PATHOLOGY- Hepatobiliary disorders Flashcards
Where is the liver located in the body
Upper right quadrant of abdominal cavity
How much does the liver weigh in adults
Around 1.5kg
What is a different about the liver
It has a dual blood supply
Describe the livers dual blood supply
- The intestines/spleen supplies blood through to the portal vein (70%)
- The aorta supplies blood through the coelia axis into the hepatic arteries (30%)
Why does the liver get most of its blood from the intestines
Organisation important - processing of materials / pathogens from gut before they enter into systemic circulation.
What is the most of the liver made up of and how are these arranged
hepatocytes, arranges in rows, cords or ‘plates’
What structures can you see on the liver microscopically
Portal tracts
Hepatic veins
Bile ducts
What is the role of the portal tracts
Supplies blood from the portal vein and hepatic arteries, allowing it to travel down the sinusoids (gaps) between the chords of hepatocytes
What is the role of the hepatic veins
Where blood exits the liver
What is the role of bile ducts
Allows bile produced by the liver cells to exit through the portal tract, against the flow of blood
what is the role of the liver
Protein metabolism
Nitrogen excretion
Carbohydrate metabolism
Lipid metabolism
Bile production/metabolism
Bilirubin metabolism
Hormone/drug inactivation
Immunological functions
Why is protein metabolism important in the liver
Mostly all circulating proteins made in liver e.g. clotting factors, albumin eti
Serious manifestation of liver failure e.g. impaired clotting, dec in albumin, resulting in oedema/ ascities
How does the liver excrete nitrogen
Amino acids are broke down in to ammonia and excreted through urine
What is carbohydrate metabolism needed in the liver
Glucose homeostasis
Blood sugar regulation
why is bile production/metabolism important ion the liver
For digestion/absorption of lipids
What is bilirubin metabolism in the liver and what is the effect of impaired excretion
Breakdown product of RBC
Jaundice
What are the 2 immunological functions of the liver
Acts a sieve for bacteria that are passed from the GI tract through the portal vein
80-90% of innate immune proteins made in liver
What is bilirubin
A product of RBC/harm breakdown
What is the initial issue with bilirubin
Not water soluble
How does bilirubin travel around the body
Albumin (bilirubin is a protein-bound molecule)
What is bilirubin known as when it is bound to albumin
Unconjugated bilirubin
When happens when unconjugated bilirubin passes through the liver
Becomes conjugated and water soluble
what is the water soluble bilirubin known as
Conjugated bilirubin
What happens to bilirubin once it has become conjugated and water soluble
Conjugated bilirubin is excreted in the bile (produced by liver cells), passes it out into the biliary tree through the bile ducts, into the gut
what happens to conjugated bilirubin in the gut
It is converted to urobilinogen/stercobilinogen
Most passes out in faces as stercobilin
Some absorbed back into the blood
Why is faeces brown
Due to stercobilin
what happens to conjugated bilirubin that is absorbed back in to the blood
Either enters enterohepatic circulation or excreted in urine
What is the most common sign of liver disease
Jaundice
when does jaundice occur
Increased bilirubin
when is jaundice visible
When bilirubin >40umol/l
What are the 3 types of jaundice
Pre-hepatic = too much bilirubin produced
Hepatic = too few functioning liver cells
Post-hepatic = bile duct obstruction
When would you see pre-haptic jaundice
Haemolytic anaemia
When would you see hepatic jaundice
- Acute diffuse liver cell injury
- End stage chronic liver disease
- Inborn metabolic errors
When would you see post-hepatic jaundice
Stone, stricture, tumour- bile duct, pancreas
What are some markers of liver cell damage
- Liver enzymes ALT and AST leakage from damaged hepatocytes
- Liver enzyme ALP leakage from damaged bile duct cells
- Albumin
- Clotting
Name 2 enzymes that leak from damaged hepatocytes in liver disease, acting as markers for liver disease
- ALT - Alanine aminotransferase
- AST - Aspartate aminotransferase
What does it mean if there is mild slow progressive increase of damaged hepatocytes causing leakage
chronic liver disease
What does it mean if there is sudden massive increase of damaged hepatocytes causing leakage
Severe acute liver disease
Name an enzyme that leaks from damaged bile duct cells in liver disease, acting as markers for liver disease
ALP - Alkaline Phosphatase
Why does low albumin indicate chronic liver disease
As it is synthesised by the liver and usually has a long half life
Why does low clotting factors indicate acute or chronic liver disease
Clotting factors produced by liver
Have a short half life
CF used to test whether blood is clotting properly, if not then LD
How would you investigate if someone has jaundice
Ultra-sound scan to check for dilated bile ducts
If you did an ultrasound scan on somebody with jaundice and there bile ducts were dilated, what does this indicate
Obstruction of bile ducts
If you did an ultrasound scan on somebody with jaundice and there bile ducts were not dilated, what would you do next and why
Biopsy of liver
To visualise the abnormality within the liver
Most non obstructive cases of liver disease are due to what
Hepatitis
What is hepatitis
Inflammation of the liver/damage to the liver that isn’t Neoplastic
What are the causes of acute and chronic hepatitis
- Viral
- Alcohol / obesity
- Drugs
- Inherited disorders:
- Haemochromatosis (iron)
- Wilson’s disease (copper)
- Alpha-1-antrypsin deficiency
- Autoimmune
What is hepatitis clinically/biochemically defined by
Raised liver enzymes (ALT/AST)
Indicates damage
What is acute hepatitis
How long does it last
What are the signs
How is it detected
- Acute sudden liver injury, caused by something that goes away
- Short-lived, resolves
- No signs (unless severe)
- Incidentally at blood tests
What is chronic hepatitis
How does it differ to acute
What does it cause
- Anything causing persistent liver injury (i.e. doesn’t go away)
- Persistent cycle of damage and repair
- Long term liver damage
What are symptoms of acute hepatitis from common to rare
Asymptomatic
Malaise
Jaundice
Coagulopathy
Encephalopathy
Death
What 2 things does the severity of acute hepatitis depend on
- How many hepatocytes are damaged as a result of the hepatitis
- How well the liver is able to regenerate the lost cells
What are the causes of acute hepatitis
Anything that causes short term liver cell injury
E.g.
Viral
Drugs
Autoimmune
Toxic/metabolic injury (alcohol/paracetamol overdose)
What is chronic hepatitis
chronic liver disease in which the damaging agent is persistent (doesn’t go away)
What can chronic hepatitis progress to
Cirrhosis- but may be partially reversible
what are the causes if chronic hepatitis
- Immunological - viral, autoimmune, drugs
- Toxic / metabolic - “fatty liver disease” - alcohol, non-alcoholic fatty liver disease (NAFLD)
- Genetic - iron, copper, alpha-1-antitrypsin
How does chronic hepatitis cause damage to the liver
- Damage begins and is concentrated around portal tracts
- The cycle of hepatocytes injury and repair causes scarring
- This gradually increases and starts to link vascular structures (the PTs and CVs) by scar tissue
- This is bridging fibrosis
- Eventually transforming the liver tissue into separate nodules
- At the end stage this results in cirrhosis
What are the causes of chronic liver disease
Viral hepatitis
List the hepatrophic (liver specific) viruses that cause viral hepatitis
- A,B and C
- D (hepatitis delta virus)
- E
Hepatitis D is found in who
Only in people with hep b
what is hepatitis E
recently discovered, fairly common, faecal-oral transmission mainly via contaminated water, mild self-limiting if healthy
List other viruses that cause hepatitis as part of systemic disease
EBV
CMV
HSV
What characteristic effect does excessive alcohol intake have on the liver
- fatty change
- alcohol steatohepatitis
- cirrhosis
What does alcohol liver injury depend on
Dose (intake)
Susceptibility
What is indicated if there are characteristic features such as fat chnage to the liver in the absence of alcohol
Non-alcoholic fatty liver disease
NAFLD
What do you see microscopically with liver damage caused by alcohol
Fatty change (steatosis)
Ballooned hepatocyte with Mallory body
Inflammatory cells
What is now regarded as the most common cause of liver disease
NAFLD
What changes can be seen microscopically with NAFLD
Same as alcoholic liver disease
- Steatosis (fatty change), steatohepatitis, cirrhosis, HCC
Why can NAFLD result in liver injury
Excessive fat accumulation
What is NAFLD associated with
metabolic syndrome (obesity, diabetes, hyperlipdaemia etc).
What is the treatment for NAFLD
Address the metabolic syndrome (causes)
What is statohepatitis
Fatty change plus hepatocyte injury
Hepatotoxicity can be either what 2 things
Intrinsic
Idiosyncratic
What can hepatotoxic drugs lead to
Drug induced liver injury (DILI)
what is intrinsic hepatotoxicity
- drug that causes everyone liver injury if excessive dose is administered
- Susceptibility will vary but liver injury is entirely predictable
- e.g. paracetamol.
What is idiosyncratic hepatotoxicity
- Liver injury is rare and unpredictable
- e.g. antibiotics - small numbers of individuals
- Mechanism - metabolic and immunologic response variability
- Production of rare drug metabolites +/- exaggerated immune response
Generally drugs cause..
Acute liver injury
What is the most common symptom for DILI
Jaundice
Which type of drugs can cause liver injury
Any drug
Same drug can cause different pattern of injury in different patients
Time of onset is variable
When does DILI usually improve and what is prevented
Stopping drug
Chronic liver disease but not always
What are the effects of paracetamol overdose
sudden (2-3 days) massive hepatocellular necrosis (pale areas)
No inflammation
Which part of the liver is affected by paracetamol overdose
Mainly around central veins
What can happen if there is no urgent transplant with paracetamol overdose
Death
Give 2 examples of an inherited liver disorder
Haemochromatosis
Wilsons disease
Alpha 1 antitrypsin deficiency
What is haemochromatosis
Inherited disorder of iron metabolism (HFE gene) causing increased iron absorption from the gut
what effect does haemochromatosis have on the liver
Iron accumulation in the liver, causing chronic liver injury and eventually cirrhosis
what is Wilson’s disease
Impaired excretion of copper causes accumulation in liver resulting in chronic liver injury/cirrhosis
What effect does alpha 1 antitrypsin deficiency have on the liver
Alpha 1 antitrypsin can’t be excreted and accumulate in the liver causing chronic liver injury, resulting in cirrhosis (and emphysema in lungs)
What are autoimmune liver diseases
Disturbance of normal immune regulation leading to recognition of self-antigens
How can autoimmune liver diseases manifest
Can manifest with either autoimmune mediated destruction of hepatocytes (autoimmune hepatitis)
OR
Autoimmune mediated damage to bile ducts (autoimmune biliary diseases primary sclerosing cholangitis / primary biliary cirrhosis)
Who is autoimmune hepatitis more common in
Women
What can autoimmune hepatitis present as
Acute or chronic hepatitis
How do you diagnose autoimmune hepatitis
- Autoantibodies e.g. anti-nuclear, smooth muscle, etc
- Raised IgG, ALT
- Assoc. autoimmune diseases
What would you see in a liver biopsy in someone with autoimmune hepatitis
- Interface hepatitis
- Lots of plasma cells
What is the treatment for autoimmune hepatitis
Immunosuppression
Why is it important to treat autoimmune hepatitis
To avoid progression to cirrhosis
Name 2 biliary diseases (autoimmune liver diseases)
Primary biliary cholangitis
Primary sclerosing cholangitis
What is seen in primary biliary cholangitis diagnosis
Anti-mitochondrial antibodies
Inc IgM
Inc ALP (bile duct damage)
Bile duct granulomas
What can primary biliary cholangitis progress to
Cirrhosis
What is primary sclerosing cholangitis associated with
Ulcerative colitis
How is primary sclerosing cholangitis diagnosed
pANCA antibodies but diagnosis is via imaging
What characteristic changes are there in primary sclerosing cholangitis
Periductal onion skin fibrosis around bile ducts
what can primary sclerosing cholangitis progress to
Cirrhosis
What is cirrhosis
Diffuse change in the liver structure due to chronic liver disease.
* Development of fibrous septa that subdivide the parenchyma into nodules as a result of bridging
fibrosis.
Cirrhosis isn’t a specific disease but
A general end point go ALL progressive chronic liver diseases
how long does cirrhosis take to develop
Slow to develop, decades
Cirrhosis is clinically silent until when
The liver function fails (decompensation) leading to signs of liver failure/portal hypertension
What ate the 2 components of cirrhosis
Regenerative nodules go hepatocytes
Surrounded by sheets/bands of fibrous tissue
What is the cause of cirrhosis
Liver disease that wont go away i.e. chronic liver disease
What are the potential complications with cirrhosis
- Liver failure
- Portal hypertension
- Infection
- Hepatocellular carcinoma
What can you develop with sudden severe liver damage
Acute liver failure e.g. paracetamol OD
Why may someone have cirrhosis and be unaware of it
Some residual function left
If original disease is removed and there’s cirrhosis, can still show no abnormality on liver function test
Is the liver is unable to maintain its normal function what can occur
Decompensated liver disease leading to liver failure
List features relating to impaired liver synthetic/metabolic function
- Hypoalbuminemia / clotting factor deficiencies - bruising / bleeding
- Ascites - due to dec in albumin & aldosterone disturbances
- Encephalopathy - due to impaired breakdown of nitrogenous substances (mimic NTs)
- Gynaecomastia - due to impaired estrogen breakdown
What is portal hypertension
- Structural abnormalitv in liver (cirrhosis)
- Impairs blood flow - back pressure in portal vein
What are the causes of portal hypertension
- Ascites (combination of liver failure and pressure effects)
- Splenomegaly (due to back pressure on spleen)
Why do porto-systemic shunts occur in portal hypertension
Blood by-passes liver due to increased resistance to blood flow
What effects do porto-systemic shunts have
- Oesophageal varices, haemorrhoids, “caput medusae”
- Peri-splenic varices
- Prone to bleeding / rupture BUT also BYPASSES functional liver
How does infection cause cirrhosis
- Cells within the liver (Kuppfer cells)
- Act to fight infection
- Impaired function / bypass -> † infection risk
What is hepatocellular carcinoma
Malignant tumour of hepatocytes
List benign liver tumours
haemangioma, bile duct adenoma, FNH, HA
List malignant liver tumours
cholangiocarcinoma, metastatic tumours(CRC)
What are some possible complications with liver disease in regard to dental tx
- Coagulopathies, drug-toxicity (dec in metabolism)
- Infection (hepatitis)
If in doubt when treating someone with liver disease, who should u consult
BNF
