You are on page 1of 76

LIVER Cells

Anatomy
Largest and heaviest gland ( 1.5 kgs or 3 lbs) beneath the diaphragm, just behind the right costal arch

sympathetic nerves - periarterial plexuses parasympathetic nerves -vagal trunk Dark red or reddish brown
both exocrine and endocrine

parenchymal cell: hepatocyte

Dual blood supply to liver

Triads: Branches of three vessels: hepatic portal vein, hepatic artery, along with bile drainage ductiles all run together to infiltrate all parts of liver. Sinusoidsspecial liver capillaries where blood mixes and liver cells actbyproducts leave as bile in caniliculi which merge to form bile ducts

Biliary flow
biliary tree bile canaliculi bile ducts hepatic ducts common hepatic duct cystic duct Gallbladder common bile duct ampulla of Vater.

Functions
Detoxification protein synthesis production of biochemicals necessary for digestion.

Functions of the liver


1. Secretory- synthesizes bile, CHO, CHON,etc. 2. Excretory- releases waste & even harmful substances for ultimate evacuation 3. Exocrine- releases bile through the duct system 4. Endocrine- releases plasma proteins, etc, directly into the circulation 5. Metabolite storage- stores glucose in the form of glycogen; lipid in the form of triglycerides 6. Vitamin storage- vitamin A is stored 7. Gluconeogenesis- amino acids, lipids are converted into glucose, catalyzed by enzymes

8. Glycogenolysis- in fasting state, hepatocytes respond to glucose- poor blood by breaking down glycogen & releasing it as glucose 9. Amino acid deamination- results in the production of urea (transported thru the blood to the kidney, where it is excreted) 10. Detoxification- inactivates various drugs, noxious chemicals & toxins, by enzymes such as oxidase system thru the process of oxidation, methylation or conjugation 11. Hemopoiesis- in the fetus and newborn

Potentials and Unique features


The liver is thought to be responsible for up to 500 separate functions, usually in combination with other systems and organs.

LIVER Cells

Cells in liver
Mainly

hepatocytes (parenchymal cells), hepatic sinusoidal endothelial cells, Kupffer cells hepatic stellate cells.
epithelial cells of the bile duct; the endothelial cells of blood and lymphatic vessels; the smooth muscles cells of arteries and veins; nerve cells, fibroblasts; inflammatory cells.

Some

III. Liver lobules 1. Classic liver lobule (hepatic lobule) - structural unit of the liver - polygonal mass made of liver plates or cords radiating like spokes from the central vein with the portal canals at its corners

a. central veins - smallest radicles of the hepatic veins at the center of a hepatic lobule - sinusoids drain into the central vein then into the sublobular vein which join to form collecting veins that drain to the inferior vena cava

b. portal area (3-6 per lobule) - portal canal or portal triad - contains the portal vein, hepatic artery, bile duct and lymph vessels c. liver sinusoids - blood vessels found in between liver cords/plates whose basal lamina is incomplete due to fenestrations and gaps - diameter is 9-12um (>capillaries) - flow of blood is from the periphery to the central vein; near its termination is a sphincteric mechanism that controls blood flow - lined by endothelial type & Kupffer cells

Hepatocytes at work

3. Hepatic acinus of Rappaport


- functional unit of the liver - a diamond shaped-area encompassing triangular sections of 2 adjacent liver lobules (central veins are its apices); divided by the portal canal branches transversely between the 2 lobules

IV. Liver parenchymal cells


- hepatocytes - large, polygonal cells( 20-35um) with 1 or 2 centrally located nuclei

Hepatocyte

Hepatocytes
80% of the cytoplasmatic mass of the liver. Storage
protein,

Synthesis
protein, cholesterol, bile salts phospholipids.

Secretion
Bile for detoxification, modification and excretion of endo and exogenous toxic products

Transformation
carbohydrates.

The hepatocytes are also the causing small liver cells cancer of the liver. The main type of liver cancer is with other words hematoma.

- arranged as branching perforated plates or cords between which are sinusoidal spaces; the plates/cords extend from the periphery of the classical lobule to the central vein in a radial fashion - contain basophilic bodies which are aggregates of rough ER in the cytoplasm (where several CHONs, e.g. albumin & fibrinogen, are synthesized) - smooth ERs in the hepatocytes are responsible for the processes needed for inactivation or detoxification of substances, as oxidation, methylation and conjugation

- up to 50 Golgi complex per cell; its functions include lysosome formation, secretion of plasma CHON, lipoChON and glycoCHON - small but numerous mitochondria are scattered in the cytoplasm (associated with glycogen storage) hepatocyte lysosome - important in the turnover and degradation of intracellular organelles peroxisomes or microbodies - enzyme-containing organelles are abundant; its functions are: 1) oxidation of excess fatty acids 2) breakdown of H2O2 (generated by oxidation)
3) breakdown of excess purines to uric acid 4) participates in the synthesis of cholesterol, bile acids, & some lipids used to make myelin

Liver glycogen

Hepatocyte surfaces: 1. Surface facing the space of Disse - with microvilli to increase surface for transfer of materials between hepatocytes and blood - site where endocrine secretions leave hepatocytes & enter the liver sinusoid

2. Surface closely applied to surface of adjacent liver cell 3. Surface partially separated from an adjacent cell to form a bile canaliculus

Limiting plate or Limiting hepatocytes - sheet of smaller modified hepatocytes (1-cell thick) lying against the periportal connective tissue; perforated by blood vessels & branches of the bile ducts
Space of Moll - separates the limiting plate from the connective tissue of the portal area

d. Space of Disse (perisinusoidal space)


interstitial space between liver cells and sinusoidal endothelial cells for active metabolic exchange between the liver and blood; may play an important role in lymph production contain reticular & collagen fibers to maintain the architecture of sinusoids, & short microvilli of hepatocytes to provide large surface area for absorption & secretion also contains mesenchymal cells which prefer to store Vitamin A

Space of Disse (perisinusoidal space)

Hepatic stellate cells (HSC)


vitamin A-storing cells, lipocytes, interstitial cells, fat-storing cells and Ito cells. store 80% of retinoids in the whole body as retinyl palmitate in lipid droplets in the cytoplasm. retinoid homeostasis receptors for retinol-binding protein (RBP), RBP by receptor-mediated endocytosis. In pathological (ECM) components including collagen, proteoglycan, and adhesive glycoproteins. The morphology of these cells also changes from the star-shaped stellate cells to that of fibroblasts or myofibroblasts. In extrahepatic organs such as pancreas, lung, kidney, and intestine. Hepatic and extrahepatic stellate cells form the stellate cell system.

Expresses receptors for synaptophysin, GFAP, neural cell adhesion molecule, nestin, Neurotrophins Four main functions including retinoid storage and homeostasis, remodelling of ECM by production of ECM components and MMPs, production of growth factors and cytokines (likely have a role in hepatocyte regeneration following injury) the contraction and dilation of the sinusoidal lumen in response to endothelin, angiotensin, thromboxane or prostaglandins. HSCs exhibit 2 physiological states. The first is quiescent where they can be seen to contain cytoplasmic lipid droplets containing retinyl esters and long cytoplasmic processes with fine branches. The second state is activated/transdifferentiated where they lack lipid droplets, display proliferative and fibrongenic myofibroblast-like phenotype (activated state expresses alpha smooth muscle actin and desmin). These states are regulated by paracrine and autocrine loops of growth factors (TGF-beta-1).

Endothelial" type cells


small, elongated with dark-staining nucleus & cytoplasmic processes

has few organelles but numerous micropinocytotic vesicles fenestrations in the attenuated cytoplasm & gaps between cells

Hepatic sinusoidal endothelial cells


50% of the non-parenchimal cells of the liver rich in lysosomal enzymes - degradation of the endocytose material.

main function
to separate hepatocytes from passing blood an important role in hepatic microcirculation. controlling the exchange of material that takes place between the blood and the liver parenchyma. most powerful scavenger system in the human body.

Hepatocytes, ITO- cell, sinusoid (monkey)

Kupffer cells
Phagocytic (stellate) cells of Kupffer 15% of hepatocytes Actively phagocytic, with larger, paler nucleus and extensive cytoplasm; on endothelial lining of the sinusoids

Karl Wilhelm von Kupffer in 1876- sternzellen" (star cells or stellate cells) 1898 Tadeusz Browicz, -Browicz-Kupffer cells and stellate macrophages complement receptor of the immunoglobulin family (CRIg

- numerous in the periportal area where they are most active - in time of need, its number is increased by differentiation of the endothelial cells
Functions of Kupffer cells: 1) remove debris & cellular fragments 2) metabolize aged RBCs 3) digest Hb to form bilirubin 4) secrete CHON for immunologic processes 5) destroy bacteria in the portal blood

hepatocytes, Kupffer and ITO cell (monkey)

Bile duct

The ELAD system is an external machine that can support liver functions for up to thirty days. This new system not only filters the blood, but is also lined with C3A human hepatocyte cells, which are grown inside the ELAD cartridges. These cells are picked up by the newly filtered blood, and transported back into the patient.

Hepatocyte markers
Albumin - a hepatic cell-specific marker. PMID: 16543069 alpha-Fetoprotein (AFP) - a hepatic cell-specific marker. PMID: 16543069 alpha-anti-Trypsin - a mature hepatocyte marker. PMID: 16543069 Annexin I and Annexin II - useful markers for detecting not only actively proliferating hepatocytes but also hepatocytes in preproliferative and postproliferative stages. PMID: 7519163 Anti-liver-kidney microsome antibody- can be considered as a marker for endoplasmic reticulum in rat hepatocytes. PMID: 3552922 C-reactive protein (CRP) - a prototype acute phase protein which has been known to be synthesized in hepatocytes.PMID: 12637157 Hepatocyte antigen (Hep)- Hep is a relatively specific marker for hepatocellular carcinoma (HCC). PMID: 12170084,PMID: 9796718 Hepatocyte Paraffin 1 (Hep Par 1) - specific for hepatocyte mitochondria, is considered the most specific and sensitive marker of normal and neoplastic hepatocytes and has been used in diagnosing hepatocellular carcinomas. PMID: 15272534, PMID: 14668552, PMID: 11732796, PMID: 17001880, PMID: 11404191 Leucine Aminopeptidase (LAP) - a domain-specific marker for hepatocyte plasma membranes. PMID: 6304108, PMID: 6201493 Prospero-related homeobox 1 (Prox1)- a stable hepatocyte marker during liver development, injury and regeneration, and is absent from "oval cells". PMID: 16770575 Rex3 - a marker for hepatocyte differentiation/dedifferentiation processes and tumor formation. PMID: 16959394 Tyrosine Aminotransferase- terminally differentiated hepatocyte marker. PMID: 15516738 Tryptophan Oxygenase- terminally differentiated hepatocyte marker. PMID: 15516738 CD-29 ( b-1 integrin) Hepatocyte specific cell surface antigen WT1- a common marker of both hepatocyte and endothelial progenitors. PMID: 15607745

Albumin (Alb) - 3.5 to 5.3 g/dL Alanine transaminase (ALT)- 9 to 40 IU/L Aspartate transaminase (AST)- 10 to 35 IU/L Ratio Alkaline phosphatase (ALP)- 30 to 120 IU/L Total bilirubin (TBIL)- 0.21.2 mg/dL Direct bilirubin (Conjugated Bilirubin)- 0.10.4 mg/dL Gamma glutamyl transpeptidase (GGT)- 0 to 42 IU/L 5' Nucleotidase (5'NTD) Coagulation test (e.g., INR) Serum glucose (BG, Glu) Lactate dehydrogenase (LDH)

Liver as lymphoid organ


a large macrophage population, termed Kupffer cells. The exposure of liver cells to antigens, and to microbial products derived from the intestinal bacteria, has resulted in a distinctive local immune environment. Innate lymphocytes, including both natural killer cells and natural killer T cells, are unusually abundant in the liver. Multiple populations of nonhematopoietic liver cells, including sinusoidal endothelial cells, stellate cells located in the subendothelial space, and liver parenchymal cells- APC - tolerance.

Important human pathogens, including hepatitis C virus and the malaria parasite, exploit the livers environment, subvert immunity, and establish persistent infection.

Summary
ANATOMY: Locate liver by percussing upper right quadrant of abdomen PHYSIOLOGY: Liver is blood processing organ with dual blood supply. HISTOLOGY: Blood mixes in sinusoids where hepatocytes do their magic CELL BIOLOGY: Multiple functions for hepatocytes. Manufacture cholesterol for use and recycling in digestion (via bile) and delivery to cells of body via circulatory system (via central vein of liver lobules).
Cholesterol is necessary for many normal metabolic processes High levels of LDL cholesterol may contribute to plaque formation in arteries HDL cholesterol may help to break down plaques

References
http://www.unchealthcare.org/site/newsroo m/news/2003/Mar/liver_assist_device http://www.msnbc.msn.com/id/28981937/ http://en.wikipedia.org/wiki/Liver http://science.slashdot.org/article.pl?sid=09 /02/04/2320250 http://biology.about.com/library/weekly/aa 040899.htm http://www.vitaltherapies.com/

Thank you

Liver in detail

I. Stroma
Glissons Capsule
- thin fibroconnective tissue covering the liver - covered by peritoneum except at the bare area (superior & posterior surfaces) - arising from the capsule is the fibroconnective tissue skeleton made of collagenous fibers and some fibroblast, within the liver substance

Porta hepatis
- transverse fissure on the inferior surface of the liver, where the portal vein, the hepatic artery, the hepatic ducts and lymphatic vessels enter.

II. Blood supply a. Portal vein - brings nutrient-rich blood from the intestinal tract, pancreas and spleen; 70-80% of the livers blood b. Hepatic artery - supplies O2- rich blood from the abdominal aorta; 20-30% of the livers blood c. Hepatic vein - union of several sublobular veins from the central veins, draining into the inferior venacava

Role
metabolism glycogen storage decomposition of red blood cells plasma protein synthesis hormone production Detoxification produces bile, an alkaline compound which aids in digestion via the emulsification of lipids

Blood flow
Dual blood supply
hepatic portal vein hepatic arteries

liver sinusoids central veins

Synthesis
Proteins produced and secreted by the liver A large part of amino acid synthesis carbohydrate metabolism:
Gluconeogenesis (the synthesis of glucose from certain amino acids, lactate or glycerol) Glycogenolysis (the breakdown of glycogen into glucose) Glycogenesis (the formation of glycogen from glucose)(muscle tissues can also do this)

protein metabolism lipid metabolism:


Cholesterol synthesis Lipogenesis, the production of triglycerides (fats). A bulk of the lipoproteins are synthesized in the liver.

Synthesis
The liver produces coagulation factors I (fibrinogen), II (prothrombin), V, VII, IX, X and XI, as well as protein C, protein S and antithrombin. In the first trimester fetus, the liver is the main site of red blood cell production. By the 32nd week of gestation, the bone marrow has almost completely taken over that task.

The liver produces and excretes bile (a yellowish liquid) required for emulsifying fats. Some of the bile drains directly into the duodenum, and some is stored in the gallbladder.
The liver also produces insulin-like growth factor 1 (IGF-1), a polypeptide protein hormone that plays an important role in childhood growth and continues to have anabolic effects in adults. The liver is a major site of thrombopoietin production. Thrombopoietin is a glycoprotein hormone that regulates the production of platelets by the bone marrow.

Breakdown
The breakdown of insulin and other hormones The liver glucoronidates bilirubin, facilitating its excretion into bile. The liver breaks down or modifies toxic substances (e.g., methylation) Drug metabolism
This sometimes results in toxication, when the metabolite is more toxic than its precursor. Preferably, the toxins are conjugated to avail excretion in bile or urine.

The liver converts ammonia to urea (urea cycle)

Other functions
The liver stores a multitude of substances, including glucose (in the form of glycogen), vitamin A (12 years' supply), vitamin D (14 months' supply), vitamin B12 (1-3 years' supply), iron, and copper. The liver is responsible for immunological effectsthe reticuloendothelial system of the liver contains many immunologically active cells, acting as a 'sieve' for antigens carried to it via the portal system. The liver produces albumin, the major osmolar component of blood serum. The liver synthesizes angiotensinogen, a hormone that is responsible for raising the blood pressure when activated by renin, an enzyme that is released when the kidney senses low blood pressure.

V. Bile Flow ( exocrine function) Bile canaliculus - 1st portion of the bile duct system which are small tunnel-like expansions of the intercellular spaces between adjacent liver cells without any lining epithelium
Bile ductule or canal of Herring - junction found between bile canaliculi and bile ducts, near the periphery of a hepatic lobule -liver cells are replaced gradually by smaller, lighter cells-ductule cells- with distinct basal lamina - lumen of the ductule eventually joins that of a bile duct at the portal area

VI. REGENERATION - liver shows remarkable degree of regeneration after injury - hepatocytes are capable of both hypertrophy and hyperplasia - bile ducts actively proliferate - after continuous or repeated damage to hepatocytes for a period of time, the multiplication of cells is followed by a marked increase in the amount of connective tissue (cirrhosis)
VII. FUNCTIONS - the liver is a detoxifying gland; thus, is susceptible to damage from absorbed toxic materials