Lecture 27 Flashcards
1
Q
What is found around the duodenum?
A
A number of sensory receptors and cells that mediate the release of pancreatic and biliary secretion
2
Q
What are the roles of the duodenum?
A
- Inhibition of gastric emptying
- Inhibition of acid secretion
- Stimulation of pancreatic and biliary secretion
3
Q
Describe the sensory function of the duodenum
A
- Endocrine cells respond to nutrients
- Vagal afferents respond to luminal contents and distension
4
Q
What does the presence of fats and proteins stimulate in the duodenum?
A
Release of cholecystokinin
5
Q
What does the presence of HCl stimulate in the duodenum?
A
Release of secretin
6
Q
What are the cells in the duodenum that detect stimuli called?
A
Enteroendocrine cells
7
Q
What are the enteroendocrine cells?
A
Specialised endocrine cells in the GI tract and pancreas that play a role in the regulation of pancreatic and biliary secretions
8
Q
What are three types of enteroendocrine cells and what do they secrete?
A
- I cells: secretes cholecystokinin
- S cells: secretes secretin
- Enterochromaffin cells
9
Q
What do the apical and basolateral surfaces of the cell face?
A
Apical surface: faces gut lumen
Basolateral surface: faces circulation
10
Q
What does the apical surface of the I cells sense?
A
Partially digested fats and proteins
11
Q
What does the detection of fat and protein cause the I cells to do?
A
Stimulates release of cholecystokinin from basolateral surface of cell
12
Q
Why is CCK released from the basolateral surface of I cells?
A
It has to enter the circulation
13
Q
What does the apical surface of S cells sense?
A
Low pH (acidic) in duodenum
14
Q
What happens when S cells sense low pH?
A
Stimulates release of secretin from basolateral surface of cell
15
Q
What are the effects of CCK and secretin
A
- Inhibit gastric emptying (when duodenum is distended with fat and protein, need to slow movement down to allow adequate absorption)
- Inhibit gastric acid secretion (need negative feedback loop to turn off the system)
16
Q
What does the apical surface of enterochromaffin cells dense?
A
Food or irritant
17
Q
What happens after enterochromaffin cells detect food or irritant?
A
Stimulates serotonin release from basolateral surface of the cell.
18
Q
What are the effects of serotonin?
A
- Stimulates gut motility
- High levels in blood activates receptors in medulla leading to vomiting
19
Q
Why do chemotherapy drugs cause GI symptoms (nausea, vomiting)?
A
They irritate enterochromaffin cells
20
Q
What are the two types of function of the pancreas?
A
Endocrine: making hormones (insulin)
Exocrine: releasing enzymes and bicarbonate for digestion
21
Q
What are the acinar cells responsible for?
A
Secreting digestive enzymes from the pancreas
22
Q
What are acinar cells brought together by?
A
Ductules and ducts
23
Q
Where does the exocrine pancreas secrete into?
A
Small intestine
24
Q
What does the exocrine pancreas secrete into the small intestine?
A
- Digestive enzymes for fat and protein digestion
- Bicarbonate ions to neutralise acidic pH
25
What do acinar cells secrete?
Digestive enzymes
26
What do ductal cells secrete?
Alkaline solution containing bicarbonate
27
What are acinar cells filled with?
Secretory granules containing precursor inactive enzymes (zymogens or proenzymes)
28
What are the granules of the acinar cells released into?
Small intestine via pancreatic duct
29
What happens to some enzymes after reaching the small intestine? Why?
Some enzymes are activated in small intestine to prevent auto-degradation of pancreas.
30
What do acinar cells contain a lot of?
RER for production of enzymes
31
What are the types of proteins that the pancreas releases?
Proteases
Lipase
Amylase
32
What are the proteases secreted by the pancreas?
Trypsinogen: cleaved by enteropeptidases in the small intestine to become trypsin
Chymotrypsinogen: cleaved by trypsin to become chymotrypsin
33
Where does the activation of inactive proenzymes take place?
In the 2nd part of the duodenal lumen (brush border) via proteolytic cleavage
34
What does trypsin cleave?
- Trypsinogen (autocatalytic)
- Chymotrypsin
- Other proenzymes
35
In what form are lipase and amylase stored in the pancreas?
Active form
36
What is the function of pancreatic lipase?
Converts triglycerides into monoglycerides and free fatty acids
37
What is the function of pancreatic amylase?
Converts starch into sugars
38
What happens to the levels of pancreatic lipase and amylase during pancreatitis?
Levels increase and can be measured in the serum as an indication of pancreatitis. These enzymes can cause further damage as they are active and are released directly into the pancreas.
39
What is the release of pancreatic enzymes controlled by?
Cholecystokinin
40
What are the two pathways by which CCK stimulates pancreatic enzymes?
- Enters blood circulation to get to acinar cells of pancreas to stimulate release of pancreatic enzymes
- Sends messages via afferent fibres next to I cells to vagus nerve in brainstem. Efferent fibres of vagus nerve transmit message to pancreas to stimulate release of pancreatic enzyme
41
What do intercalated ductal and centroacinar cells release?
Bicarbonate secretion into small intestine via pancreatic duct
42
What is the purpose of bicarbonate secretion?
Neutralises gastric acid in duodenum
43
Why does the pH have to be neutral in the duodenum?
For optimal function of pancreatic enzymes
44
Why is it important to maintain small intestinal pH near neutrality?
- Inactivate pepsin
- Prevent mucosal damage
- Increase fatty acid and bile acid solubility
- Optimise pH for pancreatic and brush border enzymes
45
Outline the process of HCO3- uptake and secretion
1) HCO3- is taken up into the ductal cell from the basolateral surface
2) Carbonic anhydrase forms HCO3- from H2O and CO2
3) HCO3- secretion into duct lumen involves
- CFTR transporter pumps Cl- outside of the cell
- Cl-/HCO3- exchanger
46
What is the release of pancreatic bicarbonate controlled by?
Secretin
47
Describe the action of secretin?
- Enters blood circulation to get to ductal cells of pancreas.
- Binds receptors on ductal cells
- Increases levels of cyclic AMP in cell
- Activates CFTR and exchangers
- Stimulates release of alkaline secretion
48
How does gastrin stimulate the pancreas?
Gastrin secreted during a meal also stimulates pancreatic acinar cells to release digestive enzymes
49
How does the vagus nerve affect the pancreas?
Vagal stimulation and Ach release during a meal also applies a low level stimulus to the pancreas for release of pancreatic enzymes and bicarbonate secretion.
50
Apart from pancreatic actions, what are the other actions of CCK?
Stimulates bile production in liver, gallbladder contraction, and sphincter of Oddi relaxation to deliver more bile into the duodenum
51
Apart from pancreatic actions, what are the other actions of secretin?
Stimulates bile duct to release bicarbonate solution from the bile duct
52
What kind of genetic condition is cystic fibrosis?
Autosomal recessive
53
What happens to CFTR ion channel in cystic fibrosis?
Becomes defective CFTR ion channel with very little to no function.
54
What is the CFTR ion channel located next to?
The Cl-/HCO3- ion exchanger
55
What does CFTR stand for?
Cystic fibrosis transmembrane conductance regulator
56
What kind of channel is CFTR?
Chloride
57
What organs does CF affect?
Lungs, liver, pancreas, GI tract, reproductive tract, sweat glands
58
What are the functions of CFTR?
- Production of sweat, mucus, digestive fluids
| - Also plays an important part in secretion of HCO3- working alongside the Cl-/HCO3- exchanger
59
How does CFTR effect sweat, digestive fluid, and mucus production?
Reduction in sweat production
Reduction in digestive fluid production
Excessive mucus production
60
What is meant by pancreatic insifficiency?
Pancreas stops producing enzymes and stops producing normally.
61
What does a defective CFTR transporter in the pancreas result in?
- Cl- accumulates in ductal cells
- Cells become more negatively charged, drawing Na+ and then H2O from ductal lumen into cells
- Pancreatic secretions become hyperviscous
- Pancreatic ducts become blocked
- Insufficient pancreatic enzymes released
- Build-up of enzymes in pancreas leads to autodigestion of pancreas. Pancreatitis can result, where pancreas becomes damaged and replaced by fibrosis.
- Pancreatic insufficiency (exo and endocrine)
62
What are the two types of pancreatitis?
Acute and chronic
63
What happens in acute pancreatitis?
- Acute inflammation
- Abdo pain
- Elevated pancreatic enzymes (specifically amylase and lipase) in serum
- Self-limiting
64
What happens in chronic pancreatitis
- Chronic inflammation due to ongoing or repeated insult
- Chronic abdo pain
- Irreversible damage leading to fibrosis and calcification of pancreas
- Progressive loss of pancreatic endocrine and exocrine function due to fibrosis can lead to endocrine and exocrine insufficiency.
65
What is meant by self-limiting?
In most people, recovery will occur
66
What are the two main causes of pancreatitis?
Alcohol and gallstones
67
What is autoimmune pancreatitis due to?
Antibodies which target receptors on pancreatic cells.
68
What are the less common causes of pancreatitis?
```
Autoimmune
Drugs
Trauma
Post-ERCP
Structural anomalies e.g. pancreas divisum
Metabolic e.g. hypertriclyceridaemia, hypercalcaemia
Viral infections e.g. mumps
CF
Hereditary/ Familial
```
69
What does ERCP stand for?
Endoscopic retrograde cholangiopancreatography
70
What is ERCP used to visualise?
Gallstones
71
What is pancreas divisum?
Common congenital anomaly. Failure of ducts of ventral and dorsal part of the pancreas to fuse.
72
What happens in endocrine insufficiency? How is it treated?
Impaired insulin production. Treated as per diabetes
73
What happens in exocrine insufficiency?
Impaired digestive enzyme production and fat malabsorption
74
How much of the pancreas must be damaged to develop exocrine insufficiency?
Over 90%
75
What loss is most critical in exocrine insufficiency?
Loss of lipase
76
What are the symptoms of exocrine insufficiency?
Fat malabsorption leading to weight loss and steatorrhea
77
What can be done to treat exocrine insufficiency?
Pancreatic enzyme supplements can be taken by mouth
78
Describe the stool of a patient with steatorrhea
Pale, bulky, floating stools, difficult to flush, oil droplets
79
What does a pancreatogram look like for someone with chronic pancreatitis?
Dilated main duct, irregular side branches
80
What is the appearance of pancreatitis on a CT scan?
Calcification of the pancreas, which indicates previous inflammation
81
How much bile is produced a day?
400-800 mL
82
What is bile composed of?
Water, electrolytes, organic molecules (bile acids, cholesterol, phospholipids, bilirubin)
83
What is the main way in which bile is recycled?
Enterohepatic circulation
84
From where is the bile recycled?
Terminal ileum where there are special receptors that pick up the bile and it enters the portal circulation via the hepatic portal vein.
85
What are the main functions of bile?
- Carries bile acids
| - Eliminates waste products including bilirubin
86
What are the bile acids important for?
Digestion and absorption of fats and fat-soluble vitamins (ADEK)
87
How is bile involved in the elimination of wastes?
Wastes are secreted into the bile and removed via the faeces
88
What are the two sources of bile acids?
- 5% newly synthesised in the liver from cholesterol
| - 95% reabsorbed from terminal ileum
89
Describe the reabsorption of bile from the terminal ileum.
- Bile in terminal ileum enters enterohepatic circulation. Enters portal vein and sinusoids into the hepatocytes.
90
What does the uptake of bile salts in the terminal ileum involve?
Bile acid/Na+ transporter (Na+/K+ ATPase pump)
91
Describe the flow of bile through the biliary tree
- Hepatocytes secrete bile
- Bile enters canaliculi and flows into larger bile ducts
- As it flows through, watery secretion rich in bicarbonate is added to the bile by ductal epithelial cells
- Bile leaves the liver, flowing down common hepatic duct and enters cystic duct into the gallbladder
92
What is bile flow driven by?
Bile flow into canaliculi
- Bile acid dependent: active transport of bile acids from blood into canaliculi draws water with it (osmotic effect)
- Bile acid-independent: transport of other solutes and electrolytes
93
What is the reabsorption and secretion of water and electrolytes by ductules and ducts into and from the bile in response to?
Secretin
94
What does bile enter the gallbladder as a result of?
Closure of sphincter of Oddi
95
What does the gallbladder do to bile?
Stores and concentrates it when not eating
96
What part of the nervous system also has an influence on gallbladder function?
Vagus nerve
97
What is cholestasis?
Obstruction to bile flow
98
What can cholestasis lead to?
- Increased pressure in the biliary tract and liver
- Leads to rupture of tight junctions and leakage of bile
- Bile contents spill back into circulation, causing jaundice
99
What is another name for jaundice?
Hyperbilirubinaemia
100
What leads to biliary obstruction?
If gallstones fall out of the gallbladder and too large to pass through bile duct, can distend it which results in pain, jaundice, liver test abnormality.
101
What can gallstones be diagnosed by?
US
102
Apart from gallstones, what else can cause obstruction?
Biliary strictures, either benign or malignant from repeated infection or primary sclerosing cholangitis
103
What is cholangiocarcinoma?
Cancer of the bile duct
104
What other cancer can cause obstruction?
A cancer in the head of the pancreas can cause narrowing of the common bile duct
105
What does prolonged bile duct obstruction typically occur in?
Malignancy
106
What are the symptoms of prolonged bile duct obstruction?
- Jaundice: yellow discolouration of skin or sclera from excess bilirubin in the blood
- Itching: from bile salt accumulation in skin
- Nausea: from bile salts
- Ecchymoses
- Palpable gall bladder
- Malabsorption of fat and fat-soluble vitamins
- Effects on renal perfusion which can lead to renal failure
107
What is ecchymoses caused by?
Malabsorption of vitamin K
108
What is Virchow's node and what does it indicate?
Palpable lymph node in left supraclavicular fossa indicates intra-abdominal malignancy
109
What is Courvoisier's sign?
Enlarged gallbladder with jaundice - unlikely to be stones
110
What is a method for treating biliary constriction?
Stent
