Liver Disease: Causes, Symptoms, Effects and Treatments

coloured-colored sickness Causes, Symptoms, Effects and TreatmentsCHAPTER 11.0 INTRODUCTIONLiver is the organ which is most important, and it plays a pivotal role in regulating confused processes in the body, such as storage, metabolism and secretion. It has great capacity to detoxify toxic substances to nontoxic substances and synthesize useful principles (Shanmugasundaram et al 2006).1.1 Anatomy of the LiverThe colorful is a triangular organ that extends across the entire abdominal cavity inferior to diaphragm. Most of the coloreds mass is located on amend side of body, where it descends inferiorly toward right(a) kidney. The colored-colored is madeup of very soft, pinkishbrown tissues encapsulated by connective tissue capsule. The capsule is covered and reinforced by the peritoneum of the abdominal cavity which protects liver-colored and holds it in the place within abdomen.Liver consists of four distinct lobes first the left lobe, second the right lobe, third caudate lob e, and last quadrate lobe. The left and right lobes argon the large lobes and argon separated by the falciform ligament. The right lobe is about five to six times larger than tapered left lobe. The nice caudate lobe extends from posterior side of the right lobe and it wraps approximately the inferior vena cava. Small quadrate lobe is inferior to the caudate lobe and it extends from the posterior side of the right lobe and it wraps around the gall bladder.Figure-1 Structure of liver.Functions of liverProduction of resentment that required for the digestion of foods.Storage of extra sugar or glucose into stored glycogen in liver cells of the body and then converts it concealment into glucose when the the body needs it for energy.Production of clotting factors.Production of amino acids that is building blocks for making proteins, that includes those used to help fight infection.The production and storage of iron which is necessity for production of red blood cells in the body.Manu facturing of cholesterol and other chemical substances that is required for fat transport.Conversion of waste products of the metabolism into urea that is excreted in urine.Metabolising medicines into their agile form (ingredient) in the body.1.2 Liver diseasesLiver disease is any disturbance in locomotes of the liver that wooing illness. The liver is responsible for various critical functions in the body and when it becomes injured or diseased, loss of those functions can cause significant damage to body. Liver diseases are also referred as hepatic disease.1.3 Types of liver diseases wet liver disease primary election liver cancer cirrhosis of the liverCystsFatty liver diseaseLiver fibrosisHepatitis sourPrimary sclerosing cholangitis1.3.1 cloudburst Liver DiseaseIn 2000, cirrhosis was 1 of the leading causes of death in U.S.A. (United States). intoxicating liver disease usually develops after large amount of alcoholic beverage intake. The retentive period during which alcohol excessively consumed, larger the amount ingested, high the rate of developing alcoholic liver disease and other liver problems.Signs and SymptomsConfusion overweening fluid between the membranes lining abdomen and abdominal organsTenderness and abdominal painDry mouthFever sapJaundice lading gainunwellnessLoss of appetiteAbnormal dark or light whittleAgitationAltered level of consciousnessBreast development in malesDifficulty concentratingHallucinationsImpaired judgmentPalenessRedness on feet or hands1.3.2 Primary Liver crabby personPrimary 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 discolour discoloration of skin.Abdominal pain (the upper right part of the abdomen)Swelling of abdomenAn enlarged liverFatigueGeneral weaknessLoss of appetiteNausea vomitingWeight l oss1.3.3 Liver CirrhosisLiver cirrhosis is generally considered to the fourth part stage of the alcoholic liver disease, it is progressive condition which causes liver damage. chronic alcoholism is the most normal 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 scarring of the liver that is liver scarring. The resulting hardening of the liver, hard liver throw ins with the blood circulation in the body, it leads to permanent damage to the liver and a completely loss of liver function.Signs and SymptomsAbdominal accumulation of fluid in abdominal cavityAbnormal pain eject from engorged veins in esophagusDark cola-colored urineExhaustionGallstoneFatigueDiabetes type 2Itchy hands and feetLoss of appetiteCancer of liverLiver failureNausea and vomittingMalfunctioning of other systems such as impotence, kidney dysfunction and failure, and osteoporosi sHypertensionSensitivity to medicationsSpider-like small blood vessels under the skinSwelling of feet and hands from retained fluidHepatic encephalopathyWeight lossWeaknessjaundiceLiver cystsLiver cyst also know as hepatic cyst, a simple liver cyst is a bubble (thin walled bubble), a fluid filled cavity in liver. A common liver problem, liver cyst can normal benign and pose no health risks. but in some cases, liver cyst whitethorn grow large enough to cause pain and discomfort in the abdomen, liver enlargement, infection of bile ducts, and bile ducts obstruction, that leads the cyst itself to become infected. In this case, it is requisite 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) are unclear. Many researchers, however, believe that the metabolic syndromea cluster of disorders that increase risk of diabetes, hear t disease, and strokeplays a significant 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 at long last entire bodyLoss of appetiteLiver failureLack of interest 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 formation 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 many diseases hepatitis A to E in which inflammation of liver occurs and its cells are damaged and then inflammatory chemicals are released and being produced in the liver. in some cases hepatitis B infection increases persons 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 formation of scar and fibrous tissue. In primary sclerosing cholangitis PSC, the bile ducts of the liver have a bun in the oven become inflamed and scarred.1.3.9 JaundiceIt is not directly the disease of liver but rather symptom that can occur as result of variety of diseases. Jaundice appears a yellow discoloration of skin and white of the eyes caused by the abnormal formation of bilirubin in the blood. Orange yellowish pigment bilirubin, bilirubin is the part of bile, it forms in the liver as a byproduct of old cells of blood. When there are many blood cells (RBC) dying 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 medicinesDrug 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 hepatitisObesityAlcoholGeneticsAutoimmune disordersDrugsToxinsCancerTable-1 Types of hepatobiliary injury or damage1.5 Mechanism of hepatotoxicityDistruption of cytoskeleton phalloidin and microcystin disrupts the integrity of hepatocyte cytoskeleton by affecting proteins that are vital to its dynamic nature. (Phillips et al, 1986)Cholastasis Bile formation is vulnerab le to toxicant effects on the functional integrity of sinusoidal transporters, canalicular exporters, cytoskeleton dependent processes for transcytosis, and the contractile engine block of the canalicular lumen.changes that weaken the junctions that form the structural barrier between the blood and the canalicular lumen allow solutes to leak out of the canalicular lumen. An immunosuppressive drug frequently reported 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 plausible 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 agentsAbacavirAcetaminophenAcitretinAlcoholAldesleukinAmiodaroneAmsacrineAnabolic steroidsAndrogensAsparaginaseBexaroteneCarbamazepineCarmustineCytarabineDantroleneDapsoneDauno rubicinDisulfiramDivalproexEpirubicinErythromycinsEstrogensEthionamideEtretinateFelbamateFluconazoleFlutamideGold compoundsHalothaneHMG-CoA reductase inhibitorsImatinibIron (overdose)IsoniazidItraconazoleKetoconazoleLabetalolmercaptopurineMethimazoleMethotrexateMethyldopaMetronidazoleNaltrexoneNevirapineNiacinNilutamideNitrofuransPemolinePhenothiazinesPhenytoinPlicamycinPropylthiouracilRifampinRosiglitazoneSulfamethoxazoleSulfonamidesTacrineTenofovirTizanidineTolcaponeToremifeneTretinoinTroleandomycinValproic 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 part the inflammatory and profibrogenic mediators, inflammatory mediators cause lipid peroxidation and profibrogenic mediators cause liver fibrosis which are responsible for the liver injury. CCl4 also acstivates Tissue inhibitor of metallo proteinase 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 stable 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 spinal column 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) Hepatocy te 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 prevent 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 lucidumGlycyrrhiza glabraArctium lappaHalenia ellipticaanklebone membranaceusMurraya koenigiiNymphaea stellataOcimum sanctumPaeonia lactifloraPergularia daemiaPicrorhiza kurrooaPhyllanthus amarusPlumbago zeylanicaSilybum marianumScoparia dulcisSalvia miltiorrhizaAmomum xanthoidesAstragalus membranaceusCichorium intybusCurcuma longaCajanus indicus,Centella asiaticaCoccinia indicaBrassica,EcliptaFlickingeria fimbriataFlickingeria fimbriataGanoderma lucidumGlycyrrhiza glabraHalenia ellipticaMurraya koenigiiNympha ea stellataOcimum sanctumPaeonia lactifloraPergularia daemiaPicrorhiza kurrooaPhyllanthus amarusPlumbago zeylanicaSilybum marianumScoparia dulcisSalvia miltiorrhizaScutellaria baicalensisSchisandra chinensisTable2 Plant tested in animal models for their hepatoprotective activity and found to be active.SBS PGI Balawala, DehradunPage 1