Functional histology of liver

Functions of the liver

Production of circulating plasma proteins Albumins Lipoproteins [VLDLs, LDLs, HDLs] Glycoproteins e.g. transferrin Prothrombin Fibrinogen Non-immune globulins

Vitamin storage and conversion Vitamin A [retinol] Vitamin D [cholecalciferol] Vitamin K

Degradation of drugs and toxins2 processes1. Oxidation2. Conjugation with glucoronic acid,

glycine and taurine [products become water soluble and removed by kidneys]

Involvement in metabolic pathways Glycogenolysis Consumption of fatty acids by beta

oxidation for energy Production of ketone bodies – used

as fuel by other organs Urea synthesis Synthesis and conversion of non-

essential amino acids

Bile production

Liver converts substrates delivered by blood from digestive tract, pancreas and spleen

Some of these products are involved in the production of bile

Bile contains conjugated and degraded waste products that are returned to intestine for disposal, as well as substances that bind to metabolites in the intestine to aid in absorption

Modification and structure and function of hormones Conversion of Vitamin D to 25-

hydroxycholecalciferol Conversion of Thyroxine to its

biologically active form, triiodothyronine

Modification of action of Growth hormone by Growth hormone releasing hormone [GHRH] produced by liver

Degradation of insulin and glucagon

STRUCTURAL ORGANISATION

Parenchyma, consisting of organised plates of hepatocytes, which are normally one cell thick and separated by sinusoidal capillaries. In children, the liver cells are arranged I plates 2 cell thick

Connective tissue stroma, that is continuous with the fibrous capsule of Glisson. Blood vessels, nerves, lymphatic vessels and bile ducts travel with the stroma

Sinusoidal capillaries (sinusoids), the vascular channels between plates of hepatocytes

Perisinusoidal spaces (spaces of Disse), between sinusoidal epithelium and hepatocytes

Classic hepatic lobule

Roughly hexagonal mass of tissue Consists of stacks of anastomosing

plates of hepatocytes, one cell thick, separated by the anastomosing system of sinusoids that perfuse the cells with the mixed portal and arterial blood.

Each lobule measures about 2.0 × 0.7 mm.

At the center of the lobule is a relatively large venule, the terminal hepatic venule (central vein)into which the sinusoids drain.

The plates of cells radiate from the central vein to the periphery of the lobule, as do the sinusoids.

At the angles of the hexagon are the portal areas (portal canals), loose stromal connective tissue characterized by the presence of the portal triads..

This connective tissue is ultimately continuous with the fibrous capsule of the liver.

The portal canal is bordered by the outermost hepatocytes of the lobule

The blood vessels and draining branches of the bile duct system course together in a relationship called portal triad.

This is a misnomer, as one or more lymphatic vessels always travel with the vein artery and bile duct

At the edges of the portal canal, between the connective tissue stroma and the hepatocytes, is a small space called the space of Mall.

This space is thought to be one of the sites where lymph originates in the liver.

In some species, e.g., the pig, the classic lobule is easily recognized because the portal areas are connected by relatively thick layers of connective tissue.

In some species, e.g., the pig, the classic lobule is easily recognized because the portal areas are connected by relatively thick layers of connective tissue.

In humans, however, there is normally very little interlobular connective tissue, and it is necessary, when examining histologic sections of liver, to draw imaginary lines between portal areas surrounding a central vein to get some sense of the size of the classic lobule

Kupffer cells

Belong to MPS- derived from monocytes SEM and TEM show that they form part

of the vessel lining Previously they were described as lying

on the luminal surface of endothelial cells. This was probably based on the fact that processes of Kupffer cells occasionally overlap endothelial processes on the luminal side

They do not form junctions with endothelial cells

They form 15% of liver cell population- most are located in the periportal region

Functions

Metabolisation of aged RBCs and digestion of Hb

Secretion of proteins related to immunologic processes

Destruction of bacteria

In the fetal liver, the spaces between blood vessels and hepatocytes contain blood-forming cells.

In cases of chronic anaemia in the adults, these cells may reappear in the perisinusoidal spaces

Perisinusoidal space/ space of Disse

lies between basal surface of endothelial cells and Kupffer cells- site of exchange of materials between blood and liver cells

Small ,irregular microvilli from hepatocytes project into this space, which increase the available surface area for exchange of materials 6 times

The portal lobule

emphasizes the exocrine functions of the liver

Morphologic axis of the portal lobule is the lobule is the interlobular bile duct of the portal triad of the “classic” lobule.

Its outer margins are imaginary lines drawn between the three central veins that are closest to that portal triad.

These lines define a roughly triangular block of tissue that includes those portions of three classic lobules that secrete the bile that drains into its axial bile duct.

This concept allows a description of hepatic parenchymal structure comparable to that of other exocrine glands

The liver acinus

Structural unit that provides the best correlation between blood perfusion, metabolic activity, and liver pathology

Lozenge shaped and represents the smallest functional unit of the hepatic parenchyma.

The short axis of the acinus is defined by the terminal branches of the portal tried that lie along the border between two classic lobules.

The long axis is a line drawn between the two central veins closest to the short axis.

In a two-dimensional view the liver acinus occupies parts of adjacent classic lobules.

This concept allows a description of the exocrine secretory function of the liver comparable to that of the portal lobule.

The hepatocytes in each liver acinus are described as being arranged in three concentric elliptical zones surrounding the short axis

Zone 1 is closest to the short axis and the blood supply from penetrating branches of the portal vein and hepatic artery.

This zone corresponds to the periphery of the classic lobules.

Zone 3 is farthest from the short axis and closest to the terminal hepatic vein (central vein). This zone corresponds to the most central part of the classic lobule that surrounds it

Zone 2 lies between zones 1 and 3 but has no sharp boundaries