DIGESTION AND ABSORPTION

DR. MASIKA
2021
 Digestion and absorption of carbohydrates
• Dietary intake of carbohydrates is 250–850 g/day, which represents 50–
60% of the diet.
1. Polysaccharides: are made up of many monosaccharides, present in the
following forms:
• Starch is the carbohydrate reserve of plants. It consists of two
polysaccharide components:
i. Amylose (15–20%). It is a water-soluble straight-chain polysaccharide and
ii. Amylopectin (80–85%). It is a water insoluble branched-chain
polysaccharide.
• Glycogen. It is available in non-vegetarian diet and so often referred to as
animal starch. In it, glucose molecules are mostly long chains (1:4 α-
linkages and 1:6 αlinkages) at branching points.
• Cellulose is another plant polysaccharide, which is present in diet in large
amounts. But, there is no enzyme in the human GIT to digest it, so it is
excreted.
 2. Oligosaccharides

• Undigested oligosaccharide contains 2–10

monosaccharide molecules which are liberated on
hydrolysis.
• Based on the number of monosaccharide units
present, oligosaccharides are further subdivided into
di-, tri-, tetra- and pentasaccharide.
Disaccharides include:
• Sucrose (glucose + fructose) is also known as table
sugar (cane or beet sugar).
• Lactose (glucose + galactose) is also called milk sugar.
• Maltose (glucose + glucose). It is a product of starch
hydrolysis. It is present in germinating seeds.
 3. Monosaccharides

• Monosaccharides consumed mostly in human diet

are hexoses such as:
• Glucose (in fruits, vegetables and honey) and
• Fructose in fruits.
• Pentoses do not occur in free form, but are found in
nucleic acid and in certain polysaccharides such as
pentosans of fruits and gums.
• Other carbohydrates that may be present in the
human diet are alcohol, lactic acid, pyruvic acid,
pectin, dextrin and minor quantities of carbohydrate
derivatives in the meat.
 Digestion of carbohydrates

• Begins in mouth, continues in stomach but occurs mainly in the small

intestine.
Digestion of carbohydrates in the mouth 
• Initial starch digestion starts in the mouth by the enzyme α-amylase
(ptyalin) present in the saliva. However, the role of salivary amylase in
the digestion of carbohydrates is limited by the short duration of stay
of the food in the mouth.
• α-Amylase present in the saliva acts on the 1-4 linkages (but not on 1-
6 linkages). It digests cooked starch to maltose
Digestion of carbohydrates in the stomach 
• ​In the stomach, there occurs minimal carbohydrates digestive activity:
• α-Amylase activity continues in the stomach for 20–30 min till the
highly acidic gastric juice mixes with the food and makes it inactive.
The optimum pH for the action of salivary amylase is 6–7, and its
activity in the stomach completely stops when pH falls below 4. The
HCl of the gastric juice may hydrolyse some sucrose.
 Digestion of carbohydrates in the small intestine 

• the carbohydrates are digested by the amylolytic enzymes present

in the pancreatic juice and brush border enzymes of small intestine.
Pancreatic α-amylase 
• is present in the pancreatic juice which is poured into the
duodenum. Its actions on the carbohydrates are similar to that of
salivary amylase, but it is much powerful and so it acts on boiled as
well as unboiled starch and variety of other carbohydrates except
cellulose. It hydrolyses almost all the starch within 15–30 min of the
entry of chyme into the duodenum. Its action occurs before the
chyme passes beyond the duodenum or upper jejunum.
• Pancreatic amylase acts in an alkaline medium and its digestive
activity is increased by the presence of bile salts. It converts the
starch (polysaccharides) into oligosaccharides such as maltose,
maltotriose and dextrin 
FIGURE: Digestion of carbohydrates.
 End products of carbohydrate digestion

• The carbohydrate digestion is completed in the

small intestine (mainly in jejunum and proximal
ileum).
• The end products of carbohydrates are
monosaccharides such as glucose, fructose and
galactose. Glucose represents 80% and galactose
and fructose combinedly represent only 20% of the
end products.
• A little amount of other monosaccharide called
pentoses are the end products of digestion of
nucleic acids and partial digestion of pentosans.
 Absorption of carbohydrates

• Are absorbed from the GIT in the form of monosaccharides. The

monosaccharides include those formed at the brush border and also those
ingested as such (e.g. glucose and fructose in fruits).
Site of absorption 
• ​Most of the monosaccharides are absorbed from the mucosal surface of
jejunum and upper ileum. The absorption is almost completed before the
remains of a meal reach the terminal ileum. Negligible absorption also
occurs in stomach and colon.
Mechanism of absorption 
• Various monosaccharides are absorbed by following mechanisms:
• Glucose and galactose are absorbed by a common Na+-dependent active
transport system.
• Fructose is absorbed by facilitated diffusion. Fructose absorption occurs
readily, because most of the fructose is rapidly converted into glucose and
lactic acid within the epithelial cells, thus maintaining a high-concentration
gradient for diffusion.
• Pentoses are absorbed by simple diffusion.
 Absorption of glucose and galactose. 

• Glucose and galactose are absorbed into the epithelial cells (enterocytes)
lining the mucous membrane of small intestine from their brush border
surface (luminal surface) by an active transport mechanism—the sodium
cotransport mechanism. 
Binding of glucose and Na+ to carrier protein
• The carrier protein (present in the cell membrane) has two binding sites,
one for sodium and another for glucose. It is called sodium-dependent
glucose transporter-1 (SGLT-1). The conformational change in the carrier
protein occurs only when the binding sites are occupied by the sodium
and glucose present in the gut lumen forming the sodium–glucose–
carrier complex.
Creation of electrochemical gradient across the epithelial cell
• The active transport of sodium by Na+–K+–ATPase pump through the
basolateral membrane into the paracellular spaces lowers the
intracellular Na+ concentration. This creates an electrochemical gradient.
FIGURE 1: Mechanism of glucose absorption across intestinal
epithelial cell.
 Movement of sodium and glucose inside the cell

• Because of the electrochemical gradient created, sodium moves into the

cell (downhill transport). The flow of sodium ions down the gradient is so
forceful that the glucose (or galactose) molecule attached to the carrier
protein also enters the cell, even against concentration gradient for glucose
(uphill movement). Because two Na+ are transported down their
electrochemical gradient, a large amount of energy is available for
transport. Thus, almost all of the glucose and galactose present in the
intestine can be absorbed (against the concentration gradient). The energy
so released is required for Na+–K+ pump activity to maintain the sodium
gradient.
Transport of glucose into blood capillaries.
• From the epithelial cell, the glucose is transported into the interstitial space
and thence to blood capillaries of portal system, through facilitated
diffusion by glucose transporter-2 (GLUT-2).
• Note: Fructose absorption is independent of Na+ transport. It is absorbed
from intestinal lumen into the enterocyte by GLUT-5, and from enterocyte
to interstitium by GLUT-2.
 Factors affecting glucose absorption

1. Presence of Na+ in the intestinal lumen. Due to common carrier

protein, the entry of glucose/galactose into the epithelial cells is
favoured by the presence of Na+ in the intestinal lumen (similarly, the
presence of glucose and galactose in the lumen favours the absorption
of Na+).
2. State of mucous membrane. Absorption of glucose is decreased in
abnormal states of mucous membrane such as in enteritis and coeliac
disease.
3. Duration of time during which the carbohydrate remains in contact
with mucous membrane. Absorption of glucose is decreased because
of intestinal hurry in conditions like diarrhoea, excision of small
intestine and gastrocolic fistula.
4. Role of endocrines in glucose absorption is as below:
• Thyroid. Thyroxine increases the glucose absorption by directly acting
on the mucosa. Therefore, in thyrotoxicosis, glucose absorption is
increased and in myxoedema it is decreased.
 4. Role of endocrines cont’

• Anterior pituitary affects the glucose absorption by its effects on

the thyroid gland. Hyperpituitarism causes hyperthyroidism and
thus increases the glucose absorption and vice versa.
• Adrenal cortex deficiency decreases glucose absorption by
decreasing the Na+ concentration.
Note: Regulation of absorption of monosaccharides does not exist,
i.e. absorption of monosaccharides is not regulated. The intestines
can absorb over 5 kg of sucrose per day. Therefore, after ingestion
of a high carbohydrate diet, glycosuria can occur, i.e. glucose
appears in the urine. This condition is called alimentary glycosuria.
Rate of absorption of monosaccharides is variable, being:
• Fastest with glucose and galactose,
• Intermediate with fructose and
•  Slowest with mannose or pentoses.
 Fate of glucose in the body

1. Storage as glycogen. About 5% of the total glucose

absorbed is stored as glycogen in the liver and
muscles.
2. Catabolism to produce energy. About 50–60% of
the glucose absorbed is catabolized in the body
tissues to produce energy. A total of 1 g of glucose
produces about 4 kcal of energy, when it is
completely oxidized to CO2 and H2O. Amino acids are
formed on transamination of some intermediary
products of glucose breakdown.
3. Conversion into fat. About 30–40% of glucose is
converted into fat and is stored in the fat depot.
 Lactose intolerance

• Congenital lactose intolerance refers to a condition in which lactose

(milk sugar) cannot be digested due to congenital deficiency of enzyme
lactase.
• The undigested lactose acts as osmotic particles and draws excessive
fluids into the intestine resulting in diarrhoea.
• In the colon, the undigested lactose is metabolized by bacteria
producing variety of gases (e.g. hydrogen, methane and CO2) and variety
of intestinal irritants, which increase the colonic motility.
• The diarrhoea so produced can lead to life-threatening dehydration and
electrolyte imbalance.
• Avoidance of milk and milk products prevents the symptoms from
developing if the infant can be fed by synthetic milk containing sucrose
instead of lactose.
• Secondary lactase deficiency occurring in adults is very common. It
produces intestinal distension, diarrhoea and flatulence. For adults, it is
usually not a problem, as they can easily avoid milk and milk products.
 Lactose intolerance cont’

• Lactose intolerance is an inability to digest lactose in dairy products caused

by a deficiency (partial or total) of lactase.
• Lactase is a brush border enzyme that converts lactose to the
monosaccharides glucose and galactose, which are then absorbed into the
bloodstream. Without lactase, lactose remains in the intestinal lumen,
where it presents as osmotic load, resulting in diarrhea. Excess gas is also
produced by fermentation of the luminal lactose to methane and hydrogen
gas. Lactose intolerance can be diagnosed by the hydrogen breath test,
which measures the amount of hydrogen produced after ingestion of a
known amount of pure lactose (following an initial period of fasting).
• If the amount of hydrogen rises by 20 ppm, then a diagnosis of lactose
intolerance can be made. The symptoms of lactose intolerance can be
minimized in lactose-intolerant individuals by limiting their intake of dairy
products or by oral ingestion of lactase-containing foods or drugs (e.g.,
Lactaid) with a meal that is high in dairy. By introducing the exogenous
enzyme and the substrate at the same time, the digestion of the substrate
can proceed almost normally within the GI tract.
 D ig es ti on an d a bs orp tion of pro tei ns

• Sources of proteins: The proteins that are digested and

absorbed in the GIT come from two sources: exogenous and
endogenous.
1. Exogenous (dietary) proteins
• Daily requirement of dietary proteins for adults is 0.5–0.7
g/kg body weight and for children (1–3 years), it is 4 g/kg.
• Quantity of dietary proteins varies with the socioeconomic
status of the individuals; a balanced diet contains about 95–
100 g/day.
• Sources of dietary proteins with high biological value are
meat, fish, eggs, cheese and other milk products. Soyabeans,
wheat and various types of pulses are also rich source of
proteins.
 1. Exogenous (dietary) proteins cont’
Proteins of important dietary items are:
• Wheat : Glutenin, glycinin and gliadin.
• Milk : Casein, lactalbumin, albumin and myosin.
• Egg : Albumin and vitelline.
• Meat : Collagen, albumin and myosin.
• Structure of dietary proteins: Dietary proteins are made of
long chains of amino acids bound together by peptide
linkages.
2. Endogenous proteins. Endogenous proteins, totaling 30–
50 g/day, are the proteins which reach the intestine
through various gastrointestinal secretions and those which
are present in the desquamated epithelial cells of the gut.
 D ig es ti on of pr otei ns

• Proteins are digested by the proteolytic enzymes to amino acids

and small polypeptides, before they are absorbed. Digestion of
proteins does not occur in the mouth, as there are no proteolytic
enzymes in the saliva. Digestion of proteins thus begins in the
stomach and is completed in the small intestine.
Digestion of proteins in the stomach
• Pepsin, secreted by chief cells of the main gastric glands in an
inactive form (pepsinogen), is responsible for digesting about
10–15% proteins entering the gastrointestinal tract.
• Pepsinogen is converted into pepsin (active form) by the action
of HCl or preformed pepsin.
• Pepsin hydrolyses the bond between aromatic amino acid
(phenylalanine or tyrosine and a second amino acid). Therefore,
pepsin splits proteins into proteoses, peptones and
polypeptides.
 Digestion of proteins in the stomach cont’

• the optimum pH for the action of pepsin is 2.0; therefore,

HCl secretion by the stomach is as essential as
pepsinogen secretion for the digestion of proteins.
• Pepsin is unique in its proteolytic action because of its
ability to digest collagen (which is a major constituent of
the intercellular connective tissue of meat). By digesting
collagen tissue, the pepsin breaks apart the meat
particles and facilitates further digestion of cellular
proteins of meat.
• Protein digestion within the stomach is particularly
important because the protein digestion products act
as secretagogues, i.e. stimulate secretion of proteolytic
enzymes of pancreas.
FIGURE 2: Digestion of proteins.
 Digestion of proteins in the small intestine
• proteins are digested by the pancreatic proteases, brush
border peptidases and intracellular peptidases.
Pancreatic proteases or proteolytic enzymes of pancreas
play a major role in protein digestion. These can digest
all the proteins, even if gastric pepsin is absent.
• Pancreatic proteases digest the proteins and split them
into dipeptides, tripeptides and small polypeptides,
which are further digested by brush border peptidases.
• Some of the dipeptides and tripeptides are absorbed
directly into the epithelial cells of mucosa of small
intestine, and are further digested by intracellular
enzymes into amino acids.
 Digestion of proteins in the small intestine cont’
Brush border peptidases are the proteolytic enzymes which
form an integral constituent of the epithelial cell membrane
with active sites projecting into the lumen.
• Brush border peptidases include aminopeptidases,
dipeptidases, tripeptidases, nuclease and related enzymes.
• These enzymes continue the digestive process initiated by the
pancreatic proteases, eventually converting the proteins to
small polypeptides and amino acids.
• Intracellular peptidases are the proteolytic enzymes present
in the cytosol of epithelial cells of small intestine. The multiple
peptidases present in the enterocytes are specific for linkages
between the various amino acids. Within minutes, these
digest the last dipeptides and tripeptides into amino acids
which then enter the blood.
 Digestion of nucleic acid and nucleoproteins

Nucleic acid and nucleoproteins are found in abundance in the

foodstuffs, which are rich in nuclei such as liver, kidney, pancreas, yeast,
etc.
In the stomach, HCl hydrolyses the nucleoproteins, removing proteins
which are digested together with other proteins.
In the small intestine, the free nucleic acids are digested by the pancreatic
enzymes and brush border enzymes.
• Pancreatic enzymes, such as ribonuclease and deoxyribonuclease in the
duodenum, digest free nucleic acids into nucleotides and nucleosides
• Brush border enzymes such as nucleases, nucleotidases and
nucleosidases convert nucleotides and nucleosides into pentoses
(purine and pyrimidine).
End products of protein digestion. Protein digestion, which starts in the
stomach, is completed in the enterocyte of small intestine. The end
products of protein digestion are amino acids.
 Ab s o rpti on of p rot ein s

• Mechanisms of absorption into the intestinal epithelial cells 

• ​The end products of protein digestion (amino acids, dipeptides
and tripeptides) are absorbed through the luminal membrane
of the epithelial cells of small intestine. Absorption of amino
acids is faster in duodenum and jejunum and slower in ileum.
Following mechanisms of absorption are known:
1. Transport systems: 
• There are seven different transport systems existing for amino
acid transport from intestinal lumen into the enterocytes. Five
of them require Na+ (Na+-dependent cotransport), and out of
these, two also require Cl−, while other two are Na+-
independent transporters.
 Absorption of proteins cont’

(i) Na+-dependent active transport mechanism. The levo amino

acids, dipeptides and tripeptides are absorbed by a Na+-
dependent active transport mechanism.
- Separate transporters (carriers) are present for the absorption of
basic, acidic and neutral amino acids. At least two different
polypeptide transporters exist.
- Steps of active transport mechanism are similar to those described
for glucose absorption. These include:
- Binding of amino acid and Na+ to carrier protein,
- Creation of electrochemical gradient across the epithelial cells and
- Movement of Na+ and amino acids inside the cell.
(ii) Na+-independent active transport mechanism. The carrier is
known as Pep T1 (peptide transporter-1) that requires H+ instead
of Na+ for transport of di- and tripeptides.
FIGURE 3: Mechanism of absorption of amino acids,
dipeptides and tripeptides by intestinal epithelial cells.
 Absorption of proteins cont’

2. Simple diffusion. The dextro amino acids are absorbed solely

by passive diffusion.
3. Endocytosis. Larger polypeptides cannot be absorbed into the
epithelial cells. Occasionally, small amounts of larger
polypeptides are absorbed by endocytosis. Proteins absorbed
by endocytosis usually excite immunological/allergic reaction. In
newborn infants, immunoglobulins present in the colostrum are
absorbed in the intestinal mucosa by endocytosis and impart
passive immunity to child.
• Further digestion in the epithelial cells. Once amino acids and
polypeptides are absorbed into the intestinal epithelial cells,
the intracellular peptidases break the remaining linkages of
tripeptides and dipeptides causing release of amino acids.
 Absorption of proteins cont’
• Transport of amino acids into blood capillaries. ​From inside the
epithelial cells, the amino acids are transported into the interstitial
space across the basolateral membrane of the cells by a series of
basolateral transport proteins. From the interstitium, the amino
acids enter the capillaries of villus by simple diffusion, and then
via the portal vein, they reach the liver and general circulation.
Therefore, after ingestion of a high-protein meal, there occurs a
sharp transient rise in the free amino acid content of the portal
blood, which provides the whole body requirements of proteins.
• Note It is important to note that almost all proteins ingested are
absorbed. About 2–5% of proteins that escape digestion and
absorption in the small intestine enter the colon and are finally
digested by bacterial digestion. Therefore, the proteins that
appear in the stool are not of dietary origin, but are derived from
the bacterial and cellular debris.
 Abnormalities of protein digestion and absorption

1. Inadequate absorption of proteins, due to lack of

trypsin, is a common consequence of pancreatic
diseases.
2. Malabsorption of amino acids due to lack of
transporters is relatively rare. For example,
in Hartnup disease, there occurs malabsorption of
neutral amino acids due to lack of specific carrier
protein, and congenital defect in the transport for
basic amino acids causing cysteinuria.
 NOTE
• The absorption of protein antigens (particularly of
bacterial and viral) occurs in the large microfold cells
(M cells), specialized epithelial cells overlying the
Peyer’s patches (aggregates of lymphoid tissue).
• These cells pass the antigen to lymphoid cells and
activate lymphocytes.
• The activated lymphocytes enter the circulation and
return back to intestinal epithelium and other
epithelial  cells, and secrete IgA antibodies in response
to subsequent exposure to same antigen—an
important defence mechanism by secretory immunity.
 Digestion and absorption of fats

Dietary fats
Fats are of three types:
• Simple fats or neutral fats, e.g. triglycerides and
cholesterol.
• Compound fats, e.g. phospholipids.
• Associated fats, e.g. steroids and fat-soluble vitamins.
• Dietary fat is of both vegetable and animal origin. Mostly,
it is in the form of neutral fat (triglycerides). It also
includes small amounts of phospholipids, cholesterol,
some free fatty acids, lecithin and cholesterol esters.
• Daily intake of fats in the diet varies widely, from about
25 to 160 g.
 Digestion of fats

• Site of digestion: ​Although lipolytic enzymes are secreted in the mouth

(lingual lipase) and stomach (gastric lipase), their action is so insignificant
that practically digestion of all the dietary fats occurs in the small intestine.
Gastric lipase which initiates fat digestion acts only on butter. Under normal
conditions, gastric lipase is soon inactivated by gastric juice (pH 1–2), as it is
inactivated at pH 2.5 and acts at an optimum pH of 4.5. Some fat digestion
in stomach may occur under the following exceptional circumstances:
• Achlorhydria (i.e. gastric juice cannot inactivate gastric lipase),
• Regurgitation of pancreatic lipase from the duodenum into the stomach and
• In young suckling animals which ingest large quantities of milk, the fat of
milk is present in an emulsified form and digested, and this inhibits the
secretion of gastric juice.
Mechanism of digestion of fats: ​The digestion of fat includes 3 steps:
• Emulsification of fat by bile salts,
• Hydrolysis of fat by pancreatic and intestinal lipolytic enzymes and
• Acceleration of fat digestion by micelle formation.
 1. Emulsification of fat by bile salts

• Emulsification, i.e. breaking of large fat drops into smaller droplets, is a

prerequisite for action of pancreatic lipase.
• It is so because the pancreatic lipase being water soluble acts only on
the oil–water interface of fat. The surface area available for the action
of lipase is increased many thousand times by the emulsification of
fats.
• caused by bile salts because of their property of lowering the surface
tension (detergent-like action).
• With the lowered surface tension of the fats, the segmentation
movements of small intestine break up large fat globules into fine
droplets (1 µm in diameter). Lecithin (a component of bile), which has
a stabilization action on the emulsions, greatly enhances the
emulsifying action of bile salts. The bile salts surround the fine fat
droplets in such a way that their lipophilic non-polar ends are towards
the fat and their hydrophilic polar ends separate the fat droplets from
the aqueous phase
FIGURE 4: Emulsification of fats by bile salts: A, a large fat particle;
and B, small fat particles surrounded by bile salts.
 2. Hydrolysis of fat droplets by pancreatic and intestinal lipolyti c enzymes

• Pancreatic juice is markedly alkaline (pH 7.8–8.4). When it mixes with the
acidic chyme (pH 6.0) coming from stomach into the duodenum, the pH of
chyme is adjusted to about 7 (which is optimal pH for the action of
pancreatic lipases).
• Pancreatic lipolytic enzymes. Pancreatic juice contains three types of
lipolytic enzymes. Their hydrolysing effects on fats are given:
i. Pancreatic lipase: is a very powerful lipolytic enzyme. Fat digestion by it
occurs very rapidly after emulsification because of the large-surface-to-
volume ratio of the small globules. Colipase, a protein present in the
pancreatic juice, displaces the bile salts from the fat droplet and allows the
action of lipase. Pancreatic lipase hydrolyses almost all the triglycerides
(neutral fat) of the food to produce two fatty acids and a 2-monoglycerides.
Note. Colipase is secreted in an inactive form and is activated by trypsin in
the intestinal lumen. When activated, colipase binds to –COOH terminal
domain of pancreatic lipase; the activity of this enzyme is facilitated by
opening of lid (helix-like structure) that covers its active site.
 2. Hydrolysis of fat droplets by pancreatic and intestinal lipolytic enzymes

ii. Cholesterol ester hydrolase. Most of the dietary cholesterol is in the

form of cholesterol esters, which are hydrolysed to cholesterol and
fatty acid by the cholesterol ester hydrolase.
• The cholesterol esterase is activated by the bile salts. Cholesterol
esterase represents about 4% of the total protein contents of
pancreatic juice. The bile salt-activated pancreatic lipase hydrolyses
cholesterol esters, esters of fat-soluble vitamins, phospholipids and
triglycerides. A similar type of lipase is also present in the human milk.
iii. Phospholipase A2. It is secreted in an inactive form prophospholipase
A2, and gets converted to active form. It hydrolyses phospholipids and
separates fatty acid from them.
• Intestinal lipolytic enzymes. Brush border of epithelial cells covering
the intestinal villi contains small amount of lipase and cholesterol
esterase. Their effects, though minor, but are similar to that of
pancreatic lipase.
 3. Acceleration of fat digestion by micelle formation 

• The hydrolysis of triglycerides is highly reversible; therefore,

accumulation of monoglycerides and free fatty acids in the vicinity of
digesting fats quickly blocks further digestion. This problem is solved by
the property of bile salts to form micelle. Micelle formation depends on
critical micelle concentration of bile salts in the aqueous solution. At a
critical micelle concentration, all the bile salts in a solution form
micelles. The lipids get collected in the centre of micelle.
• Structure. Micelles are small, water-soluble, cylindrical disc-shaped
particles. Each micelle is composed of a central fat globule surrounded
by about 30 molecules of bile salts in such a way that their lipid-soluble
nonpolar ends are in the central fat globule and water-soluble polar
ends fan out to form the outer covering of micelle. Monoglycerides and
free fatty acids released from the digestion of fat are quickly
incorporated into the central fatty portion of the micelles forming, what
are known as, the mixed micelles (Fig. 6). In this way, bile salts
accelerate the fat digestion by allowing the lipolytic action to continue.
FIGURE 6: Structure of
micelle: A, a mixed micelle
composed of lipids
(monoglycerides, fatty acids and
cholesterol) in the centre
surrounded by bile salts; B, bile
salt molecule showing globular
(hydrophilic or polar) end and
lipophilic (nonpolar) end; C, a
model of the structure of mixed
(bile salt and lipid) micelle and its
cross-section showing
arrangement of various lipid
molecules; and D, diagrammatic
structure of different lipid
molecules.
 Absorption of fats

• Most of the fat absorption occurs in the duodenum; almost all

the digested lipids are totally absorbed by the time the chyme
reaches the mid-jejunum. Absorption of fats is accomplished by
the following steps:
1. Transportation as micelles to the brush border membrane.
• The micelles so formed not only accelerate the fat digestion,
but are also essential for the fat absorption as explained.
• The insolubility of fat globules prevents their diffusion through
the aqueous medium of the intestinal lumen to reach the brush
border. This problem is solved by the bile salts by forming the
micelle. As described above, the outer surface of micelle is
formed by water-soluble polar ends of bile salts, which help the
micelle to diffuse through the aqueous medium to reach the
brush border membrane. Thus, the bile salt micelle acts as a
transport vehicle for the products of fat digestion.
2. Diffusion of lipids across the enterocyte cell
membrane
• Once the micelle comes in contact with the cell membrane, the
monoglycerides, free fatty acids, cholesterol and fat-soluble
vitamins (being soluble in the cell membrane) diffuse
passively at a rapid speed through the enterocyte cell
membrane to the interior of the cell, leaving bile salts in the
intestinal lumen. Thus, the rate-limiting step in lipid absorption
is the formation and migration of the micelles from the
intestinal chyme to the microvilli surface. It is important to
note that the bile salts must be present in certain minimum
concentration called critical micellar concentration, before
micelles are formed.
• The bile salts released from micelle after diffusion of their
associated lipids are absorbed in the terminal ileum by a Na+-
dependent active transport process.
3. Transport of lipids from inside the enterocytes to the interstitial space

• Once inside the cell, the end products of fat digestion enter
the interstitium by two mechanisms:
i. Diffusion across the basal border of enterocyte. Small-chain
fatty acids (SCFA) with less than 10–12 carbon atoms are
water soluble and are able to diffuse across the basal border
of enterocytes to enter the interstitium and are actively
transported in the portal blood and circulate in unestrified
form.
ii. Formation and excretion of chylomicrons from enterocytes
by exocytosis. Large-chain fatty acids, which more than 12
carbon atom, cholesterol and lysophosphatides enter the
smooth endoplasmic reticulum, where they are
reconstituted:
 3. Transport of lipids from inside the enterocytes to the interstitial space cont’

- 2-Monoglycerides are combined with fatty acids to produce

triglycerides. Some of the triglycerides are also formed from
glycerophosphate (a product of glucose catabolism). Glycerophosphate
is also converted into glycerophospholipids and participate in
chylomicron formation.
- Lysophosphatides are combined with fatty acids to form phospholipids
and
- Cholesterol is re-esterified.
• The reformed lipids coalesce to form a small lipid droplets (about 1 nm
in diameter) called chylomicrons, which are lined by the synthesized β-
lipoproteins. The chylomicrons are then excreted into the interstitium
by exocytosis from the basolateral membrane of enterocyte. Covering
of β-lipoproteins is essential for the exocytosis to occur. Therefore, in
the absence of β-lipoprotein, exocytosis will not occur, and the
enterocytes become engorged with lipids.
 4. Transport of lipids into circulation

• After exiting the enterocytes (i.e. in the interstitium), the chylomicrons merge
into larger droplets that vary in size from 50 to 500 nm, depending on the
amount of lipid being absorbed. From the interstitium, the lipids diffuse into
the lacteals, from where they enter the lymphatic circulation, and via thoracic
duct gain access into the blood circulation. In an adult, more than 95% of the
fat gets absorbed on moderate intake.
• Note. The process involved in fat absorption at birth is not fully matured;
thus, infants are more susceptible to ill effects of disease that reduces fat
absorption.
• Fate of short-chain fatty acids in the colon: The short-chain fatty acids (SCFA)
(2–5 carbon atoms) are weak acids produced by the action of colonic bacteria
on unabsorbed complex carbohydrates, resistant starches and components of
dietary fibers. They are absorbed from the colon by specific transporter.
Functions:
• SCFA provide significant calories.
• They have trophic effect on colonic epithelium and play an important role
during inflammation.
• Help in maintaining acid–base balance.
 Steatorrhea

• is the production of feces that have a high content of fat. They

are often oily and foul-smelling, and they tend to float.
• occurs when fat digestion or absorption is impaired.
• This can occur due to pancreatic disease (e.g., cystic fibrosis, and
chronic pancreatitis), in which there is a deficiency of pancreatic
lipase that would normally digest fats.
• It may also occur in conditions that cause hypersecretion of
gastrin (e.g., Zollinger–Ellison syndrome), in which gastrin
increases H+ secretion, which lowers duodenal pH, inactivating
pancreatic lipase. It may also occur due to liver disease, which
causes a deficiency of bile acids.
• Ileal resection will impair fat absorption due to impairment of
bile recirculation to the liver. Treatment for steatorrhea due to
pancreatic disease is pancreatic enzyme replacement (e.g.,
pancrelipase).
FIGURE 7: Steps of fat absorption: 1,
transportation of micelle to
enterocytes brush border; 2,
diffusion of lipids across the
enterocyte membrane leaving bile
salt in the lumen; 3, formation of
chylomicron in the endoplasmic
reticulum; 4, release of lipids into
interstitium by exocytosis; and 5,
diffusion of lipids from interstitium
into lacteal (from where lipids enter
into lymphatic circulation) and
through thoracic duct into
circulation. FA: fatty acid, MG:
monoglycerides, chol: cholesterol,
TG: triglycerides, LCFA: long-chain
fatty acid, SCFA: short-chain fatty
acids, NEFA: nonesterified fatty
acids and PL: phospholipid.
• Dietary triglycerides (TG) are broken down into free fatty
acids (FFA) and monoglycerides (MG) in the GIT.
• Short-chain FFA (e.g., acetic and butyric acid) do not need
to be ferried across the unstirred water layer in mixed
micelles because they are sufficiently water soluble to do
this by themselves.
• In addition, they are also sufficiently lipid soluble to diffuse
out of the enterocyte at the basolateral membrane and go
directly to the bloodstream (portal venous blood), without
the necessity of being incorporated into chylomicrons.
• Long-chain FFA and MG are not soluble in water.
• They are resynthesized to TG in the enterocytes.
• Because TG are not soluble in water, they are subsequently
loaded into chylomicrons, which are exocytosed into the
EFC, then passed on to the intestinal lymph ( bypassing the
liver), from which they finally reach the greater circulation.
 TABLE 7.7-1.
Substrate Principal
Enzyme Digestive
Source Enzymes
Activator Function and product
A. Carbohydrate
Starch • Salivary α- Salivary gland  Cl−  Hydrolyses 1:4 α-linkages,
(polysaccharide)  amylase Exocrine pancreas Cl− producing α-limit dextrin,
Disaccharides • Pancreatic maltotriose, and maltose- 
amylase same as-
Maltose • Maltriose Intestinal mucosa – Glucose
• Maltase
• α-Dextrins
Lactose • Lactase Do- – Galactose and glucose
Sucrose • Sucrase Do- – Fructose and glucose
α-Dextrins, • α-Dextrinase Do- – Glucose
maltriose and
maltose
Trehlose • Trehalase Do- – Glucose
B. Nucleic acid • Nuclease and Do- – Pentoses, purines and
related enzymes pyrimidines
RNA • Ribonucleasse Exocrine pancreas – Nucleotides
DNA • Deoxyribonucle Do- – Nucleotides
ase
C. Proteins and • Pepsinogen Gastric glands HCl Cleave peptide bonds
polypeptides (pepsin) adjacent to aromatic amino
acids
 Exocrine pancrease Enteropeptidase Cleave peptide bonds on
• Trypsinogen carboxyl side of basic
(trypsin) amino acids (arginine
and lysine)
• Chymotrypsin Do- Trypsin Cleave peptide bonds on carboxyl side
of aromatic amino acids
Elastin and some Proelastase (elastase) Do- Trypsin Cleave peptide bonds on carboxyl side
other proteins of aliphatic amino acids
Exopeptidase Do- Do- Cleave carboxyl terminal aromatic
procarboxypeptidase amino acids having branched aliphatic
A (carboxypeptidase) side chains.

Carboxypeptidase-B Do- Do- Cleave carboxyl terminal amino acid

(carboxypeptidase B) having basic amino acids side chains

Polypeptides Endopeptidase Brush border of – Cleave amino terminal amino acid

intestinal mucosa from peptide
Carboxypeptidase Do- – Cleave carboxyl terminal amino acid
from peptide
endopeptidase Do- – Cleave between residue of mid-
portion of peptide
Dipeptides Dipeptidase Do- – Two amino acids
Di, tri and Various peptidases Cytoplasm of – Amino acids
tetrapeptides mucosal cells
4. Fats (lipids) lingual lipase Lingual gland – 1,2 Diacylglycerol and fatty acids
triglycerides
Gastric lipase Stomach – Fatty acids and glycerol
Colipase Exocrine pancrease Trypsin Facilitate exposure of active site of
fancreatic lipase
Pancreatic lipase Do- – Monoglycerides and fatty acids
Cholesterol esters Bile salt acid lipase Do- – Cholesterol
Cholesterol ester Do- – Cholesterol
hydrolase
 Lipid malabsorption

• is much more common than carbohydrate and protein

malabsorption
 Causes of lipid malabsorption include:
• Deficiency of pancreatic lipase in certain pancreatic diseases and
• Bile deficiency in disorders of liver and gall bladder.
• Steatorrhoea, i.e. increased amount of fat in the stools, is a
common manifestation of fat malabsorption.
Serum lipid profile
• Lipids are present as lipoprotein complexes. Depending upon the
density, the lipoproteins are of following types:
i. Very low-density lipoproteins (VLDL). Density is < 1.060.
ii. Low-density lipoproteins (LDL).
iii. High-density lipoproteins (HDL). Density is 1.060–1.200.
Normal values:
• Serum triglycerides: 30–150 mg/dl,
• Serum cholesterol: 150–240 mg/dl,
• Serum phospholipids: 150–300 mg/dl and
 Absorption of water, electrolytes, minerals and vitamins

• Water absorption. Water balance in the GIT

• The GIT receives about 9 L of water per day, which
includes about 2 L of ingested water and about 7 L
contained in salivary, gastric, biliary, pancreatic and
intestinal secretions (Table 7.7-2).
• The GIT absorbs about 8.8 L of water (about 95% of
total water received) per day. About 60% of
absorption occurs in jejunum, 20–25% in ileum and
10–15% in colon (Table 7.7-2).
• The GIT excretes about 0.2 L of water in the faeces
per day.
 Mechanism of water absorption
• In general, water is absorbed passively and iso-osmotically
across the gastrointestinal mucosa, following the osmotic
gradient created by the active absorption of electrolytes
and nutrients.
• Because osmotic equilibrium is rapidly achieved, the fluid
in the intestine is always isotonic to plasma.
• Only a small amount of water moves across the gastric
mucosa, but water moves in both directions across the
mucosa of small intestine and colon in response to the
osmotic gradient.
• In the duodenum, the osmotic pressure created by the
entering chyme causes water to flow into it.
• In the jejunum and ileum, reabsorption of sodium chloride
(NaCl) creates an osmotic gradient favouring the
reabsorption of water.
TABLE: Daily Water Balance in GIT
Faecal
Input (L) Absorption (L)
excretion (L)
Water ingested : 2 Jejunum (60%) : 5.5 0.2
Water in GIT : 7 Ileum (25%) : 2.0
Secretions Colon (10–15%) : 1.3
• Saliva: 1.5
• Gastric juice: 2.5
• Bile: 0.75
• Pancreatic juice: 0.75
• Intestinal juice: 1.5

TOTAL 9 8.8 0.2

 Absorption of sodium

• Sodium balance in GIT. Gastrointestinal tract receives about 40 g

of sodium per day, out of which about 10 g is ingested with food
and about 30 g is contained in the gastrointestinal secretions. All
of it is reabsorbed.
• Site of absorption. Though sodium can be reabsorbed in the
entire length of the intestine, but maximum absorption occurs in
the jejunum.
• Mechanisms of absorption. Absorption of sodium is a two-step
process:
1. Transport of sodium from the lumen into the enterocyte occurs
by following mechanisms:
• Na+ glucose, Na+–amino acids and Na+–di- or tripeptide
cotransport system account for 30% of Na+transport into the cell.
• Neutral Na+–Cl− cotransport system also transports about 30% of
Na+.
• Na+–H+ exchange and
• Passive diffusion (through Na+ channels) down an electrochemical
gradient is responsible for transport of remainder 40% of Na +.
FIGURE 9:
Absorption of
sodium, chloride,
glucose and amino
acids through the
intestinal epithelium.
The absorption of
water ‘follows’
sodium through the
epithelial membrane.
 Absorption of sodium cont’

• In the small intestine, Na+–glucose cotransport, Na+–amino acid

cotransport and Na+–H+ exchange mechanisms are most important
(these cotransport and exchange mechanisms are similar to those in
renal proximal tubule). Thus, the presence of glucose in the intestinal
lumen facilitates the reabsorpiton for Na+. Because of this reason, in the
treatment of Na+ and water loss in diarrhoea, glucose is added to the
orally administered NaCl solution. Cereals containing carbohydrates are
also useful in the treatment of diarrhoea.
• In the colon, passive diffusion via Na+ channels is most important. These
channels of the colon are similar to those in the renal distal tubules, and
are stimulated by aldosterone (which greatly enhances sodium
absorption). This mechanism is especially useful in dehydration, which
leads to aldosterone secretion by the adrenal medulla.
• 2. Transport of Na+ out of the enterocytes into the interstitium occurs
against its electrochemical gradient across the basolateral membrane by
Na+–K+–ATPase active transport system.
 Absorption of chloride

• In the jejunum and proximal ileum, most of the Cl− is absorbed passively through the
enterocytes down the electrochemical gradient established by the active transport of Na +.
The mechanisms involved in the transport of Cl− are:
• Passive diffusion by a paracellular route through the leaky (permeable) junction between
the enterocytes and
• Neutral Na+–Cl− cotransport system.
In the distal ileum and large intestine, the Cl− is absorbed by an active Cl−–HCO3− exchange
mechanism. In this mechanism, Cl− is absorbed from the lumen in exchange of HCO3−,
which is secreted into the lumen. Bicarbonate (HCO 3−) secreted into the lumen helps to
neutralize the acidity produced by the action of colonic bacteria on the food.
• Absorption of bicarbonate. To neutralize acidic chyme in the duodenum and acidic pH in
colon (due to bacterial activity), large amount of bicarbonate ions are secreted into
pancreatic secretion and bile is poured into the duodenum. At the same time, epithelial
cells on the surface of villi in ileum and large intestine also secrete bicarbonate ions in
exchange for chloride ion absorption.
The bicarbonate ion is absorbed indirectly as:
• During sodium ion absorption, moderate amount of hydrogen ions get secreted into the
lumen of gut in exchange to Na+. These H+ combine with bicarbonate to form carbonic acid
(H2CO3), which then dissociates to form water and carbon dioxide.The water remains in the
intestine; however, CO2 is readily absorbed into the blood and ultimately eliminated during
 Absorption of potassium
• Passive diffusion via paracellular route down its
electrochemical gradient is the mechanism involved in the
absorption of dietary K+from the small intestine.
• Net movement of K+ across the intestinal mucosa is directly
proportional to the potential difference between the blood
and intestinal lumen. The magnitude of which is:
• Jejunum: 5mV,
• Ileum: 25 mV and
• Colon: 50 mV.
• Because of this reason, the concentration of K+ is
approximately 6 mEq/L in jejunum, 13 mEq/L in ileum and 30
mEq/L in colon. This accounts for hypokalaemia occurring due
to ileal and colonic fluid loss in chronic diarrhoea.
 Absorption of calcium

• Body calcium. Calcium is the most abundant among the minerals in the body. The total content
of calcium in an adult man is about 1–1.5 kg of which about 99% is present in the bones and
teeth. A small amount (10%) found outside the skeletal tissue performs a wide variety of
functions.
• Dietary calcium. Best sources of dietary calcium are milk and milk products. Good sources of
calcium are beans, leafy vegetables, fish, cabbage and egg yolk.
Dietary requirements of calcium are:
• Infants (<1 year): 300–500 mg/day,
• Children (1–18 years): 800–1200 mg/day,
• Adult men and women: 800 mg/day and
• Women during pregnancy, lactation and postmenopause: 1500 mg/day.
• Site of absorption. Most of the ingested calcium is absorbed in the upper small intestine
(duodenum and jejunum).
• Mechanism of absorption. Normally, about 75–80% of the daily intake (about 1000 mg) of
calcium is absorbed from the upper small intestine. Most of the calcium is absorbed by an
active transport mechanism in following two steps:
• Entry of calcium inside the enterocyte across its luminal border occurs by the active transport
mechanism involving a membrane-bound carrier that is activated by vitamin D.
• Transport of calcium out of the cell into the interstitium, from where it is absorbed into the
blood capillaries, occurs by a Ca2+–ATPase active transport system and by a Na+–Ca2+ exchange
system.
 Regulation of calcium absorption 

• Calcium absorption from the small intestine is well regulated to maintain the plasma
calcium (homeostasis of calcium) levels within a narrow range (9–11 mg/dl). Vitamin D and
parathyroid hormone (PTH) play main role in the regulation of calcium absorption as:
• Vitamin D3 is converted to 25-hydroxy vitamin D3 by the liver.
• 25-Hydroxy vitamin D3 is converted to 1,25-dihydroxy vitamin D3 [also known as 1,25-
diydroxycholecalciferol (1,25 DHCC) or calciferol] in the kidneys by a process that is
regulated by the parathyroid hormone (PTH).
• 1,25-Dihydroxy vitamin D3 (which is the physiologically active form of vitamin D, acting as
hormone) enters the enterocyte and activates the formation of ‘calcium-carrier protein’
that inserts in the luminal surface of the enterocyte.
• Calcium-carrier protein is responsible for carrier-bound transport of calcium inside the cell.
Factors promoting calcium absorption Include:
• Vitamin D (through its active form calciferol) promotes calcium absorption by inducing
synthesis of calcium-binding protein (as described above).
• Parathyroid hormone enhances Ca2+ absorption by influencing synthesis of calciferol (as
described above).
• Low pH is more favourable for Ca2+ absorption.
• Lactose promotes Ca2+ intake by the intestinal cells.
• Amino acids (lysine and arginine) facilitate Ca2+ absorption.
Factors inhibiting calcium absorption are:

• Phytates and oxalates inhibit Ca2+ absorption by forming

insoluble salts with Ca2+ in the intestine.
• High content of dietary phosphate also prevents
Ca2+ absorption by forming insoluble calcium phosphate.
The dietary ratio of Ca2+ and P between 1:2 and 2:1 is
ideal for optimum Ca2+ absorption.
• Free fatty acids inhibit Ca2+ absorption by forming
insoluble calcium soaps. It occurs particularly when the fat
absorption is impaired.
• High pH (alkaline conditions) is unfavourable for
Ca2+ absorption.
• Dietary fibres in high content interfere with calcium
absorption.
 Importance of Ca:P ratio.

• The ratio of Ca:P is important for calcification of bones.

The product of Ca × P (in mg/dl) in children is about 50
and in adults it is around 40. This product is less than 30
in rickets.
• Excretion of calcium occurs mainly in faeces and partly
in urine.
• • Excretion of Ca2+ into the faeces is a continuous
process and this is increased in vitamin D deficiency.
• • Excretion of Ca2+ into the urine occurs when the serum
Ca2+ goes beyond 10 mg/dL. Ingestion of excess proteins
causes increased Ca2+ excretion in the urine. This is
mainly due to an increase in the acidity of urine.
 Absorption of iron

• Iron deficiency anaemia is the commonest nutritional deficiency disorder

present throughout the world, but its prevalence is higher in the developing
countries. In India, iron deficiency is the commonest cause of anaemia. Iron
deficiency anaemia is much more common:
• In women between 20–45 years than in men.
• At periods of active growth in infancy, childhood and adolescence.
Iron metabolism: Iron is one of important metals present in the human body.
The body of a healthy adult contains 4–5 g (72–90 mmol) of iron in the
following forms:
• Haemoglobin contains about 70% of the total body iron (2.5 g or 45 mmol).
Storage iron amounts to about 20–23% of total body iron (1.5 g, i.e. 18–27
mmol). Two-third of the iron is stored as ferritin and one-third as
haemosiderin.
• Myoglobin (myohaemoglobin) present in the red muscles contain about 5%
of the total body iron (0.2 g or 3.6 mmol)
• Intracellular enzymes account for less than 0.1 g (1.8 mmol), i.e. about 2–3%
of total body iron. The iron containing enzymes include cytochrome oxidase,
 Daily requirement and dietary sources of iron

Daily requirement. Only 10% of the dietary intake of iron is absorbed. Therefore,
daily requirement in adult males is 5–10 mg/day and in females is 20 mg/day (to
compensate the menstrual loss). Pregnant and lactating women require about 40
mg of iron per day.
• Dietary sources. Foodstuffs vary both in their iron content and availability of iron
for absorption into the body. The dietary sources of iron are meat, liver, egg, leafy
vegetables, whole wheat and jaggery. The iron in foods of animal origin is better
absorbed than iron in foods of vegetable origin.
Absorption of iron
• Absorption occurs mainly in the duodenum and upper jejunum.
• Normally, about 10% of the 15–20 mg iron ingested each day is actually absorbed
in healthy adult male. This absorption is more in menstruating women.
Mechanism of iron absorption. Mechanism of iron absorption for the purpose of
understanding can be described under three headings:
• A. Transport of iron across the brush border of enterocyte
• B. Fate of iron in the enterocyte, and
• C. Transport of iron in the plasma.
 A. Transport of iron across brush border of enterocyte.

• In the diet, iron may be present as haem (derived from meat) or nonhaem iron.
1. Absorption of haem iron. Haem iron is the iron present in myoglobin, haemoglobin and
related compounds. From these compounds, the haem is released by proteolytic enzymes in
the gut. From the lumen, the haem is transported inside the enterocyte across the brush-
border membrane by an unidentified haem transport protein. Inside the cell, the ferrous iron
(Fe2+) is released from the haem by the enzyme haemoxygenase. The fate of Fe 2+ so released is
as that of nonhaem Fe2+ as given. Haem iron absorption is not affected by other dietary
constituents.
2. Absorption of nonhaem iron. Most of the dietary nonhaem iron is present in ferric form (Fe 3+),
whereas iron can be absorbed more efficiently in ferrous form (Fe 2+).
• Iron has got tendency to form insoluble complexes with dietary phytates, phosphates and
dietary fibres. These complexes are more soluble at low pH. Gastric HCl tends to break
insoluble iron complex apart and thus facilitates iron absorption. This explains the occurrence
of iron deficiency anaemia in patients with deficient gastric acid secretion (achlorhydria).
• Ascorbic acid and other reducing agents promote iron absorption by reducing ferric iron to
ferrous form and also by preventing iron from forming insoluble iron complexes within the
chyme.
• Ferrous iron (Fe2+) is transported across the brush border by the iron transport protein,
i.e. proton coupled divalent metal transporter (DMT-1) present on the cell membrane . This
protein is not specific for iron, as it can transport a large variety of divalent cations. Once inside
the enterocyte, the fate of nonhaem ferrous iron is the same as that of haem iron.
FIGURE 10: Absorption of iron. Haem is carried across brush border of enterocyte by a haem
transport protein (HT), and Fe2+ of nonhaem iron by iron transport protein (IT). Inside the
enterocyte, some iron binds to ferritin and some crosses the basolateral membrane by active
transport process (AT). In the blood, iron binds to the transport protein transferrin (TF).
 B . Fate of ir on in t he en te r ocyte .

• in the cytosol of enterocyte, the free ferrous iron (Fe 2+) has two fates:
• A part of Fe2+, depending upon the body’s requirement, is actively
transported across the basolateral membranes of the enterocytes
into the interstitium, from where it enters the blood. Across the
basolateral membrane of enterocytes the transport is carried out by
another protein called iron regulating protein-I (IREG-I).
• Rest of the ferrous iron is oxidized to ferric form and bound to
apoferritin forming ferritin. It is difficult to release iron from this
storage form, and in general the ferritin stays in the enterocyte until
the cell is sloughed off at the tip of villus.
C. Transport of iron in the blood.
• Normally, the iron absorbed into the blood binds with a beta globulin
(apotransferrin) to form the transferrin and is transported in this
form in the plasma. Iron combines loosely in the globulin
apotransferrin and can be released easily to enter any of the tissue
cells at any point in the body.
 Factors affecting absorption of iron 

1. Form of dietary iron

• Haem iron. Iron may be present as haem iron or nonhaem iron forming about 10–15% of the
iron present in diet of animal origin, is relatively unaffected by the composition of diet. Haem
is absorbed directly, i.e. without splitting off of iron from protoporphyrin.
• In nonhaem iron the ferrous (Fe2+) form is better absorbed than ferric (Fe3+) form. Therefore,
reducing agents such as vitamin C enhance iron absorption by converting ferric into ferrous.
2. Meat and fish in the diet considerably enhance absorption of nonhaem iron. The exact
mechanism is, however, unknown.
3. Human breast milk improves the iron absorption.
4. The acid gastric juice (HCl from stomach) favours absorption of nonhaem iron by causing its
solubilization and reduction. Therefore, absorption of ferric iron is impaired in subjects with
gastrectomy or achlorhydria.
5. Dietary factors inhibiting nonhaem iron absorption are:
• Phytates in foods (cereals) reduce iron absorption by forming insoluble iron salts.
• Phosphates, calcium, egg white and bovine milk proteins inhibit iron absorption.
• Phenols present in legumes, tea, coffee and wine cause poor absorption of iron.
6. Iron stores in the body affect iron absorption as:
• Decrease in iron store of the body (e.g. in iron deficiency anaemia or when erythropoiesis is
increased due to hypoxia) enhance iron absorption.
• An increase in iron storage in the body reduces iron absorption by the gut mucosa.
 Storage of iron in the body. 

• In the body, iron is stored in two forms, the ferritin and the haemosiderin.
• Storage of iron as ferritin. The iron released into the tissues by
apotransferrin combines with the protein apoferritin to form the ferritin.
Thus, iron is stored as ferritin in the cells of the body. Maximum amount of
iron is stored in the hepatocytes of liver and cells of reticuloendothelial
system. In other cells of the body only a small amount of iron is stored.
• Storage of iron as haemosiderin. When the intake of iron in the diet is in
extremely large quantities, some amount of iron is also stored as a
compound haemosiderin in reticuloendothelial cells. The haemosiderin is
highly insoluble and thus represents a more stable form of storage iron than
the ferritin. Therefore, iron exchanges mostly with the ferritin, since
exchange with haemosiderin is very slow.
• Regulation of body iron. Regulation of body iron, i.e. iron balance in the
body is unique in that it is achieved by control of absorption rather than by
control of excretion. Regulation of mucosal absorption has been explained
by mucosal block theory.
 Mucosal block theory of absorption 

• This theory states that:

• Iron absorption is increased when body iron stores are
depleted or when erythropoiesis is increased, and
decreased under the reverse conditions.
• As compared to normal conditions, in iron deficiency
states, a larger percentage of dietary iron enters the
circulation and a smaller amount forms ferritin in the
epithelial cells.
• In the presence of iron overload, more ferritin is
formed in the enterocytes and shed with these cells in
the stools. 
FIGURE 11: Mucosal block
theory of regulation of iron
absorption: A, normally (say,
e.g. equal amount (3+) of iron is
bound to form ferritin and
enters the blood across
basolateral membrane; B, in
iron deficiency states, less iron
forms ferritin (e.g. 1+) and more
enters the blood, e.g. 5+;
and C, in iron overload, more
ferritin is formed (5+) and less
enters the blood 1+.
 Mucosal block theory of absorption cont’

1. Saturation of apoferritin and apotransferrin. Most of the iron in the body is stored

as ferritin, which is formed by a combination of iron with the protein apoferritin
present in the cytoplasm of the body cells. When essentially all apoferritin in the
body is saturated with iron, it becomes difficult for the transferrin to release its iron
to the tissue cells. Consequently the whole of the apotransferrin is saturated with
iron and thus the mucosal cells are loaded with the transferrin. Because of the
unavailability of the apotransferrin, the mucosal cells are not able to take up any
more luminal iron. Mucosal cells have a lifespan of 3–4 days, at the end of which they
get sloughed off into the intestine. Mucosal transferrin (containing iron) is also lost
with it and the body gets rid of excess of iron.
2. Decreased rate of apoferritin synthesis. When body has excess of iron, due to
feedback mechanism, the rate of apoferritin synthesis in the liver is also decreased
and thus less iron is absorbed by the intestinal cells.
3. Role of specific iron receptors in the brush border. Recently it has been proposed
that the absorption of iron by the enterocytes is determined by the presence of
receptors on the brush border. Iron receptors in brush border preparations of the
small intestine are inversely related to the level of body iron stores. Iron deficient
animals show an increase in the number of receptor population, which can be
reversed by iron loading.
 Conclusion

• The current understanding of the regulation of body iron is

still in a state of fix with following conclusions:
• The control seems to reside primarily in the need-based
transfer of iron from the enterocyte to the portal blood.
• Some control is also exerted at the level of uptake of iron
from the intestinal lumen.
• In cases of iron overload, some iron can be transported from
the plasma to the enterocytes. This iron is lost when the
enterocytes are shed into the lumen. In this way, the
intestine serves to excrete excess iron in a bid to prevent
accumulation of excessive iron in the body. Thus, the
statement that iron content of the body is regulated only by
absorption is also true, only to a limited extent.
 The iron cycle. 

• The iron cycle refers to the continuous exchange of iron between the
plasma and RBCs. The steps of iron cycles are:
• From the plasma, the iron is transported into bone marrow as transferrin.
• In the bone marrow, the transferrin binds to the specific transferrin
receptors present on the surface of intermediate normoblasts.
• In the intermediate normoblasts, the iron is incorporated into the
haemoglobin. The mature RBCs containing haemoglobin are then released
into the plasma.
• RBCs, after their death (on completion of lifespan), are engulfed by
macrophages.
• After phagocytosis, the red cell membrane is lysed and haem is released
from the haemoglobin. By the haemoxy genase reaction, iron is liberated
from the haem.
• Macrophages lining the sinuses of liver and spleen release iron back into
the plasma where it binds with the apotransferrin to form transferrin, thus
completing the iron cycle. Each day, about 30 mg of iron goes through this
cycle. In addition, about 2 mg iron enters the plasma from the diet also.
FIGURE 12: Iron cycle.
 Role of iron in the body 

• Iron is utilized in the synthesis of:

• Haemoglobin in the RBCs (main role),
• Myoglobin in the muscles
• Cytochromes the intracellular enzymes.
Uptake of the iron by tissues
• RBCs are the main takers of iron (about 30 mg/day)
 Other tissues take up about less than 2 mg iron each day as follows:
• Liver. Out of the tissues other than RBCs, liver takes up the largest
amount of iron.
• Intestinal mucosal cells. Iron is stored as transferrin in the intestinal
mucosal cells which regulate the iron absorption as discussed above.
• Skeletal muscles. Iron is utilized to produce myoglobin by the muscles.
• Proliferating cells of the body. Iron is utilized for synthesis of enzymes
cytochrome and catalases, which are required in excess by the
proliferating cells of the body.
 Iron deficiency results in iron deficiency anaemia
• Iron excess. Iron overload may occur when its absorption
exceeds its excretion. Such a condition occurs due to:
• Excessive intake of iron, and
• Idiopathic or congenital failure of mucosal feedback
mechanism controlling iron absorption.
• Excessive destruction of erythrocytes may also be
associated with siderosis.
• The excess of iron in the body results in accumulation of
hemosiderin in the tissues producing the so-
called haemosiderosis. Excess of haemosiderin damages
the tissues and produces the condition
of haemochromatosis.
 Iron deficiency results in iron deficiency anaemia cont’
• The hereditary or primary haemochromatosis occurs
due to mutation of HFE gene located on chromosome-
6. The individual with homogeneous mutated HFE gene
absorbs excess amounts of iron because normally the
HFE gene inhibits expression of the transporter
responsible for iron intake. Haemochromatosis is
characterized by:
• Pigmentation of the skin,
• Diabetes due to pancreatic damage (bronze diabetes),
• Cirrhosis of liver,
• Carcinoma of the liver and
• Atrophy of gonads.
 Causes of iron deficiency anaemia

• Causes of iron deficiency vary with age, sex and country of residence of
patient. In general, the causes of iron deficiency anaemia can be grouped as:
1. Inadequate dietary intake of iron as in:
• Milk fed infants,
• Poor economic status individuals,
• Anorexia, e.g. in pregnancy and.
• Elderly individuals due to atrophy and poor dentition
2. Increased loss of iron (as blood loss) from the body, e.g.
• Uterine bleeding in females in the form of excessive menstruation, repeated
miscarriages, postmenopausal bleeding, etc.
• Gastrointestinal bleeding due to peptic ulcer, haemorrhoids, ulcerative
colitis, etc.
• Renal tract bleeding, e.g. haematuria.
• Nasal bleeding, i.e. repeated epistaxis.
• Bleeding from lungs as haemoptysis.
 Causes of iron deficiency anaemia cont’

3. Increased demand of iron as in:

• Infancy, childhood and adolescence,
• Menstruating females and
• Pregnant females.
4. Decreased absorption of iron, as seen in:
• Partial or total gastrectomy,
• Achlorhydria and
• Intestinal malabsorption diseases.
Clinical features, laboratory findings and treatment
1. General features of anaemia
2. Characteristic features of iron deficiency anaemia are in the form
of the following epithelial tissue changes:
• Nails become dry, soft and spoon shaped (koilonychia).
• Tongue becomes angry red (atrophic glossitis).
• Mouth may show angular stomatitis.
• Oesophagus may develop their membranous webs at the
postcricoid area leading to dysphagia (Plummer–Vinson syndrome).
Laboratory findings
1. Blood picture and red cell indices
• Haemoglobin concentration is decreased.
• RBCs are hypochromic (deficient in haemoglobin) and microcytic
(smaller in size). They show anisocytosis and poikilocytosis.
 Clinical features, laboratory findings and treatment
cont’
2. Bone marrow findings are:
• Marrow cellularity: erythroid hyperplasia,
• Erythropoiesis: normoblastic and
• Marrow iron: deficient reticuloendothelial iron stores and absence of
siderotic iron granules.
3. Biochemical findings
• Serum iron decreases, often under 50 µg/dL (normal 60–160 µg/dL).
• Serum bilirubin less than 0.4 mg/dL.
• Serum ferritin is less than 30 μg/dL indicating poor tissue iron stores.
• Total iron-binding capacity (TIBC) is increased.
Treatment. Treatment of iron deficiency anaemia consists of:
• Oral administration of Fe2+ salts, and
• Correction of causative factor if possible.
 Note

• Iron deficiency anemia is a condition in which there is

insufficient hemoglobin in red blood cells due to a lack of
iron (which is an essential component of heme).
• Approximately two thirds of the iron content of the body is
bound to hemoglobin. It is usually caused by blood loss from
menses in premenopausal women, but it can also be due to
inadequate dietary intake of iron, GI bleeding (e.g., from
peptic ulcers, long-term nonsteroidal anti-inflammatory drug
use, or certain GI cancers), from GI conditions that decrease
the absorption of iron (e.g., Crohn disease), or by pregnancy
(in which the need for iron is increased due to the increase in
maternal blood volume and for fetal hemoglobin synthesis).
• Treatment involves replenishment of iron in the form of
ferrous sulfate tablets.
 Note

• Hemochromatosis is a condition in which there is

failure of regulation of iron absorption in the bowel.
This leads to excessive iron in the body, which then
gets deposited in organs such as the liver, heart,
pancreas, and the pituitary gland. Iron toxicity
causes lipid peroxidation of cell membranes, DNA
damage, and increased collagen formation. Signs
include fatigue, arthralgia, skin pigmentation, liver
disease (cirrhosis and carcinoma), cardiomyopathy,
heart failure, arrhythmias, diabetes, and infertility.
Management is by the drainage of venous blood
until the patient is iron deficient.
 Note

• Cholera is an infectious disease caused by Vibrio cholerae, a gram-negative

bacteria. It is spread via the fecal-oral route. V. cholerae toxin increases
cyclic adenosine monophosphate (cAMP) concentrations in intestinal
mucosal cells, causing the opening of Cl − channels and massive secretion of
Cl−. This results in the production of a profuse amount of watery diarrhea,
which, in turn, causes severe dehydration. This can lead to kidney failure,
shock, coma, and death. Treatment requires rapid replacement of lost body
fluids with oral or intravenous solutions containing salts and sugar.
Tetracycline reduces fluid loss and diminishes transmission of the bacteria.
• Pseudomembranous colitis is inflammation of the colon due to
superinfection with Clostridium difficile, a gram-positive bacillus. It typically
occurs following a course of antibiotic treatment in which the normal gut
commensal bacteria are eradicated, allowing C. difficile to colonize the gut
unimpeded. The most common antibiotics that cause this condition are the
penicillins, cephalosporins, fluoroquinolone, and clindamycin. Symptoms of
pseudomembranous colitis include diarrhea, fever, and abdominal pain. It
is treated with metronidazole or vancomycin.
 Note

• Exudative diarrhea is a consequence of gross structural damage to the

intestinal or colonic mucosa. It is characterized by the presence of blood in
feces and frequent passage of a small volume of feces. Examples of causes
of exudative diarrhea are inflammatory bowel diseases such as ulcerative
colitis and Crohn disease, mucosal invasion by a protozoan
(e.g., Entamoeba histolytica), and certain bacterial infections (e.g., Shigella
and Salmonella).
• Secretory diarrhea occurs in disorders in which there is increased secretion
of fluids and electrolytes (e.g., cholera) or inhibited reabsorption of fluids
and electrolytes.
• Osmotic diarrhea occurs when ingested solutes that are osmotically active
are retained in the lumen of the GI system. Because water must also be
retained to maintain isotonicity, the volume of fluid delivered to the colon
may exceed its absorptive capacity. Osmotic diarrhea may result from
ingestion of substances that are difficult to absorb (e.g., MgSO4, a
common ingredient in laxatives), limited absorption of solutes, or
resection of the jejunum or ileum, which decreases the surface area for
absorption of digested food. It may also occur if bile salts enter the colon,
 Absorption of vitamins

• Absorption of fat-soluble vitamins: Fat-soluble vitamins (A, D, E and

K) become part of micelle formed by bile salts, and are absorbed
along with other lipids in the upper part of small intestine.
• The absorption of fat-soluble vitamins is deficient if fat absorption is
depressed because of lack of pancreatic enzymes or if bile is excluded
from the intestine by the obstruction of bile duct.
Absorption of water-soluble vitamins: Absorption of water–soluble
vitamins is rapid compared with fat-soluble vitamins.
• Most vitamins are absorbed in the upper part of small intestine
(jejunum) except vitamins B12, which is absorbed in the ileum.
• Most water-soluble vitamins, e.g. vitamin C and the vitamins B, (biotin,
folic acid, nicotinic acid, B8, i.e. pyridoxine, B2, i.e. riboflavin and B1, i.e.
thiamine), are absorbed by facilitated transport or by Na+-dependent
active transport system in the proximal small intestine.
• Vitamin B12 absorption is most complex than that of other water-
soluble vitamins and needs separate description.
 Absorption of vitam in B12 involves the following steps:

• In the stomach, vitamin B12 is exposed to specific binding protein R and vitamin B12-binding
protein called intrinsic factor (IF). As the affinity of R proteins for vitamin B12 is much more
than that of IF, so most of the vitamin B12 gets bound to R protein in the stomach.
• In the lumen of intestine, the pancreatic proteases cleave vitamin B12 from the R protein.
Then, vitamin B12 binds to IF to form a complex.
• On the brush border of enterocyte, IF–B12 complex becomes bound to the specific
receptors. Following this, the vitamin B12 is transported into the cytosol of enterocyte by
endocytosis, leaving behind IF at the brush border. It is important to note that absorption
of vitamin B12 from the IF–B12 complex can occur only after the complex binds to the
receptors. In the absence of intrinsic factor, vitamin B12 absorption is markedly decreased
and the patient may develop pernicious anaemia.
• From the basolateral border of enterocyte. Vitamin B12 enters the portal circulation after
binding with plasma globulin called transcobalamine-11.
• In the liver, vitamin B12 is stored in large amounts after binding with another globulin
called transcobalamin-1. The storage of water-soluble vitamin is unique to vitamin B12.
Liver may store up to 3 years of supply. Vitamin B12 is also stored in the muscles for some
extent. Whenever required, it is transported from the liver to the bone marrow.
 Note
• The majority of vitamin C is absorbed in the proximal small
intestine and is excreted by the kidneys. However, increasingly large
amounts are excreted in feces following megadoses.
• Vitamin C is a reductant substance, and this property allows it to
act as a H+ donor in hydroxylation reactions (e.g., during the
biosynthesis of catecholamines when it is a cofactor for dopamine-
β-hydroxylase).
• Other biological effects are based on different mechanisms, some
of which are unknown (e.g., it is involved in collagen biosynthesis).
It is also involved in the synthesis of bile acids from cholesterol, the
synthesis of hormones (e.g., gastrin, gastrin- releasing peptide
[GRP, bombesin], corticotropin-releasing hormone [CRH], and
thyrotropin-releasing hormone [TRH]), the synthesis of cytochrome
P-450 enzymes in the liver. It enhances iron absorption (by reducing
Fe3+ to Fe2+) and it has well known antioxidant properties.
 Malabsorption syndrome

• Malabsorption syndrome is not a simple disease but a group of

disorders in which multiple nutritional deficiency states are produced.
• Pathophysiology: Malabsorption occurs due to abnormalities of three
processes, which are important for normal digestion and absorption.
i. Intraluminal maldigestion: When there is deficiency of pancreatic
enzymes and bile which results in inadequate solubilization and
hydrolyses of nutrients leading to fat and protein malabsorption.
ii. Mucosal malabsorption results when there is damage of small
intestinal epithelium, thereby diminishing the surface area for
absorption and depleting brush border enzyme activity.
iii. Postmucosal lymphatic obstruction prevents the uptake and
transport of absorbed lipids into lymphatic vessels. Increased pressure
in these vessels results in leakage into intestinal lumen leading to
protein loosing enteropathy.
 General features of malabsorption are:
• Deficient absorption of amino acids, fats and
carbohydrates result in general weakness.
• Malabsorption of vitamins may produce anaemia
and signs of hypovitaminosis.
• Malabsorption of iron results in iron deficiency
anaemia.
• Malabsorption of fats produces steatorrhoea .
• Water and electrolyte depletion may result in
dehydration.
 Common conditions which can produce malabsorption are :

• Coeliac disease
• Sprue
• Lactose intolerance 
• Crohn’s disease
• Resection of small intestine
• Malabsorption after gastric surgery
• Blind loop syndrome
• Chronic pancreatitis
• Obstruction of common bile duct.
 Coeliac disease

• Aetiopathogenesis. It occurs due to deficiency of the enzyme gluten

hydrolase. As a result, gluten, the principal protein of wheat, rye,
barley and oats, is not properly hydrolysed. Consequently, gliadine, a
toxic polypeptide, is formed, which produces an inflammatory
response in the intestinal mucosa leading to destruction of microvilli.
• Clinical features of gluten-induced enteropathy are those of
generalized malabsorption. It may occur as:
• Congenital disease manifesting usually within first 3 years of life and
• Acquired disease in adults due to unknown aetiology.
Treatment consists of withdrawal of wheat and other sources of gluten
in the diet.
Sprue: Sprue or the tropical sprue is a disorder of malabsorption, which
is particularly characterized by features of failure of absorption of
folate, with or without associated malabsorption of vitamin B12. So,
general features of malabsorption with megaloblastic anaemia, which
is conspicuous, occur.
 Crohn’s disease

• Aetiopathogenesis. It is an inflammatory bowel disease (IBD)

characterized by idiopathic, nonspecific granulomatous inflammation
of the bowel.
• Clinical features vary depending upon the part and extent of bowel
involved. Common clinical features are: off and on fever, chronic
diarrhoea, abdominal discomfort and pain and weight loss is frequent,
and many patients have moderate anaemia and other features of
malabsorption. Ultimately, the patient may develop narrowing and
obstruction of intestinal lumen, fistula formation or intestinal
perforation.
• Radiological examination (barium meal study) shows pathognomonic
features in the form of string sign, due to marked narrowing of the
lumen and skip lesions due to patchy involvement.
• Treatment. It is a chronic disease with remissions and relapses over
many years. Although there is no specific cure, but corticosteroidsmay
induce remission in patients with active disease.
 Resection of small intestine

• Removal of short segment from the jejunum or ileum generally does

not produce any severe symptoms. Because there occurs
compensatory hypertrophy and hyperplasia of remaining mucosa
(intestinal adaptation), the capacity of the jejunum to adapt is less than
that of ileum.
• Removal of ileum produces greater degree of malabsorption compared
with removal of jejunum. Because ileal resection prevents absorption
of bile salts causing decreased fat absorption, the entry of unabsorbed
bile salts in the colon inhibits Na+ and water reabsorption producing
diarrhoea.
• Removal of large segment of ileum leaving behind, duodenum,
jejunum and a very small length of ileum produce malabsorption which
is characterized by:
• Normal carbohydrate absorption (99% of ingested carbohydrates are
absorbed).
• Adequate protein absorption (70% of ingested proteins are absorbed).
 Resection of small intestine cont’

• Markedly decreased fat absorption which may

produce:
• Steatorrhoea, i.e. increase in faecal fat (see page
621),
• Deficiency symptoms of fat-soluble vitamins (A, D, E
and K),
• Fatty infiltration of liver and cirrhosis,
• Markedly decreased calcium absorption due to the
formation of insoluble calcium salts. Decreased
serum calcium (hypocalcaemia) may produce
tetany.
 Gastrocolic fistula 

• In this condition, chyme enters directly into transverse

colon from the stomach. It is characterized by the
following additional features, over and above the
features of large segment resection of ileum described
above:
• Pernicious anaemia, due to the failure of absorption
of vitamin B12.
• Hypovitaminosis due to both water-soluble as well as
fat-soluble vitamins.
• Amino acid malabsorption, which produces
hypoproteinaemia (causing generalized oedema) and
marked muscular weakness with wasting.
 Blind loop syndrome 

• Blind loop syndrome is characterized by formation of the areas of the intestine where
bacteria can proliferate without being subjected to movement down the intestine.
• Causes of blind loop formation are multiple diverticula in the small intestine, afferent
loop after partial gastrectomy, areas of disordered peristalsis in small intestine and
fistula from the upper small intestine to the colon.
• Features. Colonization of small bowel by bacteria in blind loop syndrome may
produce:
• Malabsorption of fat (steatorrhoea). It occurs due to deconjugation of bile salts by
bacteria.
• Megaloblastic anaemia, due to vitamin B12 deficiency (which is taken up by bacteria).
• Amino acid deficiency (due to consumption by the bacteria) resulting in weakness and
hypoproteinaemia.
• Diarrhoea and other nutritional deficiencies.
Diagnosis is confirmed by radiological demonstration of blind loop areas.
Treatment consists of broad-spectrum antibiotics and dietary and vitamin supplements.
Occasionally, it may be necessary to correct a structural abnormality by surgical
means.
 Blind loop syndrome cont’

• Investigations are performed to confirm the malabsorption

and its cause. These include:
i. Routine blood tests. If streatorrhea is suspected, these
include urea, electrolyte, immunoglobulins, Ca2+, Mg2+,
blood counts, clotting tests, albumin, folate and coelic
antibodies.
ii. To investigate small intestine, the tests include duodenal
biopsy, barium studies and sugar absorption test.
iii. To investigate pancrease, the tests include pancreatic
function test, ultrasonography/CT scan.
iv. To investigate bile salt malabsorption:
• Se HCAT scan and
• Serum 7 α-hydroxycholestenon.
 Tests of intestinal absorption

• General principle. ​General principle of the commonly performed tests

of intestinal absorption is to give a fixed quantity of nutrient, and
measure its blood level, urinary excretion or faecal excretion . The
nutrient used for the test will depend upon the region to be tested.
• Carbohydrate absorption tests
1. D-xylose test. D-xylose is a pentose sugar that is completely absorbed
from the small intestine as such but is neither metabolized nor stored
in the body. The test is conducted in the fasting state, by giving 25 g D-
xylose orally with 3–4 glasses of water and measuring its urinary
excretion over the next 5 h.
• Absorption is considered normal if more than 4 g of xylose appears in
the urine over the 5-h period.
• Lesser excretion in urine indicates malabsorption.
• The diagnostic value of this test is compromised if the patient’s kidney
function is subnormal.
 Tests of intestinal absorption cont’

2. Lactose tolerance test. After overnight fasting, blood glucose

level and hydrogen concentration in the end-expiratory air is
estimated. The subject is made to ingest 50 g of lactose. Results
are interpreted as:
• Absorption is considered normal if the rise in blood glucose is
more than 50 mg/100 ml.
• Lack of diarrhoea, abdominal discomfort and flatulence also point
to adequate absorption.
• Hydrogen concentration in the end-expiratory air, 90 min after
ingestion of lactose, is a fairly reliable indicator of lactose
tolerance. Normally, H2 concentration is less than 15 ppm; a
concentration greater than 20 ppm indicates lactose intolerance
(in lactose intolerance, the unabsorbed lactose enters the colon,
where it generates H2 after fermentation. The H2 is absorbed in
bloodstream and eliminated by the lungs).
FIGURE 13: General principle of commonly performed tests of intestinal
absorption. The intake is known (I), the quantity absorbed (A) may be
estimated from the values of faecal loss (II) and/or blood levels (III) and
urinary excretion (IV) of the substance.
FIGURE 14:
Predominant sites
of absorption of
nutrients. It helps
to decide the
nutrient to be
used for any
particular
absorption test.
 Tests for absorption of fats and related substances
1. Faecal fat.
2. 131I-triolein test. A measured quantity of radioactive triolein (a
triglyceride) is given orally. The fraction excreted in the stool is
assessed by radioactivity.
3. Absorption of fat-soluble vitamins can also be used as an index of fat
absorption.
4. 14 C-glycine–bile acid test is performed to test the absorption of bile
acids.
Protein absorption tests
1. Faecal nitrogen excretion test.
2. Serum protein estimation. Serum protein concentration is a fair
indicator of protein absorption provided:
• Protein intake is normal,
• Liver is manufacturing adequate albumin,
• There is no loss of proteins in urine and
• There is no protein losing enteropathy.
 Protein absorption tests cont’

3. Tests for protein losing enteropathy (PLE). In PLE,

the absorption of proteins is normal but loss from
the bowels is abnormally fast, leading to high
protein content in stools. It can be tested by tagging
the albumin with 51Cr and then radioactive
chromium is followed in the blood and stool.
 Tests for absorption of water-soluble vitamin

• In practice, usually few screening procedures are sufficient to

differentiate between the common causes of malabsorption . Coelic
disease is an example of generalized malabsorption, Crohn’s disease is
a localized disease of distal ileum and colon and chronic pancreatitis is
an example of exocrine pancreatic insufficiency. Schilling test.
TABLE. Common Causes of Malabsorption and Tests for Differential Diagnosis

Test Coeliac disease Crohn’s disease Pancreatic

insufficiency
1. Faecal fat contents Increased Increased Increased
2. D-xylose Impaired Normal Normal
absorption test
3. Schilling test Normal Abnormal Normal
4. Radiological Abnormal Abnormal Normal
examination of
intestines