Liver

Diseases Of The Liver, Gall bladder & Pancreas

A- ANATOMY
1. Gross Pathology
The liver is the largest viscous of the body, (1400-1600 g) in adults
Two-thirds of the blood supply to the liver comes from the portal vein, the other third comes from the hepatic artery. Blood drains into the hepatic veins and enters the inferior vena cava.
2. Microscopic Architecture
a. Lobule: Classic hexagonal structure with portal tracts at the periphery and central vein (=terminal hepatic venule) at the center.
b. Acinus: (based on the hepatic microcirculation). The acini are roughly triangular with the bases being the terminal branches of the portal vein and hepatic artery and apices are the central vein (terminal hepatic venule). The acinus is divided into zones:
i. Zone 1: Adjacent to portal venous system, richest in oxygen and nutrient supply.
ii. Zone 2: Intermediate between 1 & 3
iii. Zone 3: At the apex, adjacent to the terminal hepatic venules; and affected most by anoxia.

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B. FUNCTION
1. Metabolic : glucose homeostasis, lipid metabolism
2. Synthetic: albumin, coagulation proteins I, II, V, VII-XIII,
specific binding proteins, immunizing substances, including gamma globulin
3. Storage: glycogen, triglycerides, iron, copper, lipid and soluble vitamins
4. Catabolic: ammonia->urea, detoxification of many foreign compounds, drugs and chemicals
5. Excretory : bile excretion


Laboratory Evaluation of Liver Disease

Test Category Serum Measurement

Hepatocyte integrity Cytosolic hepatocellular enzymes[]
Serum aspartate aminotransferase (AST)
Serum alanine aminotransferase (ALT)
Serum lactate dehydrogenase (LDH)

Biliary Substances normally secreted in bile[]

Serum bilirubin
Total: unconjugated plus conjugated
Direct: conjugated only
Delta: covalently linked to albumin

Urine bilirubin

Serum bile acids
Plasma membrane enzymes (from damage to bile canaliculus)[]
Serum alkaline phosphatase
Serum γ-glutamyl transpeptidase
Serum 5′-nucleotidase
Hepatocyte function Proteins secreted into the blood
Serum albumin[]
Prothrombin time[] (factors V, VII, X, prothrombin, fibrinogen)


Hepatocyte metabolism
Serum ammonia[]
Aminopyrine breath test (hepatic demethylation)[]
Galactose elimination (intravenous injection)[]
An elevation implicates liver disease.
A decrease implicates liver disease.
BILIRUBIN METABOLISM

Steps in Bilirubin Metabolism Etiology/Pathogenesis

1. Bilirubin production 1. Unconjugated hyperbilirubinemia
Breakdown of senescent Increased destruction of RBCs
RBC's - 85% -hemolytic anemia
Hemoproteins 15% -reabsorption of large hematoma
-ineffective erythropoiesis
2. Uptake/binding 2.Unconjugated hyperbilirubinemia
Bilirubin is transported Impaired uptake/binding
across the hepatocyte membrane -hepatocellular injury
and is taken up by a protein carrier -drugs
-newborns
-Gilberts


3. Conjugation 3. Unconjugated hyperbilirubinemia
Bilirubin is released from Impaired Conjugation
the ligand and conjugated - newborns
with 2 molecules -Crigler-Najjar syndrome
of glucuronic acid, by -Gilberts
UDP glucuronyl transferase -Breast milk jaundice (β-
glucuronidases in milk)

4. Excretion 4. Predominantly conjugated
Conjugated bilirubin diffuses hyperbilirubinemia
through the cytosol to the - Deficiency of canalicular membrane transporters (Dubin Johnson syndrome &
bile canaliculus where Rotors syndrome)
it is excreted into the bile -hepatocellular injury
-toxins
-impaired bile flow (intrahepatic or extrahepatic)

5. Eventually bile is excreted into the small bowel. Bacterial flora in the GI tract hydrolyses it to free bilirubin that is now unconjugated and reduced to urobilinogen. Most of the urobilinogen is excreted into feces, however, some returns via the enterohepatic circulation and is reexcreted in bile or in the urine.

Jaundice (icterus)

Greenish yellow discoloration of tissue.
It is a sign of disease but is not a disease.
Caused by abnormally high concentration of bilirubin in the blood
Normal bilirubin is 0.3 to 1.2.mg/dL. If serum bilirubin exceeds 2.5 -- jaundice is noticeable on skin, mucous membranes of the mouth and (especially) sclera.
Most common sign of liver disorder
There are three forms of jaundice
Hemolytic (pre-hepatic)--caused by an excess of destroyed RBCs
Hepatocellular (hepatic)--caused by liver disease
Obstructive (post-hepatic)--caused by a block in the passage of bile between the liver and intestinal tract


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Hereditary Hyperbilirubinemias

a- Gilbert syndrome
is extremely common, occurring in almost 5% of the population.
is a familial disorder characterized by a modest elevation of serum unconjugated bilirubin; the liver otherwise unimpaired, and there are no clinical consequences.
is caused by a combination of decreased bilirubin uptake by liver cells and reduced activity of glucuronyl transferase.
b- Crigler-Najjar syndrome
is a severe familial disorder characterized by unconjugated hyperbilirubinemia caused by a deficiency of glucuronyl transferase.
Type I : autosomal recessive, complete lack of the conjugating enzyme, fatal causing death within 18 months of birth secondary to brain damage(kernicterus)
Type II : autosomal dominant, less severe, nonfatal, partial defect in the conjugating enzyme, the major consequence is extraordinarily yellow skin.
c- Dubin-Johnson syndrome
is an autosomal recessive form of conjugated hyperbilirubinemia characterized by defective bilirubin transport across the canalicular membrane.
is usually asymptomatic & characterized by a striking brown to black discoloration of the liver, caused by the deposition of granules of very dark pigment, and hepatomegally.
d- Rotor syndrome
is similar to Dubin-Johnson syndrome, but the liver is not pigmented.

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Cholestasis
Cholestasis : is a pathologic condition of impaired bile flow, leading to accumulation of bile pigment in the hepatic parenchyma.
It can be caused by extrahepatic or intrahepatic obstruction of bile channels, or by defects in hepatocyte bile secretion.
Patients may have jaundice, pruritus, skin xanthomas (focal accumulation of cholesterol), or symptoms related to intestinal malabsorption, including nutritional deficiencies of the fat-soluble vitamins A, D, or K.
A characteristic laboratory finding is elevated serum alkaline phosphatase and γ-glutamyl transpeptidase (GGT )
Morphology.
The morphologic features of cholestasis depend on its severity, duration, and underlying cause.
Common to both obstructive and nonobstructive cholestasis is the accumulation of bile pigment within the hepatic parenchyma . Elongated green-brown plugs of bile are visible in dilated bile canaliculi . Rupture of canaliculi leads to extravasation of bile, which is quickly phagocytosed by Kupffer cells. Droplets of bile pigment also accumulate within hepatocytes, which can take on a fine, foamy appearance (feathery degeneration).
Obstruction of the biliary tree, either intrahepatic or extrahepatic, causes back-pressure which induce proliferation of the duct epithelial cells, and reduplication of ducts and ductules in the portal tracts. Associated histologic findings include portal tract edema and periductular infiltrates of neutrophils. Unrelieved obstruction leads to portal tract fibrosis, and ultimately, to biliary cirrhosis.


Hepatitis
Means inflammation of liver.
Causes:
-Viral
- Alcoholic
- Drug-induced
-Autoimmune
Viral Hepatitis
The hepatotropic Viruses- (A,B,C,D,E,F,G,.) all are RNA except HBV account for most viral infections of the liver. All produce similar patterns of clinical and morphological acute hepatitis, but vary in their potential to induce chronic or fulminant disease or the carrier state.

Systemic viral infections that may involve the liver include: Infectious Mononucleosis (Epstein-Barr virus), Cytomegalovirus& Herpes virus. In children, rarely: rubella, adenovirus and enterovirus.

Hepatitis A virus (HAV)

*self-limited disease, fecal-oral spread, incubation period 14-45 days.
*account for 20-25% of acute hepatitis in developing world.
*does not cause chronic disease or carrier state. Fulminant hepatitis is rare.

Hepatitis B virus (HBV)

*The most versatile hepatitis virus, producing:
- asymptomatic carrier state
- acute hepatitis with complete recovery
- chronic hepatitis, either indolent or progressive
- fulminant hepatitis with massive liver necrosis
- risk factor for hepatocellular carcinoma
* Spread mainly by ---parenteral routes (transfusion, blood products and body fluids, needle-stick accidents and shared needles)
---vertical transmission during parturition
---sexual activity
* Can result in a carrier state or in chronic liver disease
* Has a major association with hepatocellular carcinoma


Hepatitis C virus (HCV)
*Identified in 1989, account for >90% of post transfusion hepatitis that was previously designated Non-A, Non-B.
*Similar spectrum of disease to HBV. However,
LESS common than B (one fourth)
LESS dangerous than B in the acute phase
MORE likely to go chronic than B
MORE closely linked with hepatoma than B

Delta Hepatitis virus (HDV)

*A small defective RNA virus that can replicate and cause infection only when encapsulated by HBsAg. Hence, HDV can develop only when there is concomitant HBV infection, either acute coinfection or superinfection of HBV carrier.
* May cause anything from mild to fulminant acute hepatitis.

Hepatitis E virus (HEV)

* Enterically transmitted, water-borne infection.
* Occurs primarily in young to middle aged adults in epidemic form.
* Generally mild, but fatality may approach 20% in pregnant women.
* Average incubation time is 6 weeks following exposure.

Pathology of Viral Hepatitis:

A- The Carrier State:
An individual without symptoms who harbors and therefore can transmit an organism. Most HCV, some HBV (especially congenitally infected children), no HAV-infected individuals.
Pathology;
Essentially normal liver biopsy
HBV : ground glass hepatocytes, sanded nuclei
HCV : chronic hepatitis usually present histologically


B- Acute Hepatitis (similar for all hepatitis viruses):
Pathology (can be mimicked by drug reactions);
Ballooning degeneration, hepatocyte necrosis (i.e., acidophilic bodies, Councilman bodies).
Spotty , confluent , bridging or massive necrosis
Lobular disarray (i.e., loss of architecture)
Portal tract inflammation: Mononuclear infiltrate with or without spillover into the surrounding paranchyma.
Possible cholestasis.
Important points:
* HBV infection is associated with ground glass hepatocytes.
* HCV infection is associated with mild fatty change (macrovesicular steatosis ),
and lymphoid aggregates.

C- Chronic Hepatitis:

Symptomatic, biochemical or serological evidence of continuing inflammatory hepatic disease for more than six months without steady improvement. Occurs commonly with HCV and with HBV (particularly with HDV super infection).
Pathology:
Evidence of hepatocyte injury (e.g., ballooning degeneration), necrosis and regeneration.
Portal tract inflammation with or without spillover; portal tract inflammation with spillover is referred to as interface hepatitis (piecemeal necrosis)
Fibrosis: Portal, periportal, or bridging.

D- Massive Necrosis (Fulminant Hepatitis):

Defined as hepatic insufficiency progressing from onset to death (or hepatic transplantation) within 2-3 weeks. Viral hepatitis & drugs (especially acetaminophen) are the common causes, other causes include poisoning (e.g., Amanita Phalloides), acute fatty liver of pregnancy, hepatic ischemia and Reye syndrome.
Pathology; The entire liver may involved or only portions. Microscopically, entire lobules may be necrotic, collapse of reticulin framework, with little inflammatory reaction. If the patient survives for more than a week, secondary changes develop, including marked regeneration of hepatocytes, and hypertrophy and hyperplasia of surviving Kupffer cells, which become laden with lipofuscin and cellular debris.


Autoimmune Hepatitis
Is a severe type of chronic hepatitis of unknown cause that is associated with circulating autoantibodies and high levels of serum immunoglobins.
Constitute 20% of cases of chronic hepatitis
Not associated with viral infection
Mostly in young women
Widely variable clinical presentations
Asymptomatic LFT abnormality (ALT and AST)
Severe hepatitis with jaundice
Cirrhosis and complications of portal HTN
High titers of autoantibodies
antinuclear
anti-smooth muscle
anti-mitochondrial
Liver biopsy: portal lymphocytes + plasma cells
In about 1/3 of the cases, they have an other autoimmune disease; including thyroiditis, RA & UC

Alcoholic Liver Disease:

Is the most common form of liver disease in the western countries and refers to hepatic changes associated with excessive alcohol consumption.
Alcoholic Liver Disease include;
Fatty changes (steatosis), affect 80% of heavy drinkers and it is reversible.
Gross; Yellow discoloration of liver parenchyma, can be patchy or involve entire liver (i.e., diffuse fatty liver).
Microscopic; Microvesicular steatosis with acute exposure and macrovesicular steatosis in chronic exposure or both.
2- Alcoholic hepatitis (steatohepatitis), affect 10-35% of heavy drinkers and characterized by fatty changes, focal liver cell necrosis, infiltrates of neutrophils, and presence of intracytoplasmic eosinophilic hyaline inclusions (Mallory bodies); sinusoidal and perivenular fibrosis.
3- Alcoholic cirrhosis, only 10% of alcoholics develop cirrhosis but 65% of cirrhosis is due to alcohol
With continued alcohol abuse, inflammatory cells infiltrate liver causing necrosis, fibrosis and destruction of liver tissue
Regenerative nodules form, liver shrinks and is nodular


Drug-induced Liver Disease
Drug-induced liver injury is the most common cause of fulminant hepatitis in the United States. Injury may result (1) from direct toxicity to hepatocytes or biliary epithelial cells, causing necrosis, apoptosis, or disruption of cellular function; (2) indirect through hepatic conversion of a xenobiotic to an active toxin; or (3) through immune mechanisms
Drug reactions may be
predictable (intrinsic) Predictable drug reactions can occur in anyone who receives a sufficient dose of an agent.
or unpredictable (idiosyncratic). depend on the host, particularly the rate at which the host metabolizes the agent, and the intensity of the immune response. Important examples include chlorpromazine, an agent that causes cholestasis in patients who are slow to metabolize it, and halothane, which can cause a fatal immune-mediated hepatitis in some patients who are exposed to this anesthetic on multiple occasions.
Hepatocellular necrosis; acetaminophen, Isoniazid
Cholestasis; Contraceptive and anabolic steroids
Steatohepatitis; Amiodarone, ethanol
Macrovesicular Steatosis ; Ethanol, corticosteroids, total parenteral nutrition
Microvesicular Steatosis; amiodarone, IV tetracycline
Granulomas; Sulfonamides
Fibrosis and cirrhosis; Methotrexate, enalapril
Vascular lesions : - Sinusoidal obstruction syndrome High-dose chemotherapy,
-Budd-Chiari syndrome; Oral contraceptives
Neoplasms : -Hepatic adenoma; Oral contraceptives
- Hepatocellular carcinoma; Thorotrast
-Cholangiocarcinoma; Thorotrast
-Angiosarcoma ; Thorotrast , vinyl chloride

Liver Cirrhosis (Gk orange/yellow)

Definition:
Diffuse scarring of the liver with
Nodular regeneration of hepatocytes, resulting in
Severe disruption (complete loss) of hepatic architecture.
Etiology
Alcoholic liver disease 60-70%
Viral hepatitis 10%
Biliary disease 5-10%
Primary hemochromatosis 5%
Cryptogenic cirrhosis 10-15%
Wilsons, (1AT def rare
Pathogenesis:
Cirrhosis is common end result of many chronic liver disorders.
Chronic inflammation causes the release of transforming growth factor-B (TGF-β), which promotes collagen synthesis by stellate cells, leading to fibrosis.
Cycles of cell death, fibrosis, and regeneration result in cirrhosis of the liver;
As the normal liver is gradually replaced by nodules of new cells there is a gradual increase in pressure on the vessels which flow through and eventually put back pressure onto the portal system = portal hypertension.
This results in opening up of collateral circulation
Morphology
Gross: Diffusely nodular liver, with micronodular (< 3mm. nodules) or macronodular (>3mm. nodules) architecture. Macronodular cirrhosis is associated with hepatitis, autoimmune diseases, and end stage cirrhosis of all etiologies. Micronodular cirrhosis is associated with alcohol use and with other causes such as α1-antitrypsin deficiency and hemochromatosis.
Microscopic: Bridging fibrosis between the portal tracts and central veins, which divide residual and regenerating hepatocytes into nodules. Other features depend upon the cause of cirrhosis


Types according to underlying cause;

Alcoholic cirrhosis

Posthepatitic (postnecrotic) cirrhosis
Biliary cirrhosis (primary & secondary)
Pigmented cirrhosis (Hemochromatosis)
Cardiac cirrhosis
Cirrhosis due to inborn errors of metabolism

Alcoholic cirrhosis (Laennecs cirrhosis)

a. Alcohol causes metabolic changes in liver leading to fatty infiltration i.e. steatosis (stage in which abstinence from alcohol could allow liver to heal)
b. With continued alcohol abuse, inflammatory cells infiltrate liver causing necrosis (steatohepatitis) , fibrosis and destruction of liver tissue
c. Regenerative nodules form, liver shrinks and is nodular
d. Malnutrition commonly present

Biliary cirrhosis:

Bile flow is obstructed and is retained within liver causing inflammation, fibrosis and regenerative nodules to form.
increased skin pigmentation resembling a deep tan, jaundice and pruritus.
Post-hepatic cirrhosis:
Chronic hepatitis B or C and unknown cause leads to liver shrinkage and nodule formation with extensive liver cell loss and fibrosis


Cardiac cirrhosis
Right sided CHF. Liver is swollen, yet reversible if CHF is treated

Nonspecific, metabolic cirrhosis

Metabolic problems, infectious disease, infiltrative disease, GI disease could be the cause

Complications Of Cirrhosis

Include:
Portal hypertension
Ascites
Hepatocellular dysfunction
Portal vein thrombosis
Hepatocellular carcinoma
Hyperestrinism

a. Portal hypertension:

Pressures within the portal venous system become elevated as liver damage obstructs the free flow of blood through the organ
Shunting of blood to collateral blood vessels leading to
- esophageal varices, often causing upper GIT hemorrhage
- rectal hemorrhoids
- periumbilical venous collaterals (caput medusa)
- splenomegally


b. Ascites:
♦ Peripheral edema and ascites, caused by
- increased portal venous pressure (increased hydrostatic pressure) ,
- decreased plasma oncotic pressure secondary to hypoalbuminemia
- retention of sodium and water as a result of decreased hepatic degradation of aldosterone, activation of the renin-angiotensin system, or both
♦ Spontaneous bacterial peritonitis

c-Hepatocellular dysfunction

Findings associated with hepatocellular damage and liver failure include:
- jaundice, mixed conjugated and unconjugated
- hypoalbuminemia, caused by decreased albumin synthesis in damaged hepatocytes
- coagulation factor deficiencies, especially vit. K dependent factors II, VII, IX, and X leading to bleeding tendency.
- hyperestrinism, manifest as
palmar erythema,
spider nevi,
loss of body and pubic hair,
testicular atrophy and
gynecomastia

d. Hepatic encephalopathy:

Complex neuropsychiatric syndrome that complicates advanced liver disease.
Forms; acute and chronic
Pathogenesis:
Inadequate removal of nitrogenous compounds or other toxins that are ingested or formed in the GIT. Common precipitants include gastrointestinal bleeding , portosystemic shunting, and infections.
Clinical presentation:
Disturbance of sleep is often the earliest sign
Flapping tremor (Asterixis) and hyperreflexia.
Fetor hepaticus (musty order of breath)
Alteration in personality
Confusion, coma, death.


e. Hepatorenal syndrome:
renal failure with azotemia
** Pathogenesis: Severe cortical vasoconstriction
** Clinical presentation: Decreased GFR, oliguria, low urine sodium and disproportionately high ratio of blood urea to creatinine (prerenal pattern of
acute renal failure)
** Clinical course: Often progressive and fatal, with mortality rate of 95%
** Important point: Kidneys are histologically normal.
Metabolic Liver Disease
NONALCOHOLIC FATTY LIVER DISEASE (NAFLD)
HEMOCHROMATOSIS
WILSON DISEASE
α1-ANTITRYPSIN DEFICIENCY

NONALCOHOLIC FATTY LIVER DISEASE (NAFLD)

NAFLD is a group of conditions that have in common the presence of hepatic steatosis (fatty liver), in individuals who do not consume alcohol. It has become the most common cause of chronic liver disease in the United States, affects more than 30% of the population.
NAFLD includes simple hepatic steatosis, steatosis accompanied by minor, non-specific inflammation, and non-alcoholic steatohepatitis (NASH).
NASH is a condition in which there is hepatocyte injury that may progress to cirrhosis in 10% to 20% of cases. NASH affects men and women equally and the condition is strongly associated with obesity . It is the most common cause of so-called cryptogenic cirrhosis

HEMOCHROMATOSIS

Hereditary Hemochromatosis:
Autosomal recessive disorder (chromosome 6p), characterized by increase intestinal absorption of iron with subsequent deposition in the parenchymal organs such as the liver and pancreas.
Affects males > females (7:1)
Fully developed cases exhibit Triad of:
micronodular (pigmented) cirrhosis
skin pigmentation (75% of patients)
diabetes mellitus (75%) also called bronze diabetes
Lab; - marked increase in serum iron (ferritin)
- reduction in total iron binding capacity
- increased transferrin iron saturation
Secondary Hemochromatosis:
Most often associated with a combination of ineffective erythropoiesis and multiple transfusions, such as occurs in thalassemia major.
Other causes include increased oral iron intake (Bantu siderosis), iron injection,


Wilson Disease (Hepatolenticular Degeneration)
Is an autosomal recessive disorder of copper metabolism (chr. 15).
Is characterized by decreased serum ceruloplasmin (copper-binding protein): probably not a primary defect but it is secondary to increased copper.
Result in an accumulation of copper in the liver, kidney, brain and cornea.
Manifest in second & third decade as
--liver disease that varies from chronic hepatitis to cirrhosis, either micronodular or
macronodular in type.
-- extrapyramidal motor signs caused by involvement of the basal ganglia, especially
the putamen of the lenticular nucleus.
-- Kayser-Fleischer ring circumscribing the periphery of the cornea, representing
deposition of copper-containing pigment in Descement membrane.
-- aminoaciduria and glycosuria due to renal tubular damage.
-- NO increased risk for hepatocellular carcinoma.

α1- Antitrypsin Deficiency

α1- Antitrypsin (α1AT) deficiency is an autosomal recessive disorder (chr.14) resulting in an abnormally low serum levels of this protease inhibitor (Pi); deficiency leads to emphysema and hepatic disease .
Pathogenesis:
α1AT is a serum Pi synthesize in the liver. Impaired hepatic α1AT secretion leads to protein accumulation within hepatocyte endoplasmic reticulum, although the mechanism of liver damage is unclear. Lung damage results from inadequate levels of protease inhibitor.
Morphology:
Hepatic lesions include neonatal hepatitis (inflammation with cholestasis) and childhood and adulthood cirrhosis. α1AT deficiency is diagnosed by identifying periodic acid-Schiff (PAS) positive, diastase resistant cytoplasmic globules in periportal hepatocytes.


Biliary Cirrhosis
Occurs as a primary, probably autoimmune, disorder and much more frequently as a secondary form due to biliary obstruction.
A- Primary biliary cirrhosis
* is most likely of autoimmune origin. There is an increased incidence of other autoimmune disorders in these patients (84%), and antimitochondrial antibodies (95%) are characteristic.
* is most common in middle aged women (90%).
* is characterized by severe obstructive jaundice, itching, and hypercholestrolemia; cutaneous xanthoma , osteopenia, steatorrhea, DU,...
* is marked by increased paranchymal copper concentration.
Histological Progression
4 stages
I - granulomatous destruction of ducts
II - ductular proliferation and periportal hepatitis
III - scarring, septal fibrosis
IV - cirrhosis

B- Secondary biliary cirrhosis

* is characterized by extrahepatic biliary obstruction, which leads to dilation and increased pressure within intrahepatic bile ducts and cholangioles, further resulting in ductal injury, ductal and periductal inflammation, and resolution by fibrous tissue formation.
* is often complicated by ascending cholangitis and bacterial inflammation of the intrahepatic bile ducts.
* is marked histologically by evidence of bile stasis and by bile lakes, accumulation of bile within hepatic paranchyma.

Primary sclerosing cholangitis

Chronic cholestatic disorder with progressive fibro-obliterative destruction of segments of the biliary tree
Affects the extrahepatic and large intrahepatic ducts more than smaller ducts (5% have primarily small duct involvement)
Pathogenesis unknown, likely autoimmune
80% have ulcerative colitis (5% of patients with UC develop PSC), also Crohns colitis
Most are male, younger than age 45
Strong association with other autoimmune disorders
Most are asymptomatic
Diagnosis: AMA negative, ANA and SMA positive in more than half, p-ANCA positive in > 80%,
Gold standard is ERCP--- structuring and proximal dilatation gives a beaded appearance.



Vascular Disorder of the Liver
1- Portal Hypertension
Is often classified by the site of portal venous obstruction
a- Prehepatic; caused by portal and splenic vein obstruction, most often by thrombus.
b- Intrahepatic; caused by intrahepatic vascular obstruction, most often by cirrhosis or metastatic tumor, and rarely by 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)

2- Infarction

is unusual, because the liver has a double blood supply.
3- Budd-Chiari Syndrome
is caused by thrombotic occlusion of the major hepatic veins, resulting in an abdominal pain, jaundice, hepatomegally, ascites, and eventual liver failure.
is most often associated with polycythemia vera, hepatocellular carcinoma, and other abdominal neoplasm; may also occur as a complication of pregnancy.
4- Congestive heart failure
- 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.
- eventually, centrilobular fibrosis occur, resulting in cardiac cirrhosis. Similar changes may follow long standing constrictive pericarditis or tricuspid insufficiency.

Liver Tumors

Benign Tumors
Hemangiomas
are the most common benign tumors of the liver (7% of autopsy specimens),
affect all ages and both genders.
They are small and asymptomatic, although larger tumors have been reported to cause abdominal symptoms and even hemorrhage into the abdominal cavity.
- Grossly: the tumor is usually solitary and less than 5 cm. in diameter.
- Microscopically: cavernous hemangioma.


Hepatic adenoma
- Mainly affect females (85%) and often associated with oral contraceptives .
- In one third of patients with hepatic adenomas, the tumors bleed into the
abdominal cavity and require treatment as a surgical emergency.
- Grossly: the tumor is encapsulated and paler than surrounding parenchyma.
- Microscopically: the neoplastic hepatocytes resemble their normal
counterparts; except that they are not arranged in a lobular
architecture. Portal tracts and central venules are absent. The tumor is
circumscribed by a fibrous capsule of variable thickness, and the
adjacent hepatocytes appear compressed.

Bile duct adenoma

May or may not represent a neoplasm (reactive process to focal hepatic injury)
Clinical: - rare lesion
- incidental finding at surgery or autopsy
- usually solitary (83%)
- no malignant transformation

Malignant Tumors

General Features:
Hepatic malignancies are relatively uncommon in North America and Europe.
However, hepatic malignancies accounts 20-40% of all cancer in endemic areas of viral hepatitis.
Primary Tumors
1- Hepatocellular carcinoma
* is the most common primary malignancy of the liver.
* incidence varies with age, race, and geographic location.
* M > F (2-8: 1)
* commonly develops in association with pre-existing cirrhosis of any
Kind (84%), especially when associated with HBV or HCV.
* has been associated with aflatoxin B1 contamination of nuts and grains; aflatoxin B1
Is thought to cause specific point mutations in the p53 gene.
* frequently is marked by increased serum concentration of α-fetoprotein (AFP).
* has propensity for invasion of vascular channels with hematogenous dissemination.
2- Cholangiocarcinoma (bile duct carcinoma)
* is less common than hepatocellular carcinoma.
* occurs most frequently in the Far East, where it is associated with Clonorchis
sinensis (liver fluke) infestation.
* originates from intrahepatic biliary epithelium
* like hepatocellular carcinoma, has a propensity for early invasion of vascular
channels.
3- Hepatoblastoma
* the most common hepatic tumors in neonates and young children.
* very aggressive (death within few years of diagnosis).
* resistant to radiation and chemotherapy.
* microscopically, several components; epithelial, stromal and anaplastic.
4- Angiosarcoma
* is a rare malignant vascular tumor, forming 0.4% of all primary hepatic neoplasms.
* highly malignant, mean survival 6 months. Death is usually due to
hemoperitoneum and/or liver failure.
* M > F , and 85% of cases in men between age 50-60 year.
* is associated with toxic exposure to vinyl chloride, Thorotrast, and arsenic.


Secondary (Metastatic) Tumors
The most common malignancy in the liver.
Can come from many primary sites.
Usually multiple nodules with central umblication.









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Dr. Ziyad 31-3-2019