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Disease of the liver

Jaundice

It is a yellow discoloration of skin, sclerae, and tissues caused by hyperbilirubinemia. It is most often associated with hepatocellular disease, biliary obstruction, or hemolytic anemia.i

Ai. Physiologic jaundice of the newborn: i

is commonly noted during the first week of life, but is not usually clinically important. It is characterized chemically by unconjugated hyperbilirubinemia.i

This form of jaundice results from both increased bilirubin production and a relative deficiency of glucuronyl transferase in the immature liver; these phenomena are exaggerated in premature infants.i

Bi. Congenital hyperbilirubinemias:i

1i. Gilbert syndrome:i

Is extremely common, occurring in almost 5% of the population. This familial disorder is characterized by a modest elevation of serum unconjugated bilirubin. The cause is a combination of decreased bilirubin uptake by liver cells and reduced activity of glucuronyl transferase.i

2i. Crigler-Najjar syndrome:i

Is a severe familial disorder characterized by unconjugated hyperbilirubinemia caused by a deficiency of glucuronyl transferase.i

There are 2 forms of this disease:i

Ii. One form leads to early death from kernicterus; damage to the basal ganglia and other parts of the central nervous system are caused by unconjugated bilirubin.i

IIi. A less severe form responds to phenobarbital therapy.i

3i. Dubin-Johnson syndrome:i

Is an autosomal recessive form of conjugated hyperbilirubinemia characterized by defective bilirubin transport. It is characterized by a striking brown-to-black discoloration of the liver.i

 

Viral hepatitis

We have 5 RNA viruses are:ii1. Hepatitis A virus (HAV).ii2. Hepatitis C virus (HCV).ii3. Hepatitis D virus (HDV).ii4. Hepatitis E virus (HEV).ii5. Hepatitis G virus.i

And one DNA virus:iHepatitis B virus (HBV).i

Hepatitis A and E are both transmitted via the fecal-oral route, while the rest are transmitted via blood-to-blood (parenteral) contact.iMnemonics: Just as A and E are at both ends of ABCDE, so they are transmitted by elements of both ends of GIT !!!iAcute viral hepatitis is characterized by jaundice and extremely high elevations of serum aspartate [AST] and alanine aminotransferases [ALT].i

i1.Hepatitis A virus [HAV]:i

1i. Spread occurs by fecal-oral transmission.ii2. The incubation period is 15–45 days.ii3. HAV does not cause a chronic carrier state or lead to chronic hepatitis; complete recovery almost always occurs. There is no relation to hepatocellular carcinoma.i

i2. Hepatitis B virus [HBV]:i

As figures above HBV is composed of central core containing the viral DNA genome, DNA polymerase, hepatitis B core antigen (HBcAg), and hepatitis B e antigen (HBeAg), and an outer lipoprotein coat containing the hepatitis B surface antigen(HBsAg) .i

Principal considerations:i

Asymptomatic carrier: the carrier patient never develops antibodies against HBsAg (anti-HBsAg) and harbors the virus without liver injury.i

Chronic persistent hepatitis: the patient has a low-grade hepatitis.i

Chronic active hepatitis: the patient has an acute hepatitis state that continues without the normal recovery (last longer than 6-12 months).i

Fulminant hepatitis: severe acute hepatitis with rapid destruction of the liver.i

i>>>Transmission is via parenteral, sexual, and vertical (mother to neonate) routes. There is an increased incidence of HBV infection in male homosexuals.i

i>>>The incubation period averages 60–90 days.i

i>>>HBV has a major association with hepatocellular carcinoma.i

i>>>Disease can result in a carrier state or in chronic liver disease.i

i>>>The sequence in which the various antigens or antibodies to these antigens appear in the serum is of clinical significance.i

Serology:i

i1. HBsAg: the presence of HBsAg always means there is LIVE virus and infection, either acute, chronic, or carrier. When anti-HBsAg develops, HBsAg disappears and the patient is protected and immune. i

i2.HBcAg: antibodies to HBcAg are not protective but we can use them to understand how long the infection has been ongoing.i

With acute illness we will see IgM anti-HBcAg.i

With chronic illness we will see IgG anti-HBcAg.i

i.e.i

الذهبية :تقول القاعدة

IgM anti-HBcAg = NEW INFECTION (acute infection)i

IgG anti-HBcAg = OLD INFECTION ( chronic infection)i

i3. HBeAg: it is the soluble component of the core, this soluble component (HBeAg) is released during active infection.i

The presence of HBeAg indicates a high infectivity and active disease, i Presence of anti-HBeAg suggests lower infectivity.i

i.e.i

الذهبية :تقول القاعدة

HBeAg = HIGH INFECTIVITY

Anti-HBeAg = LOW INFECTIVITY

Notes:i i>>> When HBsAg is still persistent as detectable serum antigen for more than 6 months this denotes the carrier state.i

i>>> Both Anti-HBcAg and Anti-HBeAg are markers used to diagnose hepatitis during the "window phase"i

i>>> Window phase: it is a period of time in which there is neither detectable HBsAg nor Anti-HBsAg (HBsAb) in the serum of infected person.i

i>>> During window phase: i

:تقول الذهبية القاعدة

In the window phaseHBsAg number = Anti-HBsAg number

For this reason we cannot detect neither HBsAg nor Anti-HBsAg (HBsAb) in the serum of infected person in this period.i

i>>> HBV DNA can also be detected in serum and is an index of infectivity.i

The outcome of hepatitis B in adult:i

In acute hepatitis B the serum analysis become as follow:i

While in chronic state of hepatitis it become as follow:ii

i3. Hepatitis C virus [HCV]:i

Transmission is parenteral. HCV is a frequent cause of transfusion-mediated hepatitis and often leads to a carrier state and chronic hepatitis.i

HCV is frequently associated with hepatocellular carcinoma.i

The outcome of hepatitis C in adult:i

i4. Hepatitis D virus [HDV]:i

HDV is replicatively defective, requiring simultaneous infection with HBV for viral replication. It usually causes illness more severe than HBV infection alone.i

Transmission is via sexual or parenteral routes.i

Incidence is especially high in intravenous drug users.i

i5. Hepatitis E virus [HEV]:i

causes an enterically transmitted form of viral hepatitis similar to HAV infection that occurs in water-borne epidemic form in underdeveloped countries.i

It has a high incidence of mortality (about 20%) when occurring in pregnancy.i

Chronic hepatitis

Chronic hepatitis is defined by the persistence of abnormalities for more than 6 months. It may result from any of the viral hepatitides except HAV or HEV infection and also from liver damage induced by nonviral agents.i

Autoimmune hepatitis is morphologically indistinguishable from other forms of chronic hepatitis. It is secondary to various immunologic abnormalities. It is clinically marked by hypergammaglobulinemia and anti–smooth muscle antibodies.i

Microvesicular fatty liver

This group of serious disorders is associated with the presence of small fat vacuoles in parenchymal liver cells, which differ from the large fat-containing vacuoles characteristic of fatty change.i

i1. Reye syndrome:i Ai. This acute disorder of young children is characterized by encephalopathy, coma, and microvesicular fatty liver.iBi. Reye syndrome is associated with aspirin administration to children with acute viral infections.i

2i. Fatty liver of pregnancy:iIs acute hepatic failure during the third trimester of pregnancy associated with microvesicular fatty liver. This condition has a high mortality rate.i

3i. Tetracycline toxicity:iResults in an unpredictable hypersensitivity-like reaction with microvesicular fatty change.i

Alcoholic liver disease

is the summation of hepatic changes associated with excessive alcohol consumption; it varies from fatty change to alcoholic hepatitis and

cirrhosis.i

it may be asymptomatic or may be associated with mild-to-severe hepatic inflammation, cirrhosis, or encephalopathy.i

1i. Fatty change (steatosis): is the most frequent morphologic abnormality caused by alcohol and is reversible. Nonalcoholic fatty liver disease, or NAFLD, is a related condition unrelated to alcohol consumption.i

i2. Alcoholic hepatitis: is often associated with irreversible fibrosis that characteristically surrounds central veins and has been referred to as perivenular fibrosis, sclerosing hyaline necrosis, or central hyaline sclerosis. This fibrosis can lead to central vein obstruction and fibrosis surrounding individual liver cells and can result in cirrhosis.i

i3. Alcoholic cirrhosis. i

Cirrhosis

General considerations:ii

i>>> Cirrhosis is a descriptive term for chronic liver disease characterized by generalized disorganization of hepatic architecture with scarring and nodule formation. Liver cell damage, regenerative activity, and generalized fibrosis resulting in a nodular pattern are also characteristic.iii>>>i Classification can be morphologic, on the basis of nodule isize (micronodular, macro-nodular, and mixed macromicronodular forms).iii>>> In all forms, there is an increased incidence of hepatocellular carcinoma.i

mainly there are 3 types of cirrhosis:iii

i1. Alcoholic (Laennec, nutritional) cirrhosis: is the prototype for all forms of cirrhosis.i

Clinical manifestations:i

i1. Jaundice, most often mixed conjugated and unconjugated.ii2. Hypoalbuminemiai3. Coagulation factor deficienciesi4. Consequences of intrahepatic scarring with increased portal venous pressure include:i

a. Esophageal varices.ib. Rectal hemorrhoids.i

c. caput medusa.id. Splenomegaly.i

i5. Encephalopathy (portal-systemic encephalopathy) facilitated by shunting from the portal to the systemic circulation, with direct delivery of neurotoxic substances, such as ammonia and other enteric degradation products, directly into the systemic circulation. Neurologic manifestations varying from slight confusion to deep coma along with asterixis (flapping tremor of hands) are characteristic features.i

i2. Postnecrotic (macronodular, posthepatitic) cirrhosis

i>>>Morphologic characteristics include broad fibrous bands dividing the liver into large, irregular nodules, often containing intact hepatic lobules.i

i>>>This form of cirrhosis is often a sequela of chronic active hepatitis; HBV and HCV are the most common viral causes. In addition, this disease may be caused by noninfectious hepatotoxic agents. Sometimes, it can result from the progression of micronodular alcoholic cirrhosis. Often, the etiology is uncertain (cryptogenic cirrhosis).i

i>>>Postnecrotic cirrhosis leads to hepatocellular carcinoma more often than other forms of cirrhosis.i

i3. Biliary cirrhosis: occurs as a primary, probably autoimmune, disorder and much more frequently as a secondary form due to biliary obstruction.i

A. Primary biliary cirrhosis: i

i>>>This form of cirrhosis is most likely of autoimmune origin. i

i>>>Disease is most common in middle-aged women.i

i>>>Characteristics include severe obstructive jaundice, itching, and hypercholesterolemia; hypercholesterolemia leads to cutaneous xanthoma formation.i

i>>>Primary biliary cirrhosis is marked by increased parenchymal copper concentration, a finding of unknown significance.i

B. Secondary biliary cirrhosis

i>>>The cause is extrahepatic biliary obstruction.i

i>>>Complications often include ascending cholangitis and bacterial inflammation of the intrahepatic bile ducts.i

i>>>Secondary biliary cirrhosis is marked histologically by evidence of bile stasis and by bile lakes, accumulations of bile within hepatic parenchyma.i

Vascular disorders of the liver

i1. Portal hypertension:iis characterized by the development of venous collaterals with varices in the submucosal veins of the esophagus, the hemorrhoidal plexus, and other sites.i

This condition is often classified by the site of portal venous obstruction:i

A. Prehepatic: caused by portal and splenic vein obstruction, most often by thrombosis

B. Intrahepatic: caused by intrahepatic vascular obstruction, most often by cirrhosis or metastatic tumor, and more rarely by exotic entities such as schistosomiasis

C. Posthepatic: caused by venous congestion in the distal hepatic venous circulation, most often as a result of constrictive pericarditis, tricuspid insufficiency, congestive heart failure, or hepatic vein occlusion (Budd-Chiari syndrome)i

i2i. Infarction is unusual, because the liver has a double blood supply (mesenteric and hepatic).i

i

i3. Budd-Chiari syndrome:i

The cause is thrombotic occlusion of the major hepatic veins, resulting in abdominal pain, jaundice, hepatomegaly, ascites, and eventual liver failure.i

Budd-Chiari syndrome is most often associated with polycythemia vera, hepatocellular carcinoma, and other abdominal neoplasms; may also occur as a complication of pregnancy.i

4i.Congestive heart failure:i

In long-standing chronic right-sided heart failure, the cut surface of the liver can assume an appearance referred to as the nutmeg liver, with dark red congested centrilobular areas alternating with pale portal areas.i

Eventually, centrilobular fibrosis occurs, resulting in cardiac cirrhosis (cardiac sclerosis). Similar changes may follow long-standing constrictive pericarditis or tricuspid insufficiency.i

Hepatic tumors

Benign tumors

Hemangioma: is the most common benign tumor of the liver.i

Adenoma:i

The incidence is apparently related to use of oral contraceptives.i

When the adenoma is subcapsular in location, it may rupture, resulting in severe intraperitoneal hemorrhage.i

Malignant tumors

Metastatic tumors account for the majority of hepatic malignancies.i

Hepatocellular carcinoma:i

is the most common primary malignancy of the liver.i

This hepatic malignancy almost always develops in association with preexisting cirrhosis of any kind, especially when associated with HBV infection.i

iFrequently, the cancer is marked by increased serum concentration of α-fetoprotein.i

There is a propensity for invasion of vascular channels with hematogenous dissemination.i

Cholangiocarcinoma (bile duct carcinoma):i

is less common than hepatocellular carcinoma. This form of hepatic cancer occurs in association with Clonorchis sinensis

(liver fluke) infestation[يطاردنا فائق!!! .]i

The cancer originates from intrahepatic biliary epithelium.i

Like hepatocellular carcinoma, it has a propensity for early invasion of vascular channels.i

Unlike hepatocellular carcinoma, cholangiocarcinoma is not associated with HBV infection or cirrhosis.i

Diseases of gallbladder

A. Cholecystitis

Acute cholecystitis

is acute inflammation of the gallbladderThe inflammation is most often pyogenic.i

Clinical manifestations include nausea, vomiting, fever, and leukocytosis associated with right upper quadrant and epigastric pain.i

Chronic cholecystitis

Thickening of the gallbladder wall occurs as a result of extensive fibrosis.i

Chronic inflammation is frequently complicated by gallstones.i

B. Cholelithiasis (gallstones)i

has a higher incidence in women and is often associated with obesity and multiple pregnancies.i

Clinical manifestations

Cholelithiasis is often silent and asymptomatic.iFatty food intolerance is characteristic.i

Complications:i

Biliary colic.iCommon bile duct obstruction.iAscending cholangitis .iCholecystitis.iAcute pancreatitis. iMalignancy. iTumors:i

Benign tumors of the gallbladder are rare.iThe most common primary tumor of the gallbladder is adenocarcinoma, which is often associated with gallstones.i

Diseases of pancreas

A. Acute pancreatitis

i>>>The cause is activation of pancreatic enzymes, resulting in autodigestion of the organ.ii>>>Predisposing factors include gallstones and excessive alcohol intake.ii>>>Clinical manifestations include severe abdominal pain and prostration closely mimicking an acute surgical abdomen.ii>>>There is an association with increased serum amylase.ii>>>Acute pancreatitis can be superimposed on chronic pancreatitis.i

B. Chronic pancreatitis

i>>>There is almost always an association with alcoholism.i

i>>>Clinical manifestations are extremely variable and include abdominal and back pain, progressive disability, and steatorrhea, which is a manifestation of pancreatic insufficiency with lipase deficiency.i

C. Carcinoma of the pancreas is a common tumor

i>>>Incidence is increasing; the carcinoma is more common in smokers.ii>>>The carcinoma is almost always adenocarcinoma.i

i>>>Clinical manifestations may include abdominal pain radiating to the back, weight loss and anorexia.iCancer is often silent before widespread dissemination occurs.i

i>>>Death usually results within 1 year .iبعونه ...تعالى تم