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liver lecture Flashcards

1
Q

what are the functions of the liver?

A

glucose and fat metabolism
detoxification and excretion
protein synthesis
defence against infection as part of the reticuloendothelial system

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2
Q

give examples of substances that the liver detoxifies the blood from and excretes

A 
billirubin
ammonia 
drugs 
hormones 
pollutants
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3
Q

describe the normal histology of the liver

A

regular arrangement ie acinar and lobular
portal triad - hepatic artery, portal vein, bile duct
sinusoids
split into zones 1,2 and 3 receiving progressively less oxygenated blood

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4
Q

what type of epithelium lines the bile ducts?

A

cuboidal epithelium

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5
Q

what two paths can acute liver injury take?

A

liver failure

recovery

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6
Q

What three paths can chronic liver injury take?

A

liver failure
cirrhosis
recovery

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7
Q

How does acute liver failure present generally?

A

malaise
nausea
anorexia
jaundice

rarely:
confusion
bleeding 
liver pain (somatic nerves in the capsule of the liver)
hypoglycaemia
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8
Q

how does chronic liver injury present generally?

A 
ascites 
oedema (eg in ankles)
haematemesis due to varices 
malaise 
anorexia
wasting 
easy bruising 
itching 
hepatomegaly 
abnormal LFTs

rarely:
jaundice
confusion

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9
Q

which of the LFTs give SOME indication of liver function?

A

serum bilirubin
albumin
PT

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10
Q

which of the LFTs give no indication of liver function?

A

the serum liver enzymes:

  • cholestatic: ALP, gamma GT
  • hepatocellular: the transaminases ie AST and ALT
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11
Q

what is the pother name for unconjugated jaundice?

A

pre-hepatic jaundice

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12
Q

what are the causes of pre-hepatic jaundice?

A

Gilberts

haemolysis

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13
Q

Give an example of post hepatic jaundice

A

bile duct obstruction

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14
Q

what are the cholestatic jaundice types?

A

hepatic and post-hepatic jaundice

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15
Q

what are the qualities of urine, stools, itching and liver tests in pre hepatic jaundice?

A

urine: normal
stools: normal
itching: no
liver tests: normal (apart from bilirubin - isolated bilirubin rise)

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16
Q

what are the qualities of urine, stools, itching and liver tests in hepatic or post hepatic jaundice jaundice?

A

urine: dark
stools: pale
itching: maybe
liver tests: abnormal

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17
Q

give examples of liver disease

A

hepatitis
ischaemia
neoplasm
congestion - due to CCF

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18
Q

Give examples of obstruction

A

gallstones
strictures
blocked stents

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19
Q

give three causes of strictures

A

malignancy
ischaemia
inflammatory

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20
Q

what is Mirizzi’ssyndrome?

A

gallstone becomes impacted in the cystic duct or neck of the gallbladder causing compression of the common bile duct (CBD) or common hepatic duct, resulting in obstruction and jaundice

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21
Q

List some causes of acute liver injury

A 
viral A, B, EBV, hep E and CMV
drugs 
alcohol
vascular 
obstruction
congestion
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22
Q

what are the causes of chronic liver injury?

A

alcohol
viral B, C
autoimmune
metabolic - iron and copper

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23
Q

What questions would you ask to a pt who presents with jaundice?

A
  • dark urine, pale stools, itching?
  • symptoms - biliary pain, rigors, abdomen swelling, weight loss
  • PMH: biliary disease, biliary intervention, malignancy, heart failure, receiving blood products, autoimmune disease
  • drug history - any started recently including herbs
  • social history: alcohol, hepatitis contacts, IVDU, exotic travel, certain foods
  • FH and system review
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24
Q

what would very high AST and ALT suggest?

A

liver disease - remember these are the transaminases that are present in the hepatocytes

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25
Q

what test would be done for biliary obstruction and what would this show?

A

ultrasound

dilated intrahepatic bile ducts

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26
Q

what other imaging tests are there available apart from ultrasound?

A

CT
MRCP (MRI)
ERCP (endoscopic retrograde cholangiogram)

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27
Q

so overall, what tests should be done for sb with jaundice?

A

liver enzymes
ultrasound

if further imaging needed:
CT
MRCP
ERCP

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28
Q

where do most gallstones form?

A

gallbladder

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29
Q

what are the most common types of gallstone?

A

cholesterol

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30
Q

what are the risk factors for gallstones?

A

Fat
Forty - above the age of 40
Fertile -premenopausal- increased estrogen is thought to increase cholesterol levels in bile
Female
also liver disease, ileal disease, total parenteral nutrition - ie IV nutrition

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31
Q

How do gallbladder stones present?

A

biliary pain
cholecystitis - inflammation of the gallbladder
obstructive jaundice - maybe if there is Mirizzi syndrome
no cholangitis - ie no infection of the bile duct
no pancreatitis

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32
Q

how do stones in the bile duct present?

A

biliary pain
no cholecytitis - no inflammation of the gall bladder (as the stone is not in the gallbladder)
obstructive jaundice present
cholangitis present - ie infection of the bile duct, as the stone is in the bile duct
pancreatitis present

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33
Q

How are gallbladder stones managed?

A

laporoscopic cholecystectomy

bile acid dissolution therapy

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34
Q

How are bile duct stones managed?

A

ERCP with sphincterotomy and stone removal, stone crushing, stent placement
surgery done for large stones

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35
Q

Is the alkaline phosphatase normal or abnormal with acute stone obstruction?

A

usually normal

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36
Q

The ducts may not always be dilated on ultrasound in obstructive jaundice, T or F?

A

true!

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37
Q

What happens to the ALT over time with obstructive gallstones?

A

rapidly falls over a period of days from being over 1000

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38
Q

What blood test LFT results would a person with drug induced liver injury get?

A

high ALT, high AST and raised bilirubin

ALP borderline raised

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39
Q

How might drug induced liver injury present?

A

recent onset of itching, nausea and vomiting

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40
Q

Name some drugs that can cause DILI

A

diclofenac
Co-amoxiclav (Augmentin)
paracetamol

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41
Q

Does Atenolol cause DILI?

A

no

42
Q

What are the different types of DILI?

A

Hepatocellular
cholestatic
mixed

43
Q

What are the main points of abnormality in the LFT with hepatocellular DILI?

A

high ALT
High AST
(ALP may also be raised)
think high liver enzymes due to liver cell damage

44
Q

What is the main point of abnormality in cholestatic DILI?

A

high ALP

45
Q

How would you ask a pt about the drugs they take if you suspect DILI?

A

What drugs did you start recently, not what drugs are you on? - drugs taken in last 3 months are relevant

46
Q

What is the duration of onset of symptoms from starting the drug to DILI?

A

1-12 weeks

47
Q

What are the drugs that are the usual suspects for DILI?

A 
Antibiotics
CNS drugs 
immunosuppresants 
analgesics 
GI drugs 
dietary supplements
48
Q

Give examples of antibiotics that can cause DILI

A 
augmentin
flucloxacillin
erythromycin 
septrin
TB drugs
49
Q

Give an example of a GI drug that can cause DILI

A

PPIs

50
Q

which drugs do not tend to cause DILI?

A 
low dose aspirin
NSAIDs other than diclofenac
beat blockers
HRT
ACEIs
thiazides 
calcium channel blockers
51
Q

What changes would be seen in the LFT in paracetamol overdose?

A

ALT and AST are extremely high

PT time is increased (due to liver damage)

52
Q

What is the antidote of paracetamol called?

A

N acetylcysteine

53
Q

How does paracetamol overdose cause liver damage?

A

CYP450 converts paracetamol into a reactive intermediate which causes hepatocyte necrosis

54
Q

How is paracetamol induced fulminant hepatic failure managed?

A

give the antidote N acetylcysteine
supportive treatment to correct any coagulation defects, fluid electrolyte and acid base balance, renal failure, hypoglycaemia and encephalopathy

55
Q

What are the poor prognosis indicators of paracetamol induced liver failure?

A
  1. late presentation - after 24 hours, as NAC is not effective after then
  2. acidosis
  3. PT >70 sec (n = 12-13 seconds)
  4. serum creatinine >=300 µmol/L (normal is 45-90)
56
Q

should a liver transplant be considered in paracetamol induced liver failure?

A

yes

57
Q

What are the signs of alcohol related liver injury?

A 
jaundice 
ascites 
wasting
spider naevi
leuconychia
58
Q

What are the causes of ascites?

A 
chronic liver disease 
portal vein thrombosis 
hepatoma 
TB infection of the peritoneum 
neoplasia eg of the ovary, uterus, pancreas
pancreatitis 
cardiac- eg constrictive pericarditis
59
Q

explain the pathophysiology of ascites

A
  1. increased intrahepatic resistance
  2. leads to portal hypertension
  3. this causes systemic vasodilatation sop that blood can be shunted into the systemic circulation
  4. leads to activation of the RAAS, NA release and ADH release causing Na and water retention, leading to fluid retention
  5. low serum albumin due to liver damage also leads to ascites
60
Q

what may be seen in alcohol related liver injury in the LFTs?

A

raised serum bilirubin
reduced albumin
increased AST
increased PT

61
Q

What is the appearance of a liver with cirrhosis on ultrasound?

A

bright liver

62
Q

what are the histological features of acute alcohol related liver injury?

A

hepatocyte ballooning
mediated by neutrophils
Mallory’s hyaline/body - an accumulation of cytoskeletal protein (not specific to alcoholic liver disease)
fat - alcohol changes the way that the liver metabolises fat - so fat accumulates within hepatocytes = steatosis and can be associated with acute or chronic liver injury

63
Q

which zone of the liver is most affected by alcohol?

A

zone 3 - the area with the lowest oxygen and blood supply

64
Q

what are the two sequelae of fatty liver due to alcohol and which one is a more common sequelae? What do both of these lead to?

A

alcoholic hepattiis and cirrhosis
alcoholic hepatitis is the more common sequelae
they both lead to acute decompensation of the liver ie liver failure

65
Q

What percentage of people who are heavy alcohol drinkers get ALD?

A

10-20%

66
Q

What drug can be given when there are bleeding varices?

A

Terlipressin - an analogue of vasopressin, causes vasoconstriction

67
Q

What are the causes of portal hypertension?

A

cirrhosis
fibrosis
portal vein thrombosis

68
Q

what is the cause of varices?

A

portal hypertension results in collaterals forming, ie increased splanchnic blood flow

69
Q

How is ascites managed?

A

fluid and salt restriction (as they are already overloaded with fluid)
diuretics - spirolonlactone and furosemide
large volume paracentesis plus albumin
TIPS

70
Q

What is TIPS?

A

a metal stent is passed over a guide wire in the internal jugular vein
the stent is then pushed into the liver substance under radiological guidance to create a shunt between the portal and hepatic veins, lowering portal pressure
surgery

71
Q

What is the most commonly used benzodiazepine for alcohol withdrawal and what alternative is used in those at risk of drug accumulation ie pts with cirrhosis

A

Chlordiazepoxide is the drug of choice

Oxazepam and lorazepam are often used in patients at risk of drug accumulation

72
Q

what are the complications that pts with liver disease can experience?

A

constipation
due to the effects of drugs they have been given
GI bleed
infection of the ascitic fluid, blood, skin, chest
hyponatraemia, hypokalaemia, hypoglycaemia aka heatorenal syndrome - renal failure due to chronic liver disease
alcohol withdrawal
other complications eg intracranial haemorrhage due to coagulopathies

73
Q

If a pt with ascites has a high WBC count, low platelets, perhaps renal failure with low electrolytes, metabolic acidosis and high creatinine what could be the diagnosis?

A

spontaneous bacterial peritonitis

74
Q

Why do pts with liver disease get pancytopenia?

A

in portal hypertension, you get splenomegaly due to congestion and this increases the breakdown of platelets, red cells and WBCs

75
Q

Why are pts with liver disease vulnerable to infection?

A

impaired reticuloendothelial function (as the kupffer cells line the sinusoids)
reduced opsonic activity
impaired leukocyte function
permeability of gut wall increases - so greater translocation of bacteria into the blood

76
Q

what are the types infection common in pts with liver disease?

A 
spontaneous bacterial peritonitis 
septicaemia
pneumonia 
skin infections 
UTIs
77
Q

What is the diagnosis of SBP based on?

A

neutrophils in the ascitic fluid

78
Q

What should pts be given after one episode of SBP?

A

antibiotic prophylaxis

liver transplantation should be considered

79
Q

The symptoms of of SBP are very specific T or F?

A

False - they are vague!!

80
Q

What is the diagnosis of SBP based on?

A

the number of neutrophils in the ascitic fluid

needs to be over 250

81
Q

what are some of the causes of renal failure in liver disease?

A 
drugs - overuse of diuretics, NSAIDs, ACEIs, aminoglycosides
Infection 
GI bleeding 
myoglobinuria
renal tract obstruction
82
Q

What is the cause of hepatic encephalopathy?

A

build up of ammonia

83
Q

What factors may precipitate hepatic encephalopathy?

A 
infection 
GI bleed 
constipation
hypokalaemia
drugs eg sedatives and analgesics
84
Q

what are the causes of coma in pts with chronic liver disease?

A

hepatic encephalopathy
hyponatraemia/hypoglycaemia
intracranial events

85
Q

Why is hepatocellular carcinoma a risk in pts with long standing cirrhosis?

A

there is constant replication of hepatocytes due to the liver trying to repair itself from damage, and so it is more likely that mistakes will be made

86
Q

what are some other consequences of liver dysfunction that have not already been mentioned?

A

malnutrition
coagulopathies
endocrine changes
hypoglycaemia

87
Q

Name three causes of coagulopathy that can be due to liver dysfunction

A

impaired coagulation factor synthesis
vit K deficiency due to cholestasis
thrombocytopenia

88
Q

what endocrine changes can occur in liver disease?

A

gynaecomastia impotence amenorrhoea

89
Q

Which drugs should you be weary of in liver disease?

A

NSAIDs as they cause renal failure
short acting benzodiazepines use with care
look out for XS weight loss, hyponatraemia, hyperkalaemia nad renal failure with diuretics
avoid ACEIs
avoid aminoglycosides (end in -mycin eg streptomycin and gentamycin)

90
Q

How is malnutrition treated in liver disease?

A

NGT feeding

91
Q

how is variceal bleeding treated?

A

endoscopic banding
propanolol
terlipressin

92
Q

how is encephalopathy treated?

A

lactulose (remember constipation can cause encephalopathy)

93
Q

how is ascites/ oedema treated?

A

salt/fluid restriction
diuretics
paracentesis

94
Q

What should you do when a liver pt experiences complications?

A

ABC - airway breathing circulation
look at the chart - to check vital signs, O2, sugars, check the drug chart
look at the pt - is there infection or bleeding?
order tests - FBC< U+E, blood cultures, ascitic fluid, clotting, LFTs

95
Q

What are the causes of chronic liver disease?

A

alcohol
non-alcoholic steatohepatitis (NASH)
viral hepatitis ie B and C
immune - autoimmune hepatitis, primary biliary cirrhosis, sclerosing cholangitis
metabolis - haemachromatosis, Wilson’s, alpha 1 antitrypsin deficiency
vascular - Budd-Chiari

96
Q

What investigations are done for investigations of chronic liver disease?

A

viral serology
immunology
biochemistry
radiology - US (the standard radiological test), CT, MRI

97
Q

What can we look for in viral serology?

A

hepatitis B surface antigen HBsAg

hepatitis C antibody

98
Q

what antibodies can we look for in chronic liver disease?

A

autoantibodies:
1. AMA - antimitochondrial antibodies in primary biliary cholangitis
2. ANA - eg in autoimmune hepatitis, systemic lupus erythematosus, Sjögren’s syndrome, scleroderma
3. AMSA - Anti-smooth muscle antibodies in autoimmune hepatitis
4. coeliac antibodies: Total immunoglobulin A (IgA)
IgA Tissue transglutaminase antibody (shortened to tTG)
If IgA tTG is weakly positive then IgA endomysial antibodies (shortened to EMA) should be used

immunoglobulins - can tell what type of autoimmune disease you have

99
Q

What biochemistry studies should be done in chronic liver disease?

A 
iron studies 
copper studies incl. Ceruloplasmin; the major copper-carrying protein in the blood and a 24hr urine copper
alpha 1 antitrypsin level
lipids 
glucose
100
Q

How can you differentiate hepatitis from obstruction by looking at the liver enzymes values?

A

if the liver enzymes are very very high, more likely to be hepatitis rather than obstruction

101
Q

what are the differential diagnoses (different causes) of hepatitis?

A

viral A, B, C, CMV, EBV
drug induced
autoimmune
alcoholic

102
Q

If the globulins are raised what does this point to?

A

an autoimmune mechanism

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