Case 5 Flashcards
What is the name of the toxic metabolite formed in paracetamol hepatotoxicity?
N-acetyl-benzoquinoneimine
What is bilirubin conjugated with in the liver, what is formed? (include proportions)
80% with glucuronide forming bilirubin glucoronide, 10% with sulfate to form bilirubin sulfate, 10% with other substances
What is the largest visceral organ?
The liver
The liver is in mostly in which regions?
The hypochondrium and epigastric regions
What are the two recesses associated with the liver?
The subphrenic and hepatorenal recesses
What divides the left and right ares of the subphrenic recess?
The falciform ligament
What is the falciform ligament derived from?
The ventral mesentery in the embryo
The subphrenic and hepatorenal recesses are continuous where?
anteriorly
The liver coated with visceral peritoneum apart from where?
The fossa for the gallbladder and the porta hepatis
What attaches the liver to the anterior abdominal wall?
the falciform ligament
What connects the liver to the stomach?
the hepatogastric ligament
What attaches the liver to the duodenum?
The hepatoduodenal ligament
What attaches the liver to the diaphragm?
triangular ligaments on the right and left and coronary ligaments on the anterior and posterior
Which of the right lobes of the liver is visable on the anterior of the visceral surface?
quadrate lobe
Which of the the right lobes of the liver visible on the posterior of the visceral surface?
the caudate lobe
The quadate lobe of the liver is functionally related to what lobe?
The left
What forms the right and left borders of the quadrate lobe of the liver?
the fossa for the gall blader on the right and the fissure for the ligamentum teres on the left
What forms the right and left borders of the caudate lobe of the liver?
the fissure for the ligamentum venosum of the left and the groove for the vena cava on the right
Which two arteries supply the liver? where do they arise from?
The right and left hepatic arteries originating from the common hepatic artery from the celiac trunk
What does blood drun into after entering the liver the branches of the hepatic portal vein?
hepatic sinusoids
What is the name for the specialized macrophages that screen blood entering the liver?
Kupffer cells
What is the typical size of a liver lobule?
1mm
As well as engulfing pathogens and cell debris what is the other function of the kupffer cells of the liver?
storage of iron, lipids and some heavy metals such as tin or mercury
What is glycogenesis?
the formation of glycogen from glucose
What is gluconeogensis?
the formation of glucose from non carbohydrate sources
What is glycogenolysis?
the formation of glucose from glycogen
What is interconversion?
the conversion of one monosacaride to another e.g. glucose to fructose
What is used to synthesize chloesterol int he liver?
proteins and carbohydrates
What are the four main things the livershelps to store?
glucose, vitamin B12, iron and Vitamin A
What two forms does the liver store iron in?
mainly ferritin but also haemosiderin
The liver acts as a reservoir for roughly how much blood?
650mls
Which type of liver reation is catabolic?
phase 1
Which phase of liver reaction is anabolic
phase 2
What type of substance is not well eliminated by the kidneys and so is the target for liver metabolism?
lipophilic
What system does the majority of liver drug metabolism happen in?
the cytochrome p450 (CYP) system
Which organelle is most associated with drug metabolising enzymes in the liver?
The smooth endoplasmic reticulum
What is functionalisation?
The addition of a reactive group to a molecule that serves as a point if attack for the conjugating system to attach a substituent
How are non-predictable hepatotoxic drugs different from predictable hepatotoxic drugs?
Their damage is not associated to their dosage
What are the six mechanisms by which a drug can be damaging to a hepatocycte?
disruption of calcium homeostasis, disruption of bile canalicular transport mechanisms, formation of non functioning adducts that present on the surface of the cell as new antigens, induction of apoptosis and inhibition of mitochondrial function
What is the toxic dose of paracetamol?
10-15g
How does inhibition of mitochondria damage hepatocytes?
it prevents fatty acid metabolism and causes accumulation of lactate and reactive oxygen species
What is haemoglobin first converted to when it enters a macrophage?
the haemoglobin is split into haem and globin
What happens to globin one it is separated from haemoglobin in macrophages?
it is broken down into its constituent amino acids and used to synthesis other proteins
What happen to the Fe3+ when it is removed from a haeme group in a macrophage?
it attaches to the iron storage protein transferrin
What happens to the iron stored in transferrin in muscle fibres liver ells and macrophages of the spleen and liver?
It dissociates from transferrin and instead becomes associated with ferritin
What happens to the haem group in haemoglobin one it is detached from globin and iron?
It is converted to biliverdin then quickly to unconjugated bilirubin
What is unconjugated bilirubin transported by in the blood on its way to the liver?
plasma albumin
What proportion of bilirubin entering the liver is conjugated with glucoronic acid? What is formed?
80% it forms bilirubin glucuronide
What proportion of bilirubin entering the liver is conjugated with sulfate? what is formed?
10% it forms bilirubin sulfate
What highly soluble compound is bilirubin converted to in the large intestine? What proportion of bilirubin is converted?
about half is converted forming urobillinogen
What happens to urobillogen once it enters urine?
it is oxidised forming urobilin
What is the van den Bergh reaction? What two conditions does it help distinguish between? why does it distinguish between these two?
A reaction that can reveal whether the majority of bilirubin in the blood is conjugated or not this shows whether jaundice is haemolytic or obstructive as in haemolytic blood bilirubin is raised due to it being released from damaged erythrocytes whereas in obstructive it is raised due to conjugated bilirubin being released into the blood as it cannot be released into the GI tract
What are the three main types of jaundice?
prehepatic, hepatic and post hepatic
What are the two most common causes of hepatic jaundice
viral hepatitis and cirrhosis
The presence of Aminiotranferase in the blood indicates what?
hepatocyte necrosis
What is chloestasis?
the inability of bile to flow away from the liver
Which hepatotropic viruses use RNA as their nucleic acid?
A, C and E
Which hepatotropic viruses are oncogenes?
B, C and D
What is the incubation period of hepatitis A?
3-6 weeks
What is the most common form of viral hepatitis?
Hepatitis A
What is released into the blood upon the on set of symptoms in Hep A?
IgM anti HVA antibody
What type of food can cause an infection of HVA?
raw shellfish
What is the primary transmission route for hepatitis A?
faecal oral
Where is the hepatitis A virus common?
the indian subcontinent, africa, central and southern america and far & eastern europe.
What is the second most common cause of viral hepatitis?
Hepatitis B
What are the five possible outcomes of Hepatitis B infection?
Acute hepatitis with recovery and clearance of the virus, non progressive chronic hepatitis, progressive chronic disease ending in cirrhosis, fulminant hepatitis will massive liver necrosis and an asymptomatic carrier state.
In areas of endemic Hepatitis B what are the most common modes of transmission?
From mother to child and exposure to infected blood (especially from one infected child to an infected child under 5)
In areas of low endemicity what are the two most common modes of transmission of Hepatitis B
Use of contaminated needles for drug use and sexual transmission
What is the incubation period of hapatitis B
on average 75 fdays but it can vary from 30-180 days
What are the two phases of a chronic HBV infection
replicative and integrated
In what phase of a chronic infection of HBV is there active viral replication with hepatic inflammation, where the patient with be highly contagious and would have high levels of blood antigen
replicative
What is the mode of action of Peginterferon alpha 2a?
It binds to type 1 interferon receptors which upon dimerisation activate two Jak tyrosine kinases these transphosphorylate each other and their receptors. The phosphorylated receptors then bind to Stat1 and Stat2 which dimerise and activate multiple.
What is the incubation period of Hepatitis C?
7-8 weeks
What is unique about hepatitis C infection?
it is often asymptomatic however often causes scarring of the liver and ultimately cirrhosis
What is unique about hepatitis D infection?
it can only occur if a person is already is infected with hepatitis B
What is the other name for liver failure caused by hepatitis?
Fulminant hepatitis.
What is unique about hepatitis G?
It appears to replicate in bone marrow and the spleen
What are the main two routes of transmission for hepatitis G?
Exposure to contaminated blood and sexual contact
How is chronic hepatitis defined?
inflammatory disease of the liver lasting more than 6 months
What apart from hepatitis viruses can cause chronic hepatitis?
Epstein-barr virus, metabolic conditons, toxic and drug causes, autoimmuno conditions and sarcoidosis
What are the three central pathogenic processes in cirrhosis?
ecm deposition, death of hepatocytes and vascular reorganisation
What is the primary mechanism of fibrosis is cirrhosis?
proliferation of hepatic stellate cells that activate to become myofibrogenic cells that are highly fibrogenic collagen forming cells
What is released from stellate cells in their early stages of activation?
retinoids
What is the difference between micronodular and macronodular cirrhosis?
Micronodular cirrhosis has regenerating nodules of less than 3mm and effects the whole liver uniformly and is often caused by ongoing alcohol damage, macronodular cirrhosis has variable nodule size and is often seen following viral hepatitis
What is hepatorenal syndrome?
The deterioration of kidney function in individuals with cirrhosis or fulminant liver failure
What are the three main complications associated with hepatic failure?
Hepatic encephalopathy, hepatorenal syndrome and hepatopulmonary syndrome
What chemical is thought to be responsible for the majority of the effects of hepatic encephalopathy what does it cause?
ammonia is thought to be responsible and causes impaired neural function and generalized brain oedema
What usual heralds hepatorenal syndrome?
drop in urine output with rising blood urea nitrogen and creatinine.
What is the triad that heralds hepatopulmonary syndrome
chronic liver disease, hypoxemia and intra-pulmonary vascular dilations
