122; Biliary Pancreatic Flashcards
What 2 hormones are produced by the duodenum in response to a meal?
CCK (choleocystokinin)
Secretin
What stimulates the secretion of secretin?
The acidic pH of chyme entering the duodenum
What stimulates the secretion of CCK from the duodenum?
The presence of amino acids and fatty acids within the chyme
From where are Secretin and CCK secreted?
- Secretin
S cells of the crypts of Leiberkun in duodenal epithelium
- CCK
I cells of the duodenal epithelium
What is the role of Secretin?
- Stimulates the Pancreatic Ductal cells to secrete bicarbonate;
- neutralises duodenal contents
- Inhibits HCl secretion from the Parietal cells of the stomach
- Augments the effect of CCK
Neutralisation provides a negative feedback to the S cells
What is the role of CCK?
- Stimulates Vagus, Ach causes contraction of gall bladder
- Stimulates pancreatic Acinar cells to secrete enzymes
Describe the distribution of different cell types within the pancreas.
80% Acinar cells
10% Duct cells
10% Islet cells
What are the different cell types of the Islet cells, and what do they secrete?
α cells - Glucagon
β cells - Insulin & amylin
δ cells - Somatostatin
γ cells - pancreatic polypeptide
What are the roles of Glucagon, Insulin & Amylin?
- Glucagon- Raises the plasma concentration of glucose
- Insulin & Amylin- Reduce the plasma concentration of glucose (amylin directly blocks glucagon release from α cells)
What are the main causes of acute pancreatitis?
- Cholelethiasis (gall stones)
- Alcohol
- Infections (mumps)
- Pancreatic tumour
- Drugs
- Iatrogenic (ERCP)
What are the main causes of chronic pancreatitis?
- Alcohol
- Tropical
- Hereditary
- CF
- Cationic trypsinogen gene
- Idiopathic
- Trauma
- Hypercalcaemia
What is the difference between Acute and Chronic pancreatitis?
- Acute
Nacrosis of the pancreatic parnechyma
No permanent damage
- Chronic
?inapropriate activation of enzymes within the pancreas
Causing inflammation of the pancreatic duct –> Obstruction
Permanent damage
What is the difference between Hereditary and Familial pancreatitis?
Hereditary pancreatitis describes a condition caused by an identifiable gene.
Familial pancreatitis has no identified gene but has been present in multiple family members over at least 2 generations.
What is Trypsin?
A pancreatic enzyme, secreted as pro-trypsin
Once activated (by HCl) it cleaves and activates other pancreatic enztmes
What are the main enzymes secreted by the pancreas?
- Lipase
- Co-lipase
- PhospholipaseA2
- Cholesterol Esterase
- Amylase
What is the role of the Gall bladder?
Storage of Bile
What is Bile composed of?
Bile Salts + Lecithin (Phosphatidylcholine)
mainly
What is the role of Bile?
It emulsifies dietary lipids to aid their digestion
What are the main Blie acids?
Cholic Acid
Chenodeoxycholic Acid
What are bile salts derived from?
Cholesterol
Which enzyme is required for Bile acid formation from cholesterol?
Cholesterol-7- α-hydroxylase
What is the rate limiting step in the formation of bile acids?
Conversion of cholesterol to cholic acid by:
cholesterol-7- α-hydroxylase
What is the difference between bile acids and bile salts?
Bile acids
- Un-conjugated
- Carboxyl group not ionised at phisiological pH
- Amphipathic= hydro- and lipo- philic properties
Bile salts
- Conjugated
- Higher pKa, ionised at physio. pH
- More amphipathic; better emulsifiers
What controls the activity of cholesterol-7- α-hydroxylase?
Up-regulated by Cholesterol
Inhibited by Cholic Acid
Wat are the main molecules found conjucated to Bile Acids?
Glysine
Taurine
What are the main Bile salts?
Glycocholic Acid
Taurocholic Acid
Glycochenodeoxycholic Acid
Taurochenodeoxycholic Acid
What is the difference between primary and secondary bile salts?
- Primary; conjugated in the liver
- Secondary; Removal of hydroxyl side chain by gut flora
ee. Deoxycholic acid
ee. lithocholic acid
Bile salts provide a significant mechanism for cholesterol excretion, how?
- Bile salts are a metabolic product of Cholesterol
- Bile salts are a solubiliser for cholesterol also
What is the effect of intestinal flora on bile salts?
- Regenerate bile acids
- By removal of glycine/taurine
- Convert primary bile acids to secondary..
- By removal of -OH side chain
ee.
Cholic acid —> DeoxyCholic acid
Chenodeoxycholic acid —> Lithocholic acid
What percentage of bile salts secreted are reabsorbed by the intestines?
95%
Primarily in what area are the bile salts reabsorbed?
Ileum
How do the bile salts reach the liver in their hydrophobic state?
Bound to Albumin
How do the reabsorbed bile salts reach the liver?
Via the enterohepatic circulation; via the hepatic portal vein
What happens when reabsorbed primary and secondary bile salts and acids reach the liver?
They enter hepatocytes
Bile acids are conjugated
Bile salts ready to enter the bile
What percentage of bile salts are lost in the faeces daily?
5%
What is Cholestyramine?
A bile acid sequestrant.
It binds bile acids in the intestine breventing their reabsorption.
More cholesterol required to synthesise more.
- Treatment for hypercholestraemia
(High fibre diet has similar effect)
What is one risk of hypercholesteraemia associated with the liver?
Choleoliethiasis
(Gall stones)
What factors may cause choleolethiasis?
- Severe ileal disease (malabsorption of bile acids)
- Obstruction of enterohepatic circulation due to biliary tract obstruction
- Hepatic dysfunction; decreased bile production
- Excessive feedback supression of bile synthesis
What are the 3 main dietary lipids?
- Tri glyceride
- Phospholipid
- Cholesterol ester
What are the 2 essential UNsaturated fatty acids?
- Linoleic acid
- Linolenic acid
How do bile and panreatic enzymes work together to digest lipids and fat soluble vitamins?
- Bile emulsifies lipids to form emulsion droplet
- Pancreatic enzymes digest these lipids and break emulsion droplet into smaller multilamellar vesicles
- These vesicles are further broken down into mixed micelles
Wat is the substrate for Lipase, and what are the products?
Triglycerides
- Co-lipase binds TG on emulsio drpolet and provides an anchor for Lipase
- Produce Fatty Acids and Glycerol
Wat is the substrate for PhospholipaseA2, and what are the products?
Phospholipids
Products are lysolecithin and Fatty Acids
Wat is the substrate for Cholesterol Esterase, and what are the products?
Cholesterol Esterers
Products are Cholesterol and Fatty Acids
What bile pigment is the product of Haeme degeneration?
Bilirubin
What are the steps in the catabolism of haeme to bilirubin?
Haeme
Microsomal Haeme Oxygenase
**Biliverdin **(green)
Biliverdin Reductase
Bilirubin (red)
Where is haeme catabolised?
In the Reticulo-endothelial system of MØ
What happens to Bilirubin after it is produced in the MØ?
- Travels in the blood bound to albumin
- Taken to the liver via hepatic portal vein
- Enters hepatocytes
- Binds to ligandin
Following Bilirubin’s entry to hepatocytes, what is the next step of its excretion process?
Formation of Bilirubin di-glucoronide
Solubility of Bilirubin is increased by binding 2 molecules of glucuronic acid
by the enzyme glucuronyl transferase
Which enzyme catalyses the binding of glucuronic acid to bilirubin?
Bilirubin glucuronyl transferase
Why is conjugation to glucuronic acid required for bilirubin?
Bilirubin is insoluble, conjugation allows solubulisation and thus excretion of bilirubin
How is bilirubin diglucoronide excreted from the liver?
Actively transported into the liver ductules;
An energy dependent process susceptible to impairement in liver damage
How is bilirubin diglucoronide excreted from the body?
Hydrolysed and reduced by gut flora to urobilinogen
- Urobilinogen oxidised by gut flora to produce stercobilin (Brown pigment- excreted in the faeces)
- Absorbed into blood and taken to kidneys- converted to urobilin (Yellow pigment- excreted in the urine)
What is Jaundice?
Hyperbilirubinaemia
When the pathway of converting bilirubin to urobilinogen is dysfunctional; increased levels of circulating Bilirubin
Red/orange colour to skin, mucous membranes and urine; pale stools due to lack of Stercobilin…
What fat-solubloe vitamins require bile and pancreatic enzymes for digestion?
Vit A, D, E, K
List some causes of pancreatic insufficiency.
Chronic pancreatitis
Cystic Fibrosis
Duct obstruction
Pancreatic atrophy
What are the signs & symptoms of pancreatic insufficiency?
- Malabsorption; malnutrition
- Steatorrhoea
- Weight loss
- Vitamin deficiency (A, D, E, K)
- Diabetes (lack of insulin)
What imaging techniques are used for the pancreas?
- US; not always useful, pancreas deep structure and behind bowel gasses
- CT; good for parenchyma an surroundings, good to assess necrosis and blood supply
- MRI; better than CT to assess ducts
- ERCP; best test for imaging ducts, but invasive and complications
- EUS; good for biopsies and to assess operability, Highest resolution of stones in the CBD
What are the Pros and Cons of testing pancreatic exocrine function?
- PROs
- Stool sample collection is not invasive
- CONs
- Not direct assessment of secretions into the duodenum; enzymes may get digested/absorbed along the way
What enzyme is used to measure pancreatic exocrine function through stool samples?
Elastase levels in the stool
- A positive result is reliable
- Negative result can be due to other reasons
What is the tubeless pancreatic function test?
Labeled substance is ingested
Measure its clearance in urine
Which test is used for acute pancreatitis?
Measurement of serum amylase concentration
- levels 3x higher than normal is indicative of pancreatic damage
Amylase elevation does not reflect the severity of the damage
What test may be used to diagnose cystic fibrosis cause of pancreatic insufficiency?
Sweat test
The concentration of Cl in sweat is elevated
What is a serum tumour marker for pancreatic cancer?
CA19-9
What are the signs and symptoms of acute pancreatitis?
Epigastric pain –> refer to back
Vomiting and prostration
Time course of days/weeks
Able to resolve
What are the causes of acute pancreatitis?
- Gall stones
- Alcohol, young male
- Drugs, high calcium…
What are the signs and symptoms of pancreatic cancer?
- Relentless upper abdo/back pain
- Weight loss
- Diarrhoea/malnutrition
- Diabetes
- Jaundice, painless if CBD obstruction
- Enlarge liver if metastases
What are the risk factors for pancreatic cancer?
Smoking
Age >50
What sign might a head of pancreas tumour cause?
Double duct sign; obstruction of CBD and pancreatic duct
What are the signs and symptoms of chronic pancreatitis?
- Severe upper abdo & back pain
- Weight loss
- Diabetes
- Diarrhoea
- Time course months-years
- Pts may become addicted to opiates
What are the risk factors for developing chronic pancreatitis?
- Alcohol
- Nutritional causes in 3rd world
- Cystic fibrosis, and rare familial causes
- Idiopathic
What is autoimmune pancreatitis?
- Onset similar to pancreatic cancer
- Dfferentiated via identification of raised serum IgG4 levels
- Responds dramatically to steroids
