Liver and LFTs Flashcards
What are the two blood supplies of liver
portal vein and hepatic arter
75% portal vein
Where is bile formed from and what is its passage out of the liver
Bile is formed from the hepatocytes, flows through bile canaliculi to bile duct (⇒ flow is opposite to blood)
Where does blood in central veins go to
Blood collected in central veins goes to sublobular veins, then to collecting veins, and then hepatic veins leaving the liver
What maintain pressure within common bile duct
Ampulla of vater/ sphincter body
Pressure there should usually be higher than that of gallbladder
What causes gallbladder contraction (what hormone is involved)
Cholecystokinin release from mucosa in duodenum during feeding causes gallbladder contraction, reduced sphincter pressure on bile and allows bile to flow from gall bladder to duodenum
What are cholangiocytes
Bile duct epethelia, contribute to cell function
What forms the sieve plate in liver
Endothelial cells
Sinusoidal vs lateral faces in hepatocytes
- Microvilli are present on sinusoidal face to project sparsely into bile canaliculi
- A portion of the lateral faces of hepatocytes is modified to form bile canaliculi
Where are glycogen granules stored in hepatocytes
In association with SER
Difference between periportal and perivenous/pericentral zone in liver acinus
Periportal has good o2 supply and nutrient rich, involved in gluconeogenesis, glycogenolysis and bile salt formation, perivenous involved in glycolysis, lipolysis, glucuronidation, glycogenesis and cytochrome p450 reaction. Low in nutrients and relatively hypoxic
Three phases of biotransformation
I - oxidation, reduction and hydrolysis by CYP450
II- Conjuation in cytoplasm with endogenous substances like glucuronic acid to form inactive conjugates
III- secretion into bile, excretion mediated by ATP
What can conjugate with drugs in phase II metabolism
Gluthatione for oxidated species
or sulfur, acetyl or glucuronide for hydrolysed species
Glutathione conjugation in paracetamol metabolism??
Bonds with NAPQI to form non-toxic conjugates
What does N-acetyl cysteine do
Increases Glutathione to mop up NAPQI
What causes alcohol flush response
Deficiency in ALDH-2 ( Aldehyde dehydrogenase) that results in increased acetylaldehyde and catecholamine release
What happens to insulin and glucagon after feeding and main actions in liver
Increased insulin and decreased glucagon
- Hepatic glucose uptake
- Glycogen deposition in hepatocytes
- Glucose converted into glycerol and fatty acids
What happens to insulin and glucagon in fasting and main actions in liver
Reduced insulin and increased glucagon
- Glycogen breakdown in periportal hepatocytes
- Gluconeogenesis from lactate, pyruvate, AA, glycerol
Synthesis of lipids in liver
Liver also synthesizes VLDL and HDL
Also synthesises cholesterol and phospholipids, some of which is secreted into bile and some is converted into bile acids
What transport proteins are synthesised in liver
ceruloplasmin to transport copper and transferrin which transports iron
Which enzymes synthesized in liver require vitamin K
II, VII, IX, X are post-translational modified by Vitamin K dependent enzymes ⇒ synthesis impaired by VItamin K deficiency
How is unconjugated bilirubin formed
from breakdown of heme in spleen
Where does bilirubin get conjugated and by what
By glucuronyl billirubin transferase in liver
What does direct bilirubin get converted to and where
To urobilinogen in duodenum by microbiome, then to stercobilin
What vitamins stored in large amounts in liver
A, D, B12
What does an isolated rise in bilirubin suggest
What does rise suggest
Gilbert’s syndrome ⇒ problems with processing of bilirubin
Haemolysis
Rise - Biliary problems
What is prothrombin time an indicator of
Synthetic function
How is PT in ALF and cirrhosis
usually very good, also rarely abnormal in cirrhosis
PT in paracetamol overdose
Very high, 100 instead of 10 or 12
What do ALT and AST show
Increases when hepatocytes die ⇒ Leak out and give indication of how many died the previous day
ALT in Hep C vs NAFLD
150 in Hep C vs75-100 in NAFLD
Is ALT or AST usually higher and what does the ratio so
- ALT usually higher than AST
- In ALD, AST is higher
- In NAFLD, AST goes up relative to ALT due to mitochondrial dysfunction as a result of scarring ( as AST leaks from Mito.)
- Indicator of advancing fibrosis
What does high Alkaline Phosphatase mean
Need to chek GGT if ALP is high, to see if ALP is from liver, if it is, suggests irritation of bile ducts => assess cholestasis ) stoppage of bile flow)
Biliary disease eg. stones, pancreatic cancer , PBC (Cholestatic LFTs, liver biopsy with granulomas, +ve AMA)
What does high GGT suggest
- Increases by induction,not damage
- i.e. Enzyme induction by drugs
- Alcohol, phenytoin, carbamazipine
- Obesity, NAFLD cirrhosis
- i.e. Enzyme induction by drugs
What can affect albumin levels
Dehydration raises it, dilution or reduced synthesis reduces it . Can be low in pregnancy due to increased volume in circulation
When are albumin levels often low in liver disease and why
- In liver disease, retains salt and water and also dilutes albumin down.
- Often normal in cirrhosis until liver is failing
Mild ALT vs high ALT
Mild ALT
- NASH ⇒ Inflammation and scarring, cirrhosis
- AFLD ⇒ Fatty liver (umbrella term)
- HepC
- ALD, including ALcoholic Hep
High ALT⇒ Hepatitis including drug damage
- Inflammation of liver
What does isolated high GGT suggest
Usually high GGT suggests alcoholism or drugs, or inactive cirrhosis (NAFLD)
Serum markers of liver function include?
ALbumin, Pt, Bilirubin
does space of disse have a basal lamina
no
Is bilirubin high in cirrhosis
yes
What vitamins and minerals are stored in the liver
- Vit- A, D, B12, some K
- Folate
- Metabolises Vit D3 to 25-OH…
- Iron in ferritin and haemosiderin
- copper
Which autoimmune diseases target the:
Hepatocytes
Small bile ducts
Larger bile ducts
- Autoimmune hep
- PBC
- PSC, IgG4-related cholangitis
Which AI Liver/ Biliary diseases are more likely to affect:
50-60 yo
20-40 yo
Any Age
- PBC, IgG4
- PSC
- AIH
Which AI Liver/ Biliary diseases are more likely to affect:
Males
Females
- PBC and AIH
- PSC and IgG4
AMA high- what AI disease?
PBC
MRCP findings in PBC
Normal ducts since only small ducts are affected
How to diagnose and confirm PBC
- +ve AMA tgt with alk phos and GGT, can confidently diagnose PBC)
- If -ve AMA, biopsy liver
Can PBC lead to Cirrhosis?
Yes, if not treated over 2 decades
Staging disease ?severity in PBC
Transient elastography for liver fibrosis stage
Common Sx of PBC
- Itch or fatigue if Sx present, otherwise usually aSx with slowly increasing LFTs
-May have RUQ discomfort
Tx for PBC (first and second line)
- UDCA
- Obeticholic acid and bezafibrate
Multifocal stricturing and beading of bile ducts and even intra-hepatic ducts - what cause and what Ix?
PSC, MRCP
What disease is PSC assoc with and what diseases are these pts at higher risk for
- IBD, esp UC
- High risk of colorectal, bile duck and gallbladder cancers
- Risk of cirrhosis of liver
Px of pts with PSC
- Fevers and rigors in infxn in bile duct
- (Intermittent) Jaundice ( later on)
- Itch
- RUQ pain
- Fatigue, weight loss
Medical therapy for PSC
None, only transplant can help. But may given cipro for acute cholangitis attacks, and ERCP to relieve obstruction through balloon dilatation
Annual colonscopies if IBD , and annual gallbladder US
Px of AIH
Malaise and jaundice,fatigue and joint pains but may be aSx apart from raised ALT. Decompensated cirrhosis may be first px
What antibodies may be raised in AIH
ANCA, AMA, IgG4, LKM and SLA
How to confirm Dx of AIH
Liver biopsy to confirm and stage fibrosis
Tx for AIH
- Steroids like predni or budesonide for non-cirrhotic pts for 6-12 mo
- Azathioprine as maintenance therapy
How to diagnose IgG4 cholangipathy
Histology - IgG4 producing lymphocytes, plasma cells and fibrosis
Ix for IgG4 Cholangiopathy
- Serum IgG4
- Biopsy
- MRCP: No stricturing unlike PSC
- Consider steroid trial
Px of IgG4 cholangiopathy
- May mimic PSC or hilar cholangiocarcinoma
- May have obstructive jaundice due to either hilar stricturing/intrahepatic sclerosing cholangitis or a low bile duct stricture
What drug may induce AIH
Nitrofurantoin
What demographic is PBC more common amongst
Cigarette smokers
What diseases are PBC assoc with
Assoc with thyroid disease, coeliac and systemic sclerosis
What antibodies commonly found in serum of pts with PSC
ANCA
