Physiology Of Small Intestine

Question 1

Products of gastric digestion and low pH in small intestine trigger release of:

Answer 1

Alkali (to neutralise acidic chime from stomach)
Mucus (alkali so for same reason)
Water (neutralization also)
Digestive enzymes (mainly from exocrine pancreas)
Hormones (to control secretion/absorption)

Question 2

What are the secretions of the small intestine?

Answer 2

Mucus: secreted by brunners gland in duodenal mucosa
Water: Na+, Cl- and HCO3- secreted into lumen by intestinal epithelium and water follows via osmosis (net absorption from small intestine as you go further down)
Hormones: E.G. secretin, cholecystokinin (CCK), motilin, vasoactive intestinal peptide (VIP) and gastric inhibitory peptide (GIP)
-> aims to reduce acidity and hypertonicity of chyme coming through

Question 3

What are the intestinal hormones and what do they do?

Answer 3

Motilin: stimulates Migrating Motor Complexes (MMCs) via ENS and ANS
Vasoactive Intestinal Peptide: increases blow flow to GI tract
Gastric Inhibitory Peptide (GIP): glucose-dependent insulinotropic peptide that inhibits gastric secretion and insulin secretion
CCK & secretin: inhibit gastric motility and secretion & control pancreatic and biliary secretion

Question 4

What are Migrating Motor Complexes?

Answer 4

Stimulate a pattern of interdigestive motility acting between periods of digestive motility so serve to sweep contents of GI tract that cannot be digested out of GI tract (responsible for rumbling tummy between meals when digestive process quiescent)

Question 5

What does secretin do?

Answer 5

Acts on exocrine pancreas causing it to release bicarbonate ions
Stimulates liver to produce bile

Question 6

What does CCK do?

Answer 6

Acts on exocrine pancreas stimulating the secretion of pancreatic enzymes
Stimulates contraction of gallbladder

Question 7

What does the exocrine pancreas secrete?

Answer 7

Acinar cells secrete digestive enzymes;
trypsin & chymotrypsin (endopeptidases) and carboxypeptidase (ecopeptidase) cleave proteins and peptides (secreted in inactive components
Pancreatic amylase breaks down starch
Lipases break down fat
Other enzymes e.g. phospholipase, cholesterol esterase, ribonuclease etc.

Duct cells secrete alkali;
isotonic solution rich in HCO3- ions & neutralizes acidic duodenal contents

Both secreted onto epithelial surface via duct

Question 8

How do peptidase enzymes in the pancreas become active?

Answer 8

They are secreted as zymogens i.e. inactive enzymes in the form of trypsinogen
This is cleaved by membrane-bound enterokinase producing active trypsin
Can also then cleave other inactive enzymes to active enzymes in the intestinal lumen (also dietary trypsin can do this)

Question 9

What is the mechanism of pancreatic HCO3- secretion?

Answer 9

H+ pumped out of duct cells and released in blood
HCO3- secreted by duct cells move into GI lumen into pancreatic duct lumen
Catalysed by carbonic anhydrase
Contents released into small intestine

Question 10

What hormones control pancreatic secretions?

Answer 10

Enzyme secretion stimulated by CCK and acetylcholine (from parasympathetic postganglionic neurones of vagus)
Alkali secretion stimulated by secretin and potentiated by CCK and acetylcholine (vagal tone) - CCK and ACh stimulate secretin which stimulates alkali in turn

Question 11

What occurs during small intestine digestion?

Answer 11

Fats (triglycerides) digested by pancreatic lipase -> monoglyceride and FAs which are then absorbed
Starch digestion by pancreatic amylase -> disaccharides are broken down into monosaccharides by brusher border enzymes
Proteins broken down to peptide fragments by trypsin and chymotrypsin -> peptide fragments digested to free AAs by carboxypeptidase and aminopeptidase

Question 12

How are fats digesting and absorbed?

Answer 12

Emulsification of fats by bile salts and phospholipids holding them in suspension for enzymatic action
Pancreatic lipase digests fat -> monoglycerides, FAs & bile salts (fat-soluble vitamins too)
Products held in micelles combined with bile salts and phospholipids
Micelles diffuse into unstirred layer next to epithelial cells so FAs and monoglycerides can diffuse into cell membrane
Reassembled into fats in cells
Triglyceride (and fat-soluble vitamins) droplets packaged into chylomicrons
Chylomicrons exported across basolateral membrane and leave intestinal villus via lacteal lymph vessel -> circulation eventually

Question 13

How are carbohydrates digested and monosaccharides absorbed?

Answer 13

Starch broken down to produce dissacharides maltose and branched chain glucose
Sucrose and lactose from diet also present
Brush border enzyme in intestinal epithelial cell breaks disaccharides down into monosaccharides glucose, galactose and fructose in lumen
Fructose moves across luminal membrane by facilitated diffusion down concentration gradient through GLUT5 transporter
Glucose/galactose use SGLT transporter (Na+ linked - secondary active transport)
Facilitated diffusion through GLUT for all 3 to go through the basolateral membrane to the blood

Question 14

How are proteins digested and amino acids and oligopeptides then absorbed?

Answer 14

Pepsin starts digestion of proteins in the stomach
Proteins -> polypeptides -> tri/dipeptides -> breakdown of constituent AAs by aminopeptidase in SI
AAs get across epithelial cell via co-transporters linking their transport with Na+ ions (specific ones for each AA)

Question 15

How do short-chain fatty acids get into epithelial cell in contrast to long chain?

Answer 15

Simple diffusion

Question 16

How is calcium transported across the intestinal epithelium?

Answer 16

Small fraction absorbed from diet and happens mainly in duodenum and jejunum
Ca moves down concentration gradients by a Ca channel in cell
2 specialised transporters move Ca against concentration gradient across basolateral membrane: Ca ATPase & Na Ca exchanger
Vitamin D stimulates absorption of Ca

Question 17

What are the 2 forms of dietary iron?

Answer 17

Haem iron is the haem portion of haemoglobin, myoglobin and cytochromes - animal products
Free iron which is insoluble, inabsorbable Fe3+, complexed in food and digestive secretions - vegetable product
Important for oxygen binding of haemoglobin and key component of active site of enzymes so need it from diet

Question 18

How is haem iron absorbed?

Answer 18

Receptor-mediated endocytosis
Digested in enterocyte to release iron (Fe3+)
Fe3+ reduced to Fe2+
Rest of Fe2+ binds ferroportin 1 in basolateral membrane for export from enterocyte

Question 19

How is free iron absorbed?

Answer 19

Fe3+ reduced to Fe2+ by duodenal cytochrome b ferric reductase in brush border membrane of SI
Fe2+ crosses brush border via divalent metal transporter 1 (DMT1)
Some Fe2+ binds ferroportin 1 in basolateral membrane for export from enterocyte

Question 20

How is iron absorption regulated?

Answer 20

A proportion transported into enterocyte is taken up into intracellular mucosal ferritin stores instead
This is lost from body in faeces when intestinal mucosa sloughed into intestine Therefore, iron depletion upregulates ferroportin so more iron is transported into blood and less is taken up into ferritin pool and excreted

Question 21

What are the important vitamins and how are they absorbed in the SI?

Answer 21

Fat soluble vitamins A, D, E and K (follow fat absorption pathway)
Water-soluble diffusion (absorbed via diffusion, facilitated diffusion or active transport)
Vitamin B12 absorbed be special mediated-transport system`

Question 22

How is vitamin B12 absorbed?

Answer 22

Binds to R protein in stomach
Released in duodenum and jejunum, change in pH breaks down complex and B12 binds Intrinsic Factor (IF) instead
In terminal ileum, this complex is absorbed by receptor-mediated endocytosis
Complex broken down in cell and B12 released into blood where it binds to proteins to carry it in circulation

Question 23

What is malabsorption and how can it come about?

Answer 23

When digestion goes wrong there can be a specific malabsorption of lactose for e.g. or a general one due to damage of GI tract for e.g.
Can arise from failure/deficiency in pancreatic enzyme secretion, absorption, brush border enzymes or bile secretion

Question 24

What type of malabsorption is coeliac disease?

Answer 24

Damage to mucosa in duodenum and jejunum

Defect in fat absorption and lactose hydrolysis

Question 25

What type of malabsorption is pancreatitis?

Answer 25

Deficient enzyme secretion in pancreas

Defect in fat digestion

Question 26

What type of malabsorption is Crohn’s disease/surgical resection of ileum?

Answer 26

Ileum pathology

Vitamin B12 and bile salt/bile acid absorption defects

Question 27

What type of malabsorption is lactase deficiency?

Answer 27

Occurs in small intestine

Defect in lastase hydrolysis

Question 28

How does lactose intolerance work?

Answer 28

Absence/deficiency of lactase in SI wall so lactose cannot be broken down to glucose and galactose
It is carried to LI and bacteria here break it down into constituent monosaccharides
No transporters for them in LI so stay here and are further acted upon by bacteria to release molecules like gas for e.g.
Osmotically active molecules draw water across walls of LI too stimulating diarrhoea
= bloating + increased motility

Question 29

What are the symptoms of malabsorption?

Answer 29

Weight loss
Abdominal distention
Diarrhoea
Steartorrhoea (deficiency in pancreatic lipase and bile salts - struggle to breakdown/emulsify fats)
Fatty stools
Pernicious anaemia (defect in maturation of RBCs due to vitamin B12)
Hypochromic anaemia

Question 30

Explain the acid-base balance in the digestive process.

Answer 30

Large amounts of H+ and HCO3- traverse specialised epithelial of many parts of gut
Under normal conditions only a small amount of alkali lost in stool
Disruption of normal gut function can overwhelm acid-base homeostasis

Question 31

What symptoms would show if acid-base homeostasis in the gut went wrong?

Answer 31

Excessive vomiting (large losses of secreted acids from body) which may result in metabolic alkalosis
Diarrhoea (excessive lose of fluid and hence NAHCO2 in faeces) which may result in metabolic acidosis