Week 6 Flashcards
List some of the major functions of the liver
Hormone metabolism
Glycogen storage
Synthesis of albumin
Detoxification
When is the sphincter of oddi open and when does it close?
The sphincter of oddi is closed between meals and opens during a meal
What does bile contain?
Bile acids Water and electrolytes Cholesterol IgA Bilirubin
What is meant by enterohepatic recycling?
The reabsorption of bile salts in the terminal ileum, which are then transported back to the liver
Drug metabolism often proceeds in two phases. Describe what happens in each of these phases
Phase 1 - Drugs are activated by oxidation/ reduction/ hydrolysis - this makes the drug more polar to allow for conjugation
Phase 2 - An endogenous compound is added to the drug to make it more polar
The cytochrome P450 superfamily are haem proteins. Where are these located and what is their function?
Located in the endoplasmic reticulum of liver hepatocytes
Mediate oxidation reactions in phase 1 of drug metabolism
What is meant by hepatic encephalopathy?
A hepatic coma in which there is an altered level of consciousness as a result of liver failure
In severe hepatic failure, detoxification of which substance can’t occur, causing it to accumulate?
NH3
Which membrane does HC03- and Cl- exchange occur at?
The duct cell apical membrane
How does hepatic portal blood concentration of bile salts affect their synthesis?
A low concentration stimulates synthesis of bile salts
A high concentration inhibits synthesis
Which 2 hormones affect bile secretion?
Cholecystokinin
Secretin
Which hormone causes gall bladder contraction and relaxation of the sphincter of oddi?
Cholecystokinin
What is meant by ‘Glucuronidation’
the transfer of glucuronic acid to the substrate.
forms either; amide/ ester or thiol bonds
Explain the blood supply to the liver
The liver has a dual blood supply, from the hepatic arteries and from the hepatic portal vein.
The liver has single drainage, via the hepatic vein.
Which 3 cell types are contained within sinusoidal spaces?
Endothelial cells
Kuppfer cells
Stellate cells
How is acute liver failure defined?
The rapid development of hepatic dysfunction in a previously healthy liver
Give some examples of ‘LFTs’ and ‘True liver function tests’
LFTs;
ALT
AST
ALP
GGT
True liver function tests;
Bilirubin
Albumin
Prothrombin time
List some of the clinical features of acute liver disease
Jaundice Lethargy Nausea Itch Pain
list some of the causes of acute liver disease
Hepatitis Drugs Cholangitis Alcohol Malignancy
What are the suitable investigations for acute liver disease?
History and examination
LFTs
Ultrasound
Virology
How is acute liver disease treated?
Supportive
Fluids
Increased calorie intake
Sodium bicarbonate bath, Cholestyramine or Uresodeoxycholic acid (for the itch)
Why is adequate nutrition important in patients with acute liver disease?
Acute liver disease is a hypermetabolic state meaning that there is increased energy requirements
Which drugs can potentially cause acute liver failure?
PARACETAMOL
ANTIBIOTICS
Which toxic metabolite can paracetamol accumulate as?
NAPQI
List the possible causes of fulminant hepatic failure
Paracetamol
Drugs
Viral Hepatitis
What are the possible worrying clinical complications of FHF?
Encephalopathy
Hypoglycaemia
How is FHF managed?
Referral should happen quickly and patients show due in ITU with supportive care and fluids. Transplantation should be considered.
What are antimicrobials?
All agents that act against microorganisms ( Bacteria, fungi, viruses and protozoa)
How is antimicrobial resistance (AMR) defined?
When microbes are resistant to one or more antimicrobial agents used to treat infection
What is the difference between vertical and horizontal transmission in terms of antibiotic resistance?
Vertical transmission- A bacterium accumulates errors during its replication
Horizontal transmission - Resistant genes are swapped from one microbe to another
Why is resistance to antibiotics on the increase?
Use of broad spectrum antibiotics Large immunocompromised population More chronically ill patients Antibiotics used in livestock feed Antibiotics released into the environment during pharmaceutical manufacturing
What is meant by antimicrobial stewardship?
The optimal selection/ dosage/ duration of antimicrobial treatment that results in the best clinical outcome without impacting subsequent resistance
What are the possible causes of cirrhosis?
Chronic alcohol abuse
Drugs
Hepatitis
NASH
What happens to the liver in cirrhosis?
In liver cirrhosis, it becomes small and shrunken and fibrosis surrounds the hepatocytes. Reduced blood flow to the liver Reduced metabolic function Portal hypertension Reduced plasma proteins Shunting of blood
What are some of the signs of cirrhosis/ liver disease?
Leuconychia Clubbing Palmar erythema Dupuytren's contracture Spider naevi Xanthelasma Gynaecomastia
What would be the expected findings of the tests done in an investigation of liver failure?
Increased bilirubin Increased ALT/ ALP and AST Increased prothrombin time Decreased albumin Decreased platelets
How does the kidney respond to low albumin?
The kidneys detect low plasma volume and so release renin which leads to the production of aldosterone.
= secondary aldosteronism
What happens to sodium, potassium and water in the body when there is secondary aldosteronism and increased endothelia production?
Increased sodium
Decreased potassium
Increased water retention
What are some of the possible consequences of liver cirrhosis?
Gut oedema causing poor absorption
Gross oedema and ascites
Liver and kidney congestion
Heart failure
How is liver failure treated?
Paracetamol Codeine (NOT NSAIDs) Spirnolactone and the patient advised to restrict fluid intake Lorazepam (sedation for encephalopathy)
In terms of pathology, what are the three zones present in the normal liver?
Periportal
Mid acinar
Pericentral
Describe the progression from liver injury to cirrhosis
Insult to hepatocytes
Inflammation
Fibrosis
Cirrhosis
What are some of the causes of acute liver failure?
Alcohol
Drugs
Viruses
Bile duct obstruction
How is jaundice classified?
By site and type SITE - pre hepatic -hepatic -post hepatic TYPE -conjugated -unconjugated
Explain pre-hepatic jaundice
There is too much haemoglobin to break down due to; Haemolysis Haemolytic anaemias Unconjugated bilirubin
Explain hepatic jaundice
Liver cells are injured/ dead due to; Alcoholic hepatitis Decompensated cirrhosis Bile dict loss Pregnancy
Explain post hepatic jaundice
Bile can't get in to the bowel but bilirubin formation is normal Due to; Carcinoma at the head of the pancreas Gallstrones Strictures of the common bile duct
What are the complications of cirrhosis of the liver?
Portal hypertension
Ascites
Liver failure
What are the signs of portal hypertension?
Oesophageal varices
Caput media
Haemorrhoids
Which forms of alcoholic liver disease are reversible and which are irreversible?
REVERSIBLE Alcoholic fatty liver (2-3 day binge) Alcoholic hepatitis (weeks to months of alcohol abuse) IRREVERSIBLE Alcoholic fibrosis (months to years) Alcoholic cirrhosis (years)
What is the pathology of alcoholic fatty liver disease?
Steatosis
What is the pathology of alcoholic hepatitis?
Hepatocyte necrosis
Neutrophils
Pericellular fibrosis
Mallory bodies
What is the pathology of alcoholic fibrosis?
Collagen is layed down which walls of hepatocytes and disrupts blood supply
What is the pathology of alcoholic cirrhosis?
Definitive bands of fibrosis separate regenerative nodules
NASH = Non alcoholic steatohepatitis.
It is pathologically identical to alcoholic liver disease but can occur in non-drinkers. What are its causes?
Obesity
Diabetes
Hyperlipidaemia
How many months of disease defines chronic liver disease?
> 6 months
List some of the causes of chronic liver disease
Hepatitis Alcohol Drugs PSC Haemochromatosis Wilsons disease Alpha 1 antitrypsin Budd-Chiari
How is NASH/ NAFLD manages?
Weight loss and exercise
List 3 auto-immune liver diseases
PBC (primary biliary cirrhosis)
PSC (primary sclerosing cholangitis)
Autoimmune hepatitis
What does PBC involve?
Autoimmune response against M2 targets on mitochondrial antibodies
How does PBC present?
Usually asymptomatic
Can have an itch without a rash
Xanthelasma and xanthomas
More common in women than men
What tests are used to diagnose PBC and how is it treated?
Positive AMA
Cholestatic LFTs (ALP, GGT)
Liver biopsy
*Urseo deoxycholic acid
Are more men or women affected by autoimmune hepatitis?
Women
How might autoimmune hepatitis present? What are the main extra hepatic associated manifestations?
Hepatomegaly
Jaundice
Elevated AST, ALT, IgG and prothrombin time
- Grave’s disease
- Ulcerative Colitis
- Autoimmune thyroiditis
What are two genetic predisposing factors for autoimmune hepatitis and which of these is the most severe and involves early onset?
HLA DR3 - severe, early onset
HLA DR4 - less severe, late onset
How is autoimmune hepatitis treated?
Corticosteroids (prednisolone) and azathioprine
List 3 possible complications of autoimmune hepatitis?
Cirrhosis
Ascites
Encephalopathy
Oesophageal varices
What is primary sclerosing cholangitis?
An autoimmune destructive disease of large and medium sized bile ducts
Which disease is PSC strongly linked to?
Ulcerative Colitis
What would imaging of the biliary tree in a patient with PSC show?
Areas of dilation and areas of restriction
Which drug used to treat rheumatoid arthritis and psoriasis can cause fibrosis of the liver?
Methotrexate
What is haemochromatosis?
An autosomal recessive genetic condition involving iron overload
Which genes are mutated in haemochromatosis?
C282Y and H63D
How is haemochromatosis treated?
By regular venesection to iron deplete the patient
What is Wilson’s Disease?
A genetic autosomal recessive disease involving copper over-load due to loss of function of caeruloplasmin
What are some of the clinical signs of Wilson’s disease?
Cirrhosis
Involuntary movements
Kaiser-Fleischer rings
Which conditions (resp and GI) can alpha 1 anti-trypsin deficiency cause?
Lung emphysema Liver disease (cirrhosis, cholestatic jaundice and hepatocellular cancer)
What is Budd-Chiari? How does it present?
Thrombosis of hepatic veins
- Jaundice
- Tender hepatomegaly
- Ascites
What investigation is done for Budd-Chiari and how i the condition treated?
Ultrasound of the hepatic veins
Recanalisation and TIPS
Which heart conditions can cause cardiac cirrhosis (liver cirrhosis secondary to right heart pressures)
Incompetent tricuspid valve
Rheumatic fever
Constrictive pericarditis
How is portal hypertension defined in terms of pressures?
Portal vein pressure > 8mmHg
Portal vein - hepatic vein pressure >5mmHg
How might compensated cirrhosis present?
The patient may look clinically normal and feel well - may have; spider naevi clubbing palmar erythema
How might decompensated cirrhosis present?
Jaundice Ascites Encephalopathy Bruising Increased risk of bleeding
How is ascites managed/ treated?
Reduce salt intake but maintain nutrition Spironolactone Paracentesis TIPSS Transplantation
How would encephalopathy present?
Altered mood/ behaviour Drowsiness Liver flap Sleep disturbance Confusion
Oesophageal varices can develop as a consequence of cirrhosis, how would a bleed be treated?
B-blockers Variceal ligation TIPSS Shunt surgery Ballon tamponade (EMERGENCY treatment)
Which form of hepatitis has faecal-oral spread, a short incubation period, is directly cytopathic but does not involve a carrier state?
Hepatitis A
Which form of hepatitis is the most infectious, has a long incubation period and is spread by blood, sex and vertical transmission?
Hepatitis B
Which form of hepatitis is spread by blood, has a short incubation period and involves a chronic/carrier state?
Hepatitis C
What percentage of PBC patients are female?
90%
Secondary tumours of the liver (metastases from another organ) are more common than primary tumours. From which organs does cancer most commonly spread to the liver from?
Lung
Colon
Pancreas
Breast
What does the term ‘cholethiasis’ mean?
Gall stones
What are the two main types of gall stones? What causes each type?
Cholesterol stones (hypercholesterolaemia) and pigment stones (haemolytic anaemia)
What are the normal components of bile?
Cholesterol
Bile salts
Bilirubin
Phospholipids
Which enzyme is responsible for the release of bile from the gall bladder into the second part of the duodenum?
CCK
What is meant by gallstone ileus?
Gallstones enter the intestines through a fistula and cause obstruction (commonly at the ileo-caecal valve)
How can gallstones cause pancreatitis?
By blocking the sphincter of Oddi
What is meant by the term ‘Cholecystitis’?
Inflammation of the gall bladder
List some of the causes of acute pancreatitis
Alcohol
Cholethiasis
Shock
Trauma
In acute pancreatitis, there is release of two kinds of pancreatic enzymes; proteases and lipases, what do these cause?
Lipases cause intra and peri-pancreatic fat necrosis
Proteases cause tissue destruction and haemorrhage
Is pancreatitis more common in males or females?
Females
What effect does cholecystokinin have on the gall bladder and the sphincter of oddi?
Causes contraction of the gall bladder and relaxation of the sphincter of oddi
What compound mediated the synthesis of bile salts?
CYP7a1
What are the three main liver plasma proteins? Which of these is the most abundant?
A globulins, B globulins and Albumin.
Albumin is the most abundant.
What is the function of a globulins?
Transport of; Lipids Hormones Bilirubin Dietary metals
Give an example of an A globulin and a B globulin
A - Caeruloplasmin
B- Transferrin and Fibrinogen
Which plasma protein acts as the main determinant of osmotic pressure?
Albumin
What is the role of chylomicrons in the transport of fats?
Transport fat to the liver
What is the role of VLDL in the transport of fats?
Transport fat to peripheral cells - can involve deposition of cholesterol in vessels
What is the role of LDL in the transport of cholesterol?
Transport cholesterol to peripheral tissues
What is the role of HDL in the transport of cholesterol?
Removes excess cholesterol from cells and transports it back to the liver
What would the appearance of Anti-HBs in Hep B serology indicate?
Indicates immunity either due to previous exposure or due to vaccination
What would a positive HBsAg result from Hep B serology indicate?
Current infection - it indicates an infectious state
What would a positive HBeAg result from Hep B serology indicate?
A highly infectious state
What would Hep B IgM in Hep B serology indicate?
Recent or current Hep B infection
What would Hep B DNA indicate if it was present in high amounts?
A highly infectious state of current Hep B infection
What would a positive Anti-HBe indicate in Hep B serology?
Low infectivity
