liver liver Flashcards
1
Q
what are the 3 progressive stages of alcoholic liver disease
A
fatty liver disease
alchololic hepatitis
alcholic cirrhosis
2
Q
what happens in fatty liver disease
A
metabolism of alchohol to fat
accumulates in cells - steatosis
3
Q
what occures in alcoholic hep
A
infiltration by polymorphonuclear leucocytes (look for mallory bodies and giant mitochondria)
and hepatocyte necrosis occurs
inflamation
4
Q
what is alcoholic cirrhosis
A
micronodular type - regenerative
mixed pattern seen with fatty changes
5
Q
Cfs of fatty liver disease
A
asympt.
vague abdo symptoms assos w alcohol consumption
6
Q
CFs of alcoholic hep
A
mild to mod ill health - mild jaundice
chronic Liver symptoms ==> hepatic enceph
ascites
easy bruising
7
Q
CFs of alcoholic cirrhosis
A
signs of chronic L disease jaundice ascites high fever clubbing abdo pain hepatomegaly
8
Q
3 warning signs of severe alcoholic liver disease
A
coagulopathy
jaundice
encephalopathy
9
Q
Dx of fatty liver disease
A
mild abnormalities on LFT
increased ALT (increased AST to ALT ratio)
ALP increase
y-GT increase
10
Q
Dx of alcoholic hep bloods
A
elevated PTT (thrombocytopenia) elevated serum bilirubin increase AST increase WCC macrocytic anaemia low serum albumin
11
Q
Dx of alcoholic hep not bloods
A
histology - mallory bodies and giant mitochondria
perivenular fibrosis
leucocyte infiltraion
12
Q
Mx of alcoholic liver disease
A
stop drinking - in fatty liver this is reversible
alcoholic hep - pre cirrhotic
treat withdrawals with diazepam (tremor,sweats,arrythmia)
supplements - protein for encephalopathy
steroids - supress imune system
ALCOHOLIC CIRRHOSIS - liver transplant
13
Q
how do you predict alcoholic hep prognosis
A
Maddrey score
glasgow score
14
Q
chronic liver disease symptoms
A
pruitus anorexia malaise fatigue fever weakness R hypochondriac pain(liver distension) abdo distension fetor hepaticus (ammonia breath) haematemesis / dysphagia (oesophogeal varices)
15
Q
chronic liver disease sign
A
Ascites Anorexia Atrophy of testicles Asterix Bruising Clubbing Colour of nails (leukonychia) Dyspagia (varices) Erythema (palmor) Encephalopathy (confusion) Fetor hepaticus (Fishy ammonia breath) (G) Hepatomegaly Increased unconj bilirubin --> Jaundice
AAAABCCDEEF(G)HIJ
spider naevi
splenomegaly (portal HTN)
periph oedema
16
Q
Causes of chronic L disease
A
cirrhosis hep B C D Non alc fatty liver Metabolic (wilsons, haemchromatosis, alpha 1 antitrypsin defic) Biliary tract diseases n stones autoimmune hep Drugs (methotrexate, paracetabol OD)
17
Q
what is wilsons disease
A
autosomal recessive genetic defect (in ATP7B) causing a XS of COPPER deposited in tissues (liver, basal ganglia and cornea)
18
Q
what causes wilsons disease
A
ATP7B defect meaning cannot bind Cu to apoceryloplasmin turning it into ceryloplasmin (Cu carrying protein)
Rest is packaged into vesicles - exocytosed into the bile for excretion
This cannot occur so Cu builds up - free radicals - and spills out into intestinal space - blood stream - deposits in tissues
19
Q
where does copper deposit in wilsons
A
liver
cornea
basal ganglia
20
Q
Presentation of Wilsons disease in children
A
hepatic probs - hepatitis
cirrhosis
fulimant liver failure
21
Q
presentation of wilsons in teens n adults
A
CNS problems - Cu deposits in the basal ganglia = PARKINSONISM - tremor, rigidity
cerebral cortex = changing mood and mem loss
dementia
ataxia
dysarthia
22
Q
Signs of Wilsons
A
ascites
tremor
Kayser - Fleischer rings in cornea
23
Q
what is seen on examination with a slit lamp in Wilsons
A
Kayser-Fleischer rings
24
Q
Dx of Wilsons
A
bloods - low serum Copper, lowe serum ceryloplasmin 24hr urinary Cu excretion high LFT - elevated MRI - basal ganglia and cerbella degen slit lamp = KAYSER - FLEISCHER RINGS LIVER BIOPSY - increased hepatic Cu (DNA test?)
25
Mx of Wilsons
penicillamine (binds free Cu = chelation)
Zinc (prevents Cu absorption) (slow onset)
Sever? - Liver transplant
26
what is alpha 1 - antitrypsin deficiency
autosomal recessive - causes liver cirrhosis and emphesema in adults
defect in alpha 1 - antitryspin protease inhibitor so elastase over activity (not inhibited)
27
what does alpha 1 AT do
its a protease inhibitor that inhibits the activity of elastase that breaks down elastin
28
consequence of too much elastase in A1AT defic
elastin in walls of alveoli broken down causing emphysema - dyspnoea
29
consequences in liver of alpha1AT defic
misfolded = gets stuck in endoplasmic reticulum of the liver = builds up = hepatocyte death = liver cirrhosis
30
Dx of alpha 1 AT defic
serum alpha 1 A low
| Liver biopsy
31
Tx of alpha1 antitrypsin
IV alpha1AT
supportive - dont smoke
liver cirrosis tx
tranplant if req
32
Presentation of A1AT defic
SOB
dyspnoea
cirrhosis symptoms - portal HTN - varices, jaundice
33
what is hereditary haemochromatosis
XS iron depostited in organs leading to fibrosis and organ failure
autosomal recessive HFE gene mutation decreasing hepcidin production
34
what does hepcidin do
controls Fe absorbtion
| synthesised in the liver
35
how does hereditary haemochromatosis result in XS iron absorption
HFE gene mutation so decreased hepcidin gene expression = less hepcidin sythesised so doesnt do neg feedback on Fe levels == increase in iron absorption == XS taken up by the liver
36
what is a consequence of increased uptake of iron in the liver
over long period causes fibrosis due to free radical production and thus cellular damage
37
Cfs of hereditaryhaemochromatosis
liver = cirrhosis (jaundice, ascites), increased cancer risk
pancreas = type 1 diabetes (beta islet cell damage)
skin = bronze (melanin depostition)
heart = deposits in myocardium = cardiomyopathy
joints = degenerative joint disease
Jack Lost His Point and Shoot
38
acronym for hered haemochromatosis
```
Jack Lost His Point and Shoot
J- Joint = arthralgia
L- Liver = hepatomegaly
H - heart - cardiomyopathy
P - pancreas (T1DM) and pituitary (hypogonadism)
&; - erectile dysfuntion
S - skin - bronzed
```
39
what is a complication of haematochromatosis
Liver cirrhosis = increased risk of hepatocarcinoma
| bronze diabetes = bronze skin, hepatomegaly, DM
40
Dx of haematochromatosis
```
increased ferritin (stores iron in cells)
and transferrin (careful as increase in inflam)
liver biopsy = perls stain blue
genetic testing - HFE genotype
total iron binding capactiy
```
41
Mx of haematochromatosis
venesection - life long - weekly
anual monitoring
Hep A and B vaccine
DEFERIOXAMINE = iron chelation
42
what is secondary haemochromatosis cause by and how prevented
too many blood transufions = prevented by chelation
| DEFERIOXAMINE
43
haemochromatosis management disease modifying drug
DEFERIOXAMINE = iron chelation
44
functions of the liver
Protein synthesis and metabolism- albumin, carrier proteins and coag factors, hepcidin and ferratins
Lipid and glucose metabolism
hormone and drug inactivation- converts to hydrophillic
conjugation of bilirubin to be excreted
bile synthesis
Immune function- consumes antigens
activation of Vit D
45
Breakdown of RBCs
Haemoglobin in macrophage in spleen liver or bonemarrow- splits into globin (get reused) and haem.
haem broken into Fe and porphyrin which becomes unconj bilirubin (water insol so binds to albumin in blood) and leaves to liver = gets conjugated (now water sol) and is secreted into bile where it becomes urobiliogen (via enterohepatic circulation - kidneys - urine) or sterobillin (stools)
46
causes of pre hepatic jaundice and what see
Haemolytic- increased turnover= increased unconjugated bilirubin. liver functional so there is no bilirubin in urine just very dark urine due to increased urobiliogen
Cx= haemolytic anaemia, ineffective haematopoeisis
spherocytosis
47
causes of intrahepatic jaundice
failure of bile secretion
Cx= autoimmune cholangitis, viral hep, alcoholic hep, cirrhosis
pale stools dark urine itching
48
causes of extra hepatic jaundice
biliary drainage interference - pale stools dark urine
as no urobilinogen (and thus sternobilin) and itching
Cx= common duct stones
carcinoma
biliary stricture
sclerosing cholangitis
pancreatic pseudocyst
49
complications of liver failure
```
encephalopathy
jaundice
Ascites - spontanous bacterial peritonitis
sepsis
portal hypertension - varices
renal failure
Hepatiocell carcinoma
```
50
Management of liver cirrhosis
diet, stop alcohol and reduced NSAIDS and Salt to minimum
Screen every 3-6 months via ultrasound and Alpha fetoprotien for H
treat prutius by- colestyramine
put on transplant list if decompensated
51
Penicillamine SE and what used for
used as copper chelation in Wilsons disease
| S/E = skin rashes, hematuria, renal damage
52
what is liver cirrhosis
non specific disease, is an end stage of all progressive chronic liver diseases, which once fully developed is irreversible.
liver architecture is diffusely abnormal so interferes with blood flow
53
histologically what is liver cirrhosis
Histologically, loss of normal hepatic architecture with bridging and nodular regeneration
54
What cells are involved in liver cirrhosis
stellate and kuffer cells get activated
55
pathophysiology of the stellate cells in liver cirrhosis
activated by cell injury = stellate cells release cytokines that produce collagen = fibrosis (TGF-beta)
the cytokines then attract neutrophils n macrophages = further inflam and necrosis
fibrosis of space of diss = loss of fenestrations impairing L function.
Fibrosis compresses BVs = portal hypertension = fluid OUT into peritoneal cavity = ASCITES
56
pathophysiology of the kupffer cells in liver cirrhosis
phagocytose nectotic and apoptic cells - secrete pro inflam mediators - increase myofibroblasts - fibrosis and scarring
57
2 types of liver cirrhois nodules and causes of each
micro and macronodular
micro = alcohol, biliary tract disease
macro = chronic hepatitis
58
2x types of cirrosis
decompensated
| compensated
59
what is decompensated cirrhosis
cannot function adequately - extensive fibrosis
60
CFs of decomp cirrhosis
```
jaundice
clubbin
ascites
easy bruising
hepatic encephalopathy
leuconychia (low albumin = white nails)
```
61
Cfs of compensated cirrhposis
non specific - weight loss and fatigue
62
what is comp cirrhosis
still functioning effectivinly - asympt
| some fibrosis
63
causes of liver cirrhosis
```
XS alcohol consumption
prolonged viral (hep B and C)
autoimmune Hep
wilsons
alpha 1 antitrypsin defic
primary biliary cirrhosis
```
64
how does fibrosis cause ascites
portal hypertension causing fluid to accumulate in peritoneal cavity (down pressure gradient)
65
how does fibrosis lead to hepatorenal failure
portal hypertension causing incresae in pressure so a portosystemic shunt
66
why is splenomegaly a complication of cirhosis
portal hypertenion due to fibrosis causes back up of blood in spleen
67
why CNS effected in cirrhosis
HEPATIC ENCEPHALOPATHY
portal hypertenion due to fibrosis of liver, blood diverted and liver function decreased
less detoxification so ammonia not metabolized (toxic) - depostis in brain =
asterix
confusion
coma
68
in liver cirrhosis what causes parma erythema and spider naevi
failing liver function = less oestrogen metablozied therfore increase in blood
69
Dx of liver cirrhosis
livery biopsy
bloods - LFT (low albumin, long PTT)
biochem - AST and ALT increased
imaging - size texture, blood flow changes etc
70
Mx of liver cirrhosis
no alcholo
| avoid NSAIDs and Aspirins = precip GI bleeds or renal impairment
71
what is portal hypertension an effect of
cirrhosis
72
what makes up the portal vein
splenic and SMV
73
What does portal hypertension cause
dilation of vessels causes collaterals to form. if these form in gastoesophageal junction they are called varices
74
presentation of gastroesophageal varices bursting
Haematesis and Melaena
| hypovolemic shock
75
causes of portal hypertension
prehepatic- congenital abnormality, portal vein thrombosis
hepatic- cirrhosis(commonest), sarcoidosis, schistosomiasis (cause = flatworms)
post hepatic- RIGHT sided heart failure, IVC obstruction, contrictive pericarditis
76
Cfs of portal hypertension
```
GI bleed secondary to haemorrages = haematesis and melaena
ascites
jaundice
thrombocytopenia
anaemia
leukopenia
```
77
management of active gastroesophageal varices bleed
stabilise- IV plasma or blood transfusion, treat shock, prophylaxis antibiotics
endoscopy to confirm this was variceal bleed
injection scleroptherapy or variceal banding to stop hleeding
78
what are varices
abnormally dilated vessel - usually in venouse stystem
79
what causes varices to form
portal HTN - activates myofibrobalsts to contract (NO, endothelin and prstaglandin mediated). increases resistance to blood flow hence opening portosystemic anastomoses.
Na retention due to splanchnic vasodilatoin.
blood flow redirected to lower p areas so collateral circ develops - distended BV and thing walled = bleed
80
Cfs of varices bleed
signs = anaemia and liver disease
haematemesis
abdo pain
dysphagia
