Gastro MedEd tutorial Flashcards
Which blood supply takes blood away from the liver?
hepatic vein
How many subsegments are there of the liver?
8
What are the hepatic lobules?
hexagonal structural unit
centre is central vein
each corner contains a portal triad
rows of hepatocytes with sinusoid-facing sides and bile canaliculi-facing sides
What is the portal triad made up of?
1) hepatic artery - oxygen rich blood to suppport increased energy demands of hepatocytes
2) portal vein - contains venous blood from GI tract (nutrient-rich, bacteria, toxins) and spleen (waste products)
3) bile duct - hepatocytes produce bile -> bile canaliculi -> cholangiocyte-lined bile ducts
Where does blood flow towards in the liver?
towards central vein
Where does bile flow towards?
bile duct
What is the acinus?
functional unit of the liver
consists of 2 adjacent 1/6th hepatic lobules and 2 portal triads
How does blood enter the acinus?
via portal triad
How many zones are there of the acinus?
3
zone 1 - high oxygen, high toxin level
zone 2 - intermediate oxygen and toxin levels
zone 3 - low oxygen and low toxin levels bc hepatocytes have done their job
How does the blood drain out of the acinus?
via point central vein
What is the role of the Kupffer cells?
sinusoidal macrophages
attached to endothelial cells
elimate and detoxify substances entering liver via portal circulation
What is the role of the sinusoidal endothelial cells?
fenestrated, no basement membrane
allows movement of lipids and large molecules to and from hepatocytes
What is the role of the hepatic stellate cells?
dormant state = storing vit A in cytosolic droplets
active state = become fibroblasts (in response to liver damage) and proliferate and deposit collage in ECM
What is the role of hepatocytes?
cubical cells
function:
1) secretory and excretory - carry out synthesis of albumin, clotting factors and bile
2) detoxification and immunological - drug metabolism, breakdown of pathogens
3) receive nutrients from sinusoids
4) metabolic and catabolic - synthesis and utilisation of carbs, lipids and proteins
What is the role of cholangiocytes?
secrete bicarbonate ions and water into bile
example of a transamination reaction
alanine + alpha-ketoglutarate -> pyruvate + glutamate
What enzyme converts alpha-ketoglutarate into glutamate?
alanine aminotransferase
How is acetyl CoA converted into cholesterol?
HMG CoA reductase
How is acetyl CoA converted into fatty acids?
malonyl CoA
What does LDL do?
transport cholesterol to tissues
What does VLDL do?
transport fatty acids to tissues
What does HDL do?
picks up extra cholesterol = GOOD CHOLESTEROL
What makes up a lipoprotein?
cholestrol +
tri-acyl glycerol (glycerol and fatty acids) +
apoprotein phospholipid
What vitamins does the liver store?
All FAT-SOLUBLE vitamins
A, D, E and K
and B12
How is the liver involved in detoxification of xenobiotics?
1) MODIFICATION - p450 enzymes make substances more hydrophilic
2) CONJUGATION - then attach water side chain to reduce reactivity
What is bile made up of?
water 97%
bile salts
inorganic salts
bile pigments
lipids
What makes bile yellow and green?
bilirubin (yellow)
biliverdin (green)
What cells are responsible for primary secretion (60%) in the liver?
hepatocytes
What cells are responsible for secondary modification (40%)?
cholangiocytes
What occurs during secondary modification?
pH made more alkaline
water drawn in by osmosis via paracellular junctions
glucose and organic acids are reabsorbed
bicarbonate and chloride ions actively secreted into bile by CFTR channels
IgA is exocytosed
What are the uses of bile?
cholestrol homeostasis
absorption of lipids and lipid-soluble vitamins
excretion of drugs, cholesterol metabolites, steroid hormones and alkaline phosphatase
What is the main function of biliary transporters?
excretion of bile salts and toxins
What are the 2 main types of biliary transporters?
basolateral (importing bile salts from portal blood)
apical (excreting INTO bile)
What are some examples of basolateral biliary transporters? (2)
organic anion transporting peptide (OATP)
Na+ taurocholate-transporting polypeptide
What are some examples of apical biliary transporters? (3)
bile salt excertory pump (active transport of bile acids into bile)
MDR-related proteins (negatively charged metabolites)
Products of multidrug resistance genes (excretion of neutral and positively charged xenobiotics, cytotoxins and phsophatidylcholine)
What is cholestrol converted into to become primary bile acids?
cholic acid
chenodeoxycholic acid
How do primary bile acids become secondary bile acids?
removal of -OH group
What are the secondary bile acids?
deoxycholic acid
lithocholic acid
What are the functions of bile salts?
reduce fat surface tension
emulsify fat
What are micelles?
formed by bile salts
amphipathic (hydrophilic outside to dissolve water, hydrophobic core inside to dissolve fat)
contain free fatty acids and cholesterol
How is bile diverted into the gallbladder between meals?
via cystic duct
What do I-cells release and what is it stimulated by?
cholecystokinin
stimulated by free fatty acids and amino acids in duodenum
What does the release of cholecystokinin cause?
sphincter of Oddi to relax
gallbladder contracts
bile enters duodenum
What are the 2 main functions of the gallbladder?
1) stores, concentrates and acidifies bile
2) releases bile upon stimulation by cholecystokinin and parasympathetic nerve stimulation
Where is 95% of bile salts reabsorbed?
terminal ileum
How are bile salts absorbed?
Na+/bile salt co-transport Na+/K+ ATPase
Where is 5% of bile salts reabsorbed?
converted into secondary bile acids in colon
deoxycholic acid reabsorbed
lithocolic acid excreted into stool
What circulation are the bile salts reabsorbed into called?
enterohepatic circulation
What is bilirubin made from?
RBC breakdown (75%)
catabolism of haemoproteins (22%)
ineffective erythropoiesis (3%)
What are the 3 fates of bilirubin?
1) enters enterohepatic circulation (15%)
2) stercolbilin in faeces
3) enters systemic circulation and excreted by kidneys
What are the causes of obstructive jaundice?
cholangitis
Mirizzi’s syndrome
commone bile duct stoones
ampullary cancer
duodenal cancer
Hilar cholangiosarcoma
What are the investigations for obstructive jaundice?
serum amylase
prothrombin time
ultrasound scan
MR cholangio pancreatography
CT to exclude other causes
What are the treatments for common bile duct gallstones?
endoscoptic retrogrrade cholangiopancreatography to remove CBD stones
laparoscopic cholecystectomy and simultaneous exploration after patient has recovered
What are the 8 hallmarks of cancer?
1) sustaining proliferative signalling
2) evading growth suppressors
3) avoiding immune destruction
4) activating invasion and metastasis
5) enabling replicative immortality
6) inducing angiogenesis
7) resisting cell death
8) reregulating cellular energies
What is the corresponding cancers of squamous epithelium cells?
squamous cell carcinomas
What is the corresponding cancers of glandular epithelium?
adenocarcinomas
What is the corresponding cancers of enteroendocrine cells?
neurocendocrine tumours
NETs
What is the corresponding cancers of interstitial cells of Cajal?
gastrointestinal stromal tumours
GISTs
What is the corresponding cancers of smooth muscle?
leiomyomas/leimyosarcomas
What is the corresponding cancers of adipose tissue?
liposarcomas
What can histological sampling and molecular typing determine?
origin of cancer
mutations the cancer has acquired
What is the pathogenesis of oesophageal cancer?
upper 2/3rd of oesophagus = squamous cell carcinoma
lower 1/3rd of oesophagus = adenocarcinoma
develops from squamous epithelium that become columnar due to metaplasia BARRETT’S OESOPHAGUS
What is the presentation of oesophageal cancer?
dysphagia (difficulty swallowing) - late presentation
How is oesophageal cancer diagnoses?
upper GI endoscopy
oesophagogastroduodenoscopy (OGD)
What are the treatment options for oesophageal cancer?
1) curative - neoadjuvant chemotherapy then oesophagectomy
2) palliative - palliative chemo + steroids + stent
What is the pathogenesis of gastric cancer?
chronic gastritis which is caused by:
infection (H.pylori, epstein-barr virus)
autoimmune (pernicious anaemia and autoantibodies)
iatrogenic (partial gastrectomy)
genetic (family history due to E-cadherin mutations)
lifestyle (high salt diet, smoking)
What are the stages of gastric cancer?
chronic gastritis (inflammation)
mucinous metaplasia
intestinal metaplasia
dysplasia
malignancy
cancer
Clever monkeys investigate deep caves
What is the presentation of gastric cancer?
dyspepsia (post-prandial discomfort upper abdo)
red flags ALARMS 55
anaemia
loss of weight/appetite
abdominal mass palpable
recent onset of progressive symptoms
melaena (blood in stool)
swallowing difficulty
55 years old
What are the 2 components of pancreatic juice?
1) low volume, viscous enzyme rich juice from pancreatic acinar cells
2) high volume, watery, bicarb rich juice from centroacinar and duct cells
What are the acinar cell enzyme secretions stored in?
zymogen granules
What can happen to an organ producting digestive enzymes?
autodigestion -> pancreatitis
What are the 3 protective mechanisms of the pancreas to prevent autodigestion?
1) proteases released as inactive pro-enzymes
2) contains trypsin inhibitors -> prevents typsin activation
3) enzymes can only be activated in presence of enterokinase (at brush border of duodenum)
What is the aetiology of acute pancreatitis?
GET SMASHED
gall stones
ethanol
trauma
steroids
mumps and other viruses
autoimmune
scorpion/snake bite
hypercalcaemia, hypertriglyceridaemia, hypothermia
ECRP
drugs - SAND (steroids and sulphonamides, azathioprine, NSAIDs, diuretics)
What is phase 1 of pancreatitis?
activation of trypsin
What are the 3 ways in which trypsin is activated?
1) mechanical obstruction (gallstones)
2) alcohol, acetylsalicylic acid and histamine
3) premature intracellular enzyme activation
How does alcohol, acetylsalicylic acid and histamine activate trypsin?
increase permeability of pancreatic duct epithelium and precipitate proteins in ducts
obstruction increases upsteam pressure -> acinar cell ezymes diffuse into periductal interstitial tissue
How does a mechanical obstruction active trypsin?
they block ampulla so:
1) bile reflux into pancreas
2) build up of pancreatic juice leaking back into pancreatic tissues
3) if stone gets out of ampulla, stretches it, duodenal contents reflux w activated enzymes
How does premature intracellular enzyme activation active trypsin?
proezymes and lysosomal proteases are incorporated into the same vesicle -> activation of trypsin sooner
What is phase 2 of pancreatitis?
after the activation of trypsin
What are the 6 things that occur during phase 2 of pancreatitis?
PPECKS
Phospholipase A2
prothrombin
elatase
complement activation
kallikrenin
systemic effects
What does phospholipase A2 result in?
1) fat necrosis - involving Ca sequestration -> hypocalcaemia and pancreatic gangrene
2) hypoalbuminaemia -> hypocalcaermia
3) islet necrosis -> hyperglycaemia
What does prothrombin result in?
activation of thrombin -> thrombosis -> ischemia and pancreatic gangrene
What does complement activation result in?
cell toxicity ->
1) vessel erosion -> bleeding
2) islet necrosis -> hyperglycaemia
SAME AS ELASTASE
What does elastase result in?
1) vessel erosion -> bleeding -> pancreatic gangrene
2) islet necrosis -> hyperglycaemia
What does kallikrenin result in?
activation of bradykinin and kallidin -> vasodilation and plasma exudation
patients go into shock
What do the systemic effects result in?
destroys surfactants on lung and kidney epithelia -> hypoxia and anuria (little urine)
What are the symptoms of acute pancreatitis?
epigastric pain radiating to hte back
eased by sitting forward
nausea
vomiting
fevers
What are the signs of acute pancreatitis?
haemodynamic instability (tachycardic, hypotensive)
peritonism (upper generalized pain)
Grey Turner’s sign (bruising in flanks)
Cullen’s sign (bruising around umbilicus)
How do we assess the severity of pancreatitis?
Glasglow modified criteria
PANCREAS
PO2 <8kPaa
Age > 55 years old
Neutrophils > 15
Ca < 2mmol/L
Renal urea > 16mmol/L
Enzymes
Albumin < 32g/L
Sugar > 10mmol
What is the management of acute pancreatitis?
1) fluid resuscitation LOTS OF FLUIDS
2) analgesia
3) pancreatic rest and nutritional support
4) determine underlying cause
What is a pseudocyst?
sac of fluid containing enzymes which is encapsulated by a fibrous capsule on the pancreas
