Chronic Liver Disease Flashcards
(99 cards)
1
Q
what is the outcome of chronic liver disease
A
cirrhosis
2
Q
when does liver disease become chronic
A
when duration is longer than 6 months- duration may be subclinical
3
Q
what is the difference between compensated and decompensated chronic liver disease
A
compensated- patients do not have symptoms relating to their cirrhosis
decompensated- symptomatic complications related to cirrhosis
4
Q
what are symptomatic complications relating to cirrhosis
A
jaundice, ascites, variceal haemorrhage, hepatic encephalopathy
5
Q
why are sinusoidal capillaries leaky
A
to allow the movement of protein etc
6
Q
what cells initiate fibrosis and how
A
hepatocyte kupffer cells/ inflammatory cells cause quiescent hepatic stellate cells to turn into activated HSC which are pro inflammatory and then turn into apoptotic HSC
7
Q
what are the causes of chronic liver disease (cirrhosis) in order of most common
(the ddx for cirrhosis)
A
Alcohol, NAFLD, Hepatitis C, Primary Biliary Cholangitis, Autoimmune Hepatitis, Hepatitis B, Haemochromatosis, Primary Sclerosing Cholangitis, Wilsons Disease, alpha 1anti-trypsin, Budd-Chiari, Methotrexate,
8
Q
what other disease can chronic affect the liver as a bystander
A
amyloid,
rotor syndrome,
sarcoid
9
Q
what is NAFLD
A
fatty liver or steato-hepatits in absence of other cause
10
Q
what is seen microscopically in NASH
A
fat globlets, black dots- neutrophils infiltration, collagen/ fibrosis
11
Q
what is the ‘2 hit; pathogenesis of NASH
A
1st= excess fat accumulation
2nd= intrahepatic oxidative stress, lipid peroxidation, TNF-alpha; pro inflammatory cytokine cascade, lipopolysaccharide, ischaemia- reperfusion injury
12
Q
what causes oxidative stress and lipid peroxidation
A
MCD diets (methionine-choline deficient)
13
Q
what does the ‘second hit’ activate and lead to
A
activates NF-kB and the progression of NASH with increased ARE gene expression
14
Q
what metabolic syndrome factors are associated with NASH/NAFLD
A
type II diabetes, obesity, HDL cholesterol, hypertension, triglycerides
15
Q
when NASH is in conjunction with metabolic syndrome what depends what you present with
A
your genes
16
Q
what is the treatment for a simple steatosis
A
weight loss and exercise
17
Q
what are the risks of simple steatosis
A
increased cardiovascular risks
18
Q
what is the treatment for NASH
A
weight loss and exercise (some experimental treatments)
19
Q
what is the risk of NASH
A
progression to cirrhosis
20
Q
what are the types of auto immune liver disease
A
primary biliary cholangitis,
auto-immune hepatitis,
primary sclerosing cholangitis,
alcoholic related liver disease (has autoimmune components),
drug reactions
21
Q
what causes primary biliary cholangitis
A
autoantibodies (AMA- antimitochondrial antibodies) against mitochondrial antigens (M2-E2 E3 subunits of PGC-E2) in the inner leaflet of the mitochondrian
22
Q
what mediates PBC
A
T cell mediates- CD4 cells reactive to M2 target
23
Q
who is PBC most commonly seen in
A
women 10;1
24
Q
what is the presentation of PBC
A
usually symptomatic/ incidental
symptoms;
- fatigue
- itch without rash
- xanthesalma (around eyelids) and xanthomas
25
what is a xanthoma
an irregular yellow patch or nodule on the skin, caused by deposition of lipids.
26
how is PBC diagnosed
2 of 3;
- positive AMA,
- cholestatic LFT's
- liver biopsy
27
how is PBC treated
urseo deoxycholic acid
28
what are the outcomes of PBC
most will not develop symptoms of if they do majority of symptomatic will not develop liver failure
29
who does auto-immune hepatitis affect more
women 3.6:1
30
who gets type 2 auto immune hepatitis and what is involved in it
Children & young adults
- LKM-1 (Liver kidney microsomal type 1 antibody)
- AMA
31
who gets type 1 auto immune hepatitis and what is involved in it
adults
- ANA (anti-nuclear antibodies)
- ASMA (anti smooth muscle antigen (actin))
- SLA severity (anti soluble liver antigen)
- IgG
- AMA
- pANCA (Perinuclear Anti-Neutrophil Cytoplasmic Antibodies)
32
how can type 1 auto immune hepatitis present
with acute onset of symptoms similar to toxic hepatitis or acute viral hepatitis
33
what extra hepatic manifestations are associated with type 1 auto immune hepatitis
```
autoimmune thyroiditis,
graves disease,
chronic UC,
less commonly with RA (rheumatoid arthritis),
pernicious anaemia,
systemic sclerosis,
ITP,
SLE
```
34
what is the clincal presentation of auto immune hepatitis
```
hepatomegaly,
jaundice,
stigmata of chronic liver disease,
splenomegaly,
elevated AST and ALT (show liver damage),
elevated PT,
```
malaise, fatigue, lethargy, nausea, abdo pain, anorexia
35
how is autoimmune hepatitis diagnosed
elevated AST, ALT and IgG,
presence of autoimmune antibodies,
liver biopsy
36
what is the histology of autoimmune hepatitis
piecemeal necrosis and nodular involvement,
numerous plasma cells,
interface hepatitis
37
what causes autoimmune hepatitis
when a genetically predisposed patient is exposed to triggering environmental triggers
38
what are the environmental triggers of auto immune hepatitis
```
viruses, toxins, drugs (Oxyphenisatin
Methyldopa
Nitrofurantoin
Diclofenac
Minocycline
statins)
```
39
how is autoimmune hepatitis
corticosteriods (combo of prednisone and azathioprine)
40
how many of autoimmune hepatitis patients will develop cirrhosis
40%
41
what is primary sclerosing cholangitis
autoimmune destructive disease of large and small bile ducts- dilatation and stricturing seen on imaging (how its diagnosed)
42
what is the treatment for primary sclerosing cholangitis
maintain bile flow and monitor for colo-rectal cancer and cholangiocarcinoma
43
what is haemochromatosis
genetic iron overload syndrome- autosomal recessive mutation in HFE gene (C282Y or H63D)
44
what are the clinical features of haemochromatosis
cirrhosis, cardiomyopathy, pancreatic failure, 'the bronzed diabetic'
45
how is haemochromatosis treated
venesection- letting out blood, iron offloading
46
what is wilsons disease
leniculo-hepatic degeneration- mono genetic autosomal recessive disease- loss of function or loss of protein mutations in caeruloplasmin
caeruloplasmin= copper binding protein, loss of copper regulation= massive tissue deposition of copper
47
how is wilsons disease treated
copper chelation drugs, low copper diet
48
what is anti 1 anti0trypsin deficiency
when mutation on A1AT gene causes protein function loss and excess tryptic activity
49
what is the clinical presentation and treatment of alpha 1 anti-trypsin deficiency
lung emphysema,
liver deposition of mutant protein, cell damage, accumulation of protein
treatment= supportive management
50
what is budd chiari
thrombosis of the hepatic veins
51
what is the clinical presentation of budd chiari
acute- jaundice, tender hepatomegaly
chronic- ascites
52
how is budd chiari diagnosed and treated
diagnosed by U/S visualisation of hepatic veins
treatment= recanalization or TIPS
53
what is TIPS
Transjugular intrahepatic portosystemic shunt
54
what is methotrexate
drug used to treat rheumatoid arthritis and psoriasis
55
why is methotrexate bad
liver toxin causing progressive fibrosis
56
what is cardiac cirrhosis
secondary to high right heart pressure
57
what causes high right heart pressures
incompetent tricuspid valve, congenital, rheumatic fever, constrictive pericarditis
58
what is the presentation of cardiac cirrhosis
congestive heart failure- too much ascites and/or liver impairment
59
what effects does cirrhosis of the liver that lead to dysfunction
disruption of vasculature and generation of abnormal signalling
60
what makes up the portal vein
Superior mesenteric + Splenic vein+ gastric + part from inferior mesentric
61
what organs does the portal vein carry outflow from
spleen, oesophagus, stomach, pancreas, small and large intestine
62
where does blood from the livers dual blood supply )hepatic artery and portal vein) go after that
```
liver sinusoids
central vein
hepatic vein
IVC
RA of heart
```
63
what is the pressure in the portal vein
very low 5-8 mmHg
64
what are the collateral (4) pathways of the portal venous system (portocaval anastomosis with systemic venous system)
Esophageal and gastric venous plexus
umbilical vein from the left portal vein to the epigastric venous system
retroperitoneal collateral vessels
the hemorrhoidal venous plexus
65
what happens the portal vein collaterals in portal hypertension
anastamoses may become engorged, dilated, varicosed and subsequently rupture
66
what defines portal hypertension
Portal vein pressure above the normal range of 5 to 8 mm Hg
Portal vein - Hepatic vein pressure gradient greater than 5 mm Hg
67
what does portal hypertension result from
increased resistance to portal flow
increased portal venous inflow
68
what can increase resistance to portal flow
increased intra-hepatic resistance
collateral resistance increased
69
how does cirrhosis cause hyperdynamic circulation and ascites
cirrhosis
=
impaired liver function + sinusoidal hypertension and portal systemic shunting
=
endogenous vasodilators
=
splanchnic + peripheral vascular resistance
=
pooling of blood
= decreased effective arterial blood volume
=
hyperdynamic circulation
=
increased renin angiotension + symp stim + arginine vasopressin
=
increased renal vascular resistance + tubular reabsoprtion of sodium
=
ascites
70
what are the pre-hepatic causes of portal hypertension
blockage of the portal vein before the liver- portal vein thrombosis or occlusion due to congenital abnormalities
71
what are the intrahepatic causes of portal hypertension
distortion of the liver architecture pre (schistosomiasis) or post sinusoidal
(cirrhosis, alcoholic hepatitis, congenital hepatic fibrosis)
72
whats happening to the prevelence of chronic liver disease in scotland
increasing
73
describe compensated cirrhosis
Clinical normal
Incidental finding
Lab test or imaging abnormalities
Portal Hypertension may be present
74
describe decompensated cirrhosis
liver failure
- chronic
- acute on chronic (infection, insult, SIRS-sepsis)
- end stage liver disease (insufficient hepatocytes)
75
what are the sings of compensated cirrhosis
Spider naevi
Plamar erythema
clubbing
gynaecomastia
Hepatomegaly (most wont have this)
Spleenomegaly
NONE
76
what are the clinical signs of decompensated cirrhosis
Jaundice
Ascites
Encephalopathy
Easy bruising
77
what are the complications of cirrhosis
ascites
encaphalopathy
variceal bleeding
liver failure
78
how is decompensated cirrhosis treated
treat underlying cause
treat infection (common decompensator)
treat for: NaCl retention, and low threshold to switch to gluconeogensis and lipolysis and catabolism (small frequent meals 35-40 kcal/kg)
79
what supplement is mandatory in cirrhosis due to excessive alcohol intake
vit B supplementation thiamine
80
what complications arise from poor calcium intake and absorption, poor vit d synthesis, malnutrition and steroid use
osteoporosis and osteomalacia
81
retention of what causes ascites
sodium and water
82
how is ascites treated
Reduce salt intake, maintain nutrition
Diuretics- spironolactone first
Paracentsis
TIPSS
Transplantation
treat liver function, treat any infection, no NSAIDS
83
how is the treatment of heart failure the opposite of ascites
refers to diuretics
-start with spironalactone and then go onto loop
84
what does TIPSS connect
portal and hepatic veins
85
what is SBP
spontaneous bacterial peritonitis
| -translocated bacterial infection of ascites
86
what is the treatment of SBP
Urgent
Antibiotics and Alba
Vascular instability-terlipressin
Maintain renal perfusion
HRS (hepatorenal syndrome) development very poor prognosis
87
how is encephalopathy diagnosed
flap
confusion
any neurology
alcohol withdrawal
88
```
what causes hepatic Urgent
Antibiotics and Alba
Vascular instability-terlipressin
Maintain renal perfusion
HRS development very poor prognosis
encepthalopathy
```
Ammonia generated in the intestines from nitrogenous compounds in the diet is taken directly into the systemic circulation rather than being metabolized in the liver. This causes disturbances in neurotransmitter trafficking.
89
what is ammonia metabolised into in the liver
urea
90
how is encephalopathy treated
treat cause-infection, metabolic, drugs, liver failure
Lactulose to clear gut/ reduce transit time
Rifaxamin
Maintain nutritional status with small, frequent meal/snack pattern and bedtime CHO
consider transplant if spontaneous
91
where can you get varices
oesophagus, gastric, rectal, ectopic
92
what is the pathophysiology of variceal bleeding
increased intrahepatic resistance and portal blood flow
increase varicus vein size and decreased wall thickness
increased variceal wall tension
93
how are variceal bleeds prevented- prophylaxis
beta blockers (non selective): propranolol, carvideolol
variceal ligation
94
what is the treatment for acute variceal bleeds
resus
drugs
TIPSS and transection/ shunt therapy
95
what is endoscopic therapy used to do to treat varices
ligation, banding, sclerotherapy
96
when should a balloon tamponade be used
in emergency as gateway to other therapy for acute variceal bleed
97
why do patients with cirrhosis have increased pro thrombin time
as are deficient in both pro and anti thrombotic factors, coagulation balance disrupted, risk of both bleeding and clotting, give heparin unless having variceal bleed
98
when do people become eligible for transplant
when they are more likely to die from the disease than the operation
UKELD score of >= 49 to be listed
UNLESS
- variant syndrome
- small HCC
99
what are the variant syndromes of cirrhosis
Diuretic resistant ascites
Hepatopulmonary syndrome
Chronic hepatic encephalopathy
Intractable pruritus
Polycystic liver disease
Familial amyloidosis
Primary hyperlipidaemia
