Endocrinology of the gut Flashcards
Pancreatic secretions components
pancreatic duct: water,ions and digestive enzymes - acinar cells. Bicarbonate
Bile
Made by liver, stored in gall bladder - bile salts and bilirubin
Tail of pancreas
Connect to duodenum via pancreatic duct
Arterial routes
Delivering blood to three separate capillary beds. Foregut, midgut, hindgut
Venous return
All via hepatic portal system.
One single separate capillary bed for the gut leading to the liver’s own capillary bed
2 separate lymphatic systems
Lacteals - draining the villi layer
One draining the muscle layer
Lymph nodes structure and function
Dense areas of lymphocytes and macrophages.
Role: Homeostasis of immune, fluid pressure and nutrient transport
Have defined structure with capsule of connective tissue and areas of lymph nodule tissue and sinus tissue
Sympathetic innervation
From spine predominatly motor
Foregut (& adrenal medulla) innervation
T5-8
Pre-ganglionic fibres synapse near target organs
Midgut innervation
T9-12
Hindgut (& kidney, bladder) innervation
L1-3
Parasympathetic
Vagus nerve for foregut and mid-gut. Pelvic splanchnic nerve for hindgut. 75-80% sensory, 20% motor
Vagus nerve
Afferent and efferent
Sensory neurons in vagus nerve trunks are sending information from mechano -(baro-) and chemo-receptors in GI tract to brain
Brain signals secretory or contractile messages controlling gastric capacity
ENS (Enteric Nervous System)
Two layers - myenteric and submucosal
Operates independently of CNS
Submucosal plexus
GI blood flow - detecting nutrients and secreting hormones
Myenteric plexus
contraction and relaxation of gut wall
Neurotransmitter
Epinephrine and Norepinephrine can move through circulation like a hormone (neurohormone)
Gut-brain axis pathways
Bidirectional communication between gut and brain
Involves neural, hormonal, and immunological pathways
Neural: Enteric nervous system communicates via vagus nerve
Hormonal: Gut hormones like serotonin, dopamine influence mood, appetite
Immunological: Gut immune cells produce cytokines affecting brain function
Endocrine cells
Glands are for absorption but also secrete substances
Pits have different specialised cells.
Neuronal & endocrine control of gastric function
Includes negative and positive feedback
Vagal innervation via ENS
Stimulates parietal cells (secrete acid / HCl)
ECL cells (Histamine - stimulates parietal cells
G cells in antrum - (Gastrin - stimulates ECL cells
Inhibits: D-cells in the corpus & antrum (SST)
All acting to enhance HCl secretion for digestion in stomach - chyme
pH < 2 stimulates D-cells in atrum
Stimulation of D-cells - inhibit parietal & ECL cells
Chyme enters the duodenum (lowers pH. Stimulates S-cells (Secretin - stimulate D cells & stimulates pancreas to release bicarbonate)
Both working to counteract release of HCl and bring pH up for enzymes to work
Gastrin cells (G cells) in stomach
Predominate in antrum - secreted when food present Stimulate chief cells (pepsinogen -> pepsin), ECL cells (produce histamine) which stimulate parietal cells (HCl and intrinsic factor which helps uptake of Vit B12)
Upper intestine cells
Secreted in response to chyme entering duodenum
Secretin cells
Cholecystokinin cells
Secretin cells
Stimulate D cells to produce somatostatin (inhibit gastrin) and stimulate bile and pancreatic duct to secrete bicarbonate and water.
Cholecystokinin cells (CCK, I cells)
stimulates pancreatic acinar cells to secrete digestive enzymes and stimulates the gallbladder to release bile
Somatostatin (SST, D cells)
Inhibit parietal cells and ECL cells, thereby inhibiting the function of G-cells
L cell secretions
GLP-1
GLP-2
Oxyntomodulin
PYY
GLP-1
Many actions - brain, gut (slow gastric emptying) and pancreas - maintain blood glucose levels
GLP - 2
Main target is gut - increase nutrient transport and enhance gut surface area
Oxyntomodulin
Suppress appetite
PYY
Lower enzyme, bicarb and bile secretion - slow gastric emptying
K cell hormone
GIP (Gastric inhibitory peptide)
GIP (Gastric Inhibitory Peptide)
Pancreas - enhance insulin secretion and decrease glucagon secretion
P/D1 cells
Secrete Gherlin
Ghrelin
Stimulates hunger. Gastric motility and emptying
Microbiome
Gut - brain axis
Produce chemicals that interact with neurons and hormone producing cells.
Fecal microbiota transplant
Treat GI disease. Future hopes - obesity, insulin resistance.
Microbiome and appendix
Disturbances in ecosystem result in commensal populations of microbiome repopulate from the appendix
Appendix is important for linking immune function and the microbiome.
Gastrointestinal neuroendocrine tumours (NETS)
NET - tumour origination in a neuroendocrine cell, cause overproduction of hormone driving symptoms or reducte hormone production.
GI-nets
Serotonin
Gastrin
Glucagon
PNets
Insulin
Glucagon
Somatostatin
Gastrin
Vasoactive intestinal polypeptide (VIP)
Gastrinoma (Zollinger Ellison Syndrome)
Stomach ulcers and diarrhea
Insulinoma
Hypoglycemia
Glucagonoma
Hyperglycemia and diabetes
Somatostatinoma
Gallstones, intolerance to fat in the diet and fatty diarrhea
GLP-1 RA
activates GLP1 receptors (mimics GLP1) e.g Ozempic
DPP4 inhibitors
Reduces breakdown of GLP-1 and GIP (gliptins)
GIP/GLP-1 receptor co-agonist
e.g. tirzepatde recently approved overseas
GIP/GLP-1/ Glucagon receptor
Retatrutide in trials
Bypass surgery
Most effect treatment for obesity and co-morbidities (diabetes, myocardial infarction and stroke)
Gut hormones and bypass surgery success
Gut hormones: PYY & GLP-1 higher after surgery and stay higher.
GDF15
Metformin is great at driving weight loss induced GDF15 and its source is the gut and kidney.
Expression of GDF15
Healthy adults - low levels, upregulates in stress and intense exercise.
Pregnant - highly upregulated (produced by placenta)
Upregulated in several disease states including obesity and is secreted by tumours
