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
2
Q
give examples of substances that the liver detoxifies the blood from and excretes
A
billirubin ammonia drugs hormones pollutants
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
4
Q
what type of epithelium lines the bile ducts?
A
cuboidal epithelium
5
Q
what two paths can acute liver injury take?
A
liver failure
recovery
6
Q
What three paths can chronic liver injury take?
A
liver failure
cirrhosis
recovery
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
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
9
Q
which of the LFTs give SOME indication of liver function?
A
serum bilirubin
albumin
PT
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
11
Q
what is the pother name for unconjugated jaundice?
A
pre-hepatic jaundice
12
Q
what are the causes of pre-hepatic jaundice?
A
Gilberts
haemolysis
13
Q
Give an example of post hepatic jaundice
A
bile duct obstruction
14
Q
what are the cholestatic jaundice types?
A
hepatic and post-hepatic jaundice
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)
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
17
Q
give examples of liver disease
A
hepatitis
ischaemia
neoplasm
congestion - due to CCF
18
Q
Give examples of obstruction
A
gallstones
strictures
blocked stents
19
Q
give three causes of strictures
A
malignancy
ischaemia
inflammatory
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
21
Q
List some causes of acute liver injury
A
viral A, B, EBV, hep E and CMV drugs alcohol vascular obstruction congestion
22
Q
what are the causes of chronic liver injury?
A
alcohol
viral B, C
autoimmune
metabolic - iron and copper
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
24
Q
what would very high AST and ALT suggest?
A
liver disease - remember these are the transaminases that are present in the hepatocytes
25
what test would be done for biliary obstruction and what would this show?
ultrasound
| dilated intrahepatic bile ducts
26
what other imaging tests are there available apart from ultrasound?
CT
MRCP (MRI)
ERCP (endoscopic retrograde cholangiogram)
27
so overall, what tests should be done for sb with jaundice?
liver enzymes
ultrasound
if further imaging needed:
CT
MRCP
ERCP
28
where do most gallstones form?
gallbladder
29
what are the most common types of gallstone?
cholesterol
30
what are the risk factors for gallstones?
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
31
How do gallbladder stones present?
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
32
how do stones in the bile duct present?
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
33
How are gallbladder stones managed?
laporoscopic cholecystectomy
| bile acid dissolution therapy
34
How are bile duct stones managed?
ERCP with sphincterotomy and stone removal, stone crushing, stent placement
surgery done for large stones
35
Is the alkaline phosphatase normal or abnormal with acute stone obstruction?
usually normal
36
The ducts may not always be dilated on ultrasound in obstructive jaundice, T or F?
true!
37
What happens to the ALT over time with obstructive gallstones?
rapidly falls over a period of days from being over 1000
38
What blood test LFT results would a person with drug induced liver injury get?
high ALT, high AST and raised bilirubin
| ALP borderline raised
39
How might drug induced liver injury present?
recent onset of itching, nausea and vomiting
40
Name some drugs that can cause DILI
diclofenac
Co-amoxiclav (Augmentin)
paracetamol
41
Does Atenolol cause DILI?
no
42
What are the different types of DILI?
Hepatocellular
cholestatic
mixed
43
What are the main points of abnormality in the LFT with hepatocellular DILI?
high ALT
High AST
(ALP may also be raised)
think high liver enzymes due to liver cell damage
44
What is the main point of abnormality in cholestatic DILI?
high ALP
45
How would you ask a pt about the drugs they take if you suspect DILI?
What drugs did you start recently, not what drugs are you on? - drugs taken in last 3 months are relevant
46
What is the duration of onset of symptoms from starting the drug to DILI?
1-12 weeks
47
What are the drugs that are the usual suspects for DILI?
```
Antibiotics
CNS drugs
immunosuppresants
analgesics
GI drugs
dietary supplements
```
48
Give examples of antibiotics that can cause DILI
```
augmentin
flucloxacillin
erythromycin
septrin
TB drugs
```
49
Give an example of a GI drug that can cause DILI
PPIs
50
which drugs do not tend to cause DILI?
```
low dose aspirin
NSAIDs other than diclofenac
beat blockers
HRT
ACEIs
thiazides
calcium channel blockers
```
51
What changes would be seen in the LFT in paracetamol overdose?
ALT and AST are extremely high
| PT time is increased (due to liver damage)
52
What is the antidote of paracetamol called?
N acetylcysteine
53
How does paracetamol overdose cause liver damage?
CYP450 converts paracetamol into a reactive intermediate which causes hepatocyte necrosis
54
How is paracetamol induced fulminant hepatic failure managed?
give the antidote N acetylcysteine
supportive treatment to correct any coagulation defects, fluid electrolyte and acid base balance, renal failure, hypoglycaemia and encephalopathy
55
What are the poor prognosis indicators of paracetamol induced liver failure?
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
should a liver transplant be considered in paracetamol induced liver failure?
yes
57
What are the signs of alcohol related liver injury?
```
jaundice
ascites
wasting
spider naevi
leuconychia
```
58
What are the causes of ascites?
```
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
explain the pathophysiology of ascites
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
what may be seen in alcohol related liver injury in the LFTs?
raised serum bilirubin
reduced albumin
increased AST
increased PT
61
What is the appearance of a liver with cirrhosis on ultrasound?
bright liver
62
what are the histological features of acute alcohol related liver injury?
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
which zone of the liver is most affected by alcohol?
zone 3 - the area with the lowest oxygen and blood supply
64
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?
alcoholic hepattiis and cirrhosis
alcoholic hepatitis is the more common sequelae
they both lead to acute decompensation of the liver ie liver failure
65
What percentage of people who are heavy alcohol drinkers get ALD?
10-20%
66
What drug can be given when there are bleeding varices?
Terlipressin - an analogue of vasopressin, causes vasoconstriction
67
What are the causes of portal hypertension?
cirrhosis
fibrosis
portal vein thrombosis
68
what is the cause of varices?
portal hypertension results in collaterals forming, ie increased splanchnic blood flow
69
How is ascites managed?
fluid and salt restriction (as they are already overloaded with fluid)
diuretics - spirolonlactone and furosemide
large volume paracentesis plus albumin
TIPS
70
What is TIPS?
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
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
Chlordiazepoxide is the drug of choice
| Oxazepam and lorazepam are often used in patients at risk of drug accumulation
72
what are the complications that pts with liver disease can experience?
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
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?
spontaneous bacterial peritonitis
74
Why do pts with liver disease get pancytopenia?
in portal hypertension, you get splenomegaly due to congestion and this increases the breakdown of platelets, red cells and WBCs
75
Why are pts with liver disease vulnerable to infection?
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
what are the types infection common in pts with liver disease?
```
spontaneous bacterial peritonitis
septicaemia
pneumonia
skin infections
UTIs
```
77
What is the diagnosis of SBP based on?
neutrophils in the ascitic fluid
78
What should pts be given after one episode of SBP?
antibiotic prophylaxis
| liver transplantation should be considered
79
The symptoms of of SBP are very specific T or F?
False - they are vague!!
80
What is the diagnosis of SBP based on?
the number of neutrophils in the ascitic fluid
| needs to be over 250
81
what are some of the causes of renal failure in liver disease?
```
drugs - overuse of diuretics, NSAIDs, ACEIs, aminoglycosides
Infection
GI bleeding
myoglobinuria
renal tract obstruction
```
82
What is the cause of hepatic encephalopathy?
build up of ammonia
83
What factors may precipitate hepatic encephalopathy?
```
infection
GI bleed
constipation
hypokalaemia
drugs eg sedatives and analgesics
```
84
what are the causes of coma in pts with chronic liver disease?
hepatic encephalopathy
hyponatraemia/hypoglycaemia
intracranial events
85
Why is hepatocellular carcinoma a risk in pts with long standing cirrhosis?
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
what are some other consequences of liver dysfunction that have not already been mentioned?
malnutrition
coagulopathies
endocrine changes
hypoglycaemia
87
Name three causes of coagulopathy that can be due to liver dysfunction
impaired coagulation factor synthesis
vit K deficiency due to cholestasis
thrombocytopenia
88
what endocrine changes can occur in liver disease?
gynaecomastia impotence amenorrhoea
89
Which drugs should you be weary of in liver disease?
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
How is malnutrition treated in liver disease?
NGT feeding
91
how is variceal bleeding treated?
endoscopic banding
propanolol
terlipressin
92
how is encephalopathy treated?
lactulose (remember constipation can cause encephalopathy)
93
how is ascites/ oedema treated?
salt/fluid restriction
diuretics
paracentesis
94
What should you do when a liver pt experiences complications?
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
What are the causes of chronic liver disease?
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
What investigations are done for investigations of chronic liver disease?
viral serology
immunology
biochemistry
radiology - US (the standard radiological test), CT, MRI
97
What can we look for in viral serology?
hepatitis B surface antigen HBsAg
| hepatitis C antibody
98
what antibodies can we look for in chronic liver disease?
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
What biochemistry studies should be done in chronic liver disease?
```
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
How can you differentiate hepatitis from obstruction by looking at the liver enzymes values?
if the liver enzymes are very very high, more likely to be hepatitis rather than obstruction
101
what are the differential diagnoses (different causes) of hepatitis?
viral A, B, C, CMV, EBV
drug induced
autoimmune
alcoholic
102
If the globulins are raised what does this point to?
an autoimmune mechanism
