Functions and Secretions of the Pancreas Flashcards
1
Q
What are the functions of the pancreas
A
- Digestion of fats, proteins and nutrients by producing enzymes
- Regulate environment for enzymatic digestion
- Regulates both fed and fasted states (insulin and glucagon)
2
Q
What is the ampulla of Vater
A
- The swelling in the duodenal wall caused by the joining of the common bile duct and the main pancreatic duct
3
Q
What structures drain into the main pancreatic duct
A
- Intralobular duct
- Interlobular duct
- These form the ductular network which comes from the lobes of the pancreas
4
Q
What forms the sphincter of Oddi and what is its function
A
- Formed by thickening of muscular wall
- Regulates ductal flow into duodenum and prevents reflux
5
Q
What happens at the major duodenal papilla
A
- Contents of the main pancreatic duct and common bile duct empty into the descending duodenum
6
Q
What is the positional significance of the major duodenal papilla
A
- Marks transition from foregut to midgut
- Celiac trunk stops supplying thee gut, instead the superior mesenteric artery supplies the gut from this point.
7
Q
What can be caused by blockage at distal end of common bile duct
A
- Blockage of pancreatic duct
- Eventually pancreatitis
8
Q
What are the units of the pancreas that reside within the lobules called and what are they composed of
A
- Functional secretatory units
- Each composed of an acinus and a small intercalated duct
9
Q
What is the acinus of the functional secretatory units
A
- A cluster of acinar cells that make and secrete proteins into the lumen of the epithelial structure
10
Q
What organelles make acinar cells suited to their function
A
- RER
- Secretatory granules
- Exocytosis at apical pole
- Specialised for production and secretion of large number of proteins
11
Q
List some things that are secreted by pancreatic acinar cells
A
- A plethora of zymogens (inactive enzyme precursors)
- Digestive enzymes
- Isotonic, bicarbonate rich, plasma like fluid (to accompany secretatory proteins to avoid obstruction)
12
Q
What is a centroacinar cell
A
- The very first cells of the intercalated duct and thus are located at the junction of the pancreatic acinar cells and duct cells.
13
Q
What do pancreatic goblet cells do and why is this important
A
- Produce mucus which is important for:
> Lubrication
> Hydration
> Mechanical protection of surface epithelial cells
> Immunologic role
14
Q
What stimulates acinar cells to produce zymogen and through what pathway
A
- Ach - from vagal stimulation
- CCK - I cells (specialised cells that line the small intestine, stimulated by fat in food
- Through the PLC/ PKC/ Ca 2+ single transduction pathway
15
Q
What other than pancreatic acinar cells does CCK stimulate and why
A
- Gall bladder contraction
- Pumps bile into small intestine to emulsify fat, only emulsified fat can be broken down by lipase
16
Q
What do pancreatic duct cells produce and why
A
- Bicarbonate ions
- Prevent peptic ulceration
- Neutralise acidic conditions
17
Q
How is the bicarbonate ion made in the pancreatic duct cells
A
- Water and carbon dioxide makes carbonic acid which dissociates into a bicarbonate ion and a proton
18
Q
How do pancreatic duct cells counteract the alkaline tide of the stomach
A
- The bicarbonate ion remains in the lumen to neutralise stomach acid where as the proton is pumped into the blood neutralising the alkaline tide.
19
Q
How do pancreatic duct cells counteract the alkaline tide of the stomach
A
- The bicarbonate ion remains in the lumen to neutralise stomach acid where as the proton is pumped into the blood neutralising the alkaline tide.
20
Q
What stimulates pancreatic duct cells to produce bicarbonate ions
A
- Ach - vagal stimulation
- Secretin - S cells in the small bowel (stimulated by acid coming from the stomach)
21
Q
How do Ach and secretin stimulate the pancreatic duct cells to efflux bicarbonate into the lumen
A
- They stimulate a chloride channel called CFTR
22
Q
How does CFTR work
A
- Forces Cl- into the duct to produce a high enough concentration for the Cl- ions to drive the Chloride bicarb exchanger.
- Bicarbonate ion then enters the duct in exchange for Cl- ions leaving the duct
23
Q
What type of Cl- channel is CFTR and what happens if it mutated
A
- cAMP - activated
- If CFTR is mutated in someone they have Cystic Fibrosis
24
Q
What causes mutated an non functional CFTR in individuals with Cystic Fibrosis
A
- Mutation in CF gene causes premature degrading of CFTR.
25
What is the effect of non functional CFTR
- Decreased secretion of HCO3- and water
- Lack of water causes blockage in ducts due to thick secretion of acinar cells
- Blockages can cause pancreatic tissue destruction (can cause diabetes and maldigestion)
26
What is pancreatic juice
- Mixture of secretions from acinar, duct and goblet cells.
- Protein - Rich alkaline fluid
27
What is the rate of pancreatic secretion dependant on
- Whether you are fed or fasted
- Biliary and gastric secretion and intestinal motility
28
What are pancreatic secretion levels like when fasted and fed
- Fasted state - low level of pancreatic release
- Fed state - Pancreatic release is 5-20 times more than basal levels
29
What other than fat in the duodenal lining stimulates CCK secretion and what happens in the fasted state
- CCK releasing factors (e.g. LCRF)
- In the fasted state LCRFs are degraded by digestive enzymes to stop CCK production
30
What inhibits pancreatic secretion and how
- Somatostatin inhibits secretin and CCK release
- Pharmacological inhibitors that imitate somatostatin.
31
What are the phases of pancreatic secretion
- Cephalic phase - 25%
- Gastric phase - 10%-20%
- Intestinal phase - 50%-80%
32
What stimulates the cephalic phase of pancreatic secretion and what mediates it
- Sight of food
- Smell of food
- Taste of food
- Medicated by stimulation of Ach receptors on acinar (and duct) cells
33
What stimulates the gastric phase of pancreatic secretion
- Release of gastrin from antral G-cells which signals through CCK receptors on acinar cells.
- Gastric distension stimulates low levels of pancreatic secretion, through vagovagal gastropancreaytic reflex
34
What stimulates pancreatic secretion in the intestinal phase
- Chyme entering the proximal small intestine stimulates secretion via 3 mechanisms:
> S cells
> I cells
> Reflexes
35
How does stimulation of duodenal S cell by gastric acid stimulate pancreatic stimulation in the intestinal phase
- Duodenal S cells release secretin which stimulates duct cells to secrete HCO3- and fluid
36
How does stimulation of duodenal I cell by lipids stimulate pancreatic stimulation in the intestinal phase
- Duodenal I cells are stimulated to release CCK which stimulates acinar cells to release digestive enzymes
37
How do lipids stimulate pancreatic stimulation in the intestinal phase
- lipids activate vagovagal enteropancreatic reflex that predominantly stimulates acinar cells via M3 receptor
38
How does the pancreas avoid autodigestion
- Producing zymogens (inactive) enzymes
- Zymogens only activate in the small bowel
- Acinar cells package zymogens in granules
39
How does the pancreas ensure that zymogens are only activated in the small bowel
- They are only activated when they come into contact with trypsin
- Trypsinogen only becomes typsin when it comes into contact with enterokinase (Small bowel brush border enzyme only found in small bowel)
40
Describe some specialised features of the granules that acinar cells pack zymogens into
- Low pH - even if zymogens do become active enzymes, they will be non functional
- Impermeable to proteins - enzymes cannot enter the granule to activate zymogens
- Enzyme inhibitors are packed into the granules - stop enzymes from activating zymogens
41
What is autodigestion of the pancreas known as
Pancreatitis
42
What is the pneumonic to remember the causes of acute pancreatitis (which are for main causes, which are for rare causes)
- GET (main) SMASHED (rare)
- Gall stones
- Ethanol
- Trauma
- Steroids
- Mumps
- Autoimmune
- Scorpion's sting
- Hypercalcaemia, Hypertriglyceridemia, hypothermia
- ERCP
- Drugs
43
How is acute pancreatitis diagnosed
- Two of the following 3 features are required
> Abdominal pain (usually epigastric region that radiates to the back)
> Serum amylase or lipase > 3
> Findings of acute pancreatitis on a CT scan
44
What happens in phase 1 of acute pancreatitis
- Premature activation of trypsin
45
What happens in phase 2 of acute pancreatitis
- Intra-pancreatic inflammation caused by digestive enzymes activated by trypsin
46
What happens in phase 3 of acute pancreatitis
-Extra-pancreatic inflammation caused by digestive enzymes leaking out of the pancreas
47
What happens in phase 3 of acute pancreatitis
-Extra-pancreatic inflammation caused by digestive enzymes leaking out of the pancreas.
- Can lead to sepsis and multiple organ failure
48
How is acute pancreatitis treated (mild)
- Pancreas is rested - IV fluids for dehydration
- Hourly fluid balance - catheter due to severe hypovolemia
- Pain relief
48
How is acute pancreatitis treated (mild)
- Pancreas is rested - IV fluids for dehydration
- Hourly fluid balance - catheter due to severe hypovolemia
- Pain relief
49
How is acute pancreatitis treated (severe)
- Intensive care
- Multi-organ support
50
What are some investigations that can be done to work out the cause of the acute pancreatitis
- Ultrasound (gallstones)
- History (Alcohol)
- CT
- ERCP (can also be treatment)
51
What is chronic pancreatitis
- Inflammation of the pancreas that does not heal but gets worse and leads to permanent damage
52
What is the most common cause of chronic pancreatitis and what are some other causes
- Main cause: Chronic alcohol abuse
- Other causes:
> Hereditary disorders of the pancreas
> Cystic fibrosis
> Hypercalcaemia
> Hyperlipidaemia
53
How is chronic pancreatitis treated
- Hospitalisation is often required for pain, dehydration and malnutrition
- Synthetic pancreatic enzyme supplements - when returning to normal diet if pancreas does not secrete enough
- ERCP to identify and treat complications
- Diagnostic imaging to identify calcification of pancreas
- Diabetes monitoring and treatment if required
