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Cirrhosis Vs Fibrosis of Liver
Cirrhosis Vs Fibrosis of Liver
Cirrhosis Vs Fibrosis of Liver
Stage2: During this stage, abnormal tissues developed inside the liver get transformed into stiff bands of connective tissues. This process is known as fibrosis. Fibrosis and inflammation of the liver spreads and affects the portal veins and the surrounding regions.
Stage3: As the disease advances, all the stiff bands begin to merge with each other. This leads to the enlargement of the affected areas. Disruption of liver functions is generally noticed during this stage.
Stage4: The final stage of liver cirrhosis is known as the decompensated stage of cirrhosis. This stage is the most dreaded one. Liver transplant is the only treatment option.
Immune system
Cytokines
Type IV (nonfibrillary) collagen, glycoproteins (including fibronectin and laminin) and proteoglycans (including heparan sulphate).
These constituents comprise the low-density basement membrane in the space of disse
to 8 fold increase in extracellular matrix, composed predominantly of high-density interstitial fibril-forming collagens) as well as
cellular fibronectin, hyaluronic acid and other matrix proteoglycans and glycoconjugates.
Accumulation of Type I collagen results from both increased synthesis and reduced degradation, and is the hallmark of fibrogenesis.
Stellate cell activation is a central event in hepatic fibrosis and can be conceptualized as occurring in at least two stages: (1) initiation and (2) perpetuation
Chemotaxis During liver injury, the normally quiescent HSC also Proliferation myogenic features including expression of alpha acquires Since fibrosis is a normal wound-healing response to smooth muscle actin and myosin , which confer With activation, HSCs proliferate rapidly. Plateletencapsulate injury, it is not surprising that the HSCs contractile properties. is the most potent migrate towards derived growth factor (PDGF-) Endothelin-1 and nitric oxide are sites of injury driven by key chemoattractants, mitogenic factor for HSCsImmune interactions . Other stellate cell mitogens Fibrogenesis regulators that control HSC contractility through their which include PDGF, monocyte mutually antagonistic factor (VEGF), thrombin, include vascular Inflammatory endothelialIgrowthactivities .(Contractility is also effected The productionsignalling including angiotensin II, eicosanoids, protein-1 (MCP-1) and CXCR3 ligands of type Macrophages play divergent collagen is the chemotactic liver by many factor (EGF), endothelial growth other factors transforming growth factor- roles inatrial fibrosis HSCs secrete proinflammatory cytokines/ carbon monoxide, among depletion cardinal feature of the activatedfibroblast regression. For example, progression and (TGF-), naturetic peptide, somatostatin and growth keratinocyte growth factor, stellate cell. chemokinesothers ) the mostHSCs, like dendritic cells, induction of fibrosis such as MCP-1.of factor IGF-1 andduring the factor remains TGF-1(FGF), insulin-like growth macrophages CXCL12 potent fibrogenic can also function as professional antigen presenting results in decreased fibrosis cytokine. Cellular sources of TGF-1 in chronic progression, yet when cells .In addition, signalling by TLR4 in HSCs indepleted during recovery, fibrosis macrophages are liver injury bacterial sinusoidal endothelial cells, response to include lipopolysaccharide prolonged due to loss of macrophageregression is further Kupffer cells and HSCs. Other cytokines include implicates and VEGF. Angiotensin II,matrix proteases . Natural killer (NK) cells, derived the main CTGF, FGF innate immune response to injury which contribute effector of the reninangiotensin system, is a to immediate innate responses, functional cytokine that is a may suppress fibrosis by killing activated potential activator of myofibroblasts ,anti- NKT cells can express collagen production in HSCs and a target of while
fibrotic therapies profibrotic activity .
Contractility
Fibrinolysis
a net increase in Activated HSCs are interstitial collagenase the main source of activity occurs as a result MMP-2 , MMP-3 (stromelysin) of both increased MMPSand MMP-13, interstitial and decreased tissue inhibitors ofcollagenase MMP-1 MMPS (TIMPS) .
Fibrogenesis
TIMP-1, levels are TIMP-1
increased resulting in TIMP-2, both decreased and MT1degradation of type 1 MMP.
TIMP-1 plays a central role in fibrosis progression and regression. The imbalance between matrix synthesis and degradation plays a major role in ECM accumulation during hepatic fibrogenesis . The net result of the changes during hepatic injury is increased degradation of the normal basement membrane collagen, and reduced degradation of interstitial-type collagen.
Definition
Cirrhosis of the liver is a pathologic entity characterized by (1) necrosis of liver cells, slowly progressive over a long period and ultimately causing chronic liver failure and death; (2) fibrosis, which involves both central veins and portal areas; (3) regenerative nodules, the result of hyperplasia of surviving liver cells; (4) distortion of normal hepatic lobular architecture; and (5) diffuse involvement of the whole liver.
A regenerative nodule is an abnormal mass of liver cells without a normal cord pattern or central venule and surrounded completely by fibrosis Cirrhosis is defined anatomically as a diffuse process with fibrosis and nodule formation. It is the end result of the fibrogenesis that occurs with chronic liver injury.
FIBROTEST, based on 1. Bilirubin, 2. Gamma-glutamyl transferase, 3. Apolipoprotein A1, alpha-24. Macroglobulin, and 5. Haptoglobin.
Corticosteroids in autoimmune and alcoholic Abstinence from alcohol for alcoholic liver Downregulate stellate cell activation liver diseases diseases Neutralizing inflammatory cytokines using Antiviral therapy for viral hepatitis Gamma Interferon specific receptor antagonists: IL-1 receptor Antihelminthic therapy for schistosomiasis Antioxidants: alpha-tocopherol, resveratrol, quercetin, Nantagonists, soluble TNF-alpha receptor Copper chelation for Wilson's disease acetylcysteine, silymarin, OC-15161 Ursodeoxycholic acid (UDCA) Phlebotomy for hemochromatosis Cytokine-directed therapy: Discontinue hepatotoxins (eg, methotrexate) in Others: prostaglandin E, colchicine and TGF-beta antagonists colchiceine, milotilate, translast, IL-10 drug-induced liver injury Endothelin receptor antagonists Hepatic growth factor Disrupt ECM-HSC interactions: Arg-Gly-Asp (RGD) analogue Collagen synthesis inhibitors: TGF-beta antagonists, relaxin, halofuginone Others: Dilinoleylphosphotidylcholine (DLPC), HMG CoA reductase, Pentoxyphylline, HOE077, Safironil Retinoids?
Microvesicular fat
Alcoholic foamy degeneration Acute fatty liver of pregnancy Reye's syndrome Valproic acid Tetracycline Jamaican vomiting sickness Indian childhood cirrhosis Haemochromatosis Viral hepatitis B and C 1-antitrypsin deficiency
Macrovesicular fat
Alcohol Malnutrition Obesity Diabetes mellitus Corticosteroids Total parenteral nutrition Wilsons disease Viral hepatitis B and C 1-antitrypsin deficiency