PHYSIOLOGY GIT .pdf

2023-2024 Page 1 Git& Nutrition Module 2024 Fig. 6A: Serous acinus (6B) Mucous acinus. (6C) Seromucous acinus Seromucous Acini  Contain both serous and mucous cells.  The...

2023-2024 Page 1 Git& Nutrition Module 2024 Fig. 6A: Serous acinus (6B) Mucous acinus. (6C) Seromucous acinus Seromucous Acini  Contain both serous and mucous cells.  The mucous cells are organized as tubules and form the proximal part of the acini, capped by serous cells and form the distal end and appear as crescent cap of dark cells called serous demilune or crescent of Gianuzzi (Fig. 6C).  The secretion of the demilune reaches the lumen through narrow channels present between the mucous cells. Myoepithelial (Basket) Cells  They found within the basal lamina of glandular and ductal epithelia of salivary glands.  They are highly branched cells surround serous acini those associated with mucous acini and intercalated ducts are spindle-shaped and lie parallel to the length of the duct.  The cytoplasm is rich in actin and myosin filaments. Contraction of these cells press on the acini to release their products into the duct system. Duct System  The ducts are classified according to their location into: (Fig 7). 1. Intercalated ducts: They are very small ducts arise from the lumen of the acini. They are lined by low cuboidal epithelium. - 28 - Page 2 Git& Nutrition Module 2024 * Regulation of Gastrointestinal tract: A- Nervous regulation: The smooth muscle activity and the secretion of the digestive glands are regulated by: 1- External autonomic nerves: -Parasympathetic: (dominant) a-Vagus nerve → GIT from oesophagus till the 1st half of large intestine. b-Sacral division → the rest of GIT till the anal region. The effects of parasympathetic stimulation are:  contraction of the wall. (excitatory).  Relaxation of sphincters. (inhibitory)  Evacuation of GIT contents.  Evacuation of secretion – vasodilatation. -The preganglionic neurons end on the enteric plexus. - Sympathetic: a- From L.H.C of T5 → L2 b-The effect is inhibitory to motility and secretion and vasoconstriction. c- It also contains some excitatory fibers. d- The post ganglionic neurons end either direct on the smooth muscle or 2nd relay on enteric plexus. Some fibers end on postganglionic cholinergic neuron causes decrease in the released Ach via activation of presynaptic alpha 2 receptors. N.B.: Blood vessels have dual innervation: 1- Noradrenergic V.C. 2- Enteric nervous VIP & nitric oxide secreting nerves cause VD. 2-Local nerve (enteric) plexus:  In the wall of the alimentary tract there are two nerve plexuses: a. The Myenteric (Auerbach’s) plexus: - 1. It lies between the longitudinal and circular layers of smooth muscle. 2. Concerned with controlling the motor activity of GIT. 3. Its stimulation →↑ tonic contraction, ↑ intensity and rate of rhythmic contraction and ↑ conduction of excitatory waves. 4. The excitatory fibers are mainly cholinergic (secrete Acetyl choline). - 34 - Page 3 Git& Nutrition Module 2024 5. Some inhibitory fibers secrete VIP (Vaso active intestinal peptide) or purinergic (secrete ATP). b. The submucosal (Meissner’s) plexus: - 1. It lies in the submucosal layer and supply the glandular epithelium, intestinal endocrine cells and submucosal blood vessels. 2. Concerned with local secretion of GIT. 3. It’s stimulation →↑ local exocrine and endocrine secretion. 4. It contains the neurons of the sensory afferent nerves which arise from the mucosal layer.  The activity of one plexus affects the activity of other plexus, by nervous connection in-between.  The axons of both plexuses are extensively branched and contain about 100 million neurons.  Many transmitters may be secreted in the enteric plexus according to functions as substance P, enkephalin, somatostatin, Ach Serotonin, Noradrenaline, GABA also polypeptides as CCK, VIP, neuropeptide. *Gastrointestinal reflexes: Reflexes for nervous regulation are of 3 types. 1- Local enteric reflexes: (short reflex): 1. The receptors are present in the wall of the GIT, stimulated by stretch or food. 2. The afferent are the dendrites of the enteric neurons in submucosa. 3. The center: cell body of enteric neurons. 4. The efferent: is axons of neurons to smooth muscle fibers or secretory glands. - 35 - Page 4 Git& Nutrition Module 2024 5. The response: in peristalsis → 1-Ring constriction proximal to bolus by contraction of circular ms. & relaxation of longitudinal ms. (via Ach). 2- Relaxation distal to bolus by relaxation of circular ms. & cont. of longitudinal ms. (via NO, VIP). 2- Ganglionic reflexes: a. Receptors: in the wall of GIT. b. Afferent: sympathetic afferent fibers from submucosal layer. c. Center: collateral sympathetic ganglia (coeliac & mesenteric). d. Efferent: efferent sympathetic fibers to GIT. e. e.g : enterogastric reflex (inhibition of gastric motility and secretion by afferent from intestine) and gastrocolic reflex. 3-Central Nervous system reflexes: a. Receptors: in the wall of GIT. b. Afferent: usually via afferent parasympathetic submucosal fibers to dorsal root ganglia. c. Center: in brain stem (vagal center) and spinal cord as (sacral parasympathetic center- L.H.C). d. Efferent: efferent parasympathetic fibers. e. e.g.: unconditioned reflexes as peristaltic reflex in upper esophagus (vagovagal reflex) – spinal defecation reflexes. Gut law: Distension of the gut produces a peristaltic wave that starts at the point of distension and proceeds anal wards. Hormonal control: 1. The GIT hormones are polypeptides. 2. They are secreted by special mucosal cells which are involved in amine precursors uptake and decarboxylation (APUD). 3. They are secreted under different stimuli and pass to blood → general circulation → return to GIT to affect its function. 4. They are classified according to similarity in function and structure into: - 36 - Page 5 Git& Nutrition Module 2024 a- Gastrin group: gastrin and cholecystokinin. b- Secretin group: secretin, gastric inhibitory peptide (GIP), glucagons, enteroglucagon and VIP. c- Motilin. d- Somatostatin. 5. They are affected by external autonomic nerves and local nerve plexuses. Physiology of oropharynx Oral cavity * Mastication (chewing) Definition: It is the process of mechanical breakdown of large food particles into smaller ones in the mouth. Its importance:  Stimulation of taste and smell receptors → sense of satiety.  Help swallowing by lubrication of food by saliva.  Help digestion by break down of indigestive cellulose membrane around the digestive portion of fruits and vegetables also by increasing the exposed surface area to enzymatic effect.  It is partly voluntary and partly reflexly by chewing reflex in which: Presence of food in mouth → reflex relaxation of chewing muscles → drop of mandible and open the mouth → initiates a stretch reflex of the jaw muscles that leads to muscles contraction, and closure of the mouth and so on. (the mastication muscles are supplied by the motor branch of the trigeminal nerve.  The chewing center is present in the pons. Salivary Secretion  Saliva : Daily secretion average 1L /day, hypotonic, pH is 6-7 which is a favorable for the digestive action of ptyali, but during active secretion -. becomes more alkaline about 8 due to addition of HCO3 - 37 - Page 6 Git& Nutrition Module 2024  Salivary glands : three pairs of salivary glands : Parotid Submaxillary sublingual Secretion % ~ 20 %. ~70%. ~ 5 %. Type of Serous secretion (watery & rich in Mixed Mucus (thick, secretion enzymes). rich in mucin). supplied by Glossopharyngeal N Facial N Facial N N.B : Ebner’s glands and buccal glands secrete ~ 5% of saliva.  Composition of saliva: a- 99.5 % water. b- 0.5 % solids which includes: 1. 0.3 % organic constituents: These are mainly enzymes (amylase, Lipase, Lysozymes) and mucin. In addition to Ig A, lactoferrin and proline-rich proteins 2. 0.2 % inorganic ions:  -Buffers as (H2Co3: Na HCO3 & NaH2Po4: Na2 HPo4). -.  -Soluble calcium salts: Ca (HCO3 )2, Ca(H2Po)2 which saturate saliva to -. prevent decalcification of teeth.  Some electrolytes as Na , Cl , HCO3 , and K , they act as coenzymes for + - -. + salivary enzyme amylase.  Functions of saliva: 1. Facilitation of speech (keeps mouth moist) and deglutition by Prescence of mucin lubricates food. 2. Cleaning (hygiene) of the mouth by washing and antibacterial effect of lysozymes, thiothianate ions and Immunoglobulins A. 3. Buffering function: by bicarbonate and phosphate systems to keep the PH at about 7.0 → the teeth do not lose their calcium. Also, saliva neutralizes gastric secretion in case of gastroesophageal reflux. 4. Digestive function: -Ptyalin (salivary α- amylase): digest starch (especially cooked) to maltose, maltotriose, alpha limit dextrin in PH 6.9 so it is inhibited in the stomach. It requires CL- as a coenzyme activator. - 38 - Page 7 Git& Nutrition Module 2024 -Lingual Lipase: digest triglycerides forming fatty acids and glycerol. It secreted from Ebner’s gland of tongue. 5. Excretory function: of lead, mercury, iodides, fluoride and some drugs as morphine and alcohol 6. Facilitate taste sensation serves as a solvent for the molecules that stimulate the taste receptors. 7. kallikrein enzyme produce bradykinin which acts as vasodilator during salivary secretion. 8. Regulation of water balance (↓ in dehydration and give thirst sensation). 9. Contains hormones as somatostatin & glucagon. The Stages of salivary secretion: I) Salivary acini (Primary) → saliva similar in composition to plasma= isotonic (Na+= 150mmol/L, K = 10 mmol/L, CL = 113 mmol/L, HCO3- = 23-30 + - mmol/L). II) Salivary duct (secondary) due to modification by the duct cells under effect + of aldosterone hormone → active reabsorption of Na , & CL and active secretion of K+ & HCO3-. Because ductal cells are relatively water impermeable, water is not absorbed along with the solute, making the final saliva hypotonic to plasma. -So, the final concentration: Na+ = 50 mmol/L, CL- = 15 mmol/L HCO3- =50-70 mmol/L, K+ = 15 mmol/L.  If the flow of salivary secretion increased → little time for modification →↑ + Na+, CL- &, ↓ K concentration as in parasympathetic stimulation. Innervation of salivary glands: A-Parasympathetic stimulation: It arises from superior salivary nucleus in the pons → chorda tympani as a branch of the facial nerve → submandibular ganglion → submandibular and sublingual glands.Also, inferior salivary nucleus in medulla oblongata →lesser - 39 - Page 8 Git& Nutrition Module 2024 superficial petrosal nerve as a branch of glossopharyngeal nerve → otic ganglion→ parotid gland→ + -  True secretion: large in volume watery, rich in ptyalin, Na , CL , HCO3 and secretion of salivary lipase.  Its action via M receptors on duct and acinar cells →increased IP3 / Ca2+  V.D by VIP (cotransmitter to Ach) B- Sympathetic Stimulation: It arises from lateral horn cells of the upper two thoracic segments and relay in the superior cervical sympathetic ganglia→  Trophic secretion: little in volume, viscus, and rich in mucin.  V.C (alpha → V.C).  Contraction of myoepithelial cells → squeeze saliva → evacuation.  Its action via cAMP (beta) and ↑ intracellular Ca+2 (alpha). -Augmented secretion occurs by stimulation of parasympathetic then sympathetic→ large volume rich in mucus and ptyalin. Control of salivary secretion: Nervous ONLY via conditioned and unconditioned reflexes. [I] Unconditioned reflex : Inborn reflex that needs no pervious learning. a. Stimuli: Direct contact of food, chewing & Irritation of GIT. b. Receptor: Taste receptors& Receptors in GIT wall. c. Afferent: -Chorda tympani: from ant. 2/3 of tongue. -Glossopharyngeal: from post. 1/3 of tongue -Lingual nerve: movement of tongue. - 40 - Page 9 Git& Nutrition Module 2024 -Vagus nerve: from epiglottis. d. Center: superior & inferior salivary nuclei in M.O. e. Efferent: chordae tympani & glossopharyngeal. f.Response: ↑ salivary glands secretion. [II] Conditioned reflex:Acquired reflexes and need previous learning. a. Stimuli: -Sight of food. -Smelling of food. -Hearing about food. -Thinking of food. b. Receptors: special sense receptors. c. Afferent: optic, olfactory & auditory nerves. d. Center: to cerebral cortex → salivary nuclei. e. Efferent & response → as unconditioned reflex. - 41 - Page 10 Git & Nutrition 2024 Physiology Of The Pharynx And Oesophagus Pharynx It is a common pathway for respiratory and digestive system and has swallowing receptor area and the primary peristalsis waves start from it. It is separated from oesophagus by the upper oesophageal sphincter which is normally closed. I- Oesophagus: It is a muscular tube has outer longitudinal and inner circular muscle layers which are striated in the upper portion and smooth in the lower portion. So, the peristalsis in the upper portion depends on the vagovagal reflex, however in the lower portion it depends on the local enteric reflex. Swallowing (Deglutition) o It is the propelling of food bolus from mouth to stomach. o It is under control of the swallowing center in the medulla. o It is divided into 3 phases: 1- Buccal phase: (voluntary) elevation and retraction of tongue against the hard palate propels the bolus to the pharynx. 2- Pharyngeal phase (involuntary): It is very rapid (1 second), occur reflexely via: Swallowing reflex:  Receptor: in oropharynx (tonsillar pillars).  Afferent: glossopharyngeal nerves.  Center: medulla oblongata (swallowing center).  Efferent: motor fibers of cranial nerves V, 1X, X, X11.  Response: Series of reflexes to prevent entry of food into air passages: a- Elevation of soft palate → closure of nasal cavity. b- Approximation of palatopharyngeal folds → sagittal slit through which small food particles pass and prevent passage of large particles. c- Closure of glottis (opening of larynx) by approximation of vocal words & elevation of larynx and folding of epiglottis d- Inhibition of breathing (swallowing apnea).  Relaxation of pharyngoesophegeal sphincter and contraction of superior pharyngeal muscle → rapid pharyngeal peristalsis → Page 11 Page 79 Git & Nutrition 2024 forces the food into relaxed upper esophagus. 3- Esophageal phase (involuntary): a- Upper esophageal sphincter: (UES) The pharyngeo – esophageal junction is normally closed by striated muscle tone to prevent entry of inspired air into stomach. During swallowing the sphincter relaxes reflexely and then reclosed after swallowing. b- Traveling along the esophagus: Entry of food bolus into the esophagus initiate peristaltic waves of 2 types:  Primary peristaltic waves: a. They start at the upper end of oesophagus. b. They are continuation of the pharyngeal peristalsis. c. It travels at the rate of 2-4 cm/sec. But gravity may increase velocity of food bolus to about 4cm/sec.  Secondary peristaltic waves: a. Presence of bolus in the esophagus initiates peristaltic waves at site of bolus. b. These waves repeated until food bolus is driven down the stomach. c. Peristaltic movements in the upper half of esophagus are coordinated by vago – vagal reflex (striated ms.), while in lower half is coordinated by local enteric reflex so, bilateral vagotomy → difficult swallowing in the upper half only (In this case the food bolus must be small, soft and well lubricated and by aid of gravity). Page 80 Page 12 Git & Nutrition 2024 b- Lower esophageal sphincter (LES): a. It is called the cardiac sphincter. b. It is the lower 3-5 cm of the esophagus. c. It has high resting tone (High – pressure zone) and exert a pressure 15- 30 cm H2O above intra – abdominal pressure to prevent reflux of gastric content into esophagus. d. It is relaxed when food bolus reaches it with some delay, so this area is liable to damage or ulceration by cold, hot and spicey food. e. Its tone is increased by : (contracted)  Sympathetic alpha adrenergic.  Local nerve plexuses (Myenteric).  Gastrin hormone (so, drugs which neutralize gastric acidity →↑ gastrin hormone release → contraction of the LES. f. Its tone is decreased by : (Relaxed)  Inhibitory vagal via VIP secretion.  Local nerve plexus (Myenteric)  Some food as fats, chocolate & coffee. Gastric reflux into esophagus is prevented by 1. High pressure zone sphincter. 2. The intra- abdominal small part of the esophagus is squeezed by the increased intra-abdominal pressure. 3. The esophagus enters the stomach in acute angle and act as a flap. 4.Gastrin hormone increases the tone in the lower esophagus NB: DYSPHAGIA: difficult swallowing. Its common causes are: Lesions of the 9th or l0th cranial nerves (e.g. due to diphtheria). Damage of the deglutition center (e.g. in poliomyelitis). Malfunction of the swallowing muscles (e.g. in myasthenia gravis). Esophageal strictures (narrowing) e.g. due to cancer or scarring. ACHALASIA (= CARDIOSPASM) This is a condition characterized by increased resting tension in LES. As a result, food transfer from the esophagus to the stomach is delayed or blocked, so food accumulates in the esophagus and becomes severely dilated. The condition is due to deficiency of NO & VIP because of defective development of the myenteric plexus in the lower part of the esophagus. Page 81 Page 13 Git & Nutrition 2024 Stomach Functions of the stomach: 1- Storage of food. 2- Slow evacuation of meal to allow good digestion and absorption. 3- Partial digestion of proteins and fats. 4- Sterilization of ingested food by high acidity. 5- Secretion of HCl &intrinsic factor help in RBCS formation 6-Help defecation by gastrocolic reflex. 7-Absorption of small amounts of water and alcohol. Gastric secretion 2.5 – 3 L/day of acidic juice (pH may reach 1). It is secreted from gastric glands: - Stomach mucosa has two important types of tubular glands—oxyntic glands (also called gastric glands) and pyloric glands. - Simple tubular glands open at the mucosal surface at the gastric pits. - In these glands, many types of cells are present: 1) Mucous neck cells (Goblet) → Mucus. 2) Chief cells → Pepsinogen & enzymes. 3) Oxyntic (parietal) cells → Hcl & intrinsic factor (essential for life for absorption of vit.B12). 4) G. cells → Gastrin H. 5) D. cells → Somatostatin. 6) Enterochromaffin like cells → histamine - The pyloric canal and cardiac region contain goblet cells only. - The body & fundus contain all types of cells except G. cells. - The antrum of pyloric area contains 1, 2, 4& 5 types of cells. (1) HCL secretion: - Parietal cells secrete an acid solution that contains about 160 mmol/L of hydrochloric acid, which is nearly isotonic with the body fluids. - The pH of this acid is about 0.8 - Concentration of H+ ions in gastric juice is three million times the conc. in plasma. So, H+ ions is secreted against a very high gradient. - HCL secretion occurs in lumen of canaliculi inside oxyntic cells. Page 82 Page 14 Git & Nutrition 2024 Mechanism of HCl secretion:In parietal cell CO2 (from metabolism or blood) → CO2 + H2O carbonic H2 CO3 anhydrase - 1. H2 CO3 → H+ + HCO3. The bicarbonate diffuses to blood in exchange with CL-. 2. H2O in cytoplasm → H+ + OH-. The H+ is secreted in lumen in exchange with K+ by H+ - K+ pump and OH- form H2O with H+ from carbonic acid. 3. K+ transported into the cell by the Na+-K+ ATPase pump on the basolateral (extracellular) side of the membrane tend to leak into the lumen but are recycled back into the cell by the H+-K+ ATPase. 4. CL- is secreted into the lumen to unite with H+ → HCL. 5. Water diffused to lumen → iso-osmotic HCL acid. 6. Diffusion of HCO3- to blood → Na HCO3- → post prandial alkaline tide (↑ pH in blood and urine after gastric secretion). Factors affecting HCL secretion (receptors on parietal cells):  Histamine →↑ HCl secretion via stimulation of H2 receptors by ↑ cAMP (these receptors are blocked by cimetidine).  Acetyl choline →↑ HCl secretion via muscarinic M3 receptors by ↑ Ca+2 & this effect is blocked by atropin.  Gastrin →↑ HCl secretion via Gastrin CCK-B Receptors by ↑ intra cellular Ca+2.  Prostaglandin E2 causes ↓HCl secretion via ↓ cAMP (used in treatment of peptic ulcer).  Somatostatin: causes ↓HCl via Gi which ↓ cAMP Functions of HCL 1) Sterilization by acidity which kills bacteria. 2) Digestion of protein by activation of pepsinogen → pepsin & give optimum pH of its effect and hydrolysis of protein. 3) HCl enters the duodenum → ↑ secretin hormone →↑ bile and pancreatic secretion. 4) Produces curdling of milk. 5) Initiate enterogastric inhibitory reflex →↓ gastric secretion and evacuation. 6) ↑ absorption of iron (by converting ferric state into ferrous) and calcium (by prevention of calcium salts precipitation). Page 83 Page 15 Git & Nutrition 2024 (2) Secretion of enzymes: A- Pepsinogens (I & II) - Secreted by chief (peptic) cells. - Inactive pepsinogen by (HCL) converted to active pepsin. Of optimum pH 1.8 – 3.5. Digest proteins → proteases & polypeptides. Pepsinogen I is large amount, secreted by the chief cells and its secretion is linked with HCL secretion. Pepsinogen II is less in amount, secreted by mucosal cells and not linked with HCL secretion. B- Gelatinase : which liquefies gelatin. C- Gastric lipase: act on short chain fat. Its optimum pH = 3. D- Amylase (from saliva). E- Rennin: milk clotting enzymes (not present in humans). (3) Secretion of intrinsic factor: - It is a glycoprotein secreted from oxyntic cells with HCL. - It is essential for vit B12 absorption in ileum. - In gastritis → pernicious anemia (↓ B12 anemia). (4) Secretion of Mucus: There are two types of mucus:  Soluble thin mucus: secreted by mucus neck cells by vagal as mucoproteins to lubricate gastric chyme.  Insoluble thick mucus: - Secreted by the surface epithelium. - Viscid alkaline mucus layer to protect gastric wall from digestion & acidity. Page 84 Page 16 Git & Nutrition 2024 Mechanism of protection of the gastric mucosa from pepsins and HCL 1) Mucosal barrier: insoluble thick alkaline mucus gel layer (1 mm) together with HCO3- (Ph is 6-7 at surface of mucosal epithelial cells. 2) Prostaglandins stimulate the secretion of this alkaline mucus and decrease HCL secretion. 3) Tight junctions between mucosal cells to prevent passing HCL in between cells. 4) Gastric mucosa contains trefoil peptides which are acid-resistant. 5) Continuous regeneration of gastric mucosa by growth factors 6) The oxyntic cells are protected from HCL by forming it in intracellular canaliculi then secreting it in the gastric lumen Duodenum is protected by mucosal barrier + pancreatic alkaline secretion. (5) Secretion of gastrin hormone:  It is a polypeptide belong to gastrin -CCK group of 3 types according to number of amino acids G34, G17 (most important) and G14  It is secreted from G-cells in pyloric antrum. It is also present in the anterior pituitary gland, hypothalamus and medulla oblongata.  Receptors (CCK -B). Action of gastrin on: - Stomach: ↑ growth of gastric mucosa (trophic effect) , secretion & motility. - Pancreas: ↑ insulin secretion. - Sphincters: - Lower oesophageal sphincter → Contraction. - Ileocecal sphincter→ Relaxation. - ↑ growth of intestinal mucosa & Stimulation of small and large intestinal motility  NB: Persons with gastrin- secreting tumors (Zollinger-Ellison syndrome), H+ secretion is increased, and the trophic effect of gastrin causes the gastric mucosa to hypertrophy. Conversely, in persons whose gastric antrum is resected, H+ secretion is decreased and the gastric mucosa atrophies. Page 85 Page 17 Git & Nutrition 2024 Regulation of gastrin secretion: Stimulation Inhibition  Polypeptides, amino  ↑acidity PH < 2 -ve  Chemical acids, caffeine and feedback inhibition via factors alcohol. release of somatostatin.  Luminal  Distension of the ----- stomach.  Calcium, adrenaline.  Secretin, GIP,  Blood born VIP, calcitonin, glucagon  Vagal by gastrin  Neural ----------- releasing peptide Control of gastric secretion: Nervous and hormonal: Three phases: (1) Cephalic phase (30 %): - It is a nervous phase activated by conditioned and unconditioned reflexes: - In the conditioned reflex: Psychic stimulation of cerebral cortex, appetite centers of the amygdala and hypothalamus will stimulate the vagal center (dorsal motor nuclei) In the unconditioned reflex: direct contact of food stimulates taste buds which give afferent to the vagal center. - The vagal nuclei stimulate gastric secretion by: 1. Direct stimulation of gastric glands (ACh). 2. Release of gastrin hormone (Gastrin releasing peptide). - This phase increases by anxiety and decreases in depression. The role of unconditioned reflexes is proved by: - Sham feeding experiment: The esophagus of a dog is exposed and divided in the neck, so the food swallowed will pass to outside. At the same time a gastric fistula is inserted. Although no food reaches the stomach, Sham feeding increases gastric secretion. (2) Gastric phase (60 %): The presence of food in the stomach → increase gastric secretion by mechanical, chemical and neural stimuli as the following:  Gastrin secretion: by direct stimuli as polypeptides, alcohol and caffeine or via local and vago-vagal reflex to stimulate the vagal center. Page 86 Page 18 Git & Nutrition 2024  Local nerve plexus: by distension or polypeptides → stimulate Meissner’s plexus →↑secretion.  Vago-vagal long reflex: food in stomach → afferent vagus to vagal center & efferent vagal increase in gastric secretion so inhibited by atropine. N.B : hypoglycemia →↑ vagal stimuli →↑ secretion. (3) Intestinal phase (10%) : The presence of food in the duodenum, will continue to cause stomach secretion of small amounts of gastric juice (10%), because of small amounts of gastrin released by the duodenal mucosa. - Although intestinal chyme slightly stimulates gastric secretion during the early intestinal phase of stomach secretion, it paradoxically inhibits gastric secretion at other times. This inhibition results from at least two mechanisms. A- Nervous mechanism (Enterogastric reflex):  It is stimulated by presence of acid, fats or hyperosmotic solution in the duodenum or distention of the duodenum will inhibit the gastric secretion.  The reflex is conducted in the three ways: local, ganglionic or vago – vagal reflex.  The response and the importance: 1. Inhibition of gastric secretion and motility 2. Protection of duodenum from over distention by increase in the tone of pyloric sphincter → delays the emptying. 3. Protection of duodenum from hyperacidity (till neutralized by alkaline duodenal secretion). 4. Insure protein digestion. 5. Prevent rapid electrolyte changes during intestinal absorption. B- Hormonal mechanism (Enterogastric hormones): It is stimulated by the presence of fats, acid, protein breakdown products, hyperosmotic or hypo-osmotic fluids→ release of 4 hormones from the duodenum [cholecystokinin (CCK), secretin, gastric inhibitory peptide (GIP) & VIP] → hormonal feed – back inhibition of gastric secretion and motility for complete digestion of fat. Gastric Secretion During the Interdigestive Period: stomach secretes a few ml of gastric juice each hour during the ―interdigestive period,‖ when no digestion is occurring anywhere in the gut composed mainly of mucus but little pepsin and almost no acid. Emotional stimuli may increase this secretion (which is highly peptic and acidic) to 50 ml or more per hour, which may contribute to the development of peptic ulcer. Page 87 Page 19 Git & Nutrition 2024 Peptic ulcer It is an area of erosion of mucosal membrane of GIT due to increase gastric secretion (as in stress, depression, anxiety and gastrinoma )or disruption of mucosal barrier (by excess intake of aspirin, alcohol, smoking or by infection with H Pylori) mostly occur in common sites as prepyloric portion in lesser curvature of stomach, proximal duodenum, lower esophagus and rare in jejunum.  Duodenal ulcers are most common and occur more in elderly men and occur in hyperparathyroidism as calcium stimulate gastric acid secretion. Also, in patient with renal transplant and the pain occur with hungry.  The patient of peptic ulcer complains of attacks of severe pain in epigastric region, related to meals and associated with nausea, flatulence and heart burn.  Gastric ulcer is associated with anorexia and weight loss. Mechanism for secretion of hydrochloric acid. Page 88 Page 20 Git & Nutrition 2024 Gastric Motility Filling and Storage of food in the stomach: The stomach accommodates up to one liter of food without increase of intragastric pressure because: a. Plasticity of gastric wall. b. Receptive relaxation. c. Law of LaPlace: P=T/r states that distending pressure (P) in a hollow viscus equals the tension in its wall (T) divided by its radius (r). ln the stomach, since food entry increases its radius with a little increase in tension, the intragastric pressure will be kept at a low level. Gastric basic electrical rhythm (BER) (gastric slow waves): - 3-5 cycles/min. due to partial depolarization of circular smooth muscle cells in the stomach wall. - Some lead to spike potential → peristalsis. (Frequency of slow waves in all GIT determines rate at which action potentials & contractions occur. - Start at midpoint of greater curvature (pacemaker of the stomach). - Vagal stimulation, gastrin &motilin →↑ spike potential rate. - Sympathetic stimulation, secretin &GIP→↓ spike potential rate. - NB: Slow waves are more frequent in the duodenum (12 waves per minute) than in the stomach. In the ileum, the frequency of slow waves decreases slightly, to 9 waves per minute. Types of movements of the stomach: 1. Tonic gastric waves: - Regular weak contractions (3 waves/min) which take place in the fundus and body to maintain the intra-gastric pressure & mix gastric secretion with food. 2. Receptive relaxation: - It is a reflex relaxation of the fundus and body to receive the bolus of food. - Initiated by vagovagal reflex that is triggered by movements of the pharynx and esophagus. (neurotransmitter released is VIP) - Also, by plasticity of gastric muscles. 3-Peristaltic movement: - 89 - Page 21 Git & Nutrition 2024 - It occurs at a rate of 3-4 / min. & coordinated by BER of stomach. - Distension of stomach by food → stimulates stretch receptors → vago – vagal reflex peristalsis at the middle of stomach and proceeds toward the pyloric antrum with gradual increase in strength leading to:  Grinding of food to fine particles.  Emptying of fine particles into the duodenum (propulsive movements).  Peristalsis in opposite direction from pyloric antrum to fundus (Antiperistalisis) → pyloric mill or retropulsion for mixing of food with gastric secretion. 4. Hunger contractions: Hypoglycemia (fasting for 12h) → activation of the feeding center in hypothalamus →Sends impulse to limbic cortex → hunger sensation. - Also, sends impulse to vagal nucleus → hunger strong painful contraction near the fundus (Atropine injection or vagotomy abolish hunger contraction but not hunger sensation). - They start slowly, then increase → tetanic contraction for 2 minutes then disappears and reappear in the next feeding time to reach maximal intensity in 3-4 days then gradually disappear. (May due to ↓ sensitivity of feeding center to hypoglycemia) - NB.: During fasting, there are periodic gastric contractions, called migrating myoelectric complexes, which are mediated by motilin. These contractions occur at 90-minute intervals to clear the stomach of any residue remaining from the previous meal. Nervous regulation of gastric motility: a- Vagal (parasympathetic): Excitatory cholinergic effect. b- Sympathetic: Inhibitory (nor adrenergic). c- Myenteric plexus: Involved in short & long reflexes. Factors affecting gastric emptying: With a mixed meal the stomach usually empty in about 3 hours through the pyloric pump which regulates the rate of gastric emptying. The rate of emptying is controlled by: A. Factors in the stomach: 1. Type of food: carbohydrate is the most rapid, then proteins followed by fats. 2. Consistency of food: liquids more rapid which depends on type of - 90 - Page 22 Git & Nutrition 2024 food, degree of mastication and the strength of gastric peristalsis. 3. Volume of food:  Moderate volume of chyme →↑ emptying via vago-vagal reflex and release of gastrin hormone.  Large volume → over distension →↓ emptying. B. Factors in the duodenum:  Degree of duodenal distention: Excessive duodenal distention delays gastric emptying through the enterogastric reflex.  Type of food in the duodenum: Presence of excess fat in the duodenum delays gastric emptying stimulating via release of CCK that inhibit gastric motility This effect is providing adequate time for fat to be digested and absorbed.  Duodenal acidity: excess duodenal acidity delays gastric emptying by both stimulating release of gastric inhibitory hormone& enterogastric reflex.  Duodenal osmolality: hyperosmolality and hypoosmolality stimulate duodenal osmoreceptors that lead delayed gastric emptying via initiating enterogastric reflex. so, preventing rapid flow of non-isotonic flids into the small intestine (which disturbs the electrolyte balance). C. Emotional factors: 1. Pain: visceral and somatic pain→ reflex inhibition of gastric emptying. 2. Depression & sudden fear → reflex sympathetic inhibition. 3. Anxiety & anger → reflex parasympathetic stimulation of emptying. D. Chemical factors: Gastric emptying is accelerated by cholinergic drugs, alcohol, bicarbonate and coffee while it is delayed by adrenergic drugs, atropine and excessive smoking. Vomiting Definition: -It is the expulsion of gastric contents through the esophagus, pharynx and mouth. -It is a complex act controlled by vomiting center in the medulla oblongata and mediated by cranial nerves V, VII, IX, X & XII and spinal nerves to diaphragm and abdominal muscles. -It is preceded by nausea, salivation and increase respiration. Centers: a. Vomiting center: in the medulla oblongata. b. Chemo receptor trigger tone (CTZ): - 91 - Page 23 Git & Nutrition 2024 -In close to vomiting center in M.O in the wall of fourth ventricle. -Its stimulation by emetic drugs, motion sickness or metabolic causes → stimulation of vomiting center (its lesion leads to loss of this reflex). Causes of vomiting: 1- Central vomiting: Direct stimulation of CTZ by drugs as morphine, alcohol drinking, diabetic ketoacidosis, renal failure and early pregnancy. 2- Reflex vomiting: Stimuli: Unconditioned:  Irritation of back of tongue.  Irritation of gastric mucosal.  Severe visceral pain (Renal colic, coronary thrombosis…).  Irritation of semicircular canal. Conditioned: (Cortical excitation of vomiting) Visual, olfactory and psychic stimuli Afferent: According to site of stimuli. Center: Direct on vomiting center.  Some to CTZ as semicircular canal irritation and psychic. Efferent:  Via cranial nerves V, V11, 1X, X, X11.  Phrenic nerve to diaphragm.  Spinal nerves to abdominal muscles. Response: → vomiting. Mechanism of vomiting: 1- Nausea: with salivation, ↑ H.R, sweating, stomach wall is relaxed and antiperistalsis may occur in duodenum. 2- Retching: intermittent contraction of diaphragm and abdominal muscles against closed L.E.S, glottis, and diaphragmatic opening is also contracted. 3- Gastric evacuation:  Strong contraction at the incisura separating the body from the pylorus.  The cardiac sphincter relaxes and the stomach wall is completely relaxed (passive stomach). - 92 - Page 24 Git & Nutrition 2024  Powerful contraction of the diaphragm, abdominal muscles, and pelvic floor muscles →↑ intra-abdominal pressure → squeezing the relaxed stomach and expulsion its contents to the mouth (anti peristalsis may occur in oesophagus).  During vomiting the soft palate elevated, closure of glottis and inhibition of respiration to prevent the vomitus to pass to respiratory passages (as in swallowing).  When the stomach is empty, antiperistalsis waves may drive the intestinal contents into the stomach (as bile juice). Effect and complications of vomiting: a- Dehydration (loss of secretion). b- Alkalemia : due to loss acid and the resynthesis of acid is associated with ↑ alkaline tide in plasma. c- Tetany: Alkalemia →↓ ionized Ca+2 → tetany d- hypokalemia (↓ K + level). - 93 - Page 25 Git& Nutrition Module 2024 2024 Physiology of Intestine and Pancreas Small intestine Motility of small intestine of two types: [I] The segmenting movements: Nature: it is myogenic in nature (controlled by the myogenic basic electric rhythm), accentuated by the local plexus, not controlled by vagus. Mechanism: several constrictions divide the loop of intestine into equal segments (2-3cm), then, these constrictions disappear and new constrictions occur in the middle of each segment and so on Rate: 12/min in duodenum & decrease along small intestine Value: A. Help digestion by mixing the chyme with digestive juice. B. Help absorption as the food comes in control with the mucosa. C. Aids the blood and lymph circulation. [II] The peristaltic movements: Nature: it is neurogenic in nature (depend on local enteric plexus) and regulated by:  Gastroenteric reflex: distension of the stomach stimulates intestinal peristalsis reflexely.  Hormones: as gastrin, CCK, insulin and glucagons.  Vagus. Mechanism: distension by food bolus →local reflex contraction of circular muscle above distension (with relaxation of longitudinal m. by ACh, substance P, neuropeptide Y) while relaxation of circular muscle Infront of bolus with contraction of longitudinal m. by VIP, NO ) Rate: It propagates at a speed of 1-5 cm/second for short distance (20 cm) then dies out. Value: propulsive for chyme analWards. Types: 3 types of peristalses: a. Ordinary peristalsis. b-Peristaltic rush (mass peristalsis): If the intestinal mucosa is irritated by toxins, a strong peristaltic wave passes rapidly over the whole small intestine by local enteric or vago vagal reflex – normally occur 1 – 2 times/day. c-Antiperistalsis: Peristalsis in reverse direction at: 1- Duodenum: for mixing the chyme with alkaline duodenal secretion. 2- Ileocecal sphincter: to complete absorption of fluids by small intestine. Peristalsis is very strong in the esophagus then becomes weaker gradually. 131 Page 26 Git& Nutrition Module 2024 2024 Intestinal BER initiated by pacemaker interstitial cells of Cajal. in circular muscle &its rate is about 12/minute in duodenum& 9/minute in distal ileum. Spike potentials superimposed on depolarizing portions of BER increase intestinal muscle tone (BER itself rarely causes muscle contraction its function is to coordinate peristaltic activity) Control of small intestinal motility: Nervous: - Extrinsic: vagus nerve →↑ motility but sympathetic→↓ motility - Intrinsic: local myenteric plexus. Hormonal: Gastrin & CCK →↑ motility. Secretin & glucagon →↓ motility. The ileocecal sphincter: - It is the last few cm of ileum. - It is controlled mainly by the local intrinsic nerve plexus; it is tonically contracted to prevent return of cecal contents into the ileum. - It is relaxed by: - Distension of the stomach → gastro-ileal reflex. - Distension of ileum → local reflex. - Gastrin hormone - It is contracted by: Over distension of cecum → local reflex or sympathetic stimulation. (colono-ileal reflex) to inhibit ileal peristalsis. Movements of intestinal villi: - In the form of shortening and elongation → aid the lymph flow. - Controlled by local plexus and villikinin hormone. GIT movement during fasting: - migrating motor complex of peristaltic waves occurs every 90 minutes -It proceeds anal wards at a speed 10 cm/min. -It is a local enteric reflex aims to sweep any excess of GIT secretion towards the colon to prevent their accumulation. Paralytic ileus: one of the common complications following abdominal operations, trauma to intestine & peritonitis. -It is caused by increase sympathetic tone → relaxation and accumulation of chyme, fluids and gases. -It is treated by aspiration of fluids & gas by nasal tube and I.V fluids to treat the dehydration due to ↓ absorption until the motility reappear. 132 Page 27 Git& Nutrition Module 2024 2024 Intestinal secretion (succus entericus) The small intestine has 3 types of secretory cells: - Crypts of lieberkuhn. - Brunner’s gland and Goblet cells. - Enterochromaffin cells which secrete serotonin. *The Villus: is finger like projection 0.5-1 mm Long. Covered by single layer of epithelium. Has smooth muscle to help its movements and a brush border of minute microvilli to increase the absorption surface to 200 m2. The life span of mucosal cells is 3-5 days. The small intestine secretions is made up of: Mucus: -Secreted by Brunner’s glands & goblet cells. -Important for protection and lubrication. -Stimulated by vagus, local distension or acidic chyme & secretin. -Inhibited by sympathetic stimulation so, irritable persons have high incidence of duodenal ulcers. Alkaline fluid: (Na HCo3): - Dissolves the chyme. - Stimulated by secretin, CCK, VIP and PGS. - Inhibited by sympathetic. Sloughed Mucosa (enzymes): -The intestinal secretion is about 1 liter/day of pH 7.5 and have no enzymes secreted from Crypts of Lieberkühn. -The sloughed cells contain disaccharides (sucrase, maltase& lactase) dipeptidases (Aminopeptidase, enterokinase) and phosphatases. 133 Page 28 Git& Nutrition Module 2024 2024 Control of small intestine secretions: Nervous: - local enteric reflexes →↑ secretion. - Vagal →↑ mucus secretion only. Hormonal: VIP, secretin, CCK → ↑secretion. Vaso active Intestinal Peptide (VIP): It is released from the nerves of GIT and act as a hormone or co-transmitter and has the following effects: 1-It stimulates intestinal secretion (water and electrolytes) and relaxation of intestinal muscle including sphincters 2- It induces Vasodilatation. 3- It inhibits gastric acid secretion. 4- It relaxes Lower esophageal sphincter. 5- Potentiation of the action of acetylcholine in the salivary glands. 134 Page 29 Git& Nutrition Module 2024 2024 The large intestine Motility of the large intestine: 1) - Mixing segmenting movement: Predominant movement for H2O and ions absorption. The large intestine characterized by the presence of outer muscular three bands (teniae coli) → bag like sacs called haustrations with contraction of circular muscle layer. 2) - Peristaltic (propulsive) movements: A- Weak peristalsis movements. -The colon is able to restore its contents for days. It propels the chyme from the cecum to the transverse colon. B- Antiperistalsis: It may occur from transverse to ascending colon to complete water absorption. C - Mass movements: - It occurs to propel the faecal matter from transverse to sigmoid colon. - About 20 – 25 cm contract as one unit to push the contents into the rectum, usually occur after breakfast (1 to 3 times per day ) - It is initiated by gastrocolic and duodenocolic reflex by presence of food in stomach and duodenum → reflex colonic contraction through released gastrin hormone which stimulate colonic motility or local enteric or prevertebral ganglionic reflex. Functions of large intestine: 1. Absorption of water, electrolytes, some vitamins and some drugs: i. About 2 lit of water follow Na Cl absorption by osmosis. ii. Large water rectal enema →↑ water absorption & water intoxication may occur. iii. Some dugs as sedatives, steroids, anesthetics could be taken suppository. 2. Storage and evacuation of stool: i. The colon stores feces and the rectum is usually empty except just before defecation. ii. When the rectum contains 100 ml of feces, there is urge to defecate which is completed by relaxation of internal sphincter and voluntary relaxation of external anal sphincter. 3. Bacterial action in the large intestine: a. Useful bacteria: 135 Page 30 Git& Nutrition Module 2024 2024 1. Synthesis of vitamins as vit. K, thiamine, biotin & folic acid. 2. Stimulate lymphocytes in intestinal wall to secrete IgA & IgM. 3. Prevention of cecal enlargement via digesting the macromolecules. b. Harmful bacteria: 1. Ammonia formation →↑ ammonia in bl. 2. Cholesterol → hypercholesteronemia. 3. Histamine & serotonin. 4. Utilize vit B12 and ascorbic acid. 4. Secretion of alkaline mucus: 1. High alkaline (pH= 8) to protect the mucosa from acids produced by bacteria. 2. It is produced by crypts of lieberkuhn and goblet cells in response to: a- The contents of food. b- Emotional stress → stimulate pelvic nerve →↑ mucus secretion & motility → diarrhea. Guanylin : 1. It is paracrine regulator produced by the ileum & colon. 2. It has the ability to activate guanylate enzyme and production of c-GMP within cytoplasm of intestinal cells. Which stimulate epithelial cells to secret cl- & water with inhibition of Na+ absorption →↑ salt & water loss in faeces. 3. The enterotoxins of Eschericia coli bacteria → same effect. 4. Uroguanylin is a related polypeptide found in urine & stimulate the kidney to excrete salts in urine. Defecation Definition: It is the act of emptying of the colon through the anus. The anus is controlled by: o Internal anal sphincter: smooth involuntary muscle, controlled by autonomic nervous system. o External anal sphincter: striated voluntary muscle controlled by somatic (pudendal) nerve which originate from the anterior horn cells of S2, S3, S4.  Defecation centers: lateral horn cells of sacral S2, S3& S4 for involuntary defecation. These centers are under control of medullary centers and cortical control for voluntary defecation. Role of innervation in defecation: The distal colon, rectum and anal canal are innervated by: 136 Page 31 Git& Nutrition Module 2024 2024 - Somatic pudendal nerve which arises from AHC of S2, S3& S4 to supply the anal canal and external anal sphincter, but its afferent fibers carry friction sensation during stool passage. - Parasympathetic pelvic nerve which arises from LHC of S2, S3& S4 to supply the wall of rectum and the internal anal sphincter. Its afferent fibers carry fullness sensation. - Sympathetic nerve which arises from LHC of L1&2 to inhibit defecation. Defecation mechanism (reflexes): 1. Preparatory reflexes: a. Gastro-colic reflex: distention of stomach → reflex contraction of the colon. b. Duodeno-colic reflex: distention of duodenum → reflex contraction of the colon. 2. Intrinsic defecation reflex: distension of the rectum → weak peristaltic waves in the colon and relaxation of internal anal sphincter. 3. Spinal defecation reflex: -Stimulus: distension of the rectum. -Receptor: mechanoreceptors. -Afferent: Pelvic nerve and pudendal N. -Center: L.H.C of S2, S3, S4 (parasymp) & A.H.C of S2,3,4 (somatic). -Efferent: pelvic nerve & pudendal N. -Response: - Pelvic N → contraction of wall & relaxation of internal anal sphincter. - Pudendal N → relaxation of external anal sphincter. This reflex is potentiated by passage of fecal materials through the anal canal via afferent pudendal nerve to S2, S3 & S4. Voluntary control of defecation: once the rectum fills to 25% of its capacity, there is an urge to defecate. Signals are sent to carry sense of rectal fullness and the desire to defecate to the brain. 1- If the conditions are suitable: a. The cerebral cortex sends excitatory impulses to activate the defecation center in the spinal cord → more peristalsis and relaxation of anal sphincters. b- The act of defecation is facilitated by straining (forced expiration against closed glottis) →↑ intra-abdominal pressure and squeezes the rectum. Also, contraction of the levator ani muscle helps defecation. 137 Page 32 Git& Nutrition Module 2024 2024 2- If the conditions are unsuitable: The cerebral cortex sends inhibitory impulses to inhibit the defecation center with rectal wall relaxation and internal sphincter contraction by sympathetic effect. The external anal sphincter contracts voluntary via pyramidal fibers→ prevent defecation. Constipation Definition: It is the decrease in frequency of defecation → more absorption of water from the feces → dry and hard feces. Causes: 1. Mainly by frequent inhibition of defecation → weak reflex and atonic colon. 2. Overuse of laxatives → weakens the reflex. 3. Other causes: anal pain, hypothyroidism, depression, hypercalcemia. N.B: Spastic colon: In anxious persons, paroxysmal attacks of colon spasm and constipation followed by diarrhea. Laxatives not used in this case but may be treated by fiber diet, antispasmodic and stress treatment. Diarrhea *Definition: It is a frequent defecation of large volume of soft stool. *Caused by: a- Irritation of intestinal mucosa by bacteria, viruses (enteritis), parasites or enterotoxins (cholera) substances →↑ secretion and colonic motility. N.B: in cholera →↑ secretion of Na Cl & H2O → secretory diarrhea Or in inflammation →↓ absorption in colon → inflammatory diarrhea. N.B : traveler’s diarrhea is acute case with travelling. b- Psychic diarrhea in nervous tension. c- Osmotic diarrhea by undigested lactose or magnesium sulphate. * Complications: 1. Dehydration may lead to hypovolemic shock. 2. Hypokalemia (due to K+ loss). 3. Acidosis (loss of bicarbonate & reformation of bicarbonate is anticidiated with ↑ acidic tide. 138 Page 33 Git& Nutrition Module 2024 2024 Physiology of Pancreas Pancreatic secretion The pancreas has both: 1- Endocrine gland: Alpha cells → glucagon & Beta cells → insulin. 2- Exocrine gland: consisted of blind secretory acini, ducts which drain in pancreatic duct which unites with common bile duct and open together at the ampulla of Vater in the duodenum. The common opening is surrounded by sphincter of Oddi. Exocrine pancreatic secretion:  Volume: 1 – 1.5 L/day. - PH: 7.8 – 8.3  Osmolarity: iso-osmotic with plasma.  Ions: - Na+ & K+: the same concentration of plasma. - HCO3: higher than in plasma (145 mEq/L). - CL-: lower concentration than plasma.  Types: 1- Aqueous alkaline juice: -Large in volume, rich in bicarbonate & secreted by duct cells. -Stimulated by secretin hormone & inhibited by sympathetic. Mechanism of secretion: 1. CO2 from the blood diffuses to interior of duct cells and by carbonic anhydrase combines with water to form carbonic acid (H2CO3). 2. carbonic acid dissociates into HCO3− and H+. Also, Additional HCO3− enters the cell through the basolateral membrane by co-transport with Na+. 3. HCO3− is then exchanged for Cl− by secondary active transport through the luminal border into the lumen of the duct. The Cl − that enters the cell is recycled back into the lumen by special chloride channels. 4. H+ ion is pumped out to the plasma (acid tide) in exchange for sodium which is pumped into the cell then diffuses to lumen. 5. Na+also enter the cell by co- transport with HCO3− across the basolateral membrane. Sodium ions are then transported across the luminal border into the pancreatic duct lumen. 6. Movement of Na and HCO3 from the blood into the duct lumen creates an osmotic pressure gradient that causes osmosis of water also into the pancreatic duct, thus forming an almost completely isosmotic bicarbonate solution. 139 Page 34 Git& Nutrition Module 2024 2024 Acid- tide: ↑ H+ concentration in venous blood drain the pancreas to neutralize alkaline tide of gastric secretion → acid – base balance. 2- Enzymatic juice: - Small in volume, rich in enzymes. - Secreted by acinar cells. - Stimulated by cholecystokinin-pancreozymin (CCK – PZ) & vagus nerve. - Pancreatic enzymes:  Pancreatic amylase: starch, glycogen → maltose.  Pancreatic lipolytic enzymes: Lipase and phospholipase (facilitated by bile). -Triglycerides → FFA & monoglyceride. -Phospholipase A: act on lecithin → lysolecithin. - cholesterol esterase: hydrolysis of cholesterol esters  Proteolytic enzymes: -Endopeptidases as trypsinogen , chymotrypsinogen and proelastase -Exopeptidases: Procarboxypeptidases. They are secreted in inactive form and activated by enterokinase (in small intestine) and the active trypsin to prevent autodigestion of pancreas (also the pancreas has trypsin inhibitor).  Pancreatic nucleases: ribonuclease and deoxyribonuclease, act on RN A and DNA leading to formation of nucleotides. Control of exocrine pancreatic secretion: I. Nervous: three phases: cephalic phase, gastric phase, and intestinal phase. 140 Page 35 Git& Nutrition Module 2024 2024 1) Cephalic Phase: conditioned & unconditioned reflexes → vagal stimulation of enzymatic secretion from acini about 20% of the total secretion of pancreatic enzymes after a meal. Little of secretion flows immediately through pancreatic ducts into the intestine because only small amounts of water and electrolytes are secreted along with enzymes. 2) Gastric phase: the nervous stimulation of enzyme secretion continues about 5% to 10% of pancreatic enzymes secreted after a meal, only small amounts reach the duodenum because of continued lack of significant fluid secretion. 3) Intestinal Phase: After gastric chyme enters the Duodenum, pancreatic secretion becomes copious, mainly in response to the hormone secretin. ii. Hormonal: Secretin →↑ aqueous alkaline secretion from ducts. CCK. PZ →↑ enzymatic secretion from acini (70% to 80% of the total secretion of the pancreatic digestive enzymes after a meal.) Cholecystokinin pancreozymin Secretin (CCK) Structure 33 A.A (gastrin-CCK family) 27 A.A (secretin-glucagon family) 2 receptors CCK A & CCKB Site Upper part of small intestine Stimuli - Digestive products of protein and fat - Acidic chyme from stomach - Polypeptides & AA ↑ HCL pass to the duodenum with -Fats & F.A. in duodenum decrease its pH. Effect on: Stomach Inhibition of gastric functions (motility and secretion). Intestine ↑motility & enzymes secretion. ↑mucus secretion. pancreas  ↑ Secretion of enzymes. ↑ Secretion of alkaline juice.  It potentiates the effects of secretin on ↑ Insulin hormone. HCO3−secretion.  ↑ insulin H.  Trophic effect bile ↑ Evacuation of bile from gall bladder ↑Secretion of bile Na HCO3. (cholagogue). Control Positive feedback between CCK & A.A as Negative feedback as HCL causes CCK causes more digestion of protein release of secretin which in turn leading to production of AA which re- inhibit HCl secretion from the stimulates CCK stomach. Second Increase Ca++ cAMP messenger 141 Page 36 Git& Nutrition Module 2024 2024 Physiology of Liver and Biliary system Liver & bile The liver is the largest gland in the body (1.5 kg). Function of the liver: 1) Metabolic function:  CHO metabolism: - Conversion of galactose and fructose to glucose - Glucostat function: liver maintain the blood glucose within 70-110 mg %; If the blood glucose level increases, the excess is taken by the liver and is converted to glycogen (glycogenesis) and fat (lipogenesis), and if it decreases, it is added by the liver into the bloodstream (through the processes of glycogenolysis and gluconeogenesis).  Protein metabolism (a) Deamination of amino acids, and the resulting products are either oxidized (to supply energy) or converted into carbohydrates and fats. (b) Conversion of ammonia to urea: Ammonia is formed in the gut by bacteria and its conversion to urea is life-saving because it produces toxic effects specially to the nervous system (= hepatic encephalopathy). (c) Formation of uric acid (end-product of nucleoprotein metabolism). (d) Synthesis of non-essential amino acids (through transamination). (c) Synthesis of the plasma proteins (except gamma-globulins).  Fat metabolism:  (a) Oxidation of fatty acids to supply energy & formation of ketone bodies: Fat is first split into glycerol and fatty acids (lipolysis), then the fatty acids by beta- oxidation into acetyl radicles which combine with coenzyme A (CoA) forming acetyl-CoA. Part of acetyl-CoA is oxidized in the citric acid cycle while the other part is converted by condensation of 2 molecules into acetoacetic acid which is delivered by the liver cells to the bloodstream and is oxidized at other tissues.  (b) Synthesis of cholesterol, lipoproteins and phospholipids.  80 % of cholesterol is converted into bile salts. while the remainder (together with phospholipids and lipoproteins) is transported to the tissues. In the tissues lipoproteins are split and fat is stored or oxidized while phospholipids and cholesterol form cell membranes and certain intracellular organelles. 162 Page 37 Git& Nutrition Module 2024 2024  (c) Fat synthesis from carbohydrates and proteins ( lipogenesis).  2) Storage function:  The liver stores glycogen, vitamins A, D, E, K & B12 and metals as iron & copper.  Iron is stored in the form of ferritin. When the blood iron level decreases the liver ferritin releases its iron content to the blood while if the blood iron level increases, it is taken by the liver where it is stored (blood iron buffer).  Liver is essential for erythropoiesis (since it supplies vitamin B12, iron and the globin fraction of hemoglobin). The erythrocytes are also formed in the liver during fetal life. 3)plasma proteins and Blood clotting factors formation : the liver needs vit. k to synthesize factors II, VII, IX, X. 4)Vascular function:  Storage of blood about 10% of the total blood volume (450 ml) in the sinusoids and hepatic veins. When needed, this blood, can be added to the general circulation (e.g. in cases of severe hemorrhage).  Blood filtration : By kupffer cells removal of blood clots &bacteria that enter the portal blood from the intestine 5) Drug and hormonal inactivation: e.g. steroid H., pencillin & others. 6) Immune response: the liver is a part of the reticule endothelial system 1) Bile formation: - Formation and secretion of about 0.2gm of bile salts/day. - Formation and excretion of bile pigments 8)Synthesis of vitamin d (1,25 cholecalciferol). Gall bladder Motility of the gall bladder - At meal time the gall bladder contract and sphincter of Oddi relaxes → evacuation of bile. - Cholagogues: factors increase evacuation of the bile as vagal stimulation, cholecystokinin hormone and magnesium sulphate. 163 Page 38 Git& Nutrition Module 2024 2024 Functions of gall bladder: 1) Storage of bile in between meals as the sphincter is closed and the liver continue to secrete bile (max. volume up to 30-60 ml) 2) Concentration of bile: by a c t i v e absorption of N a + followed by passive absorption of water, CL- and HCO3- except Ca++ to accommodate large volume of stored hepatic bile. 3) Help continuous flow of hepatic bile in between meals by storage and concentration (Decreasing the pressure in the bile ducts). 4) Acidification of bile by absorption of Na+ bicarbonate to prevent precipitation of Ca++ bile stones (pH changed from 7.8 to 7). 5) Evacuation of bile in the duodenum. 6) Secretion of white bile as mucus to protect the bladder wall from the concentrated bile. And acts as a lubricant and buffer in duodenum. Gall stones: - The formation of biliary calculi is caused by: 1) Too much absorption of water from bile. 2) ↓ Bile salts or lecithin or increase in cholesterol → cholesterol stones. 3) Inflammation of gall bladder: bacteria and glucoronidase enzyme convert bilirubin glucuronide into free bilirubin which combines with Ca++ → calcium bilirubinate stones. - The patient is treated by intake of bile acids → ↑ bile salts → dissolve cholesterol stone. - The inflammatory (bile pigment) stone is treated by surgical removal. Bile * Volume: 600 - 1000 ml/day * PH: in liver bile: alkaline - in gall bladder bile: acidic. * Constituents: Liver bile Gall bladder bile  H2O: 97.5 gm%.  92 gm %.  Inorganic: Na+, Hco3 and CL-.  Less concentrated ions  Organic: less - bile salts: 1.1 gm % - 6 gm %. -others: cholesterol, fat lecithin, F.A, bile - More concentration. pigments, alkaline phosphatase enzyme  PH: 7.8 – 8.5.  7.0 – 7.4. 164 Page 39 Git& Nutrition Module 2024 2024 Regulation of bile secretion: a. Choleretics: factors stimulate bile flow by increasing its formation by liver as: 1- Vagal stimulation to liver and gall bladder. 2- Bile salts (via enterohepatic circulation): the most potent. 3- Secretin hormone is hydrochloretic, as it increases the bile flow via increasing bicarbonate and water secretion. 4- Vasodilator drugs which increase hepatic blood flow b. Cholagogue : factors evacuate the bile from gall bladder and increase flow of bile as : 1- Vagal. 2- Mg++ sulphate. 3- CCK – PZ. H. Mechanism of bile secretion: a) Between meals: The sphincter of Oddi is closed and the hepatic bile is stored in the bladder to be concentrated and acidificated. b) During food intake:  Swallowing causes reflex vagal relaxation of sphincter and evacuation of bile. Vagal stimulation normally occurs on taking a meal through both conditioned and unconditioned reflexes during the cephalic phase of gastric secretion.  The CCK enzyme from duodenum → evacuation of bile into the intestine. (so, after a fatty meal, the gallbladder empties completely in about 1 hour). c) After meal: 90 % to 95 % of bile salts are actively reabsorbed from the terminal ileum back to the liver via the portal vein and re-excreted in the bile stimulating more bile secretion (enterohepatic circulation), the normal rate of bile salts secretion is 0.3 gm/day and recycles 6 – 8 times/day → total amount of 3.5 gm/day of bile salts. Bile salts Types:  Primary bile salts: are tauro – and glyco salts of cholic and chenodeoxy cholic acids which are formed from cholesterol (Na+ taurocholate & Na+ glycocolate).  Secondary bile salts: are formed in the intestine by bacterial effect on the dry salts (Na+ glyco-lithocholic & Na+ tauro-lithocholic). Functions of bile salts: 1- Digestion of fats: by -Reduce the surface tension and with phospholipid help in emulsification of fats into small particles with more surface area exposed for enzymatic 165 Page 40 Git& Nutrition Module 2024 2024 actions. -Activate lipase enzymes. 2-Absorption of fats and fat-soluble vitamins (vitamins A, D, E and K) Bile salts combine with fatty acids, cholesterol and fat-soluble vitamins to form micelles (water soluble compounds) which can be easily absorbed (Hydrotropic effect). 3-Choleretic action: stimulate bile secretion (enterohepatic circulation). 4- Solvent action: bile salts keep cholesterol and F.A. in solution preventing formation of gall bladder stones. 5-Prevent protein putrefaction by: -Digestion and absorption of fats. -Increase intestinal peristalsis -Hence, they lead to protein digestion & prevent its putrefaction and colonic distension. 6-Antibacterial effect and stimulate intestinal motility (laxative effect) FUNCTIONS OF BILE In addition to the functions of bile salts. bile performs the following functions: (1) Its HC03. content shares in neutralization of HCI in the duodenum (with the pancreatic and intestinal juices). (2) Its mucin content (white bile) acts both as a lubricant, and as a buffer in the small intestine. (3) It is an excretory route for (a) Bile pigments (which have no functions) (b) Certain heavy metals, toxins and bacteria (c) The alkaline phosphatase enzyme (d) Cholesterol and lecithin. 166 Page 41 Git& Nutrition Module 2024 2024 Bile pigments Steps of bile pigments formation: RE-System Hemoglobin → Bilirubin + Iron + Globin ↓ Blood Bilirubin – Albumin →Haemobilirubin (insoluble bilirubin) ↓ Liver Bilirubin + 2 UDP Glucuronate Glucuronyl ↓ transferase Bilirubin Diglucuronide (Conjugated, Direct or Cholebilirubin) ↓ Biliary tree Bilirubin Diglucuronide ↓ Intestine Bilirubin or Bilirubin Diglucuronide Bacterial ↓ Enzymes ―Urobilinogen‖ ↓ Feaces Stercobilinogen which oxidized to stercobilin (50 – 250 mg./ day) NB; There is an enterohepatic circulation for both bile salts and bile pigments (mostly urobilinogen) In plasma: hemobilirubin , cholebilirubin , urobilinogen - In urine : conjugated bilirubin + urobilinogen - In feces : conjugated bilirubin + stercobilinogen 167 Page 42 Git& Nutrition Module 2024 2024 Jaundice (Icterus) Definition: It is a yellowish colouration of skin and mucous membrane caused by hyperbilirubinemia in which bilirubin level in the plasma is more than 2 mg% (normal level 0.2-0.8 mg%). Types and causes : Obstructive Hemolytic Hepatic J. (post-hepatic) (Pre-hepatic) (Intrahepatic extrahepatic J. cholestasis) cholestasis (toxic) ↑RBCs hemolysis Diseased hepatic Obstruction of bile ducts -hereditary cells as in : as in: spherocytosis - Hepatitis. - Biliary stone. 2. Causes -Thalasthemias - Liver cirrhosis. - Tumor in head of -Drugs (sulpha) - Some drugs. pancreas → pressure Erythoblastosis - Pregnancy. on bile duct → closed. fetalis. The rate of The diseased liver cells - Retention of formation of can’t uptake all cholebilirubin and bilirubin exceeds the hemobilirubin back diffusion to the rate of hepatic uptake →↑Hemobilinogen in blood→↑cholebilirubin →↑ Hemo bilirubin in the blood and with in the blood and ↑ its 3. Pathogenesis the bl. (not diffused to inflammation there is secretion in the urine urine because it is obstruction of some (diffused easily in carried on albumin) canaliculi so it causes urine). obstruction → back diffusion of cholebilirbin to bl. - Hemolytic - Hemo and chole ↑ cholebilirubin. anemia. bilirubin. - ↑alkaline phosphates, bile 4. Blood salts and cholesterol in - ↑ hemobilirubin. - Biphasic plasma 168 Page 43  Git& Nutrition Module 2024 - Indirect (van den - Direct reaction Bergh reaction. - Urobilinogen. - ↑ cholebilirubin. ↑ cholebilirubin. - Normal at first then - Dark brown colour - Dark brown. 5. urine from start. oxidized to urobilin → dark brown. - ↑ stercobilin. - ↓stercobilin. - Absent stercobilin. 6. feces - deep brown. - Pale. - Very pale (clay) - Anemia - hepatic disease -, Retention of bile - splenomegaly - No itching salts → - gall stones 1. bradycardia (deposit in 7. Clinical - No itching heart) picture. 2. pruritis (itching) 3. steatorrhea. 4. ↓ of vit.k → bleeding tendency. Neonatal or physiological jaundice: - It occurs in newly born infants (2-7 days after birth). - Due to rapid destruction of hemoglobin after birth and mild glucoronyl transferase deficiency in premature liver → defect in conjugation → jaundice for one week then disappear. - These infants are exposed to blue light which is absorbed by bilirubin in the plasma of the skin vessels and changed into more water-soluble isomer and excreted in bile & urine. *Non – hemolytic jaundice (Congenital hyperbilirubinemias) 1) Gilbert’s syndrome: - Common familial disease 2-5% of population. - A symptomatic increase in unconjugated bilirubin due to ↓ bilirubin uptake, ↓ glucuronyl transferase, ↓ RBCs life span. 2) Crigler – Najjar syndrome : - It is a sever type of congenital jaundice in neonates. - It is of 2 types: Type 1: absence of glucuronyl transferase enzyme. Type 2: decrease of glucuronyl transferase enzyme. Page 44 169  Git& Nutrition Module 2024 3) Dubin – Johnson syndrome : - Type of congenital hyperbilirubinaemia in which increase conjugated bilirubin due to defect in bilirubin excretion. N.B: Salicylates and sulfonamides drugs must not be given to jaundiced children because these drugs displace the bilirubin from its binding sites with albumin → bilirubin penetrate the blood brain barrier → destruction of basal ganglia → Kernicterus. Van den Bergh reaction: a. Cholebilirubin reacts directly with Erlich’s reagent to give pink colour (Direct reaction) in obstructive J. b. Haemobilirubin reacts with diazo reagent only after separation from albumin by methyl alcohol (indirect reaction) as in hemolytic J. c. When serum contains both haem- and cholebilirubin, it gives a pink colour with diazo-reagent and the colour increased with addition of alcohol (Biphasic reaction) as in hepatocellular Jaundice Page 45 170  Git& Nutrition Module 2024 Gastro intestinal absorption All parts of the GlT are capable of absorption e.g. alcohol and water are absorbed from the gastric mucosa and water and electrolytes are absorbed from the large intestinal mucosa. However, the small intestine is the chief site of absorption because of the presence of the valvulae conniventes, villi and microvilli. It is primarily a vital process as evidenced by: ( I) The intestinal O 2 consumption markedly increases during absorption. (2) If the temperature of an intestinal loop is raised, the rate of absorption in this loop markedly increases, and vice versa. (3) Occlusion of the blood supply markedly decreases the rate of absorption. (4) If serum is placed in the intestine, it will be completely absorbed although it has the same osmolality as the plasma. (5) The selective absorption of carbohydrates (e.g. galactose is absorbed faster than glucose although both have the same molecular weight). Factors that affect intestinal absorption (1) Vitality of the intestinal mucosa: depends on adequate blood blow , o2 supply and certain vitamins specially vitamin B. (2) State of digestion: Proper digestion is essential for good absorption. (3) Bile salts and lymph flow: These are essential for fat absorption. (4) Duration of contact of food to the intestinal mucosa: If this is shortened (e.g. due to diarrhea), the rate of absorption will be reduced. (5) The extent of the absorptive surface : Pathological or surgical conditions that reduce the intestinal surface by more than 50 % markedly decrease the rate of absorption. (6) Intestinal mixing movements : These help absorption by (a) Exposing the intestinal contents to the absorbing surface (b) Improving blood and lymph flow (c) Increasing the intra-intestinal pressure. Page 46 171  Git& Nutrition Module 2024 (7) Movements of the villi: lashing movement; side to side movement and pumping movement (shortening and elongation). produced