Digestion and Absorption Part 1 Lecture Notes PDF

Digestion and Absorption Part 1 Dr Vincent Ho MBBS Bsc(Med) MMed FRACP FACP PhD Clinical Academic Gastroenterologist Western Sydney University  Learning objectives  Review the anatomy and histology of the intestine  Canvass sites of absorption and overall mechanisms of absorption of nut...

Digestion and Absorption Part 1 Dr Vincent Ho MBBS Bsc(Med) MMed FRACP FACP PhD Clinical Academic Gastroenterologist Western Sydney University  Learning objectives  Review the anatomy and histology of the intestine  Canvass sites of absorption and overall mechanisms of absorption of nutrients and electrolytes  Canvass electrolyte and water absorption  Understand the digestion and absorption of carbohydrates  Understand the digestion and absorption of proteins  Describe some examples of clinical applications of this knowledge  Digestive Concentrating Vat Enzyme Inputs & Waste Reservoir Nutrient intake Pump Grinder Homogenizer Valve Waste Transfer disposal The Digestive Station (gut lumen to blood) System Cross section of small intestine From: Sherwood L. Human physiology, 2nd edn. West Publishing, St Paul, 1993 Regions of the small intestine  The absorptive surface area of the intestine is huge – about 250 m2 This is achieved by a large amount of folding - at macroscopic, microscopic and electron-microscopic levels  Histology of (small) intestine Intestinal lumen Enterocytes Villi Goblet cells (mucus) Crypts Muscularis mucosae Low-power scanning electron micrograph - looking down on villi, with crypts between them  Enterocytes (electron micrograph) Lumen Microvilli (brush border) Enterocytes Portion of goblet cell Lymphocyte Basal membrane of enterocyte Capillary (with part of an erythrocyte)  Microvilli (brush border) of enterocytes Glycocalyx  The luminal membrane of the enterocyte has its surface area greatly Microvilli increased by being folded into finger-like microvilli  The cell secretes some carbohydrate- containing enzymes (especially disaccharidases such as lactase, maltase) onto the outside of the microvillous membrane to form the glycocalyx  Functions of the small intestine Absorption of: products of digestion water electrolytes minerals drugs Food Digestion: breakdown to simpler substances by digestive enzymes from the pancreas and on the microvilli Immune barrier: protects against Hormone secretion luminal antigens and organisms Where are things absorbed? How molecules get across the enterocyte membrane Electrolyte and water absorption  Approximate volumes of water handled by gut each day INPUTS OUTPUTS  Food and drink 2.0 L  Intestinal  Saliva 1.5 L absorption 7 L  Gastric juice 2.0 L  Colonic  Pancreatic juice absorption 1.5 L 1.5 L  Bile 1.5 L  Intestinal crypts  Excreted in 0.5 L faeces 0.2 L Total ~ 9 L Transport of electrolytes and glucose across enterocytes Chloride secretion Mechanism of secretory diarrhoea Bicarbonate secretion Generating the electrochemical gradient for Na+ and H2O absorption across intestine and colon The Na/K ATPase transports 3 Na for 2 K so is not electroneutral - hence PD outside basolateral membrane is slightly positive Na+ enters the cell from gut lumen, down both a concentration AND an electrical gradient; H2O follows passively Digestion and absorption of carbohydrates Luminal digestion of carbohydrate  Digestion of both carbohydrates and proteins take place at 2 sites:  1) Enzymes secreted into the bulk lumen of the intestinal lumen begins the digestive procesess  2) Membrane-bound hydrolases located to the microvilli (brush border) of epithelial cells mediate next stage Carbohydrate digestion Monosaccharides  Epithelium can only transport monosaccharides hence even dietary disaccharides must be digested at the brush border before they can be absorbed 3 main forms of carbohydrate  Starch  Sucrose  Lactose  Structure of amylopectin (one major component of starch) Glucose units Amylose, the other main constituent of starch, is also made of glucose units, but without the branch points Major dietary disaccharides fructose glucose Lactose (milk sugar) Sucrose (cane sugar) Digestion of polysaccharides Small role Major role From: Sherwood L. Human physiology, 2nd edn. West Publishing, St Paul, 1993 Dietary fibre  Indigestible carbohydrates  Constituent polymers cannot be degraded by luminal hydrolases (including those secreted by pancreas or those expressed on surface of enterocytes) Three different types of dietary fibre How much dietary fibre daily? Carbohydrates in diet  Polysaccharides  Starch  Glycogen  Disaccharides  Sucrose (cane sugar)  Lactose (milk)  Small amounts of monosaccharides, mostly glucose but some plant sugars Lactose Intolerance Clinical Corner  The pattern of primary lactose intolerance appears to have a genetic component, and specific populations show high levels of intolerance, including approximately:  95 percent of Asians  60 percent to 80 percent of African Americans and Ashkenazi Jews  80 percent to 100 percent of American Indians  50 percent to 80 percent of Hispanics  Lactose intolerance is least common among people of northern European origin, who have a lactose intolerance prevalence of only about 2 percent Glucose and galactose share the same active transport carrier Fructose is absorbed passively The absorbed mono- saccharides are transported into portal blood From, Sleisenger and Fordtran. Gastrointestinal Diseases, 5th edn. Saunders, Philadelphia, 1993 Clinical Corner The importance of fructose A growing problem Ducks and fatty liver How does this happen?  Ducks and fatty liver High fructose Corn syrup!!  Fructose Link  Dietary fat consumption has remained static  Guru Walla Diet  Carbohydrate consumption A thin gentleman? Guru Walla Success Sugar consumption trends High fructose corn syrup is on the rise Actions of fructose Sweet beverages and serum ALT Digestion and absorption of proteins Dietary proteins – long chains of amino acids joined by peptide bonds Pancreatic acinar cells – the source of all the enzymes in pancreatic juice (saccharolytic, proteolytic, lipolytic, etc) http://www.anatomyatlases.org/Micro scopicAnatomy/Images/Plate26.jpg  Pancreatic proteolytic enzymes Enzymes activated by enterokinase - on enterocyte brush borders, but also secreted into intestinal lumen Clinical Corner Brush border hydrolysis  Like carbohydrates degradation of proteins in lumen is incomplete  Large number of brush border hydrolases Peptide transporters – PEPT1 Cytosolic proteolysis Clinical Corner Coeliac Disease Tight junctions in enterocytes Permeability of tight junctions Not all proteins are broken down effectively by proteolysis  The unique composition of cereal prolamins in wheat, barley and rye renders them resistant to gastrointestinal proteolytic enzymes.  Such partial degradation is thought to be one crucial factor in the activation of the immune response in the small-bowel mucosa and the progression of coeliac disease in genetically susceptible people.  Currently the only treatment for coeliac disease is avoidance of gluten prolamins (gliadin, hordein and secalin). Prolamines Gliadin and Glutenin Mechanism of coeliac disease Coeliac disease  Inappropriate immune response to gliadin (dietary constituent of wheat and other grains) which cannot be effectively digested  Absorptive surface area of the small intestine greatly reduced  Protein and carbohydrate assimilation can thus be affected  Treatment is strict adherence to a gluten free diet Histology of normal small intestine vs coeliac disease Coeliac disease: Investigations Coeliac disease: Complications Short gut syndrome  Defined as a type of intestinal failure which results from surgical resection, congenital defect or disease – associated loss of absorption and is characterised by the inability to maintain protein energy, fluid, electrolyte or micronutrient balances when on a conventionally accepted normal diet  Less than 200 cms of viable small bowel or loss of 5% or more of the small intestine places the patient at risk of developing short gut syndrome Aetiology of short gut syndrome Pathophysiology of short gut syndrome Pathophysiology of short gut syndrome Pathophysiology of short gut syndrome Complications Complications Complications Sample MCQ question Short bowel syndrome is characterised by all of the following except for: A)Steatorrhoea B) Hypogastrinaemia C)Diarrhoea D)Weight loss Answer – B) Hypogastrinaemia Questions? Dr Vincent Ho Email: [email protected]