ANATOMY AND PHYSIOLOGY OF GIT

1. BY
VANA JAGAN MOHAN RAO M.S.Pharm, MED.CHEM
NIPER-KOLKATA
Asst.Professor, MIPER-KURNOOL
Email: jaganvana6@gmail.com

2. CONTENTS
Anatomy
Physiology
Digestion And Absorption
Gastrointestinal Tract Structure
Regulation Of Gastric Function
Phases of Digestion
Physiological considerations that affect oral bioavailability
References
2

3. 3
A drug's life in the body. Medicines taken by mouth (oral) pass through the
liver before they are absorbed into the bloodstream. Other forms of drug
administration bypass the liver, entering the blood directly.

4. ANATOMY
4
 Study of the structure/form of the human body
 Study location of organs, reasons for location, and
shape.
 Anatomy is the science which deals with the
description of the structure of cells, tissues, organs
and organisms.

5. PHYSIOLOGY
5
 Study of the function of organs and the biochemical
make-up of those organs
 Physiology is the science which deals with the study of the
function of cells, tissues, organs and organisms, which tries
to explain with the application of physics and chemistry.

6. ANATOMY AND PHYSIOLOGY OF THE
GASTROINTESTINAL TRACT
6
the key structures involved oral drug absorption.

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8. 8

9. 9

10. Upper gastrointestinal tract
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 The upper gastrointestinal tract consists of the esophagus,
stomach, and duodenum.
 Some sources also include the mouth cavity andpharynx.
Lower gastrointestinal tract
 The lower gastrointestinal tract includes most of the small
intestine and all of the large intestine. According to some
sources, it also includes the anus.

11. 11
Small intestine, which has three parts:
Duodenum. The digestive enzymes break down proteins
and bile emulsifies fats into micelles. Duodenum contains
Brunner's glands which produce bicarbonate and
pancreatic juice contains bicarbonate to neutralize
hydrochloric acid of stomach
Jejunum - It is the midsection of the intestine, connecting
duodenum to ileum. Contain plicae circulares, and villi to
increase surface area.
Ileum - It has villi, where all soluble molecules are
absorbed intothe blood .
Large intestine, which has three parts:
Cecum
Colon
Rectum and anus

12.  The gastrointestinal system is primarily involved in reducing
food for absorption into the body.
This process occurs in 4 mainphases:
i) Fragmentation
ii) Digestion
iii) Absorption
iv) Elimination of wasteproducts
DIGESTION AND ABSORPTION
12
Initial fragmentation of food occurs along with the secretions of
the salivary glands, in the oral cavity forming a bolus.
Bolus of food is then carried to the esophagus by the action ofthe
tongue and pharynx (deglutition).

13. Esophagus carries food from mouth to stomach, where
fragmentation is completed and digestion initiated.(Eg:
protein to polypeptides followed by small peptides and
amino-acids).
13
In the stomach food is converted into semi-digested liquid
(chyme) which passes through the pylorus, into the
duodenum.
Unabsorbed liquid residue enters the cecum through ileo-
cecal valve where water is absorbed and become
progressively more solid as it passes into the anus

14. GASTROINTESTINAL TRACT STRUCTURE
 Mucosa (lumenside)
• Epithelial tissue
 Submucosa
• elastic connective tissue
• contains lymph and blood
vessels
 Muscularisexterna
• smooth muscle layers
 Serosa
• Outermost lining of
organs of GIT.
Fig 14.3
14

15.  Insert Figure
4.21
Gastrointestinal Tract
Muscular tube that extends from
mouth to anus
Major organs: mouth, esophagus,
stomach, small intestine, large
intestine
Accessory organs: liver, gall
bladder and pancreas
Function: food digestion, nutrient
absorption and distribution and
waste elimination

16. MOUTH
16
Digestion begins in the mouth
Mechanical digestion
– Biting and grinding actions of teeth
breaks and mashes food into smaller pieces.
Chemical digestion
– Saliva mixes and lubricates food.
–Salivary amylase and lipase begin breakdown
of starch and fat, respectively.

17. MOUTH (ORAL CAVITY)
17
Regions include the vestibule & oral cavity
Roof comprised of hard & soft palate; floor primarily comprised of tongue

18. Tongue
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stratified
squamous
epithelium over
skeletal muscle
intrinsic &
extrinsic muscles
papillae
filiform
fungiform
circumvallate

19. taste buds
19

20. FROM THE MOUTH TOTHE STOMACH
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 Esophagus – Tube connecting pharynx to stomach
 Epiglottis – Flap that folds down over trachea
(windpipe) when you swallow

21. ESOPHAGUS
 Transport food and water to stomach, secretesmucus
 Movement of food bolus in esophagus (and rest of GI tract) viaperistalsis
 Empties into stomach through the lower esophagealsphincter
21

22. STOMACH
 Muscular sac-like organ
 Chemical andphysical digestion
 forms chyme
 Stores food, releases small amts. to smallintestine
 takes 2-6 hours for stomach to empty
 inner surface lined with gastricrugae
 stomach is divided into 3 regions: fundus, body, and antrum (pylorus).
22

23. STOMACH -GROSS ANATOMY
Lower esophageal (cardiac) sphincter
Pyloric sphincter
23

24. STOMACH MUCOSAL CELLS
 Gastric glands (small folds in
mucosa) contain specialized
secretory cells
 parietal cells – hydrochloricacid
 goblet cells –mucus
 Gastric Mucosal Barrier protects
stomach epithelium
 chief cells -pepsinogen
 Digests protein
 endocrine cells
 ECL cells – histamine
 G-cells – gastrin
 Intrinsic factor secreting-cells
Fig 14.4
24

25. REGULATION OF GASTRIC FUNCTION
PHASES OF DIGESTION
Three basic phases
1. Cephalic phase
 Regulation of stomach
by the brain via the
vagus nerve
 Stimulates G and ECL
cell in response to
stimuli associated with
food
•ECL cells – histamine
•G-cells – gastrin
Fig 14.7
25

26. 2. Gastric phase
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Arrival of food in stomach
Distension of the stomach walls and…
Presence of amino acids and short polypeptides
stimulate pepsinogen and gastrin secretion
3. Intestinal phase
Arrival of chyme in small intestine stimulates
neural reflex that inhibits gastric motility and
secretion
Fats in chyme stimulate secretion of
enterogastrones from the intestine that inhibit
stomach function

27. 27

28. Small Intestine
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Where most
nutrients are
digested and
absorbed.
Duodenum
Jejunum
Ileum

29. SMALL INTESTINE - ANATOMY
-connects stomach to large intestine; 15-20’ long;1” diameter; held together in
abdominal cavity by “mesentery proper”
- site for completion of chemical digestion & absorption of nutrients
- comprised of three regions:
Duodenum – 10” in length;
receives chyme from stomach,
secretions from liver, gallbladder
& pancreas
Jejunum – 8’ long; most
digestion & absorption
occurs here
Ileum – 12’ long; connects
to cecum of large intestine
at iliocecal valve
(sphincter)
29

30. SMALL INTESTINE
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Modifications in mucosa & submucosa of intestinal wall
designed to increase functional surface area:
Plicae circulares (circular folds) – large
transverse ridges; most abundant in
jejunum
Villi – small finger-like projections of
mucosal folds across surface of intestine
Plicae
circulares

31. ABSORBING NUTRIENTS
31
Figure 4.26
Villi
Tiny projections that
line the small intestine
Absorptive cells
Remove nutrients from
chyme and transfer
them into intestinal
blood or lymph

32. WATER-SOLUBLE
NUTRIENTS ENTER
THE CAPILLARY OF A
VILLUS, AND TRAVEL
TO THE LIVER VIA
PORTAL VEIN.
MOST FAT-SOLUBLE
COMPOUNDS ARE
FORMED INTO
CHYLOMICRONS, THAT
ENTER A LACTEAL OF
THE LYMPHATIC
SYSTEM AND
EVENTUALLY REACH
THE BLOODSTREAM.
32

33. HOW IS INTESTINE SERVEAS A BEST SITE
FOR ABSORPTION OF MOST OFDRUG?
33
 Very large surface area.
 Blood flow to SI is very high.
 PH range 5-7.5 which is favorable for most of
drugs to remain unionized.
 Peristaltic movement of intestine is slow
compared to stomach.
 Residence time of dosage form in SI is long.
 Permeability is very high.

34. LARGE INTESTINE
Absorption of water
and minerals
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Feces – form as
chyme becomes
semisolid
Rectum – lower part of
large intestine where
feces are stored
Insert
figure
4.21

35. LARGE INTESTINE
- Begins at the ilium & ends at the anus; 5’ long; 3” in diameter
-main functions – H2O reabsorption; absorption of some vitamins & minerals;
formation & temporary storage of fecal material
Rectum
ileum
Ileocecal sphincter
Cecum
Vermiform appendix
Ascending
colon
Transverse
colon
Descending
colon
Sigmoid colon
Anal canal
Rectum
- 3 regions: cecum, colon, rectum
Hepatic (rt.
Colic) flexure
Splenic (lt. colic)
flexure
35

36. Pancreas – produces and
secretes many digestive
enzymes
Liver – processes and
stores many nutrients
makes cholesterol
Gallbladder – stores bile that
the liver makes
Accessory
Organs
36

37. ACCESSORY DIGESTIVE ORGANS: PANCREAS
Produces Pancreatic Juice
 Bicarbonate - neutralizes
stomach acidity
 Enzymes
 Pancreatic amylase - breaks
down starch
 Trypsin and other proteases
- break down polypeptides
 Pancreatic lipase -
digests triglycerides
others ( nucleases)
 Pancreatic juice enters the
duodenum through the duodenal
papilla
37

38. PANCREAS
Pancreatic juice – mixture of enzymes & buffers (sodium bicarbonate)
secreted by acinar cells into pancreatic duct & released into duodenum
pancreatic amylase
STARCH MALTOSE
Lipase
LIPIDS FATTY ACIDS + MONOGLYCEROL
proteases (trypsin, chymotrypsin, carboxypeptidase)
PROTEINS & POLYPEPTIDES small peptides tri &
dipeptides
nucleases – digest RNA & DNA
sodium bicarbonate – neutralizes acidic chyme because enzymes in
small intestine need an alkaline pH
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39. LIVER - ANATOMY
Largest organ within the body
Comprised of 4 lobes:
9
Large right & left lobes divided by falciform
ligament; small caudate & quadrate (by gall bladder
) lobes
Lobes of liver functionally divided into microscopic
lobules

40. LIVER
Hepatocytes produce bile, which gets secreted into bile
canaliculi of lobule
Bile canaliculi merge to form bile ducts which eventually
merge to create the right & left hepatic ducts
40

41. 41
The figure shows where metabolism occurs during the absorption
process. The fraction of the initial dose appearing in the portal vein is
the fraction absorbed, and the fraction reaching the blood circulation
after the first-pass through the liver defines the bioavailability of the
drug.

42. LIVER & GALL BLADDER
• muscular sac under
right lobe of liver;
stores & concentrates
bile; releases bile
through cystic duct
Right & left hepatic ducts unite to form common hepatic duct
which merges with cystic duct of gall bladder to form common
bile duct which joins with pancreatic duct & enters the
duodenum
Gall bladder – hollow
Bile released into duodenum
functions in emulsification of lipids,
absorption of fats (due to presence
of bile salts), & excretion of bilirubin
Right hepatic duct Left hepatic duct

43. • Small Intestine
enzymes
• Sucrase
• Maltase
• Lactase
• Intestinal
lipase
• Pancreatic enzymes
• Trypsin
• Chymotrypsin
• carboxypeptidase
• Nuclease
• Pancreatic amylase
43
Gastric enzymes:
•Pepsin
Main enzyme in
stomach
Breaks down
protein to peptides
•Gelatinase
Breaks down
proteins
•Gastric amylase
• Gastric lipase

44. PHYSIOLOGICAL CONSIDERATIONS THAT
AFFECT ORAL BIOAVAILABILITY
The transit of pharmaceuticals in the gastrointestinal tract
Gastrointestinal pH
Enzymatic status
Presence of foods and liquids in the gastrointestinal tract
44

45. GASTROINTESTINAL PH
F
A
S
T
E
D
F
E
D
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The pH varies considerably along the length of the GIT. Different regions along
the tract will exhibit different pH values.
STOMACH
Gastric fluid in the stomach is highly acidic, ranging
between pH 1-3.5 in the fasted state.
In the fed state, the pH rises in the range of pH 3-7
depending on the composition of the meal.
The variability in pH of the stomach is an important consideration when taking a
medicament with respect to the drugs chemical stability or achieving drug
dissolution absorption.

46. GASTROINTESTINAL PH
SMALL INTESTINE
Intestinal pH is much higher than gastric fluid due to neutralisation
with bicarbonate ions secreted into the small intestine by the
pancreas. The pH values increase along the small intestine e.g.
from pH ~6.1 in duodenum to ~7.8 in the ileum.
LARGE INTESTINE
The pH of the cecum is around 6-6.5, which increases towards the
distal parts of the colon to pH 7-7.5.
46

47. ENZYMATIC STATUS
 Luminal enzymes of the smallintestine
Pepsin is the primary enzyme found in gastric fluid. Other enzymes
such as lipases, amylases and peptides are secreted into the small
intestine via the pancreas in response to ingestion of food. Pepsins
and proteases are responsible for the breakdown of protein and
peptide drugs in the lumen. Drugs which resemble nutrients such as
fatty acids and nucleotides are susceptible to enzymatic attack.
 Colon
Presence of bacterial enzymes in the colonic region of the
gastrointestinal tract, which digest material not yet digested in the
small intestine.
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48. PRESENCE OF FOODS AND LIQUIDS IN THE
GASTROINTESTINAL TRACT
The rate and extent of drug absorption in the gastrointestinal
tract depends on the following factors:
 Presence of food
 Dietary intake
 Delayed gastric emptying
 Increased viscosity of the gastrointestinal contents
 Stimulation of gastrointestinal secretion
48

49. PRESENCEOFFOOD
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Food tends to increase the pH of the stomach by acting
as a buffer. Gastric pH is likely to decrease the rate of
absorption of a weakly basic drug but increase that of a
weakly acidic drug.

50. DELAYEDGASTRICEMPTYING
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Foods which are high in fat tend to reduce gastric
emptying, therefore delaying the onset of action of
various drugs.
In addition, the presence of fat stimulates the release of
bile salts which are surface active agents which enhance
the absorption of poorly absorbed drugs. However, they
have been found to form insoluble and non-absorbable
complexes with certain drugs.

51. GASTROINTESTINAL MOTILITY
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 There are two modes of motility patterns in the stomach and consequently
in the small intestine .
The digestive (fed) pattern consists of continuous motor activity,
characterized by a constant emptying of chyme from the stomach into the
duodenum.
The inter digestive (fasted) pattern (commonly called the migrating motor
complex, MMC) is organized into alternating cycles of activity .
Typically, the MMC sequence begins in the stomach or esophagus and
migrates to the distal ileum. Some MMC, however, originates in the
duodenum or jejunum and not all MMC.




52. 52
migrating
myloelectric
cycle (MMC),

53. 53
INCREASEDVISCOSITYOFTHE
GASTROINTESTINALCONTENTS
The presence of food increases the viscosity of
gastrointestinal content which may result in a reduction
in rate of drug dissolution

54. STIMULATIONOFGASTROINTESTINAL SECRETION
54
Gastrointestinal secretions in response to food such as
pepsin may result in enzymatic degradation of drugs
which are susceptible therefore reducing their
bioavailability.

55. The transit time simply refers to the contact time of the drug
within any part of the GI tract. Various factors affect transit time,
which include:
Age and gender of patient
Presence of disease
Posture
Emotional state
Dietary intake
Size and density of dosage form
Location and transit time within the GI tract:
1. Oesophagus
2. Stomach
3. Small intestine
4. Large intestine or colon
THE TRANSIT OF PHARMACEUTICALS IN THE
GASTROINTESTINAL TRACT
55

56. The transit time is long and variable and depends on
the following; type of dosage form, diet, eating pattern
and disease state.
Once a drug is placed in the mouth it is moved down the
oesophagus by the swallowing reflex. The transit time of the
dosage form in the oesophagus is rapid usually 10-14 seconds.
The transit time in the stomach is highly variable and depends
on the dosage form and the fed or fasted state of the stomach.
The transit time is relatively constant, at around 3 hours. This
contrasts with the stomach as it does not discriminate between
different dosage forms or between fed or fasted state. It the main site
for absorption for most drugs. Hence, an important parameter for
drug targeting.
56
THE TRANSIT OF PHARMACEUTICALS IN THE
GASTROINTESTINAL TRACT

57. REFERENCES
1. Tortora G.J.;Derrickson B.H.;Principles of AnatomyAnd Physiology,12th
Edition,Volume 2,p.921-966
2. Swarbrick J.;Boylan J.C.;Encyclopedia of Pharmaceutical Technology, Second
Edition;Volume 1;p.886-904
3. Brahmankar D. M. and Jaiswal S. B. in “Biopharmaceutics and
Pharmacokinetics”,Vallabh Prakashan, 1st edn, 1995, 347- 352.
4. Robinson JR, Lee VHL. Controlled drug delivery: fundamentals and applications, 2nd
ed. Marcel Dekker; New York : 1987. p.373-432
5. Yyas S.P.and Khar R.K., Controlled Drug Delivery Concepts and Advances,First Edition
2002,New Delhi, 196- 217.
6. Rang H.P.;Dale M.M.;RitterJ.M.;Flower R.J.;Pharmacology,6th Edition,p.385-395
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