Professional Documents
Culture Documents
Lobule: hexagonal in shape and each of the six points we sea a portal triad, consisting of a branch of
portal vein, hepatic artery and bile duct. From these ducts blood gets into the sinusoids (hepatic
open pore capillary) which are in between the hepatocytes and eventually drains away at a branch
of the central vein which then itself drains into the vena cava => systemic circulation => RV and
lungs.
Bilirubin Metabolism
RBC (life span =120 days) break down in the spleen (as a normal process or in blood as a result of
disease process) into haemoglobin => bilirubin and from there via the splenic vein into the portal
vein to the liver. It reaches the liver in an unconjugated form which is fat-soluble and travels through
blood bound to albumin. In the liver, it gets conjugated to glucuronic acid and forms a water-soluble
compound which is excreted in bile and small intestine where bacteria split conjugate into
urobilinogen. 80-90% of urobilinogen is excreted through faeces, with the rest being resorbed into
blood. So, at any given time there is conjugated and un-conjugated circulating bilirubin. Then
conjugated form is excreted via both urine (portal vein & hepatic artery => sinusoid => central vein
=> vena cava => systemic circulation => kidney) or (portal vein & hepatic artery => hepatocytes =>
bile duct => gallbladder = > small intestine => large intestine) faeces.
Hyperbilirubinemia
High levels of bilirubin in the blood could result from the hepatocytes not functioning well and not
being able to conjugate bilirubin and as a consequence the bilirubin goes back into the blood
unconjugated or when there is biliary ducts obstruction and obstruction of bile flow which causes
conjugated bilirubin goes back into the blood.
Biochemical hyperbilirubinemia (indicates that something is wrong with the liver, needs further
investigation):
Evident when levels >50 µmol/L Manifests as yellow discolouration of sclera and skin i.e.
jaundice
Jaundice = yellowish pigmentation of skin, sclerae & mucous membranes due to hyperbilirubinaemia
hyperbilirubinaemia due to increased levels of bilirubin in the blood (can be caused by both
conjugated and unconjugated)
When there are high levels of bilirubin in the blood it can deposit in the skin and being a skin irritant
people start to feel itchy.
E.g. if someone’s got cirrhosis of the liver and hepatocytes are dysfunctional because of necrosis and
scar tissue which blocks bile flow there is going to be an increase of both conj. and unconj. bilirubin
in the blood
Unconjugated hyperbilirubinaemia:
Conjugated hyperbilirubinaemia:
NB: Hepatitis & cirrhosis can both cause the two types of hyperbilirubinaemia.
Hepatitis
Inflammatory diseases of the liver are termed 'hepatitis' and many things causes inflammation of the
liver not just viruses.
Acute
o some liver cell necrosis (coagulative) if disease severe, inflammation, apoptosis of
hepatocytes forming Councilman bodies (eosinophilic – stain pink) which is a sign for
acute hepatitis
Chronic
o liver cell necrosis, inflammation, fibrosis
Aetiology:
Viral infections (A-E hepatotropic viruses which have an affinity for the liver and replicate in
the liver, but other viral infections that are not hepatotropic), non-viral infections (bacterial,
parasitic), toxins (alcohol)/drugs (anabolic steroids), metabolic (haemochromatosis) &
autoimmune diseases (leads to chronic hepatitis and predispose to cirrhosis), idiopathic.
RNA virus
Mode of transmission:
o Faeco-oral route (infected faecal matter enters mouth)
o Recreational use of waters or eating raw shellfish contaminated by sewage
o Touching nappies/linen soiled with infected faeces
Does not lead to chronic liver disease, self-limited disease with fool recovery
Pathogeneses - malaise, jaundice, then recovery
Infection leads to life-long immunity by development of serum anti-HAV Abs (which can be
detected and used in diagnosis)
Vaccine available
DNA virus
Most common liver infection
Mode of transmission:
o Blood to blood
o Mother to child
o Sexual contact via seminal fluid
IV drug abuse or tattoos can transmit the virus
It is self-limited and people can fully recover by may also cause in some individuals chronic
liver disease => chronic hepatitis => cirrhosis => liver cancer => liver failure
Vaccine also available
1. Acute self-limited hepatitis: common, short incubation period (about a month), full recovery
& have lifelong immunity; can be symptomatic or asymptomatic - patient have no symptoms
at all (sub-clinical)
2. Fulminant acute hepatitis: rare, there is massive necrosis of liver cells and life threatening
3. Chronic hepatitis: chronic infection that lasts more than 6 months with inflammation,
scaring (fibrosis); may progress to cirrhosis then hepatocarcinoma
4. Asymptomatic chronic infection: the virus goes into the dormancy and the patient becomes
a carrier, may lead to chronic hepatitis & hepatocarcinoma; it is detected in the blood via the
HepBsAg surface antigen but not the HepBeAg envelope antigen which is a marker for viral
replication; this is not all good news because the virus can in certain circumstances come out
of dormancy and start spontaneous replication and develop cirrhosis and hepatocarcinoma
or go straight to hepatocarcinoma
Liver biopsy:
First detection by H&E stain which if suspicious of Hep B inf. then further testing is required
for surface antigens and immunohistochemistry
In chronic Hep B infection, liver cells accumulate HBsAg in the cytoplasm (glassy
appearance); to detect this a special stain called immunohistochemistry (IHC) which is
immunostained brown by HBsAg antibodies – IHC
RNA virus
Mode of transmission:
o blood-to-blood
o mother-to-child
Diagnostic testing:
o Detection of antibodies to the virus
o PCR detection of Hep C viral RNA in blood
Clinical outcomes:
o Acute hepatitis → full recovery
o Acute hepatitis → fulminant hepatitis
o Chronic hepatitis (relapsing/remitting) → may progress to cirrhosis,
hepatocarcinoma
RNA virus
It is a defective virus requiring the presence of Hep B virus to be able to replicate and infect;
without the B virus the D virus is harmless
Mode of transmission:
o Blood-to-blood
Diagnostic testing:
o Detection of anti-HDV Abs (Hep D antibodies) in presence of anti-HBc Abs (Hep B cor
components antibodies)
o PCR detection of viral genomic material - HDV RNA in blood
Clinical outcomes:
o Similar to Hep B infection with more severe complications, more damage to the liver
o May cause chronic liver disease due to co-infection of Hep B and D leading to cancer =
highest mortality rate of all hepatitis infections
o Co-infection with hepatitis D prevented through hepatitis B vaccination
RNA virus
Mode of transmission:
o Similar to HepA infection (faeco-oral route)
Shorter incubation than Hepatitis A (~1month)
Clinical outcomes:
o Fatigue, malaise, jaundice, then recovery
Does not lead to chronic liver disease
Immunity is not lifelong
However, it has a high mortality rate in infected pregnant women (may result in acute
fulminant hepatitis in ~20% cases)
SUMMARY
EBV (Epstein Barr Virus) – causes glandular fever, but if the virus gets to the liver it can cause
hepatitis
CMV (Cytomegalovirus) – in patients that are immunocompromised (elderly); virus can go to
the liver and cause inflammation
Herpes Simplex Virus – can go in the blood and cause inflammation
Group B arbovirus - transmitted by female mosquitoes, gets into the blood and goes to the
liver and can cause acute haemorrhagic disease (fever, headache, abdominal pain, vomiting,
jaundice) – “Yellow fever” (tropical regions)
Non-viral Hepatitis
Bacterial Hepatitis:
Leptospira Spp.
o Transmitted by water/food/soil containing urine of infected animals; farmers or vets
are more likely to be infected
o It can cause Weil’s disease (fever, headache, vomiting, jaundice (if the virus enters
the blood and goes to the liver), purpuric skin rash (in the blood causes
haemorrhagic of blood vessels – petechiae), renal failure (if it goes to the kidney))
o In the liver we see inflammation which cause focal hepatocyte necrosis & cholestasis
(obstruction of bile flow)
Enteric bacteria
o If bacteria that is in our intestines e.g. E. coli gets into portal circulation and then
into the liver can cause liver abscesses (from haematogenous spread of enteric
bacteria through the portal vein)
Parasitic:
Protozoal infection
o Infection with amoeba Entamoeba histolytica (Amoebiasis)
Transmitted by faeco-oral route
“Anchovy paste” abscess in liver (amoebic abscess contains necrotic tissue
resembling anchovy paste) (also causes specific ulcerative colitis and bloody
diarhhoea i.e. amoebic dysentery)
o Infection and destruction of RBCs with Plasmodium spp. (Malaria)
Transmitted by female mosquitoes
Causes fever, vomiting, anaemia, hepatomegaly (because it works harder to
conjugate bilirubin), splenomegaly (because the spleen works hard to
remove excess dead RBC)
Helminth infection
o Infestation with tapeworm Echinococcus granulosus (Hydatid disease)
Contact with dog/sheep faeces infected with tapeworm eggs (e.g. handling
soil, dirt or animal hair)
Hydatid cysts form in vital organs such as the liver (more severe disease
when worm gets to the lungs and forms cysts)
Fatigue, swollen abdomen, enlarging cyst may cause jaundice
Toxins or drugs may lead to liver disease and cause various pathological changes:
Acute and chronic hepatitis - isoniazid (TB drug)
Acute necrosis - paracetamol
Fatty change - alcohol, methotrexate (cancer, autoimmune drug)
Cirrhosis - alcohol
Cholestasis - steroids (lead to hepatitis then obstruction to bile flow)
Tumours - anabolic steroids, oral contraceptives lead to adenoma of the liver
Chronic Hepatitis
Characterised by:
Cirrhosis
End-point of long-standing liver cell destruction and fibrosis (i.e. chronic hepatitis)
Characterised by:
Diffuse change of the entire liver with gross disruption to liver architecture
Regenerative nodules surrounded by necrosis, scar tissue deposition (fibrosis), hyperplasia &
dysplasia of bile ducts (because there is so much damage to hepatocytes there is a build-up
of bile and the ducts adapt by increasing in size to drain all that bile); in time you get less and
less regeneration and more and more fibrosis
Hepatocellular failure, portal hypertension (build-up of blood in the portal vein because it
does not flow freely through the liver due to the scar/fibrotic tissue), potential development
of hepatocarcinoma
Alcohol abuse
Hep B/C infection
Biliary obstruction
Alcoholic cirrhosis
Consumption of >100mL of ethanol/day for a long period of time; different people have diff
levels of tolerance to alcohol
Alcohol is absorbed unaltered into stomach and small intestine, then absorbed into
bloodstream & distributed to tissues in direct proportion to blood level
10% or less is excreted unchanged in urine, sweat or breath, but the rest goes to the liver
and it is metabolized by 3 enzyme systems: microsomal enzyme oxidase system, alcohol
dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) => convert the ethanol to
acetaldehyde (v. toxic, carcinogen) => less active byproduct called acetate (acetic acid) =>
H20 + CO2
Individuals who have low levels of ALDH cannot metabolize alcohol efficiently, but other
individuals have high tolerance to alcohol as their liver adapts to an ever increasing intake of
alcohol and ALDH production increases; over time this leads to pathological changes in liver,
brain, stomach, pancreas and heart occur leading to acute and chronic effects
Acute alcoholism:
Biliary Cirrhosis
Very similar to alcoholic cirrhosis: signs of necrosis, regenerative nodules, fibrosis but in this case
also and accumulation of bile pigments due to biliary obstruction (hence the green colour of the
liver).
Biliary obstruction (conjugated hyperbilirubinaemia, obstructive jaundice evident) => chronic hep =>
cirrhosis
Hepatocellular failure
Jaundice
o Occurs with bilirubin levels > 50µmol/L
o Skin, sclerae have a yellow colour
Xanthelasmata
o If liver cells are not working well and not allowing cholesterol to enter bile,
cholesterol will go back into the blood stream and blood cholesterol levels go up and
will deposit in skin
o Chronic cholestasis (condition where bile cannot flow from the liver to the
duodenum) leads to cholesterol accumulation within macrophages in skin (e.g.
around eyelids)
Foetor hepaticus (“liver breath”)
o Hepatocytes cannot metabolize toxins, mercaptans (sulphur containing) go into the
blood, diffuse into the alveoli and then exhaled causing bad breath
Palmar erythema (“liver palms”), gynaecomastia (increased breast size in men), spider naevi
(dilated, ruptured capillaries), testicular atrophy
o due to high oestrogen levels; normally catabolised by liver, but since liver cells are
damaged the oestrogen goes back into the blood causing all of the above
Systemic oedema
o due to hypoproteinemia – decreased albumin synthesis and hence blood levels
because of damaged hepatocytes
Haemorrhagic tendency, anaemia
o due to decreased clotting factor production
Leukonychia (white nails)
o due to ↓ albumin synthesis
Portal hypertension
Hepatocarcinoma
Causes
o Cirrhosis = premalignant state
o Mycotoxins (e.g. aflatoxin) directly causes cancer of the liver; carcinogens (e.g. azo-
compounds “butter yellow”) are other
May lead to 1o adenocarcinoma (liver is a gland, epithelial in origin hence adeno…)
Single or multiple masses, jaundice
Rapidly invasive (because the liver has the perfect chemistry and tissue architecture for
tumours to thrive, hence many other primary tumours metastasize in the liver)
Extrahepatic metastases do not occur because the liver is a great environment for cancer
cells
Prognosis is grave
Colangiocarcinoma
Cholelithiasis
Causes:
Reduced bile acids in bile (due to malabsorption, causing excessive loss of bile acids from
intestine) can lead to an increase in cholesterol synthesis
Increased cholesterol in bile will lead to the formation of cholesterol stones in the bile, but
also obesity can lead to the formation of this type of stones
Acute cholecystitis
Gall stones irritate and injure (erosions and ulcerations) the biliary mucosa causing aute
inflammation
Commonly due to cholelithiasis or obstruction of cystic duct
Patients may present with pain in right upper quadrant (RUQ) of abdomen, often radiates to
right scapula or shoulder region
Cholecystectomy
Chronic cholecystitis