anatomyandphysiologyofgi-160529053641.ppt

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1. ANATOMY AND PHYSIOLOGY
OF GIT
1
Department of Pharmacy (Pharmaceutics) | Sagar savale
Mr. Sagar Kishor savale
[Department of Pharmaceutics)]
[email protected]
2015-2016

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
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.
4

5. PHYSIOLOGY
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.
5

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

7. 7

8. 8

9. 9

10. Upper gastrointestinal tract
The upper gastrointestinal tract consists of the esophagus, stomach,
and duodenum.
Some sources also include the mouth cavity and pharynx.
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.
10

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 into
the blood .
 Large intestine, which has three parts:
o Cecum

Colon.

Rectum and Anus

11

12. The gastrointestinal system is primarily involved in reducing food
for absorption into the body.
This process occurs in 4 main phases:
i) Fragmentation
ii) Digestion
iii) Absorption
iv) Elimination of waste products
 - 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 of the
tongue and pharynx (deglutition).
12
DIGESTION AND ABSORPTIONDIGESTION AND ABSORPTION

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).
- 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
13

14. GASTROINTESTINAL TRACT STRUCTURE
Mucosa (lumen side)
Epithelial tissue
Submucosa
elastic connective tissue
contains lymph and blood
vessels
Muscularis externa
smooth muscle layers
Serosa
Outermost lining of GI
organs
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
15

16. MOUTHMOUTH
DigestionDigestion begins in the mouth begins in the mouth
Mechanical digestion Mechanical digestion
– – Biting and grinding actions of teethBiting and grinding actions of teeth
breaks and mashes food into smaller pieces.breaks and mashes food into smaller pieces.
Chemical digestion Chemical digestion
– – SalivaSaliva mixes and lubricates food. mixes and lubricates food.
– – Salivary amylaseSalivary amylase and and lipaselipase begin begin
breakdown of starch and fat, respectively. breakdown of starch and fat, respectively.
16

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

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

19. taste buds
19

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

21. ESOPHAGUS
Transport food and water to stomach, secretes mucus
Movement of food bolus in esophagus (and rest of GI tract) via peristalsis
Empties into stomach through the lower esophageal sphincter
21

22. STOMACH
Muscular sac-like organ
Chemical and physical digestion
forms chyme
Stores food, releases small amts. to small intestine
takes 2-6 hours for stomach to empty
inner surface lined with gastric rugae
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 – hydrochloric acid
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
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
26

27. 27

28. Small IntestineSmall Intestine
Where most Where most
nutrients are nutrients are
digested and digested and
absorbed.absorbed.

Duodenum Duodenum
• Jejunum• Jejunum
• Ileum• Ileum
28

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

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

32. WATER-SOLUBLE WATER-SOLUBLE
NUTRIENTS ENTER NUTRIENTS ENTER
THE CAPILLARY OF THE CAPILLARY OF
A VILLUS, AND A VILLUS, AND
TRAVEL TO THE TRAVEL TO THE
LIVER VIA LIVER VIA PORTAL PORTAL
VEIN.VEIN.
MOST FAT-SOLUBLE MOST FAT-SOLUBLE
COMPOUNDS ARE COMPOUNDS ARE
FORMED INTO FORMED INTO
CHYLOMICRONSCHYLOMICRONS , ,
THAT ENTER A THAT ENTER A
LACTEAL LACTEAL OF THE OF THE
LYMPHATIC SYSTEM LYMPHATIC SYSTEM
AND EVENTUALLY AND EVENTUALLY
REACH THE REACH THE
BLOODSTREAM.BLOODSTREAM.
Figure 4.26
32

33. HOW IS INTESTINE SERVE AS A BEST SITE
FOR ABSORPTION OF MOST OF DRUG?
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.
33

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

35. LARGE INTESTINE
- Begins at the ilium & ends at the anus; 5’ long; 3” in diameter
- main functions – H
2O 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. PancreasPancreas –– produces and
secretes many digestive
enzymes
LiverLiver –– processes and
stores many
nutrients
makes cholesterol
GallbladderGallbladder –– stores bilebile
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
Fig 14.18
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
38

39. LIVER - ANATOMY
 Largest organ within the body
 Comprised of 4 lobes:
 Large right & left lobes divided by falciform ligament; small
caudate & quadrate (by gall bladder ) lobes
 Lobes of liver functionally divided into microscopic lobules
39

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
 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
muscular sac under right lobe
of liver; stores &
concentrates bile; releases
bile through cystic duct
 Bile released into duodenum
functions in emulsification of lipids,
absorption of fats (due to presence
of bile salts), & excretion of bilirubin
Left hepatic ductRight hepatic duct
42

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


The pH varies considerably along the length of the gastrointestinal
tract.
Different regions along the tract will exhibit different pH values.
STOMACH
Gastric fluid in the stomach is highly acidic, ranging
between pH1-3.5 in the fasted state.
In the fed state the pH rises in the range of pH3-7
depending on the composition of the meal.



F
A
ST
E
D
F
E
D

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 or absorption. 45

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 small intestine
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.
47

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. PRESENCE OF FOOD
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.
49

50. DELAYED GASTRIC EMPTYING
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.
50

51. GASTROINTESTINAL MOTILITY
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 interdigestive (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.
51

52. 52
Phase II
(preburst
phase) P
h
a
se
I
(b
a
sa
l
p
h
a
se
)
P
hase III
(burst
phase)
P
h
a
s e I V

migrating
myloelectric
cycle (MMC),

53. INCREASED VISCOSITY OF THE
GASTROINTESTINAL CONTENTS
The presence of food increases the viscosity of
gastrointestinal content which may result in a reduction
in rate of drug dissolution
53

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

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 OF PHARMACEUTICALS IN THE
GASTROINTESTINAL TRACT
The transit time is long and variable and depends on
the following; type of dosage form, diet, eating pattern
and disease state.
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.
The transit time in the stomach is highly variable and depends
on the dosage form and the fed or fasted state of the stomach.
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.
56

57. REFERENCES
1.Tortora G.J.;Derrickson B.H.;Principles of Anatomy And
Physiology,12
th
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 57

58. 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,6
th
Edition,p.385-395
58

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