Liver Flashcards
2 blood supplies to the liver
what’s the benefit?
Hepatic artery (bringing oxygenated blood) Hepatic portal vein (bringing everything from gut, still has a bit of O2 in it)
don’t get big infarcts like in other organs!
portal triad
- bile duct
- hepatic artery
- hepatic portal vein
2&3 will empty into sinusoids, gets to centre of lobule and drain into terminal hepatic venule –> hepatic vein –> vene cava –> systemic
Difference in cells in periphery of lobule vs. central?
oxygen concentrations
synthesis will occur centrally (eg. protein) ZONE 3
degradation/metabolism will occur on periphery (where conjugation enzymes will be) ZONE 1
Why do we get portal hypertension?
eg. due to alcohol
fibrosis/lose cells in Zone 3 will cause venule to get less blood, pressure required to get blood in through will increase = portal hypertension
Three main functions of liver
Synthesis (albumin, clotting factors, complement)
production (bile through conjugation of bilirubin)
breakdown (of any foreign substance eg. drug, insulin ammonia)
Role of Kupffer cells
sitting in the sinusoids acting like macrophages.
phagocytose old RBCs, bacteria and foreign materials from the blood or gut
what’s the bilirubin concentration to be classified as jaundice?
over 40umol/L
Why is jaundice associated with intense itch?
It’s not to do with bilirubin - it’s the accumulation of bile acids. Tells you about where the jaundice occurred (ie. at a point where the liver wasn’t able to properly excrete the bile acid ie. at the bile duct or distal to that. OBSTRUCTIVE).
Unconjugated vs conjugated jaundice
unconjugated: water insoluble
Conjugated: water soluble (can be excreted in urine so urine will be DARK)
3 classifications of jaundice
pre-hepatic: haemolysis (maybe sickle cell disease, exposure to a toxin, autoimmune disease, causing RBCs to break down) -> release of bilirubin from RBCs
but bili isn’t getting conjugated, normal urine (can’t solubilise it in kidney to throw it out)
Intrahepatic: liver disease destroys hepatocyte -> excess bilirubin in liver and bloodstream
Post-hepatic (obstructive) - obstruction of bile outflow –> dark urine and pale stools SMELLY (and itch)
BARNEY GUMBLE
Causes
Acute Liver Injury
Causes: viral infection, ALCOHOL, adverse drug reactions, biliary obstruction (gallstones)
Presentation: jaundice, malaise.
Raised serum bilirubin and transaminases.
Liver failure: decreased albumin, ascites, bruising, encephalopathy
Where does alcohol-induced hepatocyte injury usually occur?
zone 3
Where will autoimmune hepatitis injuries usually occur?
zone 1 (mostly cell mediated and antibody)
Steatosis leads to what
steatosis: fat build up which alters metabolism. Get big fat globule (with messed up metabolism) messes up cytoskeleton into Mallory’s hyaline.
can lead eventually to cirrhosis (liver becomes scarred and lumpy. fibrosis bridges from structures. Regeneration abnormal.
can lead to liver failure)
Describe alcohol hepatitis pathology
acute inflammation of bits of the liver (spotty necrosis)
Kupffer (macros) sat and fibroblast precursor sitting waiting to create fibrosis. little bits of fibrosis eventually merge (after many binges over time)
regeneration occurs, expanding cells but scar tissue resitricts the expansaion. continuous scar tissue creates CIRRHOSIS
Define cirrhosis
continuous scar tissue.
recurrent inflammation with fibrosis (collagen) and regeneration
What’s in alcohol that causes hepatocyte damage?
acetaldehyde binds to hepatocytes causing damage, inflammatory reaction, fibrosis
Complications of cirrhosis
Liver failure: can’t detoxify things! (hepatic encephalopathy (ammonia), build up of steroid hormones –> hyperoestrogenism (palmar erythema and gynaemastia)
Portal hypertension (increased hepaticvascular resistance, AV shunting –> oesophageal varices, haemorrhoids, caput medusea)
Hepatocellular carcinoma
KRUSTY
drug-induced liver injury
10% drug reactions involve liver
Hepatocellular damage from paracetamol dose
Injury to cholestatic cells (bile production/secretion) - methyl testosterone
PATTY AND SELMA
have ACUTE BILIARY OBSTRUCTION
usually due to gallstones
causes collicky pain and jaundice (waves as peristalsis is trying to get it out)
Complication of acute biliary obstruction
infection of the blocked CBD = cholangitis
why might we want to do an ultrasound rather than xray in someone with acute biliary obstruction?
as gallstones can be radiolucent (as mostly cholesterol)
what type of jaundice would you get with acute cholesistitis (patty/selma)
dark urine and pale stools (would be obstruction +/- secondary infection)
Definition of chronic hepatitis
liver inflammation lasting more than 6 months
sustained elevation of transaminases (but liver biopsy will classify cause)
Causes of chronic hepatitis
viral
autoimmune
drugs
alcohol (but is chronic recurrent acute injury, not chronic)
Which ways would we classify chronic hepatitis
Type (aetiology)
Grade (degree of inflammation)
Stage (degree of fibrosis)
COMIC BOOK GUY
NASH/NAFLD
non-alcoholic steatohepatitis/fatty liver disease
associated with METABOLIC SYNDROME (DM II, hypertension, HDL and triglycerides increased)
fat deposition in hepatocytes (can lead to cirrhosis)
LISA SIMPSON
Autoimmune Chronic Active Hepatitis
females > males
mid to late teens
interface hepatitis (plasma cells and swollen hepatocytes. fibrosis from zone 1-zone 1 cirrhosis
diagnosis of lisa simpson/autoimmune chronic active hepatitis
presence of
ANA
SMA (smooth muscle antibodies) *** key diag!
often serum IgG and transaminases are raised as it’s an immune response
anti-LKM (liver-kidney-microsomal)
Treatment of Lisa Simpson/Autoimmune Chronic Active Hepatitis
steroids
more serious -> immunosuppression
MARGE SIMPSON
PRIMARY BILIARY CHOLANGITIS/CIRRHOSIS
females > males (40-50 y/o)
Stages:
- autoimmune destruction of bile duct epithelium (dense lymphocytic infiltration and granulomas)
- proliferation of small bile ducts
- architectural disturbance: portal and bridging fibrosis
- cirrhosis
Diagnosis of Primary Biliary Cholangitis/Cirrhosis
Jaundice, pruritis, xanthelasma
Raised ALP and IgM, AMA
Primary Sclerosing Cholangitis
inflammation in bile ducts (cholangitis) which results in hardening (sclerosis) and narrowing of ducts as result.
Bile cannot be released properly and builds up in liver where prolonged exposure results in liver damage
3 differences between PBC and PSC
Age/gender (>50, F vs. any age, M)
Serum immunoglobulins (inc IgM vs. none)
Autoantibodies (AMA, ANA vs. none)
Bile duct injury (small ducts vs. large ducts and obliterative fibrosis of them)
Portal inflammation (prominent vs. absent)
GROUNDSKEEPER WILLIE
Haemochromatosis
- iron deposition in the liver causing alteration of architecture –> fibrosis –> cirrhosis
Autosomal recessive (mutation in liver cells HFE gene - so a major RF for cancer)
Treating haemochromatosis/Groundskeeper Willie
Regular venesection - test iron and ferritin levels
alpha-1-antitrypsin deficiency
autosomal recessive disorder low levels of alpha-1-trypsin proteins build up in hepatocytes as hyaline can lead to cirrhosis associated with emphysema
CRAZY CAT LADY
WILSON’S DISEASE
young women
autosomal recessive disorder
failure of liver to excrete copper in bile –> build up of copper in liver –> cirrhosis
also deposits into brain and cause neurological dysfunction
get KAYSER FLEISCHER rings
Diagnose Wilson’s disease
low caeruloplasmin
Kayser Fleischer rings in eyes
Examples of developmental/hamartomas liver tumours
cysts
hamartomas
Examples of benign liver tumours
incidental finding
adenoma, haemangioma
liver cysts
Examples of malignant liver tumours
metastases COMMON
primary: hepatocellular carcinoma
cholangiocarcinoma
aetiology of hepatocellular carcinoma
aflatoxins - fungal origin
hepatitis B and C
cirrhosis (of any cause)
2 examples of congenital malformations of biliary system
atresia
choledocal cysts
Other name for gallstones
cholelithiasis
Cholangiocarcinoma
arises from bile duct epithelium anywhere in biliary system
associated with UC
causes obstructive jaundice, itch weight loss, lethargy
can lead to rupture of common bile duct or gallbladder (poor prognosis)
Risk factors for gallstones
Types
Complications
female fat fair forty fertile diabetes mellitus
Cholesterol, bile pigment or mixed
cholescystitis, obstructive jaundice, cholangitis, pancreatitis, cholangiocarcinoma
what is cholecystitis usually caused by?
gallstones
symptoms of cholecystitis
RUQ pain (biliary colic)
fever
nausea/vomiting
MAGGIE SIMPSON
HAS annular pancreas occurs in 2nd part of duodenum (wraps around SI)
causes OBSTRUCTION: polyhydramnios, low birth weight, poor feeding
HOMER SIMPSON
has pancreatitis
Acute: causes catastrophic metabolic consequences (decreased calcium, decreased albumin, increased glucose)
massive fluid losses can lead to SHOCK
diagnose acute pancreatitis
serum amylase
chronic pancreatitis
multiple episodes of acute
causes fibrosis of pancreas: may lead to diabetes mellitus
reduced production of enzymes (require supplements)
MONTY BURNS
has PANCREATIC CARCINOMA
an adenocarcinoma
associated with smoking and diabetes mellitus
presents with painless, progressive jaundice
weight loss
poor prognosis
operable if small and close to ampulla
adenocarcinoma
starts in mucous secreting glandular cells (breast, colorectal, lung, pancreatic, prostate)
