Endocrine Disorder Of The GI Tract Flashcards
(45 cards)
1
Q
What is the GI Tract?
A
- GIT is a 7 -10m continuous tube that runs from mouth to anus
- Partitioned into many sections, each with distinct structure, anatomy and function.
- Encased in layers of voluntary and involuntary muscle
- Large arterial system linking the sections into circulation.
2
Q
What are functions of the GI Tract?
A
Oesophagus: Ingestion and release of enzymes
Stomach: Digestion. Lowers the pH and release enzymes
Duodenum: Used for Digestion. Increase the pH, add pancreatic enzymes and bile.
Jejunum+Ileum+Colon: Used for Absorption. Does this by stabilising the pH, signal to brain and body to handle incoming nutrient and modify hunger
3
Q
Why does the GI tract need hormones?
A
- Efficient digestion and absorption requires a continuous modification of gut contents.
- Hormone signalling allowing different parts of GIT to ‘switch on’ when food arrives and ‘switch off’ when food departs each section, plus communicate to brain and body.
- The hormones are synthesised by cells scattered in the epithelium of the stomach and small intestine (not in discrete glands).
- Endocrine cells and the hormones they secrete are referred to as the Enteric Endocrine System.
4
Q
What are the principal GI hormones?
A
- Gastrin
- Cholecystokinin (CCK)
- Secretin
- Gastric Inhibitory Peptide (GIP)
- Vasoactive Intestinal Polypeptide (VIP)
- Pancreatic Polypetide (PP)
- Ghrelin
- Enteroglucagon, and Glucagon-Like Peptides
5
Q
What is the stomach and purpose of acidification of food/contents?
A
Large muscular bag for the collection and preliminary digestion of food. Incoming food + contents must be acidified to:
- Neutralise bacteria.
- Degrade food
- Provide optimal pH environment for enzymes e.g. pepsin.
6
Q
What is Gastrin?
A
- Gastrin Stimulates the stomach to secrete acid (2L per day)
- 14-17aa long
- Secreted by G-Cells in the stomach.
7
Q
What is the function of Gastrin?
A
1. Major physiological regulator of gastric acid secretion:
- Acts in concert with AcetylCholine (ACh) and Histamine to stimulate acid release by parietal cells.
- Promotes Pepsinogen & Intrinsic Factor release from Chief cells.
2. Has an important trophic (growth-promoting) influence on the gastric mucosa.
3. Stimulates stomach to empty contents in to Duodenum by contracting.
8
Q
What are he parts of the small intestine?
A
- Duodenum
- Jejunum
- Ileum
9
Q
What is the function of the Duodenum and requirements to do this?
A
Major site of enzymatic breakdown’
Requires:
- ↑ pH of stomach contents (chyme)
- Release of exocrine enzymes + juices from pancreas Bile released from gallbladder.
10
Q
What is Cholecystokinin?
A
CCK secreted (into circulation) by duodenal I Cells in response to Fatty Acids, Amino Acids + Carbohydrates
Rapidly removed by kidney: t1/2 = 3 mins
11
Q
What hormones control the action of the Duodenum?
A
- Cholecystokinin
- Secretin
12
Q
What is the purpose of CCK?
A
- Enzyme release from pancreatic Acinar cells
- Contraction of gallbladder + bile release
- Opens Sphincter of Oddi
- ↑Gastrin (in stomach), ↑ Intestinal motility, Could have satiety effect
13
Q
What is Secretin?
A
- Hormones secreted (into circulation) by duodenal S Cells in response to low pH (<4.5)
- Rapidly removed by kidney: t1/2 = 4 mins
14
Q
What is the function of Secretin?
A
- HCO3- release from pancreatic Duct cells
- Contraction of gallbladder + bile release
- ↓ Gastrin (in stomach)
15
Q
What is VIP?
A
- Vasoactive Intestinal Peptide is a 28 aa peptide that is similar structure to secretin.
- t1/2 = 1 min.
- Is very widely distributed in neuronal tissues as well as GIT
- Work to increase motility and absorption whilst turning off the upper distal sections of GIT.
16
Q
What is the function of VIP?
A
- Stimulates smooth muscle relaxation (lower esophageal sphincter, stomach, gallbladder)
- Stimulates secretion of water into pancreatic juice and bile
- Inhibits gastric acid secretion.
17
Q
What is GIP?
A
- GIP (Gastric Inhibitory Peptide)
- 42aa peptide, similar structure to secretin. t 1⁄2 = 15 mins
- Secreted from mucosal epithelial cells in the first part of the small intestine (duodenum and jejunum) in response to hyper osmolality
18
Q
What is the function of GIP?
A
- Inhibits gastric acid, gastrin and pepsin secretion
- Reduces intestinal motility.
- Enhances the release of insulin in response to infusions of glucose.
19
Q
What are Pancreatic Polypeptides?
A
- 36 aa peptide
- Secreted by the cells of the islets of Langerhans in the endocrine portion of the pancreas, in response to protein- rich meals, fasting, exercise, and acute hypoglycaemia.
- PP levels increase after ingestion of food and remain elevated from 4–8 hours
20
Q
What is the function of Pancreatic Polypptide?
A
- Inhibits gallbladder contraction and pancreatic enzyme secretion
- Relaxes the pyloric and ileocecocolic sphincters, the colon.
Like VIP & GIP, PP acts to ‘switch on’ the proximal sections and ‘switch off’ the distal completed sections’
21
Q
What is Somatostatin?
A
- Small 14 aa peptide
- Secreted from endocrine cells found all over the upper GIT (stomach, small intestine and pancreas) as well as hypothalamus.
- Regulation is complex, but is released in response to high GH.
22
Q
What is the function of Somatostatin
A
- Very powerful inhibitor of endocrine secretion: Inhibits gastrin, secretin, VIP, GIP, PP, TSH, GH, & many others.
- Decreases rate of gastric emptying, pancreatic secretions and smooth muscle relaxation.
Collectively, these activities have the overall effect of decreasing the rate of nutrient absorption and ‘turning off’ the GIT.
23
Q
How is Somatostatin used pharmacologically?
A
Synthetic versions (Octreotide and Lanreotide) used to treat endocrine tumours of the gut and body.
24
Q
What is Ghrelin and what is the cause?
A
- Synthesised in stomach endocrine cells + small intestine.
- Levels rise during fasting and fall in response to food.
- Stimulates Growth Hormone release.
- Stimulates hunger via receptors in the hypothalamus.
25
What is the action of GLP1?
Peptide produced by Intestinal L cells in response to nutrients in the gut.
* Reduces gastric emptying and inhibits gastric acid secretion.
* Stimulates insulin release from the pancreas in a glucose-dependent manner. (it is an Incretin)
* Taking glucose orally results in ~3x more insulin being released than if the same amount is given intravenously. Now recognised as a key regulator of glucose control.
* New diabetes drugs now exist which contain GLP1 (exenatide), or inhibitors of the enzyme which degrades GLP1 (called DPP-4).
26
How is GLP1 used pharmacologically?
* Now recognised as a key regulator of glucose control.
* Taking glucose orally results in ~3x more insulin being released than if the same amount is given intravenously
* New diabetes drugs now exist which contain GLP1 (exenatide), or inhibitors of the enzyme which degrades GLP1 (called DPP-4).
27
What are NETs?
* Classified as part of the large family of Neuro Endocrine Tumours (NETs)
* NETs can originate in any of endocrine or neuronal tissues but are also found in the lung and the rest of the body.
* NETs in the gut mostly occur in the intestines (80% in the ileum)
* Many are benign, while some are malignant. Generally slow growing.
* NETs have common phenotypic characteristics.
28
What are the main groups of Neuroendocrine Tumours?
* Gastro Entero Pancreatic (GEP): a) Carcinoid + b) Pancreatic
* Multiple Endocrine Neoplasia
* Ectopic hormone secreting
29
What are Carcinoid Tumours?
* ~ 2/3 of GEP-Neuro endocrine tumours
* Carcinoid is old generic term used to describe NETs that secrete Serotonin (5-HT), an indole amine.
* Now know that such tumours can secrete many other hormones
* Term ‘Carcinoid’ is still associated with tumours of the Enterochromaffin cells of the gut which are associated with excessive production of Serotonin.
30
What are the symptoms of Carcinoid Syndrome?
* Flushing
* Diarrhoea
* Asthma or wheezing
* Heart palpitations
* Heart failure
* Abdominal cramping
* Peripheral oedema
31
What is the action of Serotonin?
Serotonin is a powerful vasodilator and muscle relaxant (as well as neurotransmitter).
32
What are tests for Carcinoid Syndrome?
* Most useful test is 24hr urine 5-HIAA (5-hydroxyindoleacetic acid): 5’HT metabolite
* Also, Serum Chromogranin A
Both 5-HIAA and Chromogranin A = Tumour Markers
33
What are types of Pancreatic Endocrine Tumours?
1/3 of GEP- Neuro endocrine tumours
* **Gastrinoma**
* **Insulinoma**
* **Glucagonoma**
* **VIPoma**
* **Somatotatinoma**
* **Pancreatic Peptideomas**
Less common types include ACTHoma, CRHoma, calcitoninoma, GHRHoma, and parathyroid hormone–related peptide tumour (PTH-rp) secreting tumours.
34
What are Gastrinomas?
Excessive gastrin causes Zollinger-Ellison Syndrome with peptic ulcers and diarrhoea.
35
What are Insulinomas?
* Increase secretion of Insulin
* Hypoglycaemia occurs with concurrent elevations of insulin, proinsulin and C-peptide.
36
What are Glucagonomas?
* Secretion of Glucagonoma
* Causes rash, sore mouth, altered bowel habits, venous thrombosis, and high blood glucose levels.
37
What are VIPoma?
Also known as WDHA, or Pancreatic cholera syndrome.
* Production of excessive vasoactive intestinal peptide,
* Causes profound chronic watery diarrhoea and resultant dehydration, hypokalaemia, and achlorhydria
38
What are Somatostatinoma?
* Increased Somatostatin
* Rare tumours are associated with elevated blood glucose levels, achlorhydria, cholelithiasis, and diarrhoea.
39
What is Multiple Endocrine Neoplasia?
* Inherited cause of endocrine secreting tumours
* Suspicion if develop \>1 endocrine tumour in the body
40
What are groups of Multiple Endocrine Neoplasia?
**MEN-1**
**MEN-2: Subgroups of MEN-2**
* 2A
* Familial Medullary Thyroid Cancer (FMTC)
* 2B (Although considered to be distinct, there is some overlap in the glands affected)
41
What is MEN-1?
Due to loss of function of MENIN -1 (tumour suppressor gene). Affects 3 P’s:
* **Parathyroid** (\>90% of patients)
* **Pituitary (anterior)** up to 40%
* **Pancreato-biliary** (Pancreatic and GI) 60-70%, 50% = gastrinomas, 20% PP, \<3% each of others; VIP, glucaconomas, somatostatinomas
42
What is MEN-2A?
Due to gain of function mutation in the RET2 oncogene
* Familial Medullary Thyroid Carcinoma (MTC)
* Phaeochromocytoma
* Parathyroid (hyper para)
43
What is MEN-2B?
* MTC
* Phaeochromocytoma
* Mucosal neuromas
* Marfanoid Features
* Absence of parathryoid
44
What is the presentation of Neuroendocrine Tumours?
Early Presentation: Difficult to recognise early due to being uncommon diagnosis for common symptoms
* Ulcers
* Diarrhoea
* Flushing
Late Presentation: Patients present because of malignancy
* Tumour bulk
* Blockages
* Severe weight loss/malabsoption
* Pancreatic tumours with unexpected survival
45
What is the investigtion for Neuroendocrine Tumours?
Blood specimen:
* peptide screen: Chromogranin A
* Fasting gut hormone screen
Urine
* Urinary 5-HIAA (24 hour collection)
Scan
* US, CAT, MRI, PET
* Octreotide scintigraphy using MIBG
Biopsy or surgery
* Immuno-histological staining
