Physiology Template - 2024 PDF

25 M.k. handout Liyan khashan MOHAMMED KHATATBEH  DIGESTION AND ABSORPTION Digestion is carried out by enzymes that catalyze carbohydrates, proteins and lipids. Absorption on the other hand is done by specialized epithelial cells. Starting off with absorption, most of it occur...

25 M.k. handout Liyan khashan MOHAMMED KHATATBEH  DIGESTION AND ABSORPTION Digestion is carried out by enzymes that catalyze carbohydrates, proteins and lipids. Absorption on the other hand is done by specialized epithelial cells. Starting off with absorption, most of it occurs within the small intestine, a small portion is absorbed by the stomach, and none is absorbed by the esophagus, (which’s primary function is transporting of food) - Most nutrients are already absorbed before reaching the ileum. - The colon removes whatever is left of water and electrolytes. As the small intestine is the primary nutrient absorbent, it has a specialized structure that allows it to increase the amount of nutrients it absorbs, which happens by increasing the absorptive surface area of its mucosa. Theres more than one feature that helps achieving this: 1. The presence of Mucosal Folds, (aka folds of Kerckring or circular folds) this characteristic increases the Surface area three times. 2. Villi found in the mucosa increase the surface area 10 more times. 3. Microvilli found on the luminal surface of the epithelial cells increase it by 20 folds. So the total increase of the surface area is about 600 folds.  Villus (singular of villi) Villi are finger-like projections which are richly supplied with blood vessels. They are present in the inner lining of the small intestine and help in the absorption of nutrients by increasing the surface area for absorption. Villus has more than one component that helps achieve its function, one are the capillary networks that absorb nutrients at a very great speed, which’s needed to keep the concentration gradient constant between the lumen and the blood capillaries. The other component is the Lymphatic Network of lacteals that absorbs and maintains lipids and its concentration. There are more structures in the villi such as Enteric innervation (mainly the submucosal plexus), that regulates the secretion of secretory cells and the blood flow towards the intestinal mucosa. In addition to the Smooth muscle cells of the muscularis mucosa that allow the villi to weave in the lumen and folds to move, which allows for more spreading of chyme over the absorptive area. At the surface of microvilli (luminal membrane) there are enzymes called Brush border enzymes which help in the final digestion of carbs and proteins.  Digestion and Absorption of carbohydrates Digestion: The carbohydrates are ingested as starch (most are), sucrose lactose and cellulose. Cellulose cannot be digested by enzymes in the gut. Digestion of carbohydrates begins as soon as it enters the oral cavity, carried out by a bunch of different enzymes found within the saliva, mainly alpha amylase (ptyalin). The Alpha amylase digests chains of starch by breaking down (hydrolyzing) its 1-4 alpha glycosidic bonds. This results in a partial breakdown of the starch. In other words, it converts starch into smaller polymers of glucose and alpha limit dextrins. This enzymes works best at neutral PH and is inactive in acidic conditions, i.e. The stomach. A lot of starch may leave the oral cavity still intact, so when it reaches the small intestine, the pancreas releases another alpha amylase enzyme called pancreatic amylase to digest the remaining 50-80% of the starch coming from the oral cavity, by also attacking its 1-4 alpha glycosidic bonds, leaving us now with maltose (2 glucose units) and maltotriose (3 glucose units). Which now are awaiting yet further breakdown that will be soon carried. The bush border enzymes which we mentioned briefly earlier now comes into work. These enzymes are responsible for final hydrolysis of glucose polymers and disaccharides into monosaccharides. 4 enzymes are found at this site (brush border): Lactase split lactose → glucose + galactose Sucrase split sucrose →fructose + glucose. Maltase split maltose and other glucose polymers → Glucose. alpha- Dextranase attack at alpha 1,6 linkage in → limit dextrins. At this point now, we have glucose, fructose and galactose to be now absorbed as digestion is now concluded. Absorption: Within the lumen of the intestine, there are Na+ linked carriers present at the membrane of the epithelial cells, two sodium ions along with one glucose molecule will be transported within the cell itself by the help of this carrier. Once Na+ and glucose are within the cells, the Na+ is pumped out at basolateral membrane (base membrane that leads to the bloodstream). And glucose is removed at the basolateral membrane by a facilitated diffusion into the capillaries of the villus. The whole process depends on the pumping of Na+ out of the enterocyte (epithelial cell). The process is a secondary active co-transport. This applies to both glucose and galactose molecules, however fructose enters by facilitated diffusion by using different type of carrier than Glucose/Galactose. The carrier is not linked to Na+. At the basal membrane it diffuses passively. * Absorption with solvent drag through the tight junction. (Solvent drag the process, whereby water (the solvent) moving across an epithelium by osmosis can drag dissolved solutes along with it.)  this is extra info wasn’t in the handouts, added it just to make this clearer. Increased glucose concentration in chyme can result in increased absorption. This results in increased osmotic pressure in the paracellular space and consequently, increased fluid flow through the tight junction which carries anything dissolved in fluids also. It could be important when glucose concentration is very high in chyme.  Digestion and Absorption of proteins Around 60 grams of proteins are digested and absorbed by the gut per day. This protein is derived from food, mucus, enzymes, and desquamated cells. Digestion: Unlike carbohydrates, who’s digestion begins in the oral cavity, proteins digestion starts once it reaches the stomach, where pepsin is secreted, pepsin, along with HCL, will break down (hydrolyze) the peptide bonds between the amino acids, resulting in large polypeptide.**** The digestion of proteins in the stomach is not much at all, because the pepsin and HCl can not attack the interior of food mass. The food is in semisolid mass and the exterior of mass only can be exposed to the enzymes. Pepsin works best at 2-3 pH, and is inactivated at 5 and higher pH levels. Much like with the carbohydrates, the large polypeptides remaining now go to the small intestine, where its further digested by Proteolytic enzymes secreted by the pancreas. The Proteolytic enzymes include: Endopeptidases and Exopeptidases, these enzymes continue to hydrolyze protein by converting it to small peptides and amino acids. At last, Brush border enzymes (peptidases) convert small peptides into oligopeptides ( di-, tri-, and tetra-peptides) and amino acids. Even after absorption, peptidases within the cytosol of the enterocyte cell continue even further hydrolysis of di-, and tri-, peptides and converting these small peptides into amino acids. Absorption: Di- and Tri-peptides are transported into the enterocyte by a carrier mediated transport system. This mod of transport is a secondary active co-transport which depends upon the activity of Na+ pump to maintain a chemical gradient for Na+ across the luminal membrane. The amino acids are transported into the cell quite differently than the former, its done by a membrane bound carriers; Na+ dependent carriers: 3 different carriers: 1. For neutral amino acids. 2. Proline and hydroxyproline. 3. Phenylalanine and methionine. Digestion and Absorption of lipids An important component for digestion and absorption of lipids is the bile, which is secreted by the liver, and acts in the lumen of the small intestine. Bile salts are amphipathic (contains both hydrophobic and hydrophilic portions) The sterol nucleus is hydrophobic. The hydroxyl groups, peptide linkage and the amino acid conjugate are hydrophilic. In aqueous environment, bile salts form micelles by the orientation of hydrophobic portion toward the center and the hydrophilic portion toward the periphery. In this way, lipid and non water-soluble molecules are dissolved in the center of the micelle. Digestion: Not much digestion occurs in the stomach because bile salts are not found within it to emulsify the fats. Here’s a fun fact: lipids tend to separate from the aqueous portion of the meal and tend to empty at slower rate than the rest of the meal. Once the lipids reach the intestine, digestion formally begins, within the duodenum, lipids are emulsified into small droplets, these droplets are stabilized (coated) by bile salts, Once emulsified, pancreatic lipase and co-lipase can act on the water/oil interface to hydrolyze the 1st and 3rd ester linkages of the tri-glyceride between glycerol and fatty acids. The result of this digestion is: two free fatty acids (FFA) and a 2-monoglyceride. Now these two free fatty acids and 2-monoglyceride along with phospholipids, cholesterol, and bile salts combine to form micelles. The micelles now connect itself to the gut wall, where FFA, monoglyceride, phospholipid, cholesterol diffuse out of the micelles across the brush border into the epithelial cell. This leaves out the bile salts, which are absorbed by the terminal ileum rather than the epithelial cells. If you noticed, this goes in contrast with how the carbohydrates and proteins operated, as after the pancreatic enzymes did its role, bush border enzymes acted to even further digest the molecule, this doesn’t apply to the lipids. Absorption: Unlike carbs and proteins, there’s no Na+ carriers to facilitate the process, the components simply move into the epithelial cells by passive diffusion. Once these components are inside the epithelial cells, the Free Fatty acids and 2- monoglyceride recombine forming triglyceride again. (this process requires ATP and Co-A) Around 80-90% of the reformed Triglyceride combine with 3% of cholesterol + phospholipids (10%) + B- lipoprotein (5%) and form chylomicrons. The chylomicrons are expelled from the epithelial cells by exocytosis. It diffuses through the extracellular space and is removed from the villus by lacteals (the terminal lymphatic vessel) and lymphatic circulation. Then enters the circulation at the thoracic duct. Some glycerol molecules which are not esterified into triglyceride and short chain fatty acids pass directly through the epithelial cells and removed from the villus by diffusion into blood capillaries.  ABSORPTION of WATER and ELECTROLYTES WATER: As Na+ is transported into the cell at the basolateral membrane, water flow into the epithelial cells through the tight junctions. Water is then rapidly removed through the capillaries, keeping the gradient intact. Electrolytes: Na+ ion; sodium Electrolytes are actively absorbed in both the small intestine and the colon. It diffuses passively into epithelial cells through the luminal membrane, and it leaves the cells through the basolateral membrane and into the bloodstream by active diffusion. And not to forget that There is the co-transport system with amino acids (proteins) and monosaccharides. (Carbohydrates) - The absorption is greatest in duodenum and decreases caudad. Insight about Aldosterone hormone and it’s affects on Na+ transport; Aldosterone is a Hormone secreted by the adrenal glands when there’s dehydration. This hormone increases Na+ absorption by enhancing the enzymes and transport mechanisms of Na+. This hormone is important mainly in the colon. In this way it conserves water and Na+ from loss with feces mainly when there is a need for Na+ and water in dehydration. Absorption of Cl-: Absorbed mainly in the upper part of the small intestine. Cl- moves in passive diffusion when an electrical gradient is established by the absorption of Na+. Absorption of K+: absorbed passively in the small intestine. - In the colon its usually secreted in exchange for Na+. Absorption of Ca++: - Ca++ is actively absorbed throughout the intestine. - It binds to a protein at the brush border membrane (may be a carrier). - Once Ca++ is inside the cell, it binds to a cytosolic Ca++ binding protein called calbindin Which transports Ca++ across the cell. - Ca++ is pumped out at the basolateral membrane by an active process. - Ca++ absorption is increased by vitamin D and parathyroid hormone. Absorption of Fe++ : absorption is mainly in the upper part of the small intestine. Fe++ (ferrous iron) is more soluble than Fe+++ (ferric iron). Acidic pH and vitamin C increase the level of iron absorption. Vitamin C can increase the iron absorption by reducing it from ferric iron into ferrous iron. Phosphates, oxalates, phytic acid (found in cereals) and pancreatic juice inhibit iron absorption. Theres still no definite answer on how iron is exactly absorbed, it could be by active transport, or the most common theory is that its done by secreting a globular protein from the epithelial cells known as apoferritin. This protein binds to Fe++ → ferritin. This complex of protein and iron is transported into the cell by receptor mediated endocytosis. Then iron stored in the epithelial cell in the form of ferritin is transported into the blood where it binds to transferrin as needed. If NOT needed, iron is lost when cells are desquamated. This mechanism prevents excess iron from entering the blood and causing toxic effects. This process is known as Mucosal Block. Absorption of vitamins: Most vitamins are absorbed in the upper part of the small intestine, but vitamin B12 is absorbed in the ileum. Theres two types of vitamin, with each being absorbed differently; 1. Water soluble vitamins: water soluble vitamins are absorbed passively except for the following: Vit. C, Vit. B1, and Vit. B12. Absorption of vit. B12 requires the intrinsic factor secreted by the oxyntic cells of the stomach. 2. Lipid soluble vitamins (Vit. A, D, E, K): Follow the same route as lipids. They are solubilized in micelles and chylomicrons. ‫تمت كتابة هذا الشيت صدقة جارية عن روح والدة زميلنا عمرو رائد من دفعة تيجان‬ ♡ ‫دعواتكم لها بالرحمة والمغفرة‬ Thank you