GIT - digestion and absorption Flashcards
What is the length of the GIT
9m
Where are most nutrients absorbed
Jejunum
Where is B12 absorbed
Terminal Ileum
where is iron absorbed
duodenum
Where is dietary fat and water absorbed
Throughout
Describe the layers of the small intestine
ADVENTITIA MUSCULARIS EXTERNA (Peristalsis) - Outer longitudinal smooth muscle - Myenteric plexus - Inner Circular smooth muscle SUBMUCOSA - Meissner's plexus (secondary enteric nervous system plexus) blood vessels, lymphatics, elastic connective tissue MUCOSA - Muscularis mucosae - Lamina propria - Epithelium
What is the difference between muscularis externa and muscularis mucosa
Muscularis externa
- longitundinal muscles
- myenteric plexus
- circular muscles
–> responsible for peristalsis
Muscularis Mucosa
- Within the submucosa
- innervated by Meissner’s plexus
- Agitate mucosa increasing contact with luminal content and preventing their adherence
Where are Peyer’s patches and what do these do
Lymphoid nodules within the lamina propria of the mucosa of the terminal ileum
Where is Meissner’s plexus. What else is contained in this layer of the intestine
Within the submucosa
also
Blood vessels
Lymphatic vessels
Elastic connective tissue
What is the length and surface areaof the small intestine. How is this achieved
Length - 7m
SA: 250 m^2
- Valvulae conniventes - mucosal folds that project into the lumen of the SI
- Villi - Tiny finger-like projections of the intestinal wall
- Microvilli - microscopic projections on top of villi (brush border)
What structures lie between the villi in the small intestine and what is the function of these structures
Goblet cells –> secrete mucus
Intestinal crypts –> secrete brush border enzymes and contain stem cells
Describe blood and lymphatic supply to each villi
A single arteriole –> capillaries –> single venule
Lacteal = a single lymphatic capillary which transports absorbed fats as chylomicrons to the thoracic duct.
Where does digestion of CHO begin and how
Mouth
Salivary amylase
After the mouth when does CHO digestion recommence and how
Duodenum
Pancreatic amylase
Subsequent to salivary amylase and pancreatic amylase, how does CHO digestion proceed?
Brush border enzymes
- Sucrase
- Maltase
- Lactase
–> Disaccharides to monosaccharides
Describe the sucrose, maltose and lactose monomers
Sucrose –> glucose + fructose
maltose –> glucose + glucose
Lactose –> glucose + galactose
What causes lactose intolerase
Brush border enzyme lactase deficiency
Which CHO passes through the GIT undigested and why
Cellulose –> no brush border enzymes present for hydrolysis
How are glucose and galactose absorbed
Enterocyte
SGLT - 1
Sodium Glucose Linked Transporter- 1
This is secondary active transport subsequent to basolateral Na/K+ ATPase activity.
How is fructose absorbed
facilitated diffusion (not by Na+ transport)
How are pentose sugars (like ribose and deoxyribose) absorbed
Simple diffusion
Once secondary active transport via the SLGT-1 has transported the glucose and galactose into the enterocyte, how does absoprtion continue
Down concentration gradient. Pass through the basolateral membrane via the GLUT-2 glucose transporter (facilitated diffusion) Into the capillary network within the villi –> venule –> portal vein –> Liver
monosaccharides are osmotically active so co-absorption of water occurs
Where does protein digestion begin. Name the cells enzyme and cofactors involved
Stomach - Pepsin
Chief cells —> pepsinogen + low pH (HCl) –> pepsin
Parietal cells –> HCl
How is protein digstion continued in the duodenum
Pancreatic trypsin and chymotrypsin cleave polypeptides –> dipeptides and tripeptides
How is protein metabolism continued at the brush border?
Brush border integral membrane proteins attached to villi called peptidases cleave dipeptides and tripeptides into single amin oacids
How are amino acids absorbed into the enterocyte
Similar to glucose:
Secondary active transport (driven by basolateral Na/K ATPase)
Sodium lined co-transport.
There are different co-transporters for neutra, acidic and basic amino acids
Short peptides ( 2 or 3 linked aa’s) are also absorbed by an H linked transport system
What happens to the short peptides once absorbed into the enterocyte
Broken down into single amino acids inside the enterocyte
How are amino acids transported into portal circulation
facilitated diffusion through the basolateral membrane
Water absorbed as amino acids are osmotically active
What is a triglyceride
Glycerol backbone with three fatty acid residues attached
What other forms of dietary lipid are there
Triglycerides
Cholesterol
Fat-soluble vitamins
Phospholipid
What is emulsification. Where does it occur, How does it occur, why does it occur
Lipids are insoluble in water.
Form large droplets in the aqueous environment of the GIT.
Bile acids (secreted by the liver, stored and then released from the gall bladder) coat lipid droplets dividing them into multiple smaller droplets so increasing the surface area for digestive enzymes to work.
What is the name of the enzyme breaks down triglycerides. Describe this process
Pancreatic lipase covers the outer surface of the smaller lipid droplets and acts on TG molecules resulting in the formation of two free fatty acids and a 2 - monoglyceride.
What is a Micelle
Micelle formation
The ffa’s and 2-monglycerides released from TG combine with BILE SALTS forming micelles containing small balls of mixed lipids and bile salts
What happens when a micelle makes contact with an enterocyte
The lipid contained within is absorbed by simple diffusion.
the bile salts remain in the gut lumen until the terminal ileum when they are reabsorbed and returned to the liver - recycled.
What is a chylomicron
Monoglycerides and fatty acids travel to the smooth endoplasmic reticulum in the cytoplasm of enterocytes where they are recombined to form a TG. The TG is packaged with CHOL and phospholipid and a cellular label called APOLIPOPROTEIN to form lipid balls called chylomicrons.
What happens to chylomicrons once formed in the enterocytes
Released from enterocytes into lacteals (the lymphatic capillaries that service each villus).
Chylomicrons then flow through the lymphatic system until they are released into systemic circulation at the thoracic duct.
What is Orlistat
Orlistat is a pancreatic lipase inhibitor. Prevents breakdown of TGs and hence prevents TG absorption. TG remains undigested and unabsorbed in the GIT resulting in Steatorrhoea
Pancreatic insufficiency also presents with steatorrhoea
Describe the cells, and % cell mass, of the endocrine pancreas
The cells with endocrine function are call the ISLETS OF LANGERHANS
- Make up 1 - 2 % of pancreatic cell mass
alpha cells - glucagon
beta cells - Insulin
delta cells - somatostatin
PP cells - pancreatic polypeptide
What volume of pancreatic juice produced per day
1.5 L which drains into the duodenum via the pancreatic duct
Describe the main cell types of the exocrine pancreas
Acinar cells = produce digestive enzymes
Ductal cells = secrete HCO3- and water
What is the difference between exocrine and endocrine
Exocrine - secretes substances via a ductal system to an epithelial surface
Endocrine - secretes substances directly into the blood stream
What proenzymes and enzymes do acinar cells produce
- Protein: Trypsinogen and chymotrypsinogen
- CHO: Pancreatic amylase
- Fat: Pancreatic lipase
How are trypsinogen and chymotrypsinogen activated
After secretion into the duodenal lumen, enterokinase (mucosa of small intestine) cleaves trypsinogen into trypsin, a powerful peptidase.
Trypsin then cleaves both trypsinogen and chymotrypsinogen, resulting in chymotrypsin and more trypsin
Trypsin –> more trypsin = autocatalysis
What is autocatalysis
The process where by trypsin results in further formation of trypsin by catalysis of trypsinogen.
What is the role of trypsin in acute pancreatitis
In acute pancreatitis there is inappropriate activation of proenzymes within the pancreas.
Trypsin activates more trypsin (autocatalysis)
Trypsin also activates:
1. Phospholipase A2 –> breaks down pancreatic cell membrane phospholipids –> necrosis
- Elastase –> digests blood vessel walls –> haemorrhage
Massive release of inflammatory mediators TNF alpha and IL -1 into systemic circulation –> SIRS.
- Pancreatic lipase is releasedinto the interstitium where it digests retroperitoneal fat –> retroperitoneal haemorrhagic necrosis –> Grey-Turner’s sign (discoloration flanks) and Cullen’s sign (Periumbilical discoloration
What is Grey-Turner sign
What is Cullen’s sign
Indicate severe pancreatitis
Result from release of pancreatic lipase into instersitium –> haemorrhagic necrosis of fat
Grey-Turner’s sign: discolouration of flanks
Cullen’s sign: Periumbilical discolouration
What do the ductal cells of the pancreas secrete and why
HCO3- and water
HCO3- is to neutralize the acidic pH from the stomach which would denature the pancreatic enzymes rendering them unable to digest their respective food groups.
Describe the process of HCO3- formation and secretion in the pancreatic ductal cells
- CO2 diffuses in
- CO2 + H2O –> H2CO3 –> H+ + HCO3- (Carbonic anhydrase)
- H+ exchanged for Na+ (H+/Na+ exchanger - basolateral). Gradient for Na+ provided by Na+/K+ ATPase
- HCO3- into pancreatic duct lumen in exchange for Cl-. Cl- then returns to pancreatic duct lumen via CFTR
CFTR = Cystic Fibrosis Transmembrane conductance Regulator
This is defective in cystic fibrosis
HCO3- is osmotically active so water moves with HCO3-
How is pancreatic secretion controlled
Neural and Humoral
Neural
1. VAGUS
Meal anticipation –> Vagus –>increase acinar cell activity
Humoral
1. GASTRIN
Gastric distension –> Gastrin (G cells) –> stimulates pancreatic acinar cells to secrete digestive enzymes (feed-forward control system)
- CHOLECYSTOKININ (CCK)
Chyme in duodenum –> CCK secretion (Mucosa)
a) Increase bile production in liver
b) stimulate contraction gall bladder
c) Slow gastric emptying
d) Stimulate pancreatic acinar cells to secrete digestive enzymes - SECRETIN
Chyme in duodenum –> secretin secretion (Mucosa)
a) Slow gastric emptying
b) Stimulate ductal cells of pancreas to secrete HCO3- + Water
What are the functions of Cholecystokinin
a) Increase bile production in liver
b) stimulate contraction gall bladder
c) Slow gastric emptying
d) Stimulate pancreatic acinar cells to secrete digestive enzymes
What are the functions of secretin
a) Slow gastric emptying
b) Stimulate ductal cells of pancreas to secrete HCO3- + Water
How does intestinal motility differ between the fed and the fasted states
Fed
1. Segmental contractions x 2 compartmentalises followed by continuous longitudinal contraction-relaxation for mixing/contact
- Propulsive contractions: Co-ordinated circular then longitudinal contraction-relaxation
Fasted
- Infrequent, regular contractions of the small intestine
- Every 90 minutes there is a period of intense co-ordinated intestinal contraction spreading from the duodenum to the ileocaecal valve = Migrating Motor Complex
What is the Migrating Motor Complex
Infrequent, regular contractions of the small intestine in the fasted state.
- Every 90 minutes there is a period of intense co-ordinated intestinal contraction spreading from the duodenum to the ileocaecal valve = Migrating Motor Complex
What is the resting membrane potential of smooth muscle cells of the small intestine and when does contraction of smooth muscle occur
-40 to -70 mV
When membrane potential exceeds threshold potential –> opening of voltage gated sodium and calcium channels –> sudden influx Na and Ca –> depolarizes cell membrane and causes contraction
What are slow waves and describe the process of depolarization in the smooth muscle of the small intestine
This is a pattern of fluctuation of the membrane potential of the smooth muscle membrane of the small intestine.
The fluctuations are not enough to exceed threshold –> Instead they help to CO-ORDINATE depolarizations and contractions of the small intestine
Food bolus –> release of ntmtrs –> small depolarization + at the time of next ‘slow wave’ –> threshold will be exceeded –>spike potential –>smooth muscle contraction
Describe the neural control of intestinal motility
NEURAL
Enteric nervous system - extensive network of afferent and efferent neurons converging on two types of ganglion:
- Myenteric (Auerbach’s) plexus
- Submucosal (Meissner’s) plexus
Semi-autonomous with input from ANS
- SNS: Reduced GIT motility / secretions /blood flow
- PSNS (Vagus): Increase motility / secretion / blood flow
Describe the humoral control of intestinal motility
CCK + Secretin –> slow gastric emptying
Motilin - released from duodenal mucosa every 90 minutes –> Migrating Motor Complex.
Vasoactive intestinal peptide (VIP) - Increase GIT secretion of water an electrolytes
Which drug is a motilin agonist
Erythromycin
