•They play a role in the final breakdown of damaged or senile RBCs.•Remove bacteria and debris that reach the portal blood from gut and act as APC in adaptive immunity .

Kupffer cells(H&E, injected with India ink)

Kupffer cells and blood sinusoids

Kupffer cell,TEM

Ito cells(Hepatic stellate cells,Fat

storing cells)

- Have a mesenchymal origin.-Found in the perisunsoidal space.-They are the primary storage site for hepaic vitamin A.-They produce collagen III and growth factors required by the liver for proliferation-In certain pathologic conditions, such as

cirrhosis, they lose their lipid and vitamin A storage capability and differentiate into cells with characteristics of myofibroblasts.

- Ito cells play a role in remodelling the

extracellular matrix during recovery from liver injury.

Ito cells(Hepatic stellate

cells,Fat storing cells)

Ito cells(Hepatic stellate cells,Fat

storing cells)

Hepatocyte,Ito cell and Kupffer cell

Pit cells(Hepatic NK cells or large

granular lymphocytes)

-They exist in the liver sinusoids and often adhere to endothelial cells .

-Pseudopodia of pit cells can penetrate the

fenestrae of the endothelial cells, and enter the space of Disse and can directly contact the microvilli of hepatocytes.

-Most surface antigens found on rat pit cells are similar to that found on spleen or peripheral blood NK cells.

Pit cells(cont.)

Pit cell and Kupffer cell

Hepatocyte

Domains of Hepatocyte Plasmalemma

The plasma membranes of hepatocytes have two domains: lateral and sinusoidal .

1-lateral domains :•responsible for the formation of bile canaliculi.

• have isolated gap junctions

Bile canaliculus between two hepatocytes

Bile canaliculus,freeze fracture

2-Sinusoidal domains:

form microvilli that protrude into the

perisinusoidal space of Disse´.

Domains of Hepatocyte Plasmalemma

•Forms about 80% of cell population of the liver.•Nucleus:-Central, spherical.-Most hepatocytes of adult liver are binucleated .-has one or 2 nucleoli

Hepatocyte

Cytoplasm:•Generally acidophilic.•Has basophilic area(RER and free ribosomes).•Numerous mitochondria demonstrated by vital staining and enzyme histochemistry•Numerous Golgi complexes can be detected with silver staining.

Hepatocyte

•Many peroxisomes detected by immunocytochemistry.•Lipid droplets can be demonstrated with Sudan black.•Glycogen granules appear as foamy areas in well preserved H&E sections.

Hepatocyte

Liver ,PAS staining

Hepatocyte

Hepatocytes are large, organelle-rich cells that manufacture the exocrine secretion bile as well as a large number of endocrine secretions; in addition, these cells can perform a large array of

metabolic functions.

Hepatocyte

•Each cell contains as many as 2000 mitochondria.

•Cells near the central vein (zone 3 of the liver acinus) have nearly twice as many, but considerably smaller, mitochondria as hepatocytes in the periportal area (zone 1 of the liver acinus).

Mitochondria

Mitochondria,TEM

Golgi apparatus

•As many as 50 Golgi units may be found in hepatocyte.•They are concentrated near the bile canaliculus.• Golgi cisternae and vesicles near the sinusoidal surface contain electron dense granules that are believed to be VLDL and other lipoprotein precursors.

•Cells in zone 3 of the liver acinus have a much richer endowment of SER than those in the periportal area.

SER

•the presence of certain drugs and toxins in the blood induces an increase in the SER content of liver cells .

•They contain enzymes involved in degradation and conjugation of toxins and drugs as well as enzymes responsible for synthesizing cholesterol and the lipid portion of lipoproteins.

SER

SER,TEM

Peroxisomes

•Hepatocytes have as many as 200-300 peroxisomes.•They are relatively large and vary in diameter from 0.2 to 1.0µm.•Peroxisomes play important role in the process of detoxification and breakdown of fatty acids as well as gluconeogenesis and metabolism of purines.

Peroxisomes,TEM

Lysosomes

In addition to normal lysosomal enzymes , hepatocyte lysosomes also contain:

-Lipofuscin pigments.-Partially digested cytoplasmic organelles.-Myelin figures.

They are the primary site for iron storage.Increase in number in a wide variety of pathologic conditions.

Glycogen deposits

•Present as accumulations of electron-dense granules 20 to 30 nm in size, known as β particles, in the vicinity of the SER. •Liver cells in the vicinity of the portal area (zone 1 of liver acinus) display large clumps of β particles surrounded by SER.

•On the other hand pericentral hepatocytes (zone 3 of liver acinus) exhibit diffuse glycogen deposits.

Glycogen deposits

•They are abundant subsequent to eating and fewer after fasting.

Glycogen deposits,TEM

Lipid droplets

•They contain mainly VLDL.•They increase in numder after fatty meals.•Hepatotoxic substances causes increase of lipid droplets in cells of zone 3.

Multilamellar bodies

Tight junctions Macula adherens

Hepatic Ducts

•Bile canuliculi anastomose with one another, forming labyrinthine tunnels among the hepatocytes. •As these bile canaliculi reach the periphery of the classic lobules, they merge with cholangioles, short tubules composed of a combination of hepatocytes and low cuboidal cells, and occasional oval cells.

Hepatic Ducts

Bile from cholangioles enters the canals of Hering, slender branches of the interlobular bile ducts, that radiate parallel to the inlet arterioles and inlet venules. Interlobular bile ducts merge to form increasingly larger conduits, which eventually unite to form the right hepatic

duct and the left hepatic duct.

Hering canal

Mucosa:Epithelial lining:

Simple columnar epithelium.Lamina propria:

Thin.

Histological structure of hepatic, cystic, and common

bile ducts

•Musculosa:• Thin layer of smooth muscles

that becomes thicker near the duodenum and finally, in the intramural portion, forms a sphincter that regulates bile flow (sphincter of Oddi).

Histological structure of hepatic, cystic, and common bile ducts

Bile duct

Composition of bile

1. Water.

2. Phosphilipids(i.e.lecithin) and cholesterol.

3. Bile salts (also called bile acids):

-Primary:cholic acid and chenodeoxycholic acid.

-Secondary:deoxycholic acid and lithocholic acid.

Composition of bile

4.Bile pigments, principally the glucuronide of bilirubin produced in the spleen , bone marrow, and liver by the breakdown of hemoglobin.

5.Electrolytes:Na+,K+, Ca2+, Mg2+, Cl-, and HCO3-.

Liver Regeneration

•The liver has a great ability to regenerate after a hepatotoxic insult or even after a portion of the liver is excised.•The mechanism of regeneration is controlled by

* Transforming growth factor-α* Transforming growth factor-β

* Epidermal growth factor.* Interleukin-6.* Hepatocyte growth factor. •In most cases, the regeneration is due to the replicative capability of the remaining hepatocytes;

Liver Regeneration

•If the hepatotoxic insult is too

great, regeneration of the liver is due to the mitotic activity of the oval cells of cholangioles and canals of Hering.

Liver Regeneration

Lymphatic drainage

•Plasma in perisinusoidal space drains into space of Mall.•Then it enters lymphatic capillaries.•The lymph then moves in progressively larger vessels in the same direction of bile to the hilum of the liver then finally into thr thoracic duct.

Gall bladder

•Small, pear-shaped organ situated on the inferior aspect of the liver.

•10 cm in length and 4 cm in cross-section.

Anatomy

Histological Structure

The mucosa of the empty gallbladder is highly folded into tall, parallel ridges .

Mucosa:

Epithelial lining:simple columnar epithelium,

composed of two types of cells: 1.the more common clear cells2. the infrequent brush cells

L.M.:nucleus:basal oval

Cytoplasm:Supranuclear cytoplasm contains

occasional secretory granules.E.M.:

their luminal surface displays short microvilli coated by a thin layer of glycocalyx.

Histological Structure

The basal region of the cytoplasm is particularly rich in mitochondria.

Lamina propria:

Histological Structure

composed of loose connective tissue,rich in fenestrated capillaries and small venules with no lymphatics. It is rich in elastic and collagen fibers.

In the neck of the gallbladder, the lamina propria houses simple tubuloalveolar glands, which produce a small amount of mucus.

No Muscularis mucosa.

No Submucosa.Musculosa:thin, smooth muscle layer, composed

Histological Structure

mostly of obliquely oriented fibers, whereas others are oriented longitudinally.

Serosa or adventitia:The hepatic surface is covered by adventitia, while the remainder of gall bladder surface is covered by serosa.

Histological Structure

Gall bladder,H&E

Gall bladder,epithial lining

Gall bladder , SEM

Gall bladder , Colored SEM

•The main function of the gallbladder is to store bile, concentrate it by absorbing its water, and release it when necessary into the digestive tract. •This process depends on an active sodium-transporting mechanism in the gallbladder's epithelium. Water absorption is an osmotic consequence of the sodium pump.

Function

•Contraction of the smooth muscle of the gallbladder is induced by cholecystokinin, a hormone produced by enteroendocrine cells located in the epithelial lining of the small intestine. •Release of cholecystokinin is, in turn, stimulated by the presence of dietary fats in the small intestine.

Function

Nerve supply

•Liver and gall bladder are innervated by both sympathatic and parasympathetic fibers .•Nerves enter the liver through porta hepatis and ramify through the liver in the portal canals along with members of portal triad.

Sympathatic fibers innervate blood vessels, while parasympathatic fibers Large ducts and possibly blood vessels.

Nerve supply