GI physiology intestinal absorption

Question 1

Describe the structure of the villi

Answer 1

Villi in the small intestine are finger-like projections 0.5-1.5 mm tall that increase the surface area for absorption by 10 fold.

 Duodenum: much flatter and form a tongue-like structure.
 Jejunum: tallest villi.
 Ileum: much shorter in height. Around 0.5 mm.
 Reflects their role in absorption. Most absorption occurs in the jejunum and less in the ileum.

Question 2

Describe the structure of the microvilli

Answer 2

Microvilli on enterocytes are 1 μm long and 0.1 μm in diameter.

They increase the surface area by 20 fold.
The brush border membrane (BBM) is formed by microvilli.
Estimated total surface area for absorption is 200 m2
(both villi and microvilli).

Question 3

Describe the GI mucosal barrier

Answer 3

Optimum function of the epithelial is required for optimal digestion and absorption.
 Epithelium in the GI tract is renewed every 3-6 days in the ileum. This keeps the epithelial
cells in the optimum working capacity.
 Epithelium is held together by tight junctions which stops undigested food, bacteria and
viruses penetrating the epithelial layer.
 There are mechanisms to create mucous layers. Mucous and fluid are secreted onto the
surface of epithelium which acts as a protective layer. The mucous layer is not always
effective in the stomach, as gastric ulcers and duodenal ulcers can form due to high levels of
HCl damaging the epithelium if all of these mechanisms are not in place.
 Damage to epithelium affects absorption.

Question 4

What is malabsorption syndrome

Answer 4

Refers to a number of disorders in which the intestine’s ability to digest and absorb certain nutrients and fluids is affected.
 Pathological mechanisms are divided into:
o Intraluminal: impaired digestion (bacterial overgrowth or pancreatic insufficiency).
o Intestinal: structural changes (coeliac disease or surgical resection); impaired brush-border hydrolase activity
(lactase deficiency); impaired transporter activity (glucose-galactose malabsorption).
o Post-epithelial: obstruction of the lymphatic system.

Question 5

What happens in coeliac disease?

Answer 5

Coeliac disease: autoimmune disease caused by the aggregation of killer
T-cells in response to gluten.
 Enterocytes present on the villi are lysed.
 Stem cells in the crypt differentiate and create absorptive cells which
move up the villi and mature to allow absorption.
 Cells on the upper 1/3 are functionally able to absorb nutrients:
o Moderate villus atrophy: enterocytes are in their immature
state. Some structures but impaired absorption.
o Complete villus atrophy: complete inability to absorb nutrients.

Question 6

Define apical mebrane, basolateral membrane, transcellular transport, paracellular transport and active transport

Answer 6

Apical membrane: in contact with the lumen, and can have villi
(brush border membrane).
 Basolateral membrane: in contact with the interstitium and is
adjacent to the basement membrane.
 Transcellular transport: transport of solutes by a cell through a cell
(from the apical membrane to basolateral membrane).
o Example: movement of glucose from the intestinal lumen to
extracellular fluid by epithelial cells.
 Paracellular transport: transfer of substances across an epithelium
through the intercellular space between the cells.
o Example: proximal tubule of a kidney nephron.
 Primary active transport: utilising energy in the form of ATP to
transport molecules across a membrane against their concentration
gradient.
 Secondary active transport: utilising energy in others forms than ATP
to transport molecules across a membrane against their
concentration gradient.
 Facilitative diffusion: passive transport of molecules or ions across a
cell’s membrane via specific transmembrane integral proteins (carrier
protein or ion channel) down the concentration gradient.

Question 7

What factors determine absorption

Answer 7

 Surface area of intestine
 Extent and location of uptake.
 Transport route and protein properties.

Question 8

What is a sodium glucose transporter

Answer 8

o Transporter has a huge capacity for water absorption. For every 1 glucose
transported, 250 water molecules can enter the cell.
o Movement of water through this transporter can be through the
transporter itself, but also due to the osmotic gradient which increases the
absorption of water by these two pathways.

Glucose galactose malabsorption is a genetic disease caused by mutations in SGLT1 (sodium-glucose linked transporter 1).
 Thought that in man, SGLT1 is responsible for absorbing 5 L H2O per day.
 Water is transported through aquaporins. Aquaporin proteins are present at the brush border and basolateral membrane.
There are a large number of isoforms.

Question 9

What are the pathways for intestinal fluid secretion

Answer 9

Chloride secretion occurs from the cells lining the crypts of Lieberkühn. The crypts of Lieberkühn are tubular glands that lie between the finger-like projections of the
inner surface of the small intestine. The cells secrete intestinal juice as they gradually migrate along the side of the crypt
and the villus.
 Can occur in all intestinal segments.
 Under normal conditions CFTR levels are low. Cl
− transport through the channel makes an
electrochemical gradient due to Cl− in the lumen. Na+ travels through tight junctions, forming
an osmotic gradient which drives the secretion of water.
 Pathway can be stimulated by secretagogues1
such as VIP (vasofactor intestinal peptide) and
parasympathetic nervous system activity.

Question 10

How does the cholera toxin cause secretory diarrhoea

Answer 10

 Caused by the bacterium Vibrio cholerae.
 Toxin binds to receptors on the brush border membrane on the enterocyte.
 This increases intracellular cAMP.
 Increased promotion of CFTR transporter on the membrane.
 Increased ability to drive Cl
− secretion.
 Increased ability to drive water secretion.
 Pathway is affected in traveller’s diarrhoea and the pathway has a huge capacity to upregulate water secretion (up to 12 L
of fluid per day).
 Different to osmotic diarrhoea, where the carbohydrates cannot be absorbed. Carbohydrate remains in the lumen, and
when it reaches the colon, draws water into the intestinal lumen.

Question 11

What is the basis of rehydration therapy in secretory diarrhoea

Answer 11

 Cholera leads to increased fluid secretion from the crypts of the villi but has no effect on
the transport processes of the enterocytes (especially glucose transport through SGLT1).
 Fluid that contains glucose and NaCl stimulates transport pathways.
 ORS can alleviate some of the problems caused by cholera by allowing 4 L of reabsorption
of water.
 Not appropriate for individuals who lack SGLT1, because this creates an even greater driving
force for secretory diarrhoea.

Question 12

How does electrolyte transfer occur across upper small intestine epithelium

Answer 12

Low intracellular [Na+] so a concentration gradient is formed.
 Sodium-dependent transport processes: transport of sugars, phosphates, amino acids into the cell coupled with Na+.
 Sodium-dependent exchangers: proton exchanger, NHE3, is dependent on Na+.
As Na
+ and nutrients move across the enterocyte, an
electrochemical gradient is formed, which allows the reabsorption
of Cl
−, H2O and K
+ paracellularly.
 The osmotic gradient allows water reabsorption transcellularly and
paracellularly.
 In the upper small intestine, there is no transport of bicarbonate but
CO2 and H2O are converted into HCO3
−.
 AE exchangers bicarbonates for Cl
− at the basal membrane.

Question 13

Why are proteins important in the diet

Answer 13

Dietary protein intake: 50 g/day
 Protein digestion occurs by distinct mechanisms in different regions of the GI tract.
 Absorption occurs predominantly in jejunum and upper ileum.
 Multiple transport pathways
 Important, because it is used in the phospholipid bilayer.

Question 14

What are the processes involved in protein digestion

Answer 14

Protein digestion is initiated in the mouth which breaks
up the fibres of the protein before they are passed into
the stomach.
 Presence of HCl and pepsin denatures and hydrolyses
proteins.
 As chyme is delivered into the small intestines,
enzymes from the pancreas are delivered into the
duodenum to promote the process of luminal protein
digestion.
 This generates small peptides and amino acids which
come into contact to BBM. The BBM secretes specific
peptidases which continue the process of digestion.
 Dipeptides and tripeptides that the enzymes form are absorbed across BBM of enterocytes.
 Further digestion within the cell by dipeptidases and tripeptidases.
 Amino acids transported into the blood stream.

Question 15

What are the mechanisms of intestinal peptide and amino acid transport

Answer 15

NHE3 transporter: Na+ exchanger provides H+ into the lumen
which forms a concentration gradient which fuels this transport
process.
 PepT1 (protein dependent co-transporter): on the BBM. Transports
small peptides (dipeptides and tripeptides) into the cell along with
H+.
Once inside the cell, the small peptides are hydrolysed by
peptidases and the amino acids are transported across the
basolateral membrane by specific amino acid transporters.
20 different amino acid transporters on the BBM enables transport
of all the different types of amino acids.

Question 16

Describe the processes involved in dietary carbohydrate digestion

Answer 16

Complex carbohydrates are first
digested in the mouth by saliva and
amylase.
 Neutralisation occurs as it passes
through the stomach (no
carbohydrate digestion).
 Luminal digestion in the duodenum occurs by amylase that is formed in the pancreas converts polysaccharides into
disaccharides.
 Disaccharides are further broken down by enzymes on the brush border into monosaccharides and are absorbed across the
enterocyte epithelium.
 Table sugars do not require much digestion, leading to rapid absorption which has a huge and rapid increase in blood
glucose levels and insulin secretion.

Question 17

What are the mechanisms of intestinal sugar transport

Answer 17

The intestines has the capacity to absorb glucose, galactose and fructose.
 GLUT2: transports glucose and galactose across the basolateral membrane.
GLUT2 is inserted into the brush border membrane from its normal location on
the basolateral membrane to provide a high capacity route for glucose
absorption.
 SGLT1: transports glucose and galactose with Na
+ across the basolateral
membrane.
 GLUT5: transports fructose across the basolateral membrane.

Question 18

Describe bariatric surgery as a treatment option for obesity and diabetes

Answer 18

Promotes weight loss by changing the anatomy of the GI tract limiting food intake and processes of digestion and
absorption.
 Those with a BMI of > 40, or a BMI of >35 with serious obesity related health problems qualify.
 Health survey for England reported 336,000 men and 806,000 women with morbid obesity in 2010.
 8,000 procedures are performed annually in England (50% of which are vertical sleeve gastrectomy).

Question 19

What are the common types of bariatric surgery

Answer 19

 Adjustable gastric band (AGB): band is inserted to the top of the stomach.
Receiver under skin that can be filled with saline solution to constrict the band.

 Roux-en-Y gastric bypass (RYGB): staples are used to severely restrict the size of the stomach. Part of the intestine is re-connected to bypass the rest of the stomach. Initially, it was believed that the greater the region of the intestine bypassed, the fewer nutrients could be absorbed, so greater weight loss, however, research has shown that even bypassing a small part of the intestine achieves
the same effect.

Vertical sleeve gastrectomy (VSG): small section is dissected out.

Question 20

What are the benefits and risks of gastric bypass

Answer 20

Significant long-term weight loss (typical loss of 50% of excess weight).
 Improved control of diabetes and reduced risk of CVD events.
 20-40% reduction in mortality.

7.2. Risks of gastric bypass
 Hypoglycaemia and dumping syndrome (immediate and long term dumping syndrome).
o Immediate dumping syndrome: patients eats a high carbohydrate diet (when they shouldn’t be) and this is rapidly
passed to the small intestine, creating a high osmotic gradient, causing water to enter the lumen.
o Long term dumping syndrome: increase of GLP1 3-4 hours later (not immediate). More carbohydrates are entering
the ileum. GLP1 is an incretin hormone, which stimulates insulin secretion, driving hypoglycaemia.
 Nutritional deficiencies
 Anaemia, metabolic bone disease and osteoporosis.

Question 21

Why is iron important

Answer 21

An essential element (e.g. Haem synthesis). However, iron is toxic in excess. High body levels of iron cause tissue damage.
 Iron deficiency is the most common nutritional problem worldwide. Some cereals are now iron fortified.
 There is no physiological control of iron excretion. Therefore, regulation of intestinal iron uptake is the only mechanism for
controlling body iron content.

Question 22

Describe iron homeostasis

Answer 22

Iron plasma levels are kept low at 3 mg. It is bound to the
protein transferrin (because iron is toxic) which reduces
toxicity in cells.
 The main stored are in erythrocytes. As they reach
maturation, they are degraded by macrophages and the iron
is stored within the macrophages.
 20-25 mg of iron per day is recycled through the production
of new erythrocytes.
 The liver stores 1,000 mg of iron and responds to changes in
circulating serum iron.
 The gut absorbs 1-2 mg of iron per day enters the circulating
pool.
 1-2 mg of iron per day is excreted.

Question 23

Describe iron uptake in the duodenum

Answer 23

Specific haem transporter on the basolateral membrane
of the enterocyte allows free absorption of haem
generated from the breakdown of proteins.
 When haem enters the cell, it is transported across the
basolateral membrane via ferroportin or stored within
the cell bound to ferritin.
 Free ferric iron (Fe3+) is reduced to ferrous iron (Fe2+) by Dcytb before it can enter the cell via DMT1. Ferrous iron
can then be stored as ferritin or be transferred to the
blood.
 Ferrous iron is oxidised to ferric iron to be bound to
transferrin.
 Enterocytes are replaced every 3-6 days which accounts to the loss of iron in faeces.

Question 24

How does body iron status increase/decrease iron absorption

Answer 24

Decreased iron stores: anaemia, haemorrhage, hypoxia.
o Surface area of villus increases
o Number of iron transporters increases
 Increased erythropoietic activity

5.2. Decreases with
 Inflammation
 Increased iron stores

Question 25

How does hepcidin impact intestinal iron absorption

Answer 25

 HFE acts on the liver to produce hepcidin.
 High levels of iron in the body or inflammation inhibits intestinal
absorption. These promote the synthesis and secretion of hepcidin
from the liver.
 Hepcidin stops absorption in the duodenum and stops the release
of iron from the macrophages by binding to its receptor and
inhibiting the protein, ferroportin which is part of the basolateral
efflux pathway.
 Decreased O2 or increased demand for the production of RBC
stops production of hepcidin so it no longer has a blunting effect
on ferroportin (freely absorb iron or release iron from
macrophages).
 This maintains serum iron concentrations and restoration of iron
stores.

Question 26

How does disease occur in altered iron absorption

Answer 26

TIBC (total iron-binding capacity):
indicates the maximum amount of
iron needed to saturate plasma
transferrin.
o TIBC is done instead of
transferrin because
transferrin is expensive.
 Transferrin saturation:
Serum iron
TIBC×100
indicates how much iron is bound.
 Ferritin: universal intracellular protein that stores iron. Indicates how much iron is stored.
 Hemochromatosis: hereditary condition increasing iron uptake from the intestines.

Question 27

What regulates calcium

Answer 27

Dietary calcium intake: 1 g per day. 30% absorbed, occurs in the duodenum.
 Absorption is increased by calcitriol (1,25 [OH2
] − D3
), a vitamin D metabolite.
 Ca
2+ level in extracellular fluid is also regulated by kidneys and skeleton.

Question 28

How does body calcium homeostasis

Answer 28

Absorbed calcium (1 g) enters the extracellular fluid. This can be
exchanged with the exchangeable calcium pool (4 g).
 Calcium is replenished by calcium from the skeleton.
 Process of bone formation (0.5 g) and resorption (0.5 g)
continuously occurs in the body to maintain the pool of calcium.
 Calcium is filtered in the kidney, of which 99% is reabsorbed.
 Calcium in urine is equal to calcium absorbed from the intestine.
This is important for the homeostatic level of Ca
2+ to adjust level of
excretion to match absorption.

Question 29

Describe intestinal calcium uptake

Answer 29

 Under conditions of a low Ca
2+ diet, the transcellular process is responsible for absorption which is the predominant
pathway.
 Transient calcium receptor channel (TRPV6): moves calcium into the cell.

Intracellular Ca
2+ needs to be low to prevent intracellular signalling
pathways caused by calcium.
 Calbindin binds all the intracellular calcium and can move across the
basolateral membrane.
 Bound calcium can then be moved across the basolateral membrane, and
transported across the cell (into the blood) by PMCA (plasma membrane
Ca
2+-ATPase) which uses ATP to drive calcium efflux.
 When Ca
2+ is high, the paracellular pathway is responsible for absorption.
Occurs more in the jejunum (than the duodenum).
 Vitamin D3 regulates the absorption of calcium by the active transcellular
route and passive route. This is not well established, but activation of the
vitamin D receptor on the enterocyte by vitamin D increases production of
different transporters.

Question 30

Describe the regulation of calcium homeostasis

Answer 30

During low-normal dietary calcium intake, 1,25(OH)2D supports calcium homeostasis
by stimulating intestinal calcium transport.
 When intestinal calcium absorption alone does not suffice PTH (parathyroid hormone)
will aim to preserve serum calcium levels by acting on the kidney and bone.

Question 31

What are the differences between the villi in the small intestine and colon

Answer 31

Small intestine: villi are lined with enterocytes on the small intestine (for absorption).
 Colon: goblet cells are in high numbers (secrete mucous to protect the epithelial layer
from continually solid faecal contents that pass through the colon). Lack of villus means
there is not much absorption in the colon. Surface epithelium only.

Question 32

How does electrolyte and water absorption occur

Answer 32

0.4-1 L fluid reabsorbed per day.
 Na+ uptake stimulated by aldosterone and is coupled to K+ secretion
into the lumen.
 Na+ uptake stimulated by short-chain fatty acids (produced by colonic
microflora).
 HCO3− secretion/Cl− uptake coupled to Na+ uptake/K+ secretion.
Overall effect: increased NaCl uptake.

Question 33

What is the role of luminal bacteria

Answer 33

 Bacteria make up 50% of faecal dry weight.
 Synthesise small amounts of some vitamins (e.g. vitamin K).
 Degrade many toxic products.
 Synthesise short chain fatty acids (SCFA) from undigested food matter.

Question 34

how do electrolytes transfer across the colonic epithelium

Answer 34

𝐍𝐚+/𝐊+-ATPase: on basolateral membrane and actively transports Na+
in exchange for K+ and keeps [Na+] in the cell low.
 Low intracellular [Na+] allows Na+ transport across the apical membrane.
There is no nutrient absorption in the colon but short chain fatty acids
(SCFA) can be transported into the cell through 𝐍𝐚
+/𝐒𝐂𝐅𝐀 transporters.

Na
+ can also be absorbed through ENaC (epithelial 𝐍𝐚
+ channel) which is aldosterone sensitive. Regulating ENaC has a
major effect on maintaining circulating Na
+ levels in the body and therefore blood pressure.
 Water is drawn into the cell by aquaporins or into the blood via the paracellular route. The high level of Na
+ in the blood
caused by Na
+/K
+-ATPase draws water from the lumen.
 The BK channel (big K
+ channel) reduces the [K
+] in the blood as it secretes K
+ into the lumen of the colon.
 Cl
− is exchanged for HCO3
− at the brush border membrane and leaves the cell via 𝐂𝐥
− channels present on the basolateral
membrane.
 CLC-2 channel maintains the [Cl
−] gradient within the
cell.

Question 35

Describe the gut microbiome and its role

Answer 35

4. The gut microbiome
    Gut microbiota weighs 2 kg.
    Evolves throughout life and is altered by: genetics,
   stress, hygiene, drugs/antibiotic, diet, infections, and
   environment.
    The gut microbiome is unique to each individual.
    Diversity of the microbiome has decreased compared
   to indigenous populations.

Asthma/eczema
 Diabetes and obesity: believed changing microbiome has increased carbohydrate absorption efficiency, increasing calorie
uptake.
 Non-alcoholic fatty liver disease
 Depression
 Heart disease
 Colon cancer
 Inflammatory bowel disease
7. Dietary modification of the microbiome
 Prebiotic: ingested digestion-resistant oligosaccharide that maintains a health gut bacterial population.
 Probiotic: live microbial food supplement that beneficially benefits affects the host by improving gut microbial balance (i.e.
increases ratio of good:bad bacteria).