Embed Size (px)
Citation preview
ANATOMY AND PHYSIOLOGY OF GIT
1
Department of Pharmacy (Pharmaceutics) | Sagar savale
Mr. Sagar Kishor savale[Department of Pharmaceutics)]
CONTENTS Anatomy Physiology Digestion And Absorption Gastrointestinal Tract Structure Regulation Of Gastric Function Phases of Digestion Physiological considerations that affect oral
bioavailability References
2
3A 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.
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
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
ANATOMY AND PHYSIOLOGY OF THE GASTROINTESTINAL TRACT
6
the key structures involved oral drug absorption.
7
8
9
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
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
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
- 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
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
Insert Figure 4.21
Gastrointestinal TractMuscular 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
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
MOUTH (ORAL CAVITY)
Regions include the vestibule & oral cavity
Roof comprised of hard & soft palate; floor primarily comprised of tongue
17
Tongue – stratified squamous epithelium over skeletal muscle
intrinsic & extrinsic muscles
papillae filiform fungiform circumvallate
18
taste buds
19
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
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
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
STOMACH - GROSS ANATOMY
Lower esophageal (cardiac) sphincter
Pyloric sphincter
23
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
REGULATION OF GASTRIC FUNCTION PHASES OF DIGESTION
Three basic phases1. 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
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
Small IntestineSmall Intestine
Where most Where most nutrients are nutrients are digested and digested and absorbed.absorbed. Duodenum Duodenum
• Jejunum• Jejunum• Ileum• Ileum
28
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
SMALL INTESTINEModifications 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
ABSORBING NUTRIENTS
Figure 4.26
VilliVilli Tiny projections that line the small intestine
Absorptive Absorptive cellscellsRemove nutrients from chyme and transfer them into intestinal blood or lymph
31
WATER-SOLUBLE WATER-SOLUBLE NUTRIENTS ENTER NUTRIENTS ENTER THE CAPILLARY OF A THE CAPILLARY OF A VILLUS, AND TRAVEL VILLUS, AND TRAVEL TO THE LIVER VIA TO THE LIVER VIA PORTAL VEIN.PORTAL 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
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
LARGE INTESTINEAbsorption of waterand minerals
FecesFeces –– form aschyme becomessemisolid
RectumRectum –– lower partof large intestinewhere feces are stored
Insert figure 4.21
34
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
ileumIleocecal 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
PancreasPancreas –– produces and secretes many digestive enzymes
LiverLiver –– processes andstores many
nutrients makes cholesterol
GallbladderGallbladder –– stores bilebile that the liver makes
Accessory Organs
36
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
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 peptidestri & dipeptides
nucleases – digest RNA & DNA sodium bicarbonate – neutralizes acidic chyme because enzymes in small intestine need an alkaline pH
38
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
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
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.
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
• 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
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
GASTROINTESTINAL PH
The pH varies considerably along the length of the gastrointestinal tract. Different regions along the tract will exhibit different pH values.
STOMACHGastric 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 pH3-7depending on the composition of the meal.
FASTED
FED
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
GASTROINTESTINAL PHSMALL 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
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
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 secretion48
PRESENCE OF FOODFood 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
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
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
Phase II
(preburst
phase) Phas
e I
(bas
al ph
ase)
Phase III
(burst
phase)
Phase IV
migrating myloelectri
c cycle (MMC),
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
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
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
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
REFERENCES 1.Tortora G.J.;Derrickson B.H.;Principles of Anatomy And
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 57
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
58
59
