1. THE LIVER

2. Introduction
The liver is the largest internal organ in the body and is situated in the right hypochondrium. Functionally, it is divided into right and left lobes by the middle hepatic vein.
The liver has the enormous task of maintaining the body`s metabolic homeostasis. This includes the processing of dietary amino acids, carbohydrates, lipids and vitamins; synthesis of serum proteins including coagulation factors; and detoxification and excretion into bile of endogenous waste products .

3. Viral hepatitis
Viral hepatitis is caused mainly by hepatitis viruses A(HAV), B (HBV), C (HCV), D (HDV), and E (HEV).
These viruses and their infections have distinct features.

4. Hepatitis A virus
Hepatitis A usually is a benign, self-limited disease.
It is a single stranded RNA virus with incubation period of 2 to 6 weeks.
HAV does not cause chronic hepatitis or a carrier state.
Rarely there is fulminant hepatitis; fatalities occur at a rate of only 0.1%.
Occurs worldwide & is endemic in places with substandard hygiene (people may have detectable antibodies by age of 10y).
Spread is by contaminated water & food (fecal-oral).
Viral hepatitis is caused mainly by hepatitis viruses A
(HAV), B (HBV), C (HCV), D (HDV), and E (HEV). These
viruses and their infections have distinct features

5. virus Hepatitis A
Virus is shed in stool for 2-3 wks before & 1 wk after onset of jaundice.
HAV is not shed in any significant quantities in saliva, urine, or semen.
Because HAV viremia is transient, blood-borne transmission of HAV occurs only rarely; therefore, donated blood is not routinely screened for this virus.
Detection of anti-HAV IgM antibody is the best diagnostic marker for the disease.
IgG antibody persists for years and is the primary defense against reinfection.

6. Hepatitis B Clinicopathological syndroms: DNA virus.
Incubation period 4-26 wks
Clinicopathological syndroms:
Acute hepatitis with recovery
Nonprogressive chronic hepatitis
Progressive chronic disease>cirrhosis
Fulminant hepatitis
Asymptomatic carrier state (presence of HBsAg in serum for 6 months or longer).

7. Modes of transmission
whereas blood and body fluids are the primary vehicles of transmission, virus also may be spread by contact with body secretions such as semen, saliva, tears, breast milk, and pathologic effusions.
In endemic regions, vertical transmission from mother to child during birth constitutes the main mode of transmission.

8. Prevention
Vaccination
Screening of donor blood & tissues

9. Hepatitis C Single stranded RNA. Incubation period 2-26 weeks
Most common chronic blood-borne infection
Routes of transmission
Inoculations
Blood transfusions
Sexual intercourse
Perinatal

10. Clinicopathological syndroms
1. Acute hepatitis (rarely fulminant). 2. Chronic hepatitis. 3. Cirrhosis in 20%-30% of patients with chronic infection after 5-20y of acute infection.

11. Hepatitis D Virus
HDV is a unique RNA virus that is replication- defective, causing infection only when it is encapsulated by HBsAg
.Delta hepatitis arises in two settings:
(1) acute coinfection after exposure to serum containing both HDV and HBV.
(2) superinfection of a chronic carrier of HBV with a new inoculum of HDV

12. Hepatitis E Virus Single stranded RNA Incubation period 6 weeks
Water-borne infection affecting young to middle-aged adults (oral route)
the disease is self-limited; HEV is not associated
with chronic liver disease or persistent viremia
A characteristic feature of the infection is the high mortality rate among pregnant women, approaching 20%.

13. Morpholpgy of acute and chronic viral hepatitis
Grossly :
liver involved by mild acute hepatitis appears normal or slightly mottled.
in massive hepatic necrosis the liver may shrink to
and become transformed into a limp, red organ
covered by a wrinkled, baggy capsule.

14. Microscopical changes in acute viral hepatitis
The first is swelling (ballooning degeneration), producing cells with emptyappearing pale cytoplasm.
Necrosis (cytolysis), the necrotic cells appear to
have dropped out, leaving collapsing sinusoidal collagen.
Apoptosis, in which hepatocytes shrink, become intensely eosinophilic, and have fragmented nuclei;
In severe cases, bridging necrosis (central-central, portal-portal, central-portal).
Inflammation (mononclear), spillover into adjacent parenchyma.

15. Microscopical changes in chronic viral hepatitis
Changes shared with acute hepatitis,hepatocytes injury, necrosis,apoptosis.
Dense mononuclear portal infiltrates of variable prominence are the defining lesion of chronic hepatitis.
Fibrosis
Ground-glass hepatocytes (HBV)
Lymphoid aggregate formation (HCV)

16. Fulminant viral hepatitis

18. Chronic HBV hepatitis, ground-glass hepatocytes

19. Chronic HCV hepatitis

20. Primary Biliary Cirrhosis
Primary biliary cirrhosis (PBC) is a chronic, progressive, and sometimes fatal cholestatic liver disease.
PBC is primarily an immune disease of middle- aged women.
Peak incidence between the ages of 40 and 50 years.

21. Primary Billiary Cirrhosis
Characterized by:
Destruction of intrahepatic bile ducts(The cardinal feature of PBC is a nonsuppurative destruction of small and medium-sized intrahepatic bile ducts).
Portal inflammation
Scarring
Development of cirrhosis.
Liver failure over years to decades

22. Clinical Course The onset of PBC is insidious. Common early symptoms:
Fatigue
Pruritis
Dry eyes and mouth
Later signs and symptoms:
Jaundice(is an indication of how far the disease has progress)
Skin hyperpigmentation and xanthoma.
Edema
Ascites
Musculoskeletal pain, arthritis.
Renal stone and gallstone.

23. Morphology
Stage1: Interlobular bile ducts are actively destroyed by lymphocytic or plasmacytic inflammation with or without granulomas (the florid duct lesion).
Stage2: periportal fibrosis and/or inflammation.
stage3: fibrous septa formation.
Stage4: nodules formation.

24. Hepatic Failure
The most severe clinical consequence of liver disease is hepatic failure.
The patterns of injury that cause liver failure fall into three categories:
Acute liver failure with massive necrosis : Most often caused by drugs or viral hepatitis, or toxins.
Chronic liver disease (chronic hepatitis,cirrhosis)
Hepatic dysfunction without overt necrosis (tetracycline, fatty liver in pregnancy

25. Clinical Features Jaundice is invariable finding.
Coagulopathy, attributable to impaired hepatic synthesis of blood clotting factors.
Hypoalbuminemia that predispose to edema.
palmar erythema (local vasodilatation).
Hypogonadism, gynecomastia (due to hyperestrogenemia)
Hyperammonemia due to defective hepatic urea cycle function.
Spider angiomas.

26. Complications Hepatic encephalopathy
Hepatorenal syndrome (renal failure)
Hepatopulmonary syndrome

27. Cholelithiasis(gallstones)
Affect 10%-20% of adults
Types -cholesterol-containing stones, (80%) -bilirubin-containing stones, (20%)
Risk factors I. cholesterol stones .old age .female sex hormones (oral contraception,pregnancy) .obesity & metabolic syndrome(insulin resistence) .rapid weight reduction .gallbladder stasis .inborn errors of bile acid metabolism .dyslipidemia syndromes.

28. II. Pigment stones. chronic hemolytic syndromes(sickle cell anemia)
II. Pigment stones .chronic hemolytic syndromes(sickle cell anemia). .biliary infection .gastro-intestinal disorders (Crohns disease, cystic fibrosis).

29. Pathogenesis Cholesterol stones
Super-saturation of bile with bilirubin & cholesterol Pigment stones
Disorders associated with elevated levels of unconjugated bilirubin in bile
Hemolytic syndromes
Severe ileal dysfunction.
Bacterial contamination of biliary tree

30. Morphology Cholesterol stones Ovoid and firm. Multiple mostly.
Pure cholesterol stones are: pale yellow,and (radiolucent)
Mixed stones (calcium carbonate, phosphates, & bilirubin) are: gray-white to black, (radio opaque)
Pigment stones .Black-sterile bile (radio-opaque) .Brown-infected bile (all radiolucent)

31. Gall bladder, cholesterol stones

32. Gall bladder, pigment stones

33. Clinical features: asymptomatic
Biliary colic Complication in gall bladder (empyema,Perforation, fistulas, cholecystitis, carcinoma)
Cholangitis & cholestasis
Pancreatitis
Intestinal obstruction