Liver lobe is formed from cells and cell parenkimal non-parenkimal. Tues parenkimal on the liver are called hepatocytes, occupies about 80% of liver volume and perform a variety of primary liver functions. 40% of cells contained in the lobe of the liver sinusoidal. Endodermal cells are hepatocytes is stimulated by mesenchymal tissue is continuously during embryo to develop into cells parenkimal. During this period, an increase of albumin mRNA transcription as a stimulant of proliferation and differentiation of endodermal cells into hepatocytes.
Lumen lobes formed from the SEC and is occupied by three other cell types, such as Kupffer cells, Ito cells, intrahepatic lymphocytes such as pit cells. Tues non-parenkimal occupies about 6.5% by volume of the liver and produce many substances that control many functions of hepatocytes.
Filtration is one function that separates the lumen of the lobe sinusoidal surface of hepatocytes from the blood, the SEC has a very large capacity of endocytosis with various ligands such as glycoproteins, immune complexes, transferrin and ceruloplasmin. The SEC also serves as an antigen presenter cells that provide expression of MHC I and MHC II to T cells Secretion that occurs include various sitokina, such as prostanoid and leukotriena eikosanoid, endothelin-1, nitrogen monoxide and some ECM components.
Tues perisinusoidal Ito is on the network, a cell with many fatty vesicles in the cytoplasm that binds the SEC is very strong that it gives a double layer in the lumen of sinusoidal lobes. When the heart is in normal condition, Ito cells store vitamin A in order to control the flexibility of the extracellular matrix formed with the SEC, which is also the flexibility of the sinusoid lumen.
Kupffer cells located on the network intrasinusoidal, is makrofaga with endocytic and phagocytic ability of astounding. Kupffer cells interact daily with the material coming digestive tract containing the bacterial solution, and prevent the activation of the toxin effects of these compounds into the liver. Solution of high bacterial exposure, especially exposure to LPS, Kupffer cells do make sitokina that triggers the secretion of various inflammatory processes and may result in injury to the liver. Secretion include reactive oxygen species, eikosanoid, nitrogen monoxide, carbon monoxide, TNF-α, IL-10, a derivative of an immune response in primary infection phase.
Tues pits are lymphocytes with large granules, such as NK cells that reside in the liver. Tues pit can induce instant death in tumor cells without relying on the expression of major histocompatibility complex antigen on. Pit cell activity can be enhanced by interferon-γ stimulation.
In addition, the liver is still there-γδ T cells, αβ T cells and NKT cells.
Stem cells
In addition to hepatocytes and non-parenkimal cells, the liver still contained other cell types of intra-hepatic cells are often called oval cells, and hepatocytes duktular. liver regeneration after partial hepatektomi, generally do not involve intra-hepatic progenitor cells and extra-hepatic stem cells (hemopoietik), and depend on hepatocyte proliferation. But under current conditions hampered or delayed proliferation of hepatocytes, oval cells in periportal areas will experience the proliferation and differentiation into mature hepatocytes. Tues oval is a form of differentiation of progenitor cells residing on the portal and periportal areas, or canal Hering, and is only found when the liver injury. The proliferation that occurs in oval cells will form a channel that connects the excretion parenkima area where the occurrence of liver damage in bile duct. Epimorfin, a role morphogens which are found on many epithelial organs, seems to also play a role in the formation of bile ducts by hepatic stem cells. After that oval cells differentiated into hepatocytes would duktular. Duktular hepatocytes is considered a transitional cell associated among others with:
* Duktular metaplasia of hepatocytes parenkimal into intra-hepatic biliary epithelium
* Conversion metaplasia of the epithelium into hepatocytes parenkimal duktular
* Differentiation of stem cells of hepatocyte lineage
depending on the type of disorder that attacks the liver.
In a rat model with 70% hepatektomi, and induction of hepatic regeneration by asetilaminofluorena-2, found that stem cells derived from bone marrow can be differentiated into hepatocytes, with hormonal mediation of G-CSF as kemokina and mitogen. Regeneration can also be triggered with the D-galaktosamina.
Tues Immunological
The liver also plays a role in the immune system with a number of immunological cells in the system that serves as a filter retikuendotelial antigens carried to the liver via the liver portal system. Phase displacement of the primary phase of infection into an acute phase, characterized by the heart by lowering the secretion of albumin and increase the secretion of fibrinogen. Prolonged acute phase will result in hypoalbuminemia and hiperfibrinogenemia simtoma.
At the time of liver injury, white blood cells will be stimulated to migrate to the liver and together with Kupffer cells secreting sitokina which makes the modulation behavior of Ito cells. Th1 cells produce sitokina that enhance cellular immune responses such as IFN-gamma, TNF, and IL- 2. Tues TH2 will produce sitokina that enhance humoral immune responses such as IL-4, IL-5, IL-6, IL-13 and enhance the fibrotic response. Sitokina secreted by Th1 cells would inhibit the differentiation of T cells into TH2 cells, secretion of TH2 sitokina otherwise would inhibit the proliferation of TH1 cells. Therefore, the immune response is often said to be polarized to the cellular or humoral immune response, but never both.
Liver Function
Various types of duties performed by the liver, performed by hepatocytes. Until now has not found another organ or an artificial organ or device capable of replacing all the functions of the liver. Some liver function can be replaced with the liver dialysis, but the technology is still being developed for the treatment of patients with liver failure.
As the gland, the liver produces:
* Bile that reaches ½ liters per day. Bile is a greenish fluid and tastes bitter, derived from the hemoglobin of red blood cells that have been elderly, which is then stored in the gallbladder or excreted into the duodenum. Bile contains cholesterol, mineral salts, bile salts, pigments bilirubin and biliverdin. Bile secretion is useful for digesting fats, activate lipases, help power the absorption of fat in the intestine, and changing the substance is not soluble in water into a substance that dissolves in water. If the bile ducts in the liver congestion, bile into the blood circulation so that the sufferer becomes yellowish skin. Such a person is said to suffer from jaundice.
* Most of the amino acid
* Coagulation factors I, II, V, VII, IX, X, XI
* Protein C, protein S and anti-thrombin
* Kalsidiol
* Triglycerides through the trajectory of lipogenesis
* Cholesterol
* Insulin-like growth factor 1 (IGF-1), a polypeptide protein which plays an important role in body growth in childhood and still have anabolic effects in adults.
* Arginase enzyme that converts into ornitina arginina and urea. Ornitina formed can bind NH and CO ² ³ which are toxic.
* Trombopoietin, a glycoprotein hormone that controls the production of platelets by the bone marrow.
* In the initial quarter of growth of the fetus, the liver is the principal organ of synthesis of red blood cells, to reach around the spinal cord is capable of taking over this task.
* Albumin, the major osmolar component in blood plasma.
* Angiotensinogen, a hormone that acts to increase blood pressure when activated by renin, an enzyme secreted by the kidneys when blood pressure is suspected the lack of the juxtaglomerular apparatus.
* Enzyme glutamate-oxaloacetate transferase, glutamate-pyruvate transferase and lactate dehydrogenase
In addition to performing the process of glycolysis and the citric acid cycle as the cell in general, the liver also plays a role in the metabolism of other carbohydrates:
* Gluconeogenesis, glucose synthesis of several amino acid substrates, lactic acid, non-fatty acid esters and glycerol. In humans and several species of mammals, this process is not able to convert glycerol into glucose. Trajectory is accelerated by the hormone insulin as the hormone tri-iodotironina through accretion rate of Cori cycle.
* Glycogenolysis, glycogen into glucose catabolism trajectory and then released into the blood in response to the increasing energy demands by the body. The hormone glucagon is the main stimulator of both glycogenolysis and gluconeogenesis trajectory menghindarikan simtoma body from hypoglycemia. In mouse models, deficiency of glucagon to inhibit both these passages, but improves glucose tolerance.Panorama of these, along with the trajectory of gluconeogenesis in the gastrointestinal tract is controlled by the hypothalamus gland.
* Glycogenesis, glycogen from glucose anabolism trajectory.
and the trajectory catabolism:
* Degradation of red blood cells. Hemoglobin is contained in it is broken down into iron, globin, and heme. Globin iron and recycled, while reformed into metabolites to the heme is excreted with bile as bilirubin and biliverdin are bluish green. In the intestine, bile substance is oxidised into urobilin so the yellowish color of feces and urine.
* Degradation of insulin and several other hormones.
* Degradation of ammonia into urea
* Degradation of toxins with detoxification path, such as methylation.
The liver also reserve some substance, besides glycogen:
* Vitamin A (reserve 1-2 years)
* Vitamin D supply (1-4 months)
* Vitamin B12 (reserve 1-3 years)
* Iron
* Copper.
Regeneration of Liver Cells
The liver's ability to regenerate is a very important process so that the liver can recover from damage inflicted from the process of detoxification and immunological. Regeneration is achieved with a very complex interaction between the cells contained in the liver, including hepatocytes, Kupffer cells, sinusoidal endothelial cells, Ito cells and stem cells; with extra-hepatic organs, such as thyroid gland, adrenal gland, pancreas, duodenum, hypothalamus.
Hepatocytes, the cells are very unique. The potential for proliferation of hepatocytes, appeared at times of loss of cell mass, called the phase or phases primed replicative competence which is generally triggered by Kupffer cells through sitokina secretion of IL-6 and TNF-α. In this phase, hepatocytes enter the cell cycle from G0 phase to G1 phase.
TNF-α may provide proliferative or apoptotic effects, depending on the reactive oxygen species and glutathione, at least four transcription factors are activated before hepatocytes enter the proliferation phase, namely NF-κB, STAT-3, AP-1 and C / EBP-beta.
Hepatocyte proliferation induced by stimulation sitokina HGF and TGF-α, and EGF with two tracks. HGF, TGF-α, and EGF is a growth factor derived from Serina and protein substrate metal which induces DNA synthesis. The first path is the path IL-6/STAT-3 that play a role in cell cycle through cyclin D1 / p21 and cell protection by increasing the ratio of FLIP, Bcl-2, Bcl-xL, Ref1, and MnSOD. The second trajectory is the trajectory PI3-K/PDK-1/Akt that controls cell size through the molecule mTOR, as well as an anti-apoptotic and antioxidant.
Tri-iodotironina hormone, in addition to lowering cholesterol in the liver, also have the capacity in the proliferation of hepatocytes as a mitogen that acts on cyclin D1, accelerate the O2 consumption by mitochondria by activating gene transcription in respiration to increasing production of reactive oxygen species. The secretion of ROS into the cytoplasm of hepatocytes activates transcription factor NF-κB. In Kupffer cells, ROS in the cytoplasm, activates the secretion of TNF-α sitokina, IL-6 and IL-1 for secretion. Bonding that occurs between the three sitokina this will induce the expression of hepatocyte perceiving antioxidant enzymes, such as manganese superoxide dismutase, i-nitrogen monoxide synthase, anti-apoptotic protein Bcl-2, haptoglobin and fibrinogen-β required in the proliferation of hepatocytes. Stress Oxidative that can be caused by ROS and the damage can be caused by various sitokina, can be eliminated with tosoferol intake (100 mg / kg) or inhibitory compounds of gadolinium chloride (10 mg / kg) as owned by the Kupffer cells, before stimulation hormone tri-iodotironina , whereas the rate of hepatocyte proliferation is controlled by levels hepatotrofik etanolamina as humoral factors.
The liver's ability to regenerate has been known since ancient Greece from the mythical story about a titan named Prometheus. This capability can be dissipated, until hepatocytes can not enter into the cell cycle, despite losing some of its mass, in case of liver fibrosis. Trajectory fibrosis who do not get immediate care, will eventually develop into cirrhosis of the liver and requires the sufferer to undergo liver transplantation or hepatektomi for survival.
Liver regeneration after partial hepatektomi is a very complicated process under the influence of hemodynamic changes, modulation sitokina, hormone and growth factor activation of transcription factors, which lead to the process of mitosis. PRL hormone secreted by the pituitary gland induces hepatotrofik response as a mitogen involved in proliferation and differentiation processes. PRL giving effect to the increased activity of transcription factors that play a role in cell proliferation, such as AP-1, c-Jun and STAT-3; and differentiation and the maintenance of metabolism, such as C / EBP-alpha, HNF-1, HNF-4 and HNF-3. c-Jun is one of the AP-1 constituent proteins. Induction of NF-κB in this phase is required to prevent apoptosis and cell cycle triggers a reasonable pace. At this time, the role of retinyl acetate is vital, because its function which adds to the mass of DNA and protein it contains.
Diseases of the liver
The liver is the organ that sustains the survival of almost all other organs in the body. Because of its strategic location and multi-dimensional functions, the liver becomes very vulnerable to the arrival of various diseases. Hearts will respond to these diseases with inflammation, which is called hepatitis
Hepatitis often begins with an inflammatory reaction called patobiokimiawi liver fibrosis, with simtoma paraklinis by increasing the ratio of plasma laminin, a glycoprotein secreted Ito cells, a type of hyaluronic acid and procollagen type III aminopeptida ie, and CEA. Liver fibrosis can be caused by the low ratio of plasma HGF, or due to viral infections, like hepatitis B, a pathogen that caused by acute infectious viral DNA that has a similar focus in the form of infection called cccDNA transcriptional template is methylated, or hepatitis C, a similar pathogen hepatitis B infection caused by RNA viruses with a focus of infection in the form of DNA methylation, especially through the mechanism of genetic expression GADD45B beam, resulting in cell cycle of hepatocytes became halting.
Liver fibrosis requiring handlers as early as possible, as in the mouse model, stimulation of hepatocyte proliferation will shed the focus of infection with hepatitis B virus, before it develops into liver cirrhosis or hepatocellular carcinoma. After liver cancer, siklosporina compounds which have the potential to trigger proliferation of hepatocytes, it will accelerate the development of cancer cells, because of the cancer cells have hepatic hyperplasia, which is not accompanied by proliferation of genetic activation of transcription factors. It can be induced by stimulation of lead nitrate (LN, 100 micromol / kg), cyproterone acetate (CPA, 60 mg / kg), and nafenopin (NAF, 200 mg / kg).
Hepatitis can also be initiated with a deficiency of mitochondria in hepatocytes, which is called steatohepatitis. Mitochondrial dysfunction will have an impact on the homeostasis of lipid compounds and an increase in the ratio of reactive oxygen species that induce TNF-α. This will continue on fat deposition, oxidative stress and lipid peroxidation, and makes the mitochondria become susceptible to death by necrosis due to low ratio of ATP in mitochondrial matrix, or by apoptosis through the formation apoptosom and increased permeability of the mitochondrial membrane by the mechanism of Fas / TNF-α. High energy demand in this condition causes mitochondrial ATP reserves can not recover until the liver can lead to cirrhosis, whereas lipid peroxidation will cause damage to mitochondrial DNA and the mitochondrial membrane in the so-called sardiolipin, with an increased rate of fatty acid beta-oxidation, accumulation will occur in the respiratory electron chain complexes I and III, which lowers levels of antioxidants.
Tues apoptotic hepatocytes are digested by Ito cells into the reaction of fibrinogen with fibrogenesis after activated by products of lipid peroxidation and the ratio of leptin are high. Chronic Apoptosis then compensated with an increased rate of proliferation of hepatocytes, accompanied by damaged DNA by mitochondrial dysfunction, and causes genetic mutations and cancer.
In mouse models, melatonin is a compound that decreases the liver fibrosis, being in a rabbit model, curcumin is an organic compound that decreases paraklinis steatohepatitis, is the hormone serotonin and the lack of intake and kolina metionina gives the opposite effect with adiponectin resistance.
Mitochondrial dysfunction is also found in the pathogenesis of heart, from cases of inflammation to cancer and transplantation. In chronic cholestasis, ursodeoksikolat acid together with GSH as an antioxidant that protects bersinergis sardiolipin and phosphatidyl Serina to prevent the occurrence of liver cirrhosis.
The Influence of Alcohol
Alcohol is known to have the function of immunosuppressive to the immune system, including reducing the expression of cluster of differentiation CD4 + and CD8 + are required in the defense of the liver against viral infection, especially HCV. Alcohol also reduce the ratio kemokina IFN on the trajectory of cellular signal transduction, in addition to increasing the risk of fibrosis
Many trajectories contribute to alcohol metabolism to induce oxidative stress. One of the metabolic path that is often activated by ethanol is the induction of enzyme cytochrome P450 2E1. These enzymes cause reactive oxygen species such as superoxide anion radicals and hydrogen peroxide, as well as activating the toxic substrate into products including ethanol are more reactive and toxic. Dendritic cells seems to be the cells most affected by the content of ethanol in alcohol. In experiments using a rat model, ethanol increases the ratio of plasma IL-1β, IL-6, IL-8, TNF-α, AST, ALT, ADH, γ-GT, TG, MDA and reduce the ratio of IL-10, GSH, transcription factor NF-κB and AP-1.
Coffee, one of the complex alkaloid compound from the class of Purina xanthine with chlorogenic acids and lignans, in epidemiological studies, summed up as one of the factors lowering the risk of type 2 diabetes mellitus, Parkinson's disease, liver cirrhosis and carcinoma hepatocellular, and improved glucose tolerance. proved chronic coffee consumption does not cause high blood pressure acutely but resulted in an increase in blood pressure while in the short time interval, and plasma homosisteina so that it can be a threat to patients with cardiovascular disorders.
Regular coffee consumption can reduce the enzyme ALT ratio and the enzymatic activity on hepatic metabolism trajectory, which is often caused by viral infections, induction drugs, poisoning, ischemic conditions, steatosis (due to alcohol, diabetes, obesity), autoimmune diseases, and insulin resistance, metabolic syndrome, and iron overload. In addition to ALT, liver enzymes coffee also lowered the other, the gamma-GT and alkalina phosphatase. and the effect of antioxidants and phase II detoxification because diterpena compound, kafestol and kahweol, possibly preventing carcinogenesis process. This process is accompanied by gamma-GT as a leading indicator.
Liver Transplant
Technology liver transplantation is a result that was developed from research in several fields of study medicine. In 1953, Billingham, Brent, and Medawar found that tolerance kimerisme can be induced by infusion of donor cells in mouse models hematolimfopoietik.
In 1958 the canine study develops a theory about the molecular hepatotrofik the portal vein to the liver and found insulin as the main hepatotrofik factor of several other factors that exist. At about the same theory about multiviseral and liver transplantation are also evolving from studies immunosuppression is an empirical study of pattern recognition algorithms and therapeutic response. In early 1960, demonstrated that the canine and human allograft tolerance can be induced kimersime automatically with the aid of immunosuppression, until in late 1962 concluded wrongly, that the transplant involves two different immune systems. The consequences of these conclusions to be dogma that the heart tolerogenisitas, in essence, different, not only with the spinal cord, but with all the other organs. This error is not corrected properly until 1990.
The first heart transplant performed in Denver in 1963, The first success was recorded in 1967 with azatioprina, prednisone and anti-lymphoid globulin, by Thomas E. Starzl of the United States, followed by successful human bone marrow transplant in 1968. Time span between 1967 and 1979 recorded 84 times of liver transplantation in children with 30% survival to 2 years.
Study the development of immunosuppression and provide fixes and longer life expectancy for patients, among others, by the turn azatioprina with siklosporina in 1979, then replaced with tacrolimus in 1989.
In 1992, developed the theory mikrokimerisme donor leukocytes with a range of donors from different genealogies, which provide extremely long life expectancy for an organ donor recipient, having known the relationship between immunological aspects of transplantation, infection, tolerance by spinal cord, and neoplasm autoimmune disorders, called the seminal mechanism. Immune response and immune tolerance between donor organs and the body was found is a function of leukocyte migration and localization. One of the findings are derived immune system activation by NK cells and interferon-γ immediately after the transplant is completed. In a mouse model, Hepatocyte cell donor was found to be highly antigenic triggering a rejection response, which can be done independently or jointly between the CD4 T cells and CD8 T cells.
It required intensive immunosuppressive therapy before the transplant is done, which is called preparative or conditioning regimen to prevent rejection of donor organs by the host's immune system. Immunosuppressive therapy is intended to suppress T cell and host NK cells in order to provide space in the spinal cord for hematopoietic stem cell transplantation from organ donors through mielosupresif therapy, for the balance of donor cell repopulation with cell differentiation of stem cells from the host.
Today, liver transplantation is performed only when the liver has entered the final stage of a disease, or dysfunction has been called acute fulminant hepatic failure. Cases of liver transplantation in humans is generally caused by cirrhosis of the liver resulting from chronic hepatitis C, alcohol dependence, etc. autoimmune hepatitis.
A common technique is to transplant ortotopik, the placement of donor organs at the same anatomic position with the initial position of the previous organs. Liver transplantation could potentially be applied, only if the recipient of donor organs has no other aggravating conditions, such as metastatic cancer outside the liver, the dependence on drugs or alcohol. Some experts based on Milan criteria for liver transplant patient selection.
Organ donor, called an allograft, usually derived from another human being who has just died from traumatic brain injury (kadaverik). Another technique using human organ transplants are still alive, 20% operating hepatektomi lift Coinaud liver segments 2 and 3 of the adults to donate to a child, in 1989.
0 comments:
Post a Comment