L19 - Pathology of hepatitis and cirrhosis Flashcards

1
Q

Overview of liver function

A
  • Processing of dietary amino acids, carbohydrate and lipids
  • Synthesis of serum albumin and coagulation factors (I, II, V, VII, IX, X)
  • Detoxification of drugs and chemicals
  • Metabolism of bilirubin
  • Stores glycogen (for gluconeogenesis to regulate blood glucose level)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Liver unit classification

A

Can be classified into three types:

1) Classical lobule (Structural)
2) Portal lobule (Functional - bile drainage)
3) Liver acinus (Functional - blood supply)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Liver acinus

A
  • Provides the best correlation between blood perfusion, metabolic activity and liver pathology
  • Diamond-shape
  • Smallest functional unit of liver
  • Two portal areas and two central vein reside on the angles of liver acinus
  • Can be devide into zone 1, zone 2, zone 3

- Perfusion, nutrients and metabolism (from greatest to least): zone 1> 2> 3

- pathophysiological events like poisoning, (from most affected to least): zone 1> 2> 3

- Under ischaemic condition, most affected (i.e. most prone to shock): zone 3> 2> 1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Hepatitis definition

A

A diffuse necroinflammatory disease of the liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Aetiology of acute hepatitis

A

1) Infections:

i) Viral infection

  • Hepatitis A, B, C, D, E Viruses
  • Epstein-Barr virus
  • Cytomegalovirus
  • Yellow fever virus (South America & Africa)
  • Echovirus
  • Ebolavirus
  • Varicella

ii) Bacterial Infection

  • leptospirosis
  • Q fever

iii) Parasitic Infection

2) Toxins and Drugs

  • e.g. Alcoholism

3) Autoimmune diseases

  • e.g. autoimmune hepatitis

4) Metabolic diseases

  • e.g. Wilson’s disease

(5) Obeisity ?)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

viral hepatitis definition

A

While it can mean any hepatitis caused by any viruses e.g. cytomegalovirus and Epstein-Barr virus, the term “viral hepatitis” is conventionally restricted to infections with the Hepatitis Viruses A, B, C, D and E.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Acute viral hepatitis general presentaion and prognosis

A

In general, acute hepatitis due to different hepatitis viruses show the same clinical picture - malaise, anorexia & jaundice:

Clinical Course

1) The disease begins after a variable incubation period.
2) Malaise (i.e. generalized weakness) and anorexia (loss of apetitite) are the earliest symptoms
3) Some patients may recover without becoming jaundiced so the patients may not be aware of the disease. Most patients, however, develop the characteristic symptom of jaundice.
4) The serum transaminases and bilirubin levels are raised.
5) In nearly all patients, the jaundice clears within 3 weeks. The duration of the recovery phase is variable, usually more prolonged in hepatitis B and in hepatitis C.
6) Most patients show complete clinical and biochemical recovery within 3 months after the onset of jaundice.

  • Grossly, the liver is swollen and congested
  • diffuse parenchymal damage
  • swelling of the hepatocytes
  • cholestasis
  • Kupffer cell hyperplasia
  • acidophilic bodies in the liver acini (apoptosis - scattered individual cell death)
  • Bridging necrosis or even panacinar necrosis in severe cases

(? - The portal tracts are expanded and infiltrated by mononuclear inflammatory cells)

  • concomitant hepatocyte regeneration

This fully developed stage of acute hepatitis with spotty necrosis usually lasts several weeks and is followed by complete resolution without scarring.

In some patients, the disease is more severe with massive liver cell necrosis, which corresponds to the clinical syndrome of fulminant hepatitis. A significant proportion of patients with fulminant hepatitis die of the disease.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

HAV virology

A
  • Picornavirus
  • RNA
  • unenveloped
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

HAV transmission & epidemiology

A

Transmission:

  • faeco-oral route; spreads by ingestion of contaminated water and foods especially shell fish
  • Shed in the stool for 2–3 weeks before and 1 week after the onset of jaundice
  • Transmission often seasonal from December to May
  • Faecal virus titres falling by the time jaundice appears
  • No carrier state

Epidemiology:

  • occurs throughout the world and is endemic in countries with substandard hygiene and sanitation.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

HAV clinical presentation and prognosis

A

Clinical presentation:

  • 2-6 weeks incubation period
  • direct cytopathic effect
  • 10% symptomatic in children; 50% symptomatic in adult
  • acute onset, no chronic carrier state

Prognosis:

  • Type A hepatitis is an acute self-limiting disease
  • does not become chronic.
  • Mild disease will 99% full recovery
  • May lead to protracted hepatitis, cholestatic hepatitis, relapsing hepatitis; these will all recover
  • Very rarely fatal, e.g in the case of developing fulminant hepatitis (0.1%)
  • No cross infection
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

HAV lab diagnosis & prevention

A

Lab diagnosis:

  • Serology: Anti-HAV (IgM antibody) appears during the attack and persists
  • no virus culture

Prevention

  • Passive immunity: normal human immunoglobulin
  • Active immunity: HAV vaccine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Hepatitis B virology

A
  • A hepadnavirus
  • Causes hepatitis
  • 8 genotypes (A to H)

Genome:

  • Contains DNA genomes
  • Small genome with 3200 nucleotides
  • Utilizes limited genome to maximal effect - with overlapping Open Reading Frames (4 ORF that translate to 7 proteins)
  • DNA genomes are replicated via an RNA intermediate. In other words, their replication involves reverse transcription

Structure:

(from innermost to outermost)

1) (+)-DNA & (-)-DNA encased
2) capsid
3) Outer envelope membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Transmission and epidemiology of HBV

A

Transmission:

  • Parenteral route
  • Vertical (mother-baby) transmission in perinatal period
  • intimate physical contact esp. sexual
  • Blood transfusion/ blood products/ needle contamination/ tattooing
  • Carrier state exists

Epidemiology

  • extremely common in Hong Kong and Southern China
  • Every 5 of 10 ppl have been infected by HBV in Hong Kong (1 in 10 is carrier)
  • Its incidence varies greatly in different parts of the world (HBsAg is present in 5 - 20% of apparently healthy persons in Southeast Asia and tropical Africa but in only 0.1 - 0.6% in Western Europe and America)
  • Globally 350 million chronic HBV carriers (75% are Chinese)
  • High risk groups: family members of HBV carrier, harmophiliacs, chronic liver disease patients
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Clinical presentation and prognosis of HBV

A

Clinical presentation:

  • The usual clinical attack of acute hepatitis B tends to be more severe than hepatitis A or C
  • Incubation period 2-6 months
  • 50% of infected adults are symptomatic
  • Infected neonates usually asymptomatic, much higher risk of chronicity (up to 95%)
  • Acute or insidious onset

Prognosis:

  • 95% will recover from acute HBV hepatitis
  • subclinical infection is also frequent especially in infants and children
  • A proportion of otherwise normal adult patients will not clear HBV from the serum. They become persistent chronic carriers or develop chronic hepatitis
  • up to 25-40% of chronic carriers succumb to HBV related illness
  • Chronic hepatitis may lead to cirrhosis,
  • Chronic hepatitis may progress to develop hepatocellular carcinoma (HCC) – 80%-90% of HCC associated with HBV in Hong Kong (i.e. HBsAg carriers have a much higher risk of HCC than non-carriers)
  • In 0.1 – 1% of cases, fulminant hepatitis occurs
  • Cross infection may occur
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Lab diagnosis and prevention of HBV

A

Lab diagnosis:

  • Serology: HBsAg positive; HBeAg indicates high infectivity; HBV DNA quantitatively indicates viral replication and activity

Prevention

  • Vaccination (Active immunity) – based on genetically engineered analogues of HBsAg, leading to production of Anti-HBs
  • Passive immunisation: Hyperimmune Hep B Immune globulin (HBIG)
  • All infants in HK are immunised
; All health care workers should be immunised
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

HCV Virology

A
  • Flaviviridae
  • a single-stranded linear RNA virus
  • enveloped
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

HCV transmission & epidemiology

A

Transmission:

  • Parenteral route
    • Blood transfusion/ blood products(0.02% of HK blood donors)/ needle contamination/ tattooing

(? Vertical (mother-baby) transmission in perinatal period)

(? intimate physical contact esp. sexual)

  • carrier state exist in >90% of patients

Epidemiology:

  • 170 million carriers worldwide
  • 100,000 cases of hepato-cellular carcinoma annually, worldwide
  • Greatest incidence rate in Egypt, due to reuse of injection needles in the past
  • Carrier state occurs in >90% of patients
  • uncommon in Hong Kong, with
  • High risk groups include IV drug users, haemophiliacs, chronic dialysis patients, patients with liver disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

HCV clinical presentation and prognosis

A

Clinical presentation:

Clinical Presentation:

  • Usually asymptomatic, lead to chronic carrier state in >90% of patients
  • Long incubation period (7-8 weeks)
  • insidious onset

Prognosis:

  • very rarely leads to fulminant hepatitis
  • About 50% of patients with acute hepatitis C progress to chronic hepatitis, leading to cirrhosis with or without development of hepatocellular carcinoma
  • Acute hepatitis C tends to be mild clinically. It is associated with a wide spectrum of disease outcome, similar to the pattern of HBV infection
  • Cross infection may occur
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

HCV Lab diagnosis & prevention

A

Lab diagnosis:

  • Serology: HCV infection is recognised by positive anti-HCV antibodies
  • PCR: HCV RNA is detectable early, preceding the appearance of anti- HCV by several weeks; quantitatively represent viral load
  • No viral culture

Prevention:

  • None
  • passive anti-HCV is NOT protective
  • No vaccination
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

HCV Infection Treatment

A
  • Pegylated inferferon + ribavirin: >50% viral clearance, reduce liver fibrosis and reverse cirrhosis
  • Virus genotype predicts response to treatment

– Genotypes 2 and 3: 88% response
– Genotypes 1, 4, 5, 6 : 48% response

  • Duration (24-48 weeks) of treatment depends on genotype and clinical assessment.
  • New antiviral drugs licenced: Protease inhibitors: Telapravir, Bocepravir (need to be used in combination with interferon+ribavirin)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

HDV Virology

A
  • Defective/ incomplete RNA virus

Special note:

  • under natural conditions replicates only in hosts who are HBs-antigenaemic. This is because HDV requires surface antigen of hepatitis B (HBsAg)
  • HDV infection is therefore either an acute HBV/HDV coinfection or a superinfection on chronic HBV infection
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

HDV Clinical Presentation & Prognosis

A
  • Acute HBV/HDV coinfection may be indistinguishable from hepatitis B, though it is associated with a relatively high rate of fulminant hepatitis.
  • HDV can transform mild chronic hepatitis B into severe chronic hepatitis & cirrhosis.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

HEV virology

A
  • Calicivirus
  • RNA
  • Unenveloped
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

HEV Transmission

A

Transmission:

  • faecal-oral route; has caused massive outbreaks of water-borne hepatitis
  • No chronic carrier state
  • Convalescent patients will shed HEV for weeks
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

HEV clinical presentation & prognosis

A

Clinical Presntation:

  • 2-9 weeks incubation period
  • Acute onset; no chronic carrier state

Prognosis:

  • low risk of chronicity
  • Full recovery is expected
  • No cross infection
  • Low risk of chronicity
  • Fulminant hepatitis in 1-2% patients; 10-20% in Pregnant
  • It may cause severe disease especially in pregnant women
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

HEV Lab diagnosis & prevention

A

Lab diagnosis:

  • Serology: rising IgG antibody and IgM antibody against HEV antigen
  • No viral culture

Prevention: none

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Pathogen of Non- ABCDE viral hepatitis

A
  • Cytomegalovirus (CMV)
  • Epstein-Barr virus (EBV)
  • Varicella
  • Yellow Fever
  • Echovirus
  • Ebola virus

Note: These viruses cause injuries to other organs. The liver is not their main target

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Laboratory diagnosis of acute hepatitis

A

1) Clinical Biochemistry

  • Elevated liver enzymes (aspartate aminotransferase
    AST, alanine aminotransferase ALT) and bilirubin

2) Virology

– Serologic markers for different hepatitis viruses (viral
antigen or antibody), viral DNA or RNA analysis

3) Hematology

– Coagulation studies in very severe form of hepatitis (e.g. fulminant hepatitis)

4) Histopathology

– Liver biopsy has only limited role in uncomplicated cases of acute hepatitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Histopathology of acute hepatitis

A
  • 5 forms of necrosis:
    1) Acidophil bodies; as a result of apoptosis, apoptotic bodies indicating scattered individual cell death (seen in acute viral hepatitis)
    2) Zonal necrosis; as a result of death of hepatocytes involving an acinar zone (usually toxic or haemodynamic causes)
    3) Bridging necrosis; necrosis across acinar zones (in sever viral hepatitis)
    4) Interface necrosis; necrosis around the portal tract (usually autoimmune hepatitis)
    5) Panacinar necrosis; necrosis involving all acinar zones (e.g. toxins or severe viral hepatitis)

[necrotic regions/ necrotic cells stained deeper & more pinkish in H&E]

[Massive & sub-massive necrosis will be observed in severe cases]

  • concomitant hepatocyte regeneration
  • diffuse parenchymal damage
  • swelling of the hepatocytes
  • cholestasis
  • Kupffer cell hyperplasia
30
Q

Chronic hepatitis definition

A

a primary necroinflammatory disease of the liver for at least 6 months

31
Q

Chronic hepatitis clinical features

A
  • some patients experience repeated attacks of acute exacerbation of hepatitis, others may remain asymptomatic until the disease progresses to cirrhosis or hepatocellular carcinoma
  • presenting symptoms may be similar to acute hepatitis
  • insidious with constitutional symptoms or as complications from portal hypertension
  • Overall, about 25% of HBV carriers ultimately die of cirrhosis with or without HCC.
32
Q

Aetiology of chronic hepatitis

A

– Hepatitis viruses HBV, HCV, HDV (not HAV and HEV)

– Alcohol

– Drugs (e.g. isoniazid, methyldopa)

– Autoimmune hepatitis

33
Q

Epidemiology of chronic hepatitis

A
  • in HK, majority of chronic active liver disease seen in Chinese are HBV-associated.
  • The disease is more common in male subjects (M:F = 3:1)
34
Q

Laboratory diagnosis of chronic hepatitis

A

1) Clinical Biochemistry

– Elevated liver enzymes (AST, ALT), bilirubin

2) Virology

– Serologic markers for the causative virus

3) Immunology

– Autoantibodies, e.g. ANA, Anti-SM, anti-LKM1

4) Histopathology

– Assess activity and degree of fibrosis – Prediction of progression to cirrhosis

35
Q

Histopathology of chronic hepatitis

A

1) *** portal tract infiltrates of mononuclear inflammatory cells
2) Some of the hepatocytes are loaded with HBsAg and their cytoplasm appears ‘ground-glass’.
3) spotty necrosis of hepatocytes
4) intralobular inflammation
5) often accompanied by periportal piecemeal necrosis causing erosion of the limiting plate

36
Q

Toxin and drug-induced liver injury

A
  • easily occur because at least 10% of drug reactions involves the liver
  • Lead to acute or chronic hepatitis

Pathogenesis may be:

  1. dose-related (predictable) e.g. Alcohol, Paracetamol, etc
  2. idiosyncratic (unpredictable) (related to individual factors; not dose-related) e.g. Halothane, Isoniazid, Chlorpromazine, etc.

Mechanisms:

  • direct toxicity
  • hepatic conversion from xenobiotic to active toxin
  • immune mechanisms
37
Q

Alcoholic liver diseases

A

1) Normal liver exposed to alcohol, may develop a reversible condition of steatosis (fatty liver; fatty change, perivenular necrosis). Severe exposure of alcohol to normal liver will also lead to a reversible condition of alcoholic hepatitis (Liver cell necrosis, inflammation, Mallory bodies, fatty change)
2) Severe exposure of alcohol in steatolic stage liver will also lead to alcoholic hepatitis
3) If alcohol abstinence is achieved, steatotic stage and alcoholic hepatitis will be reversed and liver becomes normal.
4) However, continued exposure to alcohol in steatosis will lead to fibrosis, further fatty change, inflammation & scaring. The fibrotic scar tissues will irreversibly replace hepatocyte, leading to cirrhosis
5) Repeated attacks of alcoholic hepatitis will also contribute to repeated extensive fibrosis, and the irreversible cirrholis

38
Q

Fatty liver

A

A reversible condition wherein large vacuoles of triglyceride fat accumulate in liver cells via the process of steatosis

Can be classified by aetiology into:

1) alcoholic steatosis (progress to alcoholic steatohepatitis)
2) Non-alcoholic fatty liver disease; NAFLD (progress to non-alcoholic steatohepatitis; NASH)

39
Q

Autoimmune Hepatitis

A

Definition: Autoantibody-mediated liver necro-inflammatory disease

Epidemiology: occurs predominantly in young women

Classification: Classified into type 1 and type 2, based on the patterns of circulating antibodies:

1) Type 1

  • anti-nuclear antibodies (ANA)
  • anti-smooth muscle antibodies (SMA)
  • anti-actin antibodies (AAA)
  • anti-soluble liver antigen /liver- pancreas (anti-SLA/LP) antibodies

2) Type 2
- anti-liver kidney microsome-1 (anti-LKM-1) antibodies

Clinical Presentation: Acute and chronic hepatitis, clinically similar to viral hepatitis

**Lab diagnosis: **

  • serologic studies identifying autoantibodies can distinguish autoimmune hepatitis from viral hepatitis (which identifies viral antigens and antibodies)
  • histopathologically will demonstrate rich infiltrates of plasma cells in portal tracts
40
Q

Clinical course of HBV infection

A
41
Q

Cirrhosis definition

A
  • Diffuse process affecting the entire liver
  • normal acinar structure of the liver is replaced by nodules of regenerative hepatocytes (regenerative nodules) separated from one another by irregular bands of fibrous tissue (fibrous septa)
  • End-stage liver disease; irreversible
42
Q

Curative treatment of cirrhosis

A

The only currently effective and potentially curative treatment is liver transplantation

43
Q

Cirrhosis histopathology

A
  • normal acinar structure of the liver is replaced by nodules of regenerative hepatocytes (regenerative nodules) separated from one another by irregular bands of fibrous tissue (fibrous septa)
  • diffuse presentation affecting the entire lung
44
Q

Cirrhosis pathogenesis & etiology

A

Pathogenesis:

  • Cirrhosis is end-result of continued loss of hepatocytes with persistent chronic inflammation, which lead to fibrosis and compensatory nodular hyperplasia of the hepatocytes.
  • The resultant architectural distortion and excess fibrous tissue interfere with blood flow so that further hepatocyte loss continues as a result of ischemia and the changes become progressive

Etiology:

1) Post- chronic viral hepatitis (HBV, HCV, HDV)
2) Alcoholic/ drugs/ toxins
3) Autoimmune hepatitis (e.g. primary biliary cirrhosis)
4) Hereditary diseases
5) Cryptogenic cirrhosis (i.e. idiopathic)

45
Q

Classification of cirrhosis

A

Can be classified morphologically & aetiologically:

I. Morphological Classification

1) micronodular cirrhosis (regenerating nodules are small and regular in size, i.e. up to 3 mm in diameter)

2) macronodular cirrhosis (regenerative nodules are large and of variable size ranging up to 2 cm or more in diameter)

3) mixed nodular cirrhosis (both small and large nodules are present)

[usefulness is doubtful because the correlation between the aetiology and the macroscopic appearance of the liver is poor]

II. Aetiological Classification

1) Post-viral cirrhosis
2) Alcoholic cirrhosis
3) Biliary Cirrhosis
i) Primary (autoimmune) biliary cirrhosis
ii) Secondary (obstructive) biliary cirrhosis
4) Cirrhosis resulting from inborn errors of metabolism (hereditary)
5) Cryptogenic cirrhosis

46
Q

Post-viral cirrhosis

A
  • Result of chronic viral hepatitis caused by HBV, HCV, HDV
  • Post-viral cirrhosis with persistent HBs antigenemia is the commonest type of cirrhosis (> 60%) in Hong Kong.
47
Q

Alcoholic cirrhosis

A
  • Excessive alcohol consumption is associated with several pathological changes in the liver: fatty change, alcoholic hepatitis, hepatic fibrosis, and cirrhosis.

Epidemiology:

  • In chronic alcoholics with a daily consumption of > 60 g alcohol in males (or > 20 g in females) for at least 10 years, only about 35% of them develop hepatitis and only 1/3 of these develop cirrhosis. There are wide individual variations.

Pathogenesis:

1) Normal liver exposed to alcohol, may develop a reversible condition of steatosis (fatty liver; fatty change, perivenular necrosis). Severe exposure of alcohol to normal liver will also lead to a reversible condition of alcoholic hepatitis (Liver cell necrosis, inflammation, Mallory bodies, fatty change)
2) Severe exposure of alcohol in steatolic stage liver will also lead to alcoholic hepatitis
3) If alcohol abstinence is achieved, steatotic stage and alcoholic hepatitis will be reversed and liver becomes normal.
4) However, continued exposure to alcohol in steatosis will lead to fibrosis, further fatty change, inflammation & scaring. The fibrotic scar tissues will irreversibly replace hepatocyte, leading to cirrhosis
5) Repeated attacks of alcoholic hepatitis will also contribute to repeated extensive fibrosis, and the irreversible cirrholis (The pathogenesis of alcoholic hepatitis and cirrhosis is not understood)

48
Q

Primary biliary cirrhosis

A

Epidemiology:

  • Uncommon in Chinese
  • Affects middle-aged females

Clinical Presentation:

  • The liver shows chronic inflammation with destruction of the small septal and interlobular bile ducts, causing cholestasis and parenchymal loss and progressing to cirrhosis.
  • Anti- mitochondrial antibody (AMA) is demonstrable in nearly all cases
  • Many patients have associated connective tissue diseases.
49
Q

Secondary (obstructive) biliary cirrhosis

A
  • This evolves from chronic obstruction to the common hepatic or common bile ducts (e.g. due to congenital biliary atresia)
  • Portal tract inflammation, fibrosis and continued liver cell necrosis eventually result in an enlarged and firm, dark green (due to bile) liver showing cirrhosis.
  • Death is most often due to liver failure or infection.
50
Q

Herditary diseases leading to cirrhosis

A

1) Wilson’s disease
2) genetic hemochromatosis
3) α1-antitrypsin deficiency
4) galactosemia
5) glycogen storage disease

51
Q

Cryptogenic cirrhosis

A
  • A mixed group of cirrhosis of unknown etiology
  • As etiological factors of cirrhosis are progressively elucidated, the size of this group diminishes.
52
Q

Effects and complications of cirrhosis

A

1) Portal hypertension
i) Varices (e.g. esophageal varices, hemorrhoids, periumbilical caput medusae)
ii) Porto-systemic shunting -> hepatic encephalopathy
iii) Fibrocongestive splenomegaly -> anaemia, thrombocytopenia and granulocytopenia
iv) ascites
2) Portal Vein Thrombosis
3) Hepatocellular failure
4) Hepatocellular carcinoma (HCC)

53
Q

Cirrhosis & portal hypertension

A

In the liver, the pressure of the hepatic artery is very high while the pressure in hepatic portal vein is very low. Hepatic portal vein supploed 3/4 of liver blood

Under normal condition, sphincter exists in hepatic arterioles that contract to decrease the pressure of arterial blood before meeting and mixing with the low blood pressure portal vein, so that both bloodstream will be drained into sinusoids

In cirrhosis, however, architectural damage will lead to disruption of these arterial sphincters and create sinusoidal & post-sinusoidal block, due to extensive fibrosis & damage

As a result, blood pressure of arterial blood will not be reduced before meeting with portal vein stream. Moreover, resistannce in sinusoid also increase.

Consequently, blood from the haptic artery may enter hepatic portal vein (which is usually under low pressure & low resistance), leading to portal hypertension

54
Q

Portal hypertension & varices

A
  • The portal venous bed dilates and the portal-systemic collateral anastomoses enlarge.
  • This increase in pressure will lead to varicose vein in the esophagus (esophageal varices), in stomach (gastric varices) around the umbilicus (perumbilical caput medusae) & at the anus (anorectal varices - NOT hemorrhoids)
  • The most clinically significant is at the gastro-esophageal junction where esophageal varices occur as bleeding from these esophageal varices is very often torrential and can be fatal.
55
Q

Portal hypertension & hepatic encephalopathy

A
  • The portal venous bed dilates and the portal-systemic collateral anastomoses enlarge.
  • The enlarged portal-systemic anastomoses divert portal blood to the systemic circulation by-passing the liver
  • thus toxic and nitrogenous bacterial metabolites absorbed from the gut may avoid detoxification in the liver, and travel freely in bloodstream (even to the brain)
  • this increase the risk of hepatic encephalopathy
  • CNS syndrome (confusion, coma, flapping tremor) will develop
56
Q

Portal hypertension and splenomegaly

A
  • Portal blood forced back into the spleen, leading to severe chronic venous congestion of the spleen (fibrocongestive splenomegaly and consequent hypersplenism)
  • consequent sequestration of red blood cells (anemia), white blood cells (granulocytopenia) and platelets (thrombocytopenia) will lead to mild pancytopenia
57
Q

Ascites & Liver injury

A

Ascites is the accumulation of extracellular fluid in the peritoneal cavity due to:

  1. Portal hypertension (which forces portal blood into the perotoneal cavity)
  2. Low serum albumin (Leading to low osmotic pressure in blood, fluid will enter perontoneal cavity)

Portal hypertension can be a result of cirrhosis; low serum albumin can be seen in end stage liver diseases in which albumin synthesis is reduced

58
Q

Cirrhosis & Hepatocellular failure

A

Chronic liver failure in cirrhosis is attributable in part to the interference with hepatic blood flow:

1) some of the portal blood by-pass the liver through portal-systemic anastomoses
2) some of the blood which does enter the liver is shunted into hepatic veins without its passing between and perfusing liver cells

Symptoms:

  • neurological disturbances (hepatic encephalopathy)
  • coagulation defects (thrombocytopenia)
  • ascites & edema
  • Renal failure
  • metabolic and circulatory disturbances
  • low serum albumin level
  • Jaunduce; the degree and type of jaundice depend on the cause of cirrhosis. In biliary cirrhosis, jaundice precedes other signs of liver failure and is of obstructive type. In other cirrhosis, overt jaundice is a late and bad prognostic sign, and is usually only of mild or moderate degree.
59
Q

Cirrhosis & Hepatocellular carcinoma

A
  • Usually a late complication in advanced cirrhosis
  • often remains asymptomatic
  • more frequently complicates post-viral cirrhosis especially where there is persistent HBs antigenemia and in males.
  • HCV has also been implicated as an important etiologic agent of HCC.
60
Q

Liver cancer epidemiology

A
  • Liver cancer is the 2nd / 3rd killing cancer in HK
  • About 1,400 deaths per year
  • > 80% of liver cancer patients are HBV carriers (HBV carriers have 100 times risk of liver cancer)
  • HCV carriers also have higher chances of development of liver cancer
61
Q
A

acidophil/ apoptotic body (usually found in acute viral hepatitis)

  • more pinkish and deeper stained
  • diffused
62
Q
A

Sub-massive/ massive necrosis of hepatocytes (hepatitis)

  • (?) possibly zonal necrosis as the more pinkish patches surrounds central vein
63
Q
A

Typical Presentation of chronic hepatitis, showing:

portal tract infiltrates of mononuclear inflammatory cells (blue arrow; darkly stained cells)

64
Q
A

Classical histology of liver under chronic HBV infection:

  • Homogenous ‘ground-glass’ cytoplasm indicates accumulation of HBsAg in these hepatocytes
65
Q
A

Autoimmune hepatitis, because:

  • Plasma cell-rich infiltrate in the portal tracts
66
Q
A

Cirrhosis of the liver

  • Diffuse presentation
  • regenerative nodules
  • fibrosis
67
Q
A

Cirrhosis

  • Fibrotic septa
  • Diffuse replacement by regenerative hepatocytes
68
Q
A

Fatty Liver

  • fatty change of hepatocytes
  • liver enlargement
69
Q
A

Esophageal varices

70
Q
A

Perumbilical caput medusae