1. Gastrointestinal system
Xiang-Yao LI, PhD
Department of Physiology
Zhejiang University School of Medicine

2. Phases of gastrointestinal control
Cephalic phase
Gastric phase
Intestinal phase

3. Efferent fibers Secretin, CCK， GIP
Factors: Distension, acidity, AA, peptides
Factors: Distension, Acidity, Osmolarity, digestive products
Secretin, CCK， GIP

4. Digestion in the stomach

5. Difficult to see food bolus (raw liver
Difficult to see food bolus (raw liver?)– can a brighter color be used (blueberry yogurt)?
The swallowing reflex is coordinated by the medulla oblongata, which stimulates the appropriate sequence of contraction and relaxation in the participating skeletal muscle, sphincters, and smooth muscle groups.

6. The coordinated sequence of contraction and relaxation in the upper esophageal sphincter, the esophagus, and the lower esophageal sphincter is necessary to deliver swallowed food to the stomach.

7. Digestion in the stomach

8. fluid, enzyme precursors, hydrochloric acid, and hormones.
Specialized cells
in the stomach
synthesize and
secrete mucous
fluid, enzyme precursors,
hydrochloric acid,
and hormones.
Note esophageal sphincter correction.
The abundant smooth muscle in the
stomach is responsible for gastric motility.

10. Gastric juice Properties Major components Role of HCl pH 0.9~1.5
1.5~2.5 L/day
Major components
Hydrochloric acid (>150mM, parietal cells)
Pepsinogen
Mucus
Intrinsic factor
Role of HCl
Acid sterilization
Activation of pepsinogen
Promotion of secretin secretion
Assisted effect of iron and calcium absorption

11. Mechanism of HCl secretion
Active transport
Huge H+ gradient (3 million)
active transport

12. One inhibitory and
three stimulatory
signals that alter
acid secretion by
parietal cells
in the stomach.

14. Pepsinogen
MW: 42,500
Secreted by the chief cells as an inactive precursor of pepsin
Activated in the stomach, initially by H+ ions and then by active pepsin, autocatalytic activation
Active pepsin (MW: 35,000) an endopeptidase, which attacks peptide bonds in the interior of large protein molecules

15. The acidity in the gastric lumen converts the protease precursor pepsinogen to pepsin; subsequent conversions occur quickly as a result of pepsin’s protease activity.

16. Mucus Secreted by the epithelial cells Role
Gastric pit
Secreted by the epithelial cells
Role
Lubrication of the mucosal surface
Protection of the tissue from mechanical damage by food particles

17. Mucus-HCO3- barrier

18. Secretion of other enzymes
Intrinsic factor
A high molecular weight glycoprotein, synthesized and secreted by the parietal cells
The intrinsic factor binds to Vit B12 and facilitates its absorption
Secretion of other enzymes
Gastric lipase
Gastric amylase
Gelatinase

19. Regulation of gastric secretion
Basic factors that stimulate gastric secretion
Acetylcholine (+ all secretory cells)
Gastrin (+ parietal cells)
Histamine (+ parietal cells)

20. Regulation of gastric secretion
Nervous regulation
‘Short’ reflex pathways
‘Short’ excitatory reflexes: mediated by cholinergic neurons in the plexuses
‘Short’ inhibitory reflexes: mediated by non-adrenergic non-cholinergic (NANC) neurons
Long’ autonomic pathways
‘Long’ excitatory reflexes: parasympathetic
‘Long’ inhibitory pathways: sympathetic

21. Regulation of gastric secretion
Humoral regulation
Excitatory
ACh
Histamine
Gastrin
Inhibitory
Somatostatin
Secretin
5-hydroxytryptamine (5-HT)
Prostaglandin

22. Inhibition of gastric secretion
The functional purpose of the inhibition of gastric secretion by intestinal factors is presumably to slow the release of chyme from the stomach when the small intestine is already filled or overactive

23. Inhibition of gastric secretion
Reverse enterogastric reflex: initiated by the presence of food in the small intestine
Secretin secretion: stimulated by the presence of acid, fat, protein breakdown products, hyperosmotic or hypo-osmotic fluids, or any irritating factors in the upper small intestine

24. Delivery of acid and nutrients into the small intestine initiates signaling that slows gastric motility and secretion which allows adequate time for digestion and absorption in the duodenum.

25. Motor function of the stomach
Proximal stomach
cardia
fundus
corpus (body)
Distal stomach
antrum
pylorus
pyloric sphincter

26. Waves of smooth muscle contraction mix and propel the
ingested contents of the gastric lumen, but only a small amount of the material enters the small intestine (duodenum) as a result of each wave cycle.

27. Motor function of the stomach
Receptive relaxation
Storage function (1.0~1.5 L)
Vago-vagal reflex
Peristalsis
BER in the stomach

28. Contractions in the empty stomach
Migrating Motor Complex (MMC)
Periodic waves of contraction, which move along the gastrointestinal tract from stomach to colon
Purpose of this activity: to ‘sweep’ debris out of the digestive tract during the interdigestive period
MMCs can lead to hunger contractions, which are associated with discomfort, referred to as ‘hunger pains’

29. Emptying of the stomach
Emptying rate
Fluid > viscous
Small particle > large particle
Isosmotic > hyper- & hypo-osmotic
Carbohydrates > Protein > Fat
Regular meal 4～6 hrs

30. Regulation of stomach emptying
Gastric factors that promote emptying
Gastric food volume
Gastrin
Duodenal factors that inhibit stomach emptying
Enterogastric nervous reflexes
Fat
Cholecystokinin

31. Pancreatic secretion

33. Pancreatic juice pH 7.8~8.4 ~1500 ml/day Isosmotic Components:
Pancreatic digestive enzymes: secreted by pancreatic acini
Sodium bicarbonate: secreted by small ductules and larger ducts

35. Secretion of bicarbonate ions
Secreted by the epithelial cells of the ductules and ducts that lead from acini
Up to 145mmol/L in pancreatic juice (5 times that in the plasma)
Neutralizing acid entering the duodenum from the stomach

37. Pancreatic acinar cell secretory products
Zymogens
Function
Trypsinogens
Digestion
Chymotrypsinogen
Proelastase
Proprotease E
Procarboxypeptidase A
Procarboxypeptidase B
ACTIVE ENZYMES
α-Amylase
Carboxyl ester lipase
Lipase
RNAase
DNAase
Colipase

38. OTHERS Trypsin inhibitor Blockade of trypsin activity Lithostathine
Possible prevention of stone formation; constituent of protein plugs
GP2
Endocytosis?; formation of protein plugs
Pancreatitis-associated protein
Bacteriostasis?
Na , Cl , H2O
Hydration of secretions Ca ?

39. Secretion of pancreatic digestive enzymes
Carbohydrates -- Pancreatic amylase Pancreatic lipase Fat Cholesterol esterase Phospholipase Trypsinogen Proteins Chymotrypsinogen Procarboxypolypeptidase Proelastase

41. Trypsin Inhibitor
Inhibits the activity of trypsin and thus guards against the possible activation of trypsin and the subsequent autodigestion of the pancreas

42. Regulation of pancreatic secretion
Basic stimuli that cause pancreatic secretion
Ach
Cholecystokinin:
Secreted by I cells
Stimulates the acinar cells to secrete large amounts of enzymes
Secretin:
Released by S cells
Acts primarily on the duct cells to stimulate the secretion of a large volume of solution with a high HCO3- concentration

44. Regulation of pancreatic secretion
Phases of pancreatic secretion: A meal triggers cephalic, gastric, and intestinal phases of pancreatic secretion
Cephalic Phase
Gastric Phase
Intestinal Phase

45. The three phases of pancreatic secretion
Stimulant
Regulatory Pathway
Percentage of Maximum Enzyme Secretion
Cephalic
Sight
Smell
Taste
Mastication
Vagal pathways
25%
Gastric
Distention
Gastrin?
Vagal-cholinergic
10%-20%
Intestinal
Amino acids
Fatty acids H+
Cholecystokinin
Secretin
Enteropancreatic reflexes
50%-80%

46. Mechanisms that protect the acinar cell from autodigestion
Protective Factor
Mechanism
Packaging of many digestive proteins as zymogens
Precursor proteins lack enzymatic activity
Selective sorting of secretory proteins and storage in zymogen granules
Restricts the interaction of secretory proteins with other cellular compartments
Protease inhibitors in the zymogen granule
Block the action of prematurely activated enzymes
Condensation of secretory proteins at low pH
Limits the activity of active enzymes
Nondigestive proteases
Degrade active enzymes

47. Acute pancreatitis
Acute pancreatitis is sudden swelling and inflammation of the pancreas
The symptomatology and complications of acute pancreatitis are caused by autodigestion (resulting from the leakage of pancreatic enzymes) of the pancreas and surrounding tissue
It is commonly due to biliary tract disease, complications of heavy alcohol use, or idiopathic causes
Mortality rates range from below 10% to more than 50%, depending on severity

48. Bile secretion

50. Bile is stored and concentrated in the gall bladder during the interdigestive period

51. Composition of bile HCO3- Bile salts Phospholipids Cholesterol
Bile pigments (include: bilirubin) …

52. Synthesis of bile acids

53. Jaundice
Jaundice is the most visible manifestation of an underlying hepatic and/or biliary tract disease.
This is a yellow discoloration of the skin, sclerae, and mucous membranes that occurs secondary to elevated serum bilirubin in adults.
Jaundice is usually not clinically apparent until the serum bilirubin concentration is >2.5mg/dL.

54. Functions of bile Emulsifying or detergent function of bile salts
Bile salts help in the absorption of:
Fatty acid
Monoglycerides
Cholesterol
Other lipids

55. Increasing bile synthesis & secretion

57. Regulation of bile secretion
Substances increasing bile production
Bile salts (Enterohepatic circulation of the bile)
Secretin: stimulating H2O and HCO3- secretion from the duct cells
Substance inhibiting bile production
Somatostatin

58. Contraction of the gall bladder
Substances causing gall bladder contraction
ACh
CCK
Gastrin

60. Small intestine

61. Small intestinal juices
Secreted by:
Brunners glands
Crypts of Lieberkuhn
1~3 L/day
pH 7.6
Isosmotic
Components
H2O
Electrolytes (Na+, K+, Ca2+, Cl-)
Mucus
IgA
Enterokinase

62. Small intestinal juices
Function: Completing the digestion of peptides, carbohydrates & fat
Secretion by intestinal glands is mainly due to the local effects of chyme in the intestine and is regulated by both neural and hormonal factors

63. Movement of small intestine during digestion
Tonic contraction: maintaining a basal state of intestinal smooth muscle contraction
Segmentation: consisting of the alternate contraction and relaxation of adjacent bands of circular smooth muscle
Peristalsis: a ring of muscle contraction appears on the oral side of a bolus of ingesta and moves toward the anus, propelling the contents of the lumen in that direction; as the ring moves, the muscle on the other side of the distended area relaxes, facilitating smooth passage of the bolus

65. Migrating motor complex (MMC)
Local areas of peristaltic contraction
Present in the interdigestive period and disappear when feeding begins
Sweeping material (undigested food residues, dead mucosal cells, bacteria) into the colon and keeping the small intestine clean
Regulated by autonomic nerves and by the release of motilin

66. Contractions at three loci in the small bowel
Contractions at three loci in the small bowel. Note that at each locus, phases of no or intermittent contractions are followed by a phase of continuous contractions that ends abruptly. Also note that the phase of continuous contractions appears to migrate aborally along the bowel. Such a pattern is called the migrating motor complex (MMC). min, minute; mm Hg, millimeters of mercury

67. Regulation of intestinal motility
Autoregulation: Regulated by BER
Neural Reflexes:
mainly by ‘short’ reflexes in the intrinsic plexuses which are responsible for peristalsis and segmentation
also by extrinsic nerves (sympathetic & vagal nerves) which mediate ‘long’ reflexes
Hormonal control:
Gastrin, CCK, motilin, 5-HT (+)
Secretin, VIP, glucagon (-)

68. Large intestine

69. Function of large intestine
The principle functions of the colon:
Absorption of water and electrolytes from the chyme to form solid feces
Storage of fecal matter until it can be expelled
Digestion in large intestine: very limited
Bacteria: vitamin B, K

70. Motility of the colon Haustration: mixing movement
Mass movement: propulsive movement
Segmentation

71. A normal colon, with the typical haustration

72. Two mass movements. A, Appearance of the colon before the entry of barium sulfate. B, As the barium enters from the ileum, it is acted on by haustral contractions. C, As more barium enters, a portion is swept into and through an area of the colon that has lost its haustral markings. D, The barium is acted on by the returning haustral contractions. E, A second mass movement propels the barium into and through areas of the transverse and descending colon. F, Haustrations again return. This type of contraction accomplishes most of the movement of feces through the colon

73. Absorption

74. General mechanisms of digestion and absorption

75. Sites of nutrient absorption

76. Major gastrointestinal diseases and nutritional deficiencies
Organ Site of Predominant Disease
Defects in Nutrient Digestion/Absorption
Celiac sprue
Duodenum and jejunum
Fat absorption, lactose hydrolysis
Chronic pancreatitis
Exocrine pancreas
Fat digestion
Surgical resection of ileum; Crohn disease of ileum
Ileum
Cobalamin and bile acid absorption
Primary lactase deficiency
Small intestine
Lactose hydrolysis

77. Summary General properties of GI Stomach Pancrea
Small and large intestine
Absorption