pancreas, liver Flashcards
how are pancreatic acinar cells MAINLY stimulated?
CCK - released from duodenal I cells when they detect lipids etc, also stimulated to release CCK when LCRF’s (release factors) are not degraded (enzymes acting on chyme instead during digestion)
Also Ach (branch of vagus nerve) in response to stomach distension etc
intracellular cascade leads to increase Ca2+ levels
How are pancreatic duct
cells MAINLY activated?
S cells produce secretin in response to detecting acid in the duodenum
also Ach stimulation
leads to increase cAMP and PKA activity
increases HCO3/Cl antiporter
and activity of CFTR
Explain the blood supply to the liver?
hepatic artery (nutrients/ oxygenated blood for hepatocytes), hepatic portal vein (venous blood 75% of venous blood from gut flows right through for detoxification) - merge and mix in the sinusoids before draining through the central vein, leaving via the hepatic vein
Explain the ECM of the liver
ECM - produced by stellate cells
Stroma protective ECM around liver - strongest at tracts to provide support
consists of fibres e.g. collagen, macromolecules and glycoproteins / integrins that link cells to
ECM
what is an indicator of ECM turnover rate?
hydroxyproline produced as a metabolite from stellate cells as they make ECM
how is ECM of liver disrupted in disease?
cirrhosis / fibrosis, excessive ECM turnover rate leading to higher ECM to cell ratio
What is the role of goblet cells in the pancreas?
lubrication, immune protection (trapping pathogens), mechanical protection, hydration
how does somatostatin effect the pancreas and why is this useful?
decreases CCK and secretin release from I and S cells, decreases pancreatic secretions
somatostatin analogues can be used clinically e.g. pancreatitis
what are the 5 main cell types in the liver?
Hepatocytes, Kupfer cells, biliary epithelium, endothelium, stellate cells
explain the role and structure of biliary epithelium
- Form vessels of increasing size to collect canicular bile
- Modify content e.g. PH, water
- Polarised structure as well e.g. tight adherence to basement membrane to stop damaging bile from secreting into surrounding tissue
Explain Kupfer cells
- Hepatic resident Macrophages located in the sinusoids
- Phagocytosis, regulation of microcirculation (by controlling vascular tone) and removal of endotoxin (part of bacteria cell walls)
Can secrete cytokines to illicit a larger immune response, become APC and allow tolerance of favourable molecules e.g. amino acids
Explain Stellate Cells
- Star shaped with multiple extended membrane processes
- In response to disease, can transform into a fibroblast like morphology where they rapidly divide and secrete ECM
Perisinusoidal fat / retinoid storing cells
explain the function of liver endothelial cells
- Squamous epithelial cells that line the vessels of the liver e.g. capillaries
- Selective absorption of molecules into the liver, protects from bacteria blood cells etc
They also have normal endothelium functions e.g. anti-thrombogenic surface and regulate coagulation and leukocyte activity
explain the function of hepatocyte
- Make up 60-65% of the liver
- Polarised epithelial cells
- Main functional cell e.g. metabolism, detoxification, bile production
Over 100 day life span as they have specialised energy intensive structure
what enzymes detoxify compounds in the liver?
When do there levels vary
CYP’s
levels vary with age, gender, genetics, etc
e.g. alcohol abuse = higher levels of CYP540 - problematic for paracetamol overdose
CYP may make drugs bioactive or inactive
what are the 2 stages of metabolism in the liver?
phase 1 (CYP540) - oxidation / reduction / hydrolysis etc
phase 2 - conjugation - makes substance water soluble less toxic for excretion via bile or urine
what is jaundice?
Jaundice is a yellow appearance of skin, eyes and other tissues due to the buildup of bilirubin, in excess of 2mg/ml
how is unconjugated bilirubin transported?
conjugated to albumin as its only lipid soluble
where is bilirubin produced?
Macrophages (mainly in spleen where rbc are destroyed)
how is unconjugated bilirubin processed?
in the liver, its conjugated to guluronic acid by the enzyme UDP glucoronyltransferase
it is then conjugated bilirubin
what happens to conjugated bilirubin in the small intestine?
its acted on by bacteria to convert it to urobilinogen
what happens to 90% of urobilinogen?
converted to stercobilin (brown pigment) which is excreted in faeces
what happens to 10% of urobilinogen?
it is a lipid soluble substance so is bound to albumin and transported back to the liver, where its excreted into bile again as conjugated bilirubin
where does conjugated bilirubin go ?
excreted into bile and to a lesser degree in urine
