jaundice Flashcards
what is jaundice
the clinical manifestation of biochemical hyperbilirubinemia, detected by the change of skin colour and sclera
what is icterus
jaundice e.g. the sclera can be icteral
where is juandice normally first noticable
in the sclera - get them to look down as it usually accumulates above the pupil
what is eryptosis
apoptosis of erythrocytes - erythrocyte shrinkage, blebbing, and phospholipid scrambling of the cell membrane
what is ferrous converted to by ROS in erythrocyte damage
ferric iron
what happens to the glycolytic enzymes in RBCs as they age
decreases
examples of markers for macrophage digestion of senescent RBCs (5)
- reduced glycolytic enzyme
- loss of membrane
- neoantigen appearance
- exposure of membrane phosphadtidylserine
- desaialyation of surface proteins
what are heinz bodies
inclusions of irreversibly denatured hemoglobin attached to the erythrocyte cell membrane -> indicative of oxidative injury
what is white pulp
the lymphatic tissue of the spleen -> trebecular arteries are surrounded by it in the spleen
how do red blood cells go from the radial arteries to the veins (spleen)
they must leave the radial arteries and traverse the red pulp to reach the veins
what are howell-jolly bodies
inclusions of nuclear chromatin remnants -> indicate spleen damage
what are siderocytes
RBCs containing granules of iron that are not part of the cell’s haemoglobin
what are pappenheimer bodies
inclusion bodies formed by phagosomes that have been engulfing excessive amounts of iron
how does the spleen remove old rbcs (3)
- in order to reach the vein, rbcs must squeeze through gaps in the bv wall
- ages rbcs loose their membrane elasticity and become trapped in the red pulp as they cannot squeeze through
- they are engulfed by macrophages
in macrophages what are the main haemaglobin breakdown steps (3)
Hb -> Heam + Fe -> globin + porphyrin -> bilirubin
- Hb -> haem +Fe
- haem -> globin + prophyrin
- porphyrin -> bilirbin
what is the reaction that ALA dehydrogenase is used in (haem synthesis)
2ALA –(ALA dehydrogenase)–> porphobilinogen (PBG)
what is the last main step in haem synthesis
protophorphyrin IX + Fe2+ –(ferrochelatase)–> haem
what is the intermediate compound in the haem breakdown pathway that gives bile its colour
biliverdin
what enzyme is used in the formation of biliverdin
haem oxygenase (there are 2 forms of the enzyme)
what enzyme is used in the conversion of biliverdin to bilirubin
biliverdin reducatse
what are the 2 forms of the biliverdin reducatse gene (BLVR) and which is predominant
BLVRA -> forms biliverdin IXa
BLVRB -> forms biliverdin IXβ
biliverdin IXβ is the predominant form
what type of bilirubin is produced in the macrophage
unconjugated bilirubin or indirect bilirubin (non water soluble)
what can unconjugated bilirubin bind to and for what reason
it can binds to albumen -> allows for it to be carried in the blood
where cant unconjugated bilirubin appear
in the urinw
where is unconjugated bilirubin taken up
by the hepatocytes
where does bilirubin conjugation occur
in the liver (hepatocytes)
what enzyme is key in bilirubin conjugation
UDP glucuronyl transferase
what is bilirubin conjugated to
glucaronic acid
where is conjugated bilirubin secreted into from the liver
the bile
what is conjugated bilirubin broken down into in the bowel(3)
- urobilinogen
- unconjugated bilirubin
- stercobilin (majority)
what breaks down conjugated bilirubin into urobilinogen
the bacteria
what happens to urobilinogen after the bowel
it is soluble so it taken up into the kidneys to be excreted
what happens to unconjugated bilirubin after the bowel
it enters teh eneterohepatic circulation to be retaken up by the liver
what happens to stercobilin after the bowel
is its egested in the faeces -> it is what turns faeces brown
what does pale faeces indicate
no conjugated bilirubin the bowel -> biliary or pancreatic problem
what receptor is key in transporting UC bilirubin into the hepatocytes
OATP1
what is gilbert syndrome
an autosomal recessive condition where the liver in unable to process bilirubin properly
what transmemebrane protein is implicated in gilberts syndrome
UGTA1
how does conjugated bilirubin enter the GI tract
carried in bile and travels through the ampulla of vater into the duodenum
what is hepatocyte hopping
while the majority of conjugated bilirubin is transported into the bile, some is effluxed back into the sinusoid (via MRP3) which is then taken up by neighbouring cells, this is then excreted further up into the bile duct
why does hepatocyte hopping occur
to stop overwhelming the cannicular system
what 4 bacteria are responsible for the bibirubin -> urobilinogen reduction
- Clostridium ramosum
- Clostridium perfringens
- Clostridium difficile
- Bacteroides fragilis
what happens to the urobilinogen in the intestines (3)
- turned into stercobilin
- enters the enterohepatic circulation to be transported back to the liver
- deposited in the kidneys to be oxidised to urobilin (yellow pigment seen in urine)
what are the 3 types of jaundice
- pre hepatic
- hepatic
- post hepatic /obstructive
what is pre hepatic jaundice
increase in the blood of UNconjugated bilirubin -> build up and failure to conjugate bilirubin leading to build up of UC bilirubin in the blood
what urine/faeces change is seen w pre hepatic jaundice
none -> UC bilirubin is not soluble but any bilirubin that manages to be conjugated will be excreted
3 causes of pre-hepatic jaundice
- increased red cell break down -> too much bilirubin is being delivered to the liver and it can conjugate it all
- large hameatoma (lots of rbcs broken down again)
- failure of hepatic conjugation e.g. genetic condition
what blood results indicate pre-hepatic jaundice due to haemolytic process
raised reticulocytes; raised LDH; low Hb
what are the 2 types of haemolysis
intravascular; extravascular
examples of autoimmune intravascular haemolysis (3)
- acute haemolytic transfucton reaction e.g. incompatible ABO group
- warm autoimmune haemolysis
- cold autoimmune haemolysis
exampls of autoimmune extravascular haemolysis (4)
- warm autoimmune haemolysis
- cold autoimmune haemolysis
- haemolytic disease of the foetus and newborn (RhD incompatibility)
- delayed haemolytic transfusion reaction (atypical cell antibodies from prior transfusion)
where is the mutation in gilberts syndrome
the gene promoter box (TATA box) -> less transport protein produced -> less conjugation of bilirubin
what is crigler najjar syndrome
an autosomal recessive inherited disorder that leads to congenital non-hemolytic jaundice -> caused by an absence or profoundly decreased level of the enzyme UDP-glucuronosyltransferase due to a genetic defect in the UGT1A1 gene
how does crigler nijjar (T1) syndrome present
shortly after birth with kernicterus
crigler nijjar (T1) syndrome mgx (2)
- photo therapy -> changes the bilirubin structure so that it becomes soluble
- liver transplant
how does UC bilirubin build up cause kernicterus
due to the non-polar nature of UC bilirubin, it can easily cross the BBB and destroy neurons in the brain
what is breast milk jaundice
a common and benign cause of jaundice in newborns who are primarily breast milk fed -> may inhibit UGT1A1 protein leading to lack of bilirubin conjugation
substitution w formula milk leads to rapid recovery
what is hepatic jaundice
jaundice that occurs when liver disease affects the ability to both conjugate and secrete bilirubin
5 underlying causes for hepatic jaundice
- acute liver injury
- acute liver failure
- chronic liver disease
- cirrhosis decompensation
- acute on chronic liver faliure
what kind of bilirubin is elevated in hepatic jaundice
a mixture of UC and conjugated bilirubin
what may the urine of a hepatic jaundice pt look like
dark urine and pale stool -> conjugated bilirubin is excreted into the urine (as goes into the blood but not GI tract) but wont enter the bowel
what is dubin johnson syndrome
an autosomal recessive condition in which the MRP2 protien is mutated and so bilirubin cannot be excreted into the bile => conjugated bilirubin enters the blood stream instead (leads to dark urine, pale faeces)
what is the appearance of the liver in dubin-johnson syndrome
liver appears black as NA excretion from the liver is also impaired which causes the liver to turn black
what is rotor syndrome
an autosomal recessive condition where hepatocyte hopping is impaired meaning that bilirubin entering the blood cant reenter the hepatocytes => excreted in the urine
what is post-hepatic jaundice
jaundice that occurs due to disruption preventing the bile and the bilirubin inside it from draining out of the gallbladder and into the digestive system -> usually due to an obstruction e.g. tumour, gallstones
what LFT are raised in post-hepatic jaundice
ALP, GGT
causes of post hepatic jaundice (5)
- Common bile duct stone
- Cholangitis
- Bile duct strictures (PSC)
- Malignancy
- Pancreatitis
what test is useful when determing what type of jaundice is present
split bilirubin -> shows levels of UC and C bilirubin
post hepatic jaundice urine and faeces change
pale stool, dark urine
how does bilirubin enter the blood stream in post hepatic jaundice
the cholangiocytes become “leaky” and the bilirubin moves into the bloodstream; hepatocytes also excrete this directly into the blood
why does pruritis occur in post hepatic jaundice
due to build up of bile acids as they are not being excreted
