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