Liver Disease: Causes, Symptoms, Effects and Treatments

colored malady Causes, Symptoms, Effects and TreatmentsCHAPTER 11.0 INTRODUCTION coloured is the organ which is most important, and it plays a pivotal role in ordinance various processes in the body, such as retentiveness, metabolism and secretion. It has great competency to detoxify toxic substances to nontoxic substances and synthesize useful principles (Shanmugasundaram et al 2006).1.1 manakin of the colored-colored-coloredThe colorful-colored is a triangular organ that extends across the broad(a) abdominal pit inferior to diaphragm. Most of the livers plentitude is located on right side of body, where it descends inferiorly toward right kidney. The liver is madeup of real soft, pinkishbrown tissues encapsulated by connective tissue capsule. The capsule is covered and reinforced by the peritoneum of the abdominal cavity which protects liver and holds it in the place within abdomen.liver-colored consists of four distinct lobes first the left lobe, second the right l obe, ternary caudate nucleus lobe, and last quad drift lobe. The left and right lobes be the oversize lobes and argon separated by the falci convention ligament. The right lobe is about five dollar bill to six times larger than tapered left lobe. The small caudate lobe extends from posterior side of the right lobe and it wraps rough the inferior vena cava. minuscular quadrate lobe is inferior to the caudate lobe and it extends from the posterior side of the right lobe and it wraps around the gallbladder.Figure-1 Structure of liver.Functions of liverProduction of impudence that required for the digestion of foods.Storage of peculiar(a) sugar or glucose into stored glycogen in liver cells of the body and so converts it back into glucose when the the body needs it for energy.Production of clotting factors.Production of amino group acids that is building blocks for making proteins, that includes those used to help fight infection.The production and storage of iron which is ne cessary for production of red affinity cells in the body.Manufacturing of cholesterin and other chemical substances that is required for fat transport.Conversion of waste products of the metabolism into urea that is excreted in peeing.Metabolising medicines into their active form (ingre snap offnt) in the body.1.2 liver infirmitysLiver complaint is any disturbance in functions of the liver that cause illness. The liver is responsible for various critical functions in the body and when it blend ins injured or disorderd, liberation of those functions can cause significant violate to body. Liver diseases ar also referred as hepatic disease.1.3 Types of liver diseases downpour liver diseasePrimary liver genus CancercirrhosisCysts greasy liver diseaseLiver fibrosisHepatitis spininessPrimary sclerosing cholangitis1.3.1 Alcoholic Liver DiseaseIn 2000, cirrhosis was 1 of the leading causes of death in U.S.A. (United States). Alcoholic liver disease usually develops after large am ount of alcohol intake. The unyielding period during which alcohol excessively consumed, larger the amount ingested, high the rate of developing alcoholic liver disease and other liver problems.Signs and Symptoms amazementExcessive fluid between the membranes lining abdomen and abdominal organsTenderness and abdominal painDry mouthFever tire outJaundice pack gain nausea expiry of appetite abnormal dark or light skinAgitationAltered direct of consciousnessBreast breeding in malesDifficulty concentratingHallucinationsImpaired popular opinionPalenessRedness on feet or give1.3.2 Primary Liver CancerPrimary cancer of the liver which is a growing liver problem called primary liver cancer, it generally remains undetected until when this disease has reached the advanced stage because most people do not exhibit these symptoms early on.Signs and SymptomsJaundice that is yellow discoloration of skin. group AB pain (the velocity right part of the abdomen) pompousness of abdomenAn enlarge d liver frighten offGeneral weakness passing play of appetiteNausea vomitingWeight loss1.3.3 Liver CirrhosisLiver cirrhosis is generally considered to the 4th stage of the alcoholic liver disease, it is progressive condition which causes liver damage. degenerative alcoholism is the most familiar cause of this disease. 40% of the 27000 people die from this disease. Cirrhosis is characterized by the replacement of normal healthy tissue by fibrous tissue, regenerative nodules and stonering of the liver that is liver scarring. The resulting hardening of the liver, hard liver interferes with the blood circulation in the body, it leads to irreversible damage to the liver and a completely loss of liver function.Signs and Symptomstype AB accumulation of fluid in abdominal cavityAbnormal painBleeding from scarf out veins in esophagus shameful cola-colored urineExhaustionGallstone jadeDiabetes type 2whiny hands and feetLoss of appetiteCancer of liverLiver misfortuneNausea and vomitting Malfunctioning of other systems such as impotence, kidney dysfunction and failure, and osteoporosis high blood pressureSensitivity to medicationsSpider-like small blood vessels under the skinSwelling of feet and hands from retained fluidHepatic encephalopathyWeight lossimpuissancejaundiceLiver cystsLiver cyst also known as hepatic cyst, a simple liver cyst is a cardcastle (thin walled bubble), a fluid filled cavity in liver. A common liver problem, liver cyst can normal benign and limit no health chances. moreover in around cases, liver cyst may grow large enough to cause pain and self-consciousness in the abdomen, liver enlargement, infection of bile ducts, and bile ducts obstruction, that leads the cyst itself to endure infected. In this case, it is necessary to drain and remove the cyst.Fatty Liver DiseaseFatty Liver Diseases (steatosis) are generally considered to the first stage of Alcoholic Liver Disease. The exact causes of Non Alcoholic Fatty Liver Disease (NAFLD) a re unclear. Many researchers, however, believe that the metabolic syndromea cluster of disorders that increase risk of diabetes, heart disease, and strokeplays a crucial role in development of NAFLD.NAFLD Levels of SeveritySimple fatty liver (steatosis).NASH (Non-alcoholic steatohepatitis), it is the inflammation and signs of necrosis.Cirrhosis is characterized by scarring of liver, results in a hard liver which is un-able to function proper. so Cirrhosis can be fatal.Signs and SymptomsBleeding in esophagus from engorged veinsFatigueFluid in the abdominal cavityItching of feet and hands, and eventually finished bodyLoss of appetiteLiver failureLack of enliven in sexMentally confusion, such as forgetfulness and trouble concentratingNausea and vomittingSmall red spider veins under skinSwelling of feet and legs from retained fluidWeight lossWeaknessCola-colored urineJaundice1.3.6 Liver FibrosisLiver fibrosis is generally considered to the third stage of Alcoholic Liver Disease, liver fibrosis is a liver condition which is very progressive. Liver fibrosis is characterised by the arrangement of the fibrous tissue, regenerative nodules and scarring of liver, which interfere circulation of blood and lead to loss of functions of liver. caused by chronic alcoholism and hepatitis C, cirrhosis is a disease which is degenerative disease of liver.Signs and SymptomsAbdominal accumulation of fluids in abdomenAbnormal painBleeding from engorged veins in intestines or oesophagusDark cola coloured urineEasy bruisingExhaustionFatigueItchy feet and handsLoss of appetiteLack of interest in sexNausea and vomittingSwelling of feet and legs by retained fluid (edema)Enlargement of the liverWeaknessLoss of weightJaundice1.3.7 HepatitisHepatitis is gastroenterological disease, means inflammation of liver. Hepatitis is not 1, but legion(predicate) diseases hepatitis A to E in which inflammation of liver occurs and its cells are change and then inflammatory chemicals are released and being produced in the liver. in some cases hepatitis B infection increases individuals chance to development of liver cancer by 100 times.Signs and Symptoms of HepatitisDiarrheaDark urineAbdominal painEnlarged liverFeverFatigueGeneral achinessJaundice1.3.8 Primary Sclerosing CholangitisCholangitis is inflammation of bile ducts of liver. Sclerosing is inflammation leads to the excessive makeup of scar and fibrous tissue. In primary sclerosing cholangitis PSC, the bile ducts of the liver have become inflamed and scarred.1.3.9 JaundiceIt is not directly the disease of liver but rather symptom that can occur as result of conformation of diseases. Jaundice appears a yellow discoloration of skin and white of the eyeball caused by the abnormal formation of bilirubin in the blood. Orange lily-livered pigment bilirubin, bilirubin is the part of bile, it forms in the liver as a byproduct of old cells of blood. When at that place are many blood cells (RBC) demise for liver to cope with yellowish pigment forms in the body resulting in jaundice, it is visible sign of liver problems.Jaundice is an indicator that a person is suffering from 1 of a many diseases including,Paracetamol toxicityAlcoholic liver diseasesAutoimmune hepatitisAn abnormal narrowing of the bile ductBlocked bile ducts caused by stones, infection, and tumorsChronic hepatitisDrug induced cholestasis, bile pools in the gallbladder as a result of certain drugsDrug induced hepatitisFatty liver diseaseHemolytic anemiaIntra-hepatic cholestasis of pregnancy, bile pools in the gallbladder because of the pressure in the abdomen during pregnancy.Ischemic hepatocellular jaundicepancreatic cancerPrimary biliary cirrhosisPrimary liver cancerViral hepatitisMalariaCauses of liver diseaseViral hepatitisObesityAlcohol geneticsAutoimmune disordersDrugsToxinsCancerTable-1 Types of hepatobiliary injury or damage1.5 chemical mechanism of hepatotoxicityDistruption of cytoskeleton phalloidin and microcystin disrupts t he fairness of hepatocyte cytoskeleton by affecting proteins that are vital to its dynamic nature. (Phillips et al, 1986)Cholastasis Bile formation is vulnerable to toxicant effects on the functional integrity of sinusoidal transporters, canalicular exporters, cytoskeleton dependent processes for transcytosis, and the contractile closure of the canalicular lumen.changes that weaken the junctions that form the structural barrier between the blood and the canalicular lumen yield solutes to leak out of the canalicular lumen. An immunosuppressive drug frequently account to cause elevated level of serum bile salts and bilirubin as well as a reduction in bile flow.Mitochondrial damage Preferential injury to mitochondrial DNA, as opposed to nuclear DNA, is a believable mechanistic basis for structural and functional alterations to hepatic mitochondria associated with nucleoside analog therapy for hepatitis B and AIDS infections and with alcohol abuse.1.6 Hepatotoxic agentsAbacavirAceta minophenAcitretinAlcoholAldesleukinAmiodaroneAmsacrineanabolic steroidsAndrogensAsparaginaseBexaroteneCarbamazepineCarmustineCytarabineDantroleneDapsoneDaunorubicinDisulfiramDivalproexEpirubicinErythromycinsEstrogensEthionamideEtretinateFelbamateFluconazoleFlutamideGold compoundsHalothaneHMG-CoA reductase inhibitorsImatinibIron (overdose)IsoniazidItraconazoleKetoconazole labetalolMercaptopurineMethimazoleMethotrexateMethyldopaMetronidazoleNaltrexoneNevirapineNiacinNilutamideNitrofuransPemolinePhenothiazines diphenylhydantoinPlicamycinPropylthiouracilRifampinRosiglitazoneSulfamethoxazoleSulfonamidesTacrineTenofovirTizanidineTolcaponeToremifeneTretinoinTroleandomycinValproic acidVitamin AZidovudineLamivudine1.7 Mechanisms of liver injury by some hepatotoxic substances1.7.1 Mechanism of liver injury by CCl4CCl4 converts into CCl3 and CCl3OO free radicals in the presence of enzyme CYP2E1, these free radicals then trigger the inflammatory and profibrogenic mediators, inflammatory mediat ors cause lipid peroxidation and profibrogenic mediators cause liver fibrosis which are responsible for the liver injury. CCl4 also acstivates Tissue inhibitor of metalloproteinase 1 (TIMP-1), Tissue inhibitor of metalloproteinase 2 (TIMP-2), Matrix metalloproteinase 2 (MMP-2) and MMP-9 these expressions also activate profibrogenic mediators which cause liver fibrosis.Fig-2 Mechanism of liver injury by CCl41.7.2 Mechanism of liver injury by acetaminophenIn therapeutic dose acetaminophen metabolises by glucuronyl transferases and sulfotransferases to enduring metabolites which excreted throughout the body but in over dose acetaminophen metabolises by CYP2E1,CYP3A4 and CYP1A2 to toxic metabolite NAPQI(N-acetyl parabenzo quinine immine). this toxic metabolite covalently binds with the hepatocyte and causes damage to hepatocyte.After binding of NAPQI to hepatocyte there are two possibility, first is stimulation of CD44 receptor expression on T cell which recovers hepatocyte and second is the reduced expression of CD44 receptor on T cell causes hepatocyte apoptosis which is fatal condition to liver.Fig-3 (a)Liver injury by acetaminophen (b) Hepatocyte recovery and apoptosis process.1.7.3 Mechanism of liver injury by alcoholFig-4 Pathways through which alcohol (ethanol) can contribute to apoptosis.1.8 HepatoprotectionHepatoprotection is the ability to thwart damage to the liver.One medicine of hepatoprotection is silymarin, derived from Milk Thistle which selectively inhibits formation of leukotrienes by Kupffer cells.1.8.1 List of Herbs have potentially hepatoprotective constituents (Jia et al, 2011)Almond oilGanoderma lucidumgenus Glycyrrhiza glabragenus Arctium lappaHalenia ellipticaAstragalus membranaceusMurraya koenigiiNymphaea stellataOcimum sanctumPaeonia lactifloraPergularia daemiaPicrorhiza kurrooaPhyllanthus amarus graphite zeylanicagenus Silybum marianumScoparia dulcisSalvia miltiorrhizaAmomum xanthoidesAstragalus membranaceusCichorium intybusCurcuma l ongaCajanus indicus,Centella asiaticaCoccinia indicaBrassica,EcliptaFlickingeria fimbriataFlickingeria fimbriataGanoderma lucidumGlycyrrhiza glabraHalenia ellipticaMurraya koenigiiNymphaea stellataOcimum sanctumPaeonia lactifloraPergularia daemiaPicrorhiza kurrooaPhyllanthus amarusPlumbago zeylanicaSilybum marianumScoparia dulcisSalvia miltiorrhizaScutellaria baicalensisSchisandra chinensisTable2 Plant tested in animal models for their hepatoprotective body process and found to be active.SBS PGI Balawala, DehradunPage 1