Case 16: My skin is looking yellow Flashcards
another word for jaundice
icterus (comes from the past belief that jaundice could be cured by looking at a yellow bird)
what disorders cause and increase in unconjugated bilirubin
extravascular haemolytic anaemia (RBCs are broken down too young)
infective haematopoiesis (blood cells don’t from properly in the bone marrow, therefore macrophages break them down)
why is jaundice mainly seen in the eyes first
elastin in the eyes has a high affinity for bilirubin
what causes jaundice in newborns
the liver had lower levels of UGT enzyme (this is what converts unconjugated bilirubin to conjugated)
this causes an increase in unconjugated bilirubin
complications of an increase in unconjugated bilirubin (in newborns)
can collect in the basal ganglia (kernicterus)
this can cause brain damage and death
treatment for newborn jaundice
bilirubin lights (phototherapy)
light induces structural changes in the bilirubin molecule- makes it more soluble so it can be excreted in urine
those with Gilberts have low levels of what
UGT enzyme
what is crigler najjar syndrome
rare autosomal recessive disease characterized by significant unconjugated hyperbilirubinemia
there is no UGT enzyme
can lead on to kernicterus (is usually fatal)
management of crigler najjar syndrome
phototherapy or plasmapheresis helpful in short term
liver transplant only curative option
what is Dubin-Johnson syndrome
autosomal recessive defect in MRP2 meaning reduced movement of conjugated bilirubin from hepatocytes to bile ducts
this causes the up regulation of MRP3 meaning the conjugated bilirubin moves from hepatocytes to blood
this is transported to kidneys too making the urine dark also
obstructive jaundice is causes by an increase in which type of bilirubin
conjugated
what viral infection leads to an increase in both conjugated and unconjugated bilirubin
viral hepatitis
the death of hepatocytes mean less bilirubin is conjugated (unconjugated rises)
death of hepatocytes also causes bile to leak into the blood (increase in conjugated bilirubin)
will see darker urine
at low levels what is alcohol converted to
CO2 and water
this is excreted via urine, lungs and sweat
at high levels what is alcohol converted to
acetaldehyde via alcohol dehydrogenase
this happens in gastric mucosal cells and hepatocytes
then undergo lipogenesis to form fatty acids and glycerol
how can alcohol lead to hepatitis
the lipogenesis of acetaldehyde to fatty acids and glycerol can deposit in hepatocytes causes hepatitis and inflammation
mechanisms for how alcohol damages the liver
it is directly toxic
acetaldehyde is carcinogenic
induced fatty changes
inflammation and fibrosis
induces cp450
prevents absorption and storage of essential nutrients (particularly B vitamins)
the order of changes in alcoholic liver disease
fatty liver
hepatitis
fibrosis
cirrhosis
hepatocellular carcinoma
description of fibrosis
the reversible deposition of pericellular fibrous glands
description of cirrhosis
irreversible nodules that comprise a hypo plastic hepatocyte surrounded by fibrous tissue
how does alcohol affect CNS
is lipophilic so can cross BBB and act on neurones
chronic consumption interferes with absorption and utilisation of B1 (thiamine) with is essential for CNS glucose metabolism
at high levels acts on respiratory centres in brainstem
is a CNS depressant in high levels via activating GABA receptors
prehepatic causes of jaundice
gilberts
drugs
haemolytic anaemia
crigler-najjar syndrome
hepatic causes of jaundice
hepatitis
metabolic (haemachromatosis, Wilsons)
alcohol
NAFLD
autoimmune (primary biliary cholangitis, primary sclerosis cholangitis)
malignancy of biliary system (HCC, cholangiocarcinoma, gallbladder cancer)
drugs (cirprofloxacin, co-amoxiclav, phenytoin, erythromycin, nirtofurantoin)
post hepatic cases of jaundice
gallstones
surgical strictures
extrahepatic malignancy (pancreatic cancer)
pancreatitis
what may cause stigmata of alcoholic liver disease on examination
high oestrogen
low albumin
portal hypertension
signs of hepatic encephalopathy (asterixis/liver flap)
muscle loss (sarcopenia)
examination findings of high oestrogen
palmar erythema
spider naevi
gynacomastia
loss of secondary body hair in males
male genital atrophy (testicles shrink)
examination findings of low albumin
leukonychia (white nails)
examination findings of portal hypertension
caput medusae (painless swollen veins around umbilicus)
ascites
complete vs incomplete biliary obstruction
complete when there is development of pale stools
what suggests obstructive jaundice
darkened stools
itching
what would suggest pancreatic cancer
weight loss
epigastric pain radiating to back
what causes benign biliary strictures
develop due to damage to the bile ducts during surgery/trauma to the abdomen, a recurring condition (pancreatitis or bile duct stones) or a chronic disease (PSC)
prehepatic metabolism of bilirubin
RBCs are phagocytosed by macrophages when they reach the end of their life (120 days)
haemoglobin is broken down into haem and globin
haem is broken down into iron and portporphyrin
portporphyrin broken down into unconjugated bilirubin (in spleen)
albumin in blood binds to unconjugated bilirubin and transports it to liver
hepatic metabolism of bilirubin
unconjugated bilirubin is taken up by hepatocytes in liver
here it is conjugated via UGT enzyme
conjugated bilirubin is water soluble, unconjugated is not
conjugated bilirubin is secreted into bile duct and stored in gall bladder as bile
posthepatic metabolism of bilirubin
when you eat fatty food bile is excreted into duodenum from gallbladder
conjugated bilirubin in the bile is converted into urobilinogen by microbes in small intestine
some urobiliogen is converted to stercobilin which is excreted in stool giving them brown colour
reset of urobilinogen is reabsorbed into blood converted to urobilin and either sent to liver or excreted by kidneys giving urine yellow colour
what is whipples procedure
operation to treat tumours and other conditions in the pancreas, small intestine and bile ducts
removal of head of pancreas, first part of small intestine, gall bladder and bile ducts
negatives of benzodiazepines
can mask signs of underlying condition
can cause respiratory depression (more dangerous if have cardio-respiratory disorder)
may cause CNS depression
may limit their ability to give accurate history
may worsen delirium
may increase fall risk
symptoms of alcohol withdrawal
anxiety
nausea/vomiting
insomnia
alcohol craving
tremor
sweating
palpitations
diarrhoea
confusion
hallucinations
seizures
excessive alcohol may increase risk of GI bleed as it is a risk factor for
oesophagitis
mallory weiss tear
gastritis and peptic ulceration
oesophageal varices
oesophogastric malignancy
alcohol withdrawal mechanism
chronic excessive alcohol up regulates GABA and inhibits NMDA
abrupt cessation unmasks this response leading to an overall over excitation of the CNS
what ions increase due to excitatory neurones
glutamate causes Na+ and Ca2+ to increase
what ion increases due to inhibitory neurones
GABA causes Cl- to increase
clinical presentation of alcohol withdrawal
autonomic hyperreactivity (insomnia, tremulousness, mild anxiety, GI upset, anorexia, headache, diaphoresis, palpitations)
withdrawal seizures- generalised tonic-clonic seizures, singular/brief slurry of seizures over short period, usually happens in 4th-5th decade of life
alcoholic hallucinosis- usually visual but may be auditory/tactile, they are aware they’re hallucinating
delerium tremens- associated with abnormal vital sings, fluid status and electrolyte levels, not alert
mortality of delirium tremens
5%
death usually due to dsyrrythmia, pneumonia
tools to identify the severity of alcohol withdrawal
clinical institute withdrawal assessment
glasgow alchol score
