pancreas, liver

Question 1

how are pancreatic acinar cells MAINLY stimulated?

Answer 1

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

Question 2

How are pancreatic duct
cells MAINLY activated?

Answer 2

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

Question 3

Explain the blood supply to the liver?

Answer 3

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

Question 4

Explain the ECM of the liver

Answer 4

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

Question 5

what is an indicator of ECM turnover rate?

Answer 5

hydroxyproline produced as a metabolite from stellate cells as they make ECM

Question 6

how is ECM of liver disrupted in disease?

Answer 6

cirrhosis / fibrosis, excessive ECM turnover rate leading to higher ECM to cell ratio

Question 7

What is the role of goblet cells in the pancreas?

Answer 7

lubrication, immune protection (trapping pathogens), mechanical protection, hydration

Question 8

how does somatostatin effect the pancreas and why is this useful?

Answer 8

decreases CCK and secretin release from I and S cells, decreases pancreatic secretions
somatostatin analogues can be used clinically e.g. pancreatitis

Question 9

what are the 5 main cell types in the liver?

Answer 9

Hepatocytes, Kupfer cells, biliary epithelium, endothelium, stellate cells

Question 10

explain the role and structure of biliary epithelium

Answer 10

• 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

Question 11

Explain Kupfer cells

Answer 11

• 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

Question 12

Explain Stellate Cells

Answer 12

• 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

Question 13

explain the function of liver endothelial cells

Answer 13

• 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

Question 14

explain the function of hepatocyte

Answer 14

• 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

Question 15

what enzymes detoxify compounds in the liver?
When do there levels vary

Answer 15

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

Question 16

what are the 2 stages of metabolism in the liver?

Answer 16

phase 1 (CYP540) - oxidation / reduction / hydrolysis etc
phase 2 - conjugation - makes substance water soluble less toxic for excretion via bile or urine

Question 17

what is jaundice?

Answer 17

Jaundice is a yellow appearance of skin, eyes and other tissues due to the buildup of bilirubin, in excess of 2mg/ml

Question 18

how is unconjugated bilirubin transported?

Answer 18

conjugated to albumin as its only lipid soluble

Question 19

where is bilirubin produced?

Answer 19

Macrophages (mainly in spleen where rbc are destroyed)

Question 20

how is unconjugated bilirubin processed?

Answer 20

in the liver, its conjugated to guluronic acid by the enzyme UDP glucoronyltransferase
it is then conjugated bilirubin

Question 21

what happens to conjugated bilirubin in the small intestine?

Answer 21

its acted on by bacteria to convert it to urobilinogen

Question 22

what happens to 90% of urobilinogen?

Answer 22

converted to stercobilin (brown pigment) which is excreted in faeces

Question 23

what happens to 10% of urobilinogen?

Answer 23

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

Question 24

where does conjugated bilirubin go ?

Answer 24

excreted into bile and to a lesser degree in urine

Question 25

what are the 3 different caused of jaundice?

Answer 25

Causes can be pre-hepatic (before the liver), intrahepatic (caused within the liver) and extra hepatic (downstream of the liver)

Question 26

List 5 causes of pre-hepatic jaundice

Answer 26

Haemolytic anaemia
Sickle cell disease
Paroxysmal nocturnal haemaglobulinurea (PNS)
gilberts syndrome
neo-natal jaundice

Question 27

what is haemolytic anaemia

Answer 27

excess rbc destruction

Question 28

what is gilberts syndrome?

Answer 28

UPC glucuronryl transferase mutation - less efficient normally not an issue but when the body / liver are under other stresses unconjugated bilirubin builds up resulting in jaundice. Diagnosis would involve serum tests to exclude haemolysis etc then patient would be monitored

Question 29

what is neo natal jaundice?
how can it be treated?
when is it cause for concern?

Answer 29

common when babies are first bone, as old red blood cells are cleared leading to excess bilirubin temporary jaundice as a result of the lag / build up can be treated with phototherapy to help conjugate the bilirubin. In conjunction with pale stool and dark urine - cause for concern of liver disease

Question 30

What is Paroxysmal nocturnal haemaglobulinurea (PNS)

Answer 30

Fragile rbc - genetic condition

Question 31

what complications can pre- hepatic jaundice cause for the liver

Answer 31

iron overload, AST/ALT levels elevated, gallstones hepatomegaly (enlarge liver), splenomegaly (enlarged spleen)

Question 32

what are the causes of intrahepatic jaundice?

Answer 32

viral hepatitis (e.g. hep A causes acute hepatitis)
cirrhosis associated with metabolic dysfunction-associated steatotic liver disease (MASLD)
alcoholic liver disease

Question 33

How are gall stones formed?

Answer 33

abnormal make up of bile leads to stone formation
can be due to excess bilirubin (pigment stone), or excess cholesterol

Question 34

what do gallstones cause?

Answer 34

Cholestasis (impaired bile flow ) this can lead to extra-hepatic jaundice
infection of bile ducts (cholangitis)
pancreatitis

Question 35

what are the causes of extra hepatic jaundice?

Answer 35

Cholestasis (bile flow impaired) can be caused by obstruction to bile ducts due to cancer / gall stones or the destruction of bile ducts due to autoimmune conditions / drug toxicity etc.

Question 36

what type of jaundice is indicated by a build up of unconjugated bilirubin?

Answer 36

pre and intra hepatic

Question 37

what type of jaundice is indicated by a build up of conjugated bilirubin?

Answer 37

extra-hepatic