Digestion

1. Digestion

2. Types of digestion systems 2/23 • in unicellular and primitive multicellular organisms intracellular digestion • in more developed multicellular organisms – extracellular digestion • diverse extracellular digestion systems exist in animals – there are three basic types based on the functioning of the „reactor” • intermittent, stirred – saclike; one portion in, digestion, undigested remnants out (e.g. hydra) • continuous flow, stirred – continuous intake, content mixed, continuous output (e.g. ruminant forestomach) • plug-flow, unstirred – continuous input, continuous output, tubelike reactor, composition depends on place, but not on time (e.g. small intestine in vertebrates)  Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-13.

3. Alimentary canal in vertebrates 3/23 • topologically external to the body • entrance and exit are protected by sphincters and other devices • ingested material is subjected to various mechanical, chemical and bacterial effects • digestive juices break down the ingested material chemically, nutrients are absorbed, undigested, unabsorbed material is expelled with the feces • tubular organization allows for functional specialization (i.e. acidic and alkaline environment) • parts of the alimentary canal: headgut, foregut, midgut, hindgut  Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-15.

4. Headgut 4/23 • food enters here – structures related to feeding and swallowing: mouth-parts, buccal (oral) cavity, pharynx, bills, teeth, tongue, salivary glands, additional structures to direct the flow of ingested materials and inspired water or air • most multicellular organisms have salivary glands to help swallowing (mucin - mucopolysaccharide) • saliva may contain: enzymes, toxins, anticoagulants (vampires, leeches, etc.) • tongue from chordates on – mechanical digestion, swallowing, grasping food (chameleon, anther), chemoreception (taste buds) • snakes take olfactory samples from the air and wipe the samples in the Jacobson’s organ (vomeronasal organ)

5. Foregut 5/23 • in most species it consists of the esophagus and the stomach • esophagus carries food from headgut to stomach • in infrequently feeding animals it can contain a saclike expanded section – crop (leeches) to store food, birds might use it to feed nestlings • digestion starts in the stomach • in most vertebrates: pepsinogen and HCl • monogastric stomach in omnivorous and carnivorous vertebrates • invaginations with gastric pits with gland cells  • digastric stomach in ruminants: fermentative (rumen+reticulum - cellulose) and digestive (omasum+abomasum [enzymes only here]) parts • camel, llama, alpaca, vicuñas: similar stomach • fermentation occurs before the stomach also in other species: kangaroo, chickenlike birds • birds might have a muscular gizzard following the stomach – chyme moves back and forth Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-18.

6. Midgut I. 6/23 • in vertebrates it consists of the small intestine (duodenum, jejunum, ileum), it is separated from the stomach by the pylorus • shorter in carnivores, longer in herbivores – dynamic changes • in tadpoles longer than in frogs relative to body size • duodenum: production of mucus and fluids + receives secretions from liver and pancreas – neutralization of stomach acid and digestion • jejunum: secretion of fluids, digestion, absorption • ileum: mainly absorption, some secretion • small intestine is characterized by a large surface epithelium: gross cylindrical surface would be 0.4 m2, but circular folds, intestinal villi, brush border - 200-300 m2  Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-20.

7. Midgut II. 7/23 • circular folds also slow down the progress of food – more time for digestion • each villus (approx. 1 mm long) sits in a circular depression (crypt of Lieberkühn) – inside: network of arterioles, capillaries and venules, in the middle: central lacteal (lymph vessel)  • longitudinal smooth muscle fibers – their contraction empties the lymph vessels • epithelium is made up of enterocytes (lifespan 3-6 days) proliferating at the bottom of the crypts (chemotherapy!) and bearing brush border (~1  long, 0.1  wide, 200,000/mm2); tight junctions, desmosome  • on the microvilli (brush border) glycocalyx: hydrolases (glycoproteins) and luminal transporters, inside actin filaments – in the basolateral membrane Na-K-pumps and different transporters • among the enterocytes sporadic goblet cells (mucus) Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-21c,d. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-21a,b.

8. Hindgut 8/23 • stores remnants of digested food – absorption of inorganic ions and water • in vertebrates it consists of the final portion of small intestine and of the large intestine (colon) • the hindgut is the major site of fermentation in many herbivores • colon fermentation (plug-flow reactor) – large animals, like horses, zebras, elephants, rhinos, sirenians (sea cows), etc. • cecal fermentation (continuous-flow, stirred reactor) - smaller animals, like rabbits, many rodents, koalas, opossums, etc.  • hindgut terminates in the cloaca in many vertebrates (cyclostomes, sharks, amphibians, reptiles, birds and egg laying mammals), or in the rectum • defecation and urination are under behavioral control  • the alimentary canal in invertebrates have many differences, but similarities as well  Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-22. The Far Side Gallery 3, G.Larson, Andrews and McMeel, Kansas City. 1994, p..21. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-17.

9. Motility of alimentary canal I. • motility is the ability of the alimentary canal to contract • its roles: • propulsion of food from intake to excretion • grinding and kneading the food to mix it with digestive juices and to convert it to a soluble form • stirring the gut contents to ensure the continuous renewal of material in contact with the epithelium • in arthropods and chordates it is achieved exclusively by muscular motility, in other animal groups ciliary motility might play a supplemental or exclusively role • in vertebrates at the entrance (buccal cavity, pharynx, first third of the esophagus) and exit (external anal sphincter) of the alimentary canal striated muscles – providing an at least partial voluntary control, in other places smooth muscles and the enteric nervous system dominates 9/23

10. Motility of alimentary canal II. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-22. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-24. • layers of the alimentary canal in vertebrates: serosa, longitudinal and circular muscle, submucosa, muscularis mucosa, lamina propria, epithelium  • there are two basic forms of motility: peristalsis (longitudinal and circular muscles) and segmentation (circular muscles)  • sphincters: upper and lower esophageal, cardia(functional), pylorus, ileocecal valve (between the small and large intestine), internal and external anal • swallowing is a complex reflex: tongue presses the food to the palate, soft palate closes the nasal cavity, food is propelled into the pharynx, mechanoreceptors induce the reflex, swallowing is unstoppable • upper esophageal sphincter relaxes, peristalsis moves the food toward the stomach, lower esophageal sphincter relaxes, cardia opens, food enters the stomach 10/23

11. Motility of alimentary canal III. • vomiting – complex reflex, helped by the respiratory muscles – reverse peristalsis in the small intestine, inspirational muscles contract – negative pressure in the chest, abdominal muscles contract – large pressure difference – lower esophageal sphincter relaxes, chyme enters the esophagus • chyme returns to the stomach during retching • during vomiting expiratory muscles contract, upper esophageal sphincter relaxes • centers in the medulla: central vomiting (without retching), retching (without vomiting), chemoreceptive trigger zone • stimuli: direct (meningitis, disgust), chemical (e.g. apomorphine), mechanical (back of the throat), visceral (peritoneum, uterus, renal pelvis, testis), organ of equilibrium • reflux – cardia is leaking, acidic chyme reenters the esophagus – can lead to inflammation, cancer • regurgitation: in ruminants – chyme reenters the buccal cavity without vomiting 11/23

12. Motility of alimentary canal IV. • peristalsis in the stomach by partially closed contraction ring - mixing, but it is not complete – rat experiment with differently colored food • small intestine – circumscribed expansion induces peristalsis • obstruction of passage – very dangerous • causes: mechanical (e.g. tumor), physiological (sympathetic hyperactivity – caused by peritoneal excitation) - mechanism not completely clear • large intestine absorption of water and ions, excretion of feces • following eating gastrocolic reflex distal movement of the chyme – might involve mass movement – frequently occurs in babies: eating leads to defecation • defecation is a complex process: posture, contraction of abdominal wall, sphincters • internal sphincter autonomic, external voluntary regulation 12/23

13. Regulation of the intestines I. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-25. • intrinsic control: contraction is myogenic in the alimentary canal – smooth muscle is capable of inducing electrical activity (rhythmic hypo-, and repolarization – might lead to Ca-spike and contraction; influenced by stretching and chemical stimuli from the chyme  • extrinsic control: enteric nervous system, central nervous system, peptide hormones • enteric nervous system • myenteric (Auerbach's) and submucosal (Meissner’s) neuronal networks • local reflexes • sensory neurons: transmit information of mechano-, chemo-, and osmoreceptors - substance-P • interneurons: n-Ach (excitatory), enkephalinergic, somatostatin releasing(inhibitory) • effector neurons: excitatory: colocalized ACh and tachykinin (e.g. substance-P); inhibitory: VIP, NO, ATP - morphine excites the latter neurons, long-lasting contraction, constipation; on glands VIP can also be excitatory 13/23

14. Regulation of the intestines II. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-34. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-26. • central nervous system • parasympathetic innervation (preganglionic): • acting mostly on interneurons of the enteric nervous system – excitatory effect  • to a smaller extent on efferent neurons – stomach functions, sphincter relaxation (e.g. esophagus) • sympathetic innervation (postganglionic): • vasoconstriction • pre-, and postsynaptic inhibition through 2-receptors • direct excitatory effect on sphincters through 1 receptors • local peptide hormones • proved hormones: secretin, gastrin, CCK, GIP (glucose-dependent insulinotropic peptide (formerly: gastric inhibitory peptide) – many more candidates • hormonal role is difficult to prove: measurement of levels, administration (physiological vs. pharmacological dose), antagonists • gastrin family - five C-terminal amino acids of gastrin and CCK are the same, both are active at different lengths • secretin family – secretin, GIP, glucagon, VIP • produced by unicellular glands detecting the composition and pH of the chyme directly – neuronal regulation in some of them  14/23

15. Gastrointestinal hormones 15/23

16. Gastrointestinal secretions Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-29. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-28. The Far Side Gallery 3, G.Larson, Andrews and McMeel, Kansas City. 1994, p..24. 16/23 • three types of secretion exist: • secretion-reabsorption type – proteins, water, electrolytes secreted in the acinus, reabsorption in the secretory duct, e.g. salivary glands • sequential secretion type – protein secretion in the acinus, water and electrolytes in the secretory duct, e.g. pancreas, liver • parallel secretion type – e.g. stomach; chief cells: pepsinogen, parietal cells: HCl, intrinsic factor, goblet cells: mucin and HCO3– • in one day about 5-6 l digestive secretions  • production of saliva • three pairs of large salivary glands: parotid, submandibular, sublingual + many small ones in the buccal cavity • function: lubrication (dry mouth - thirst), mucin, lysozyme, IgA, rinsing (dog-breath), amylase  • serous and mucous acinus cells • saliva is hyposmotic because of the reabsorption of NaCl  • mostly parasympathetic innervation, sympathetic activation results in thick, viscous saliva • unconditional and conditional reflexes – trumpet player and licking of lemon

17. Secretion in the stomach Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-33. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-32. 17/23 • secretion is parallel in the stomach; in addition, G-cells produce gastrin • fluid is acidic and isosmotic • functions of the low pH: optimal environment for pepsin, chemical degradation of the food (denaturation), killing of bacteria • large invaginations (canaliculi) in the membrane of the parietal cells with H-K-ATPase molecules - 106 concentration gradient – “world” record (exit of Cl– and K+ through channels) • source of H+: CO2 and water (carbonic anhydrase, HCO3–/Cl– exchange)  • facilitation: vagus nerve (m-ACh), gastrin, histamine • cephalic, gastric, intestinal phase • inhibition: HCl level, fatty acids longer than 10 C in the small intestine • secretion of chief cells increased by n-ACh, HCl 

18. Secretion of the pancreas 18/23 • indispensable for digestion • sequential secretion • acinus cells: • active enzymes (-amylase, lipase, DNAase, RNAase) • proenzymes (trypsinogen, chymotrypsinogen, procarboxipeptidases, prophospholipases, etc.) • secretory duct: • large amount of fluid with high HCO3– content (alkaline) • CO2 - HCO3– and H+ (carbonic anhydrase), Na+/H+ antiporter, Na+-pump, apical HCO3– exit • secretory duct enters the duodenum along with the bile duct at the ampulla of Vater • enteropeptidase (enterokinase) secreted by the duodenum activates trypsin, which in turn activates all the other (there is also a trypsin inhibitor in the pancreas) – during inflammation early activation, necrosis and death can occur • activation of acinus cells: CCK, m-ACh, VIP • activation of HCO3– secretion - secretin

19. Functions of the liver 19/23 • secretion (bile acids) and excretion (bilirubin, cholesterol, poisons, medicines, hormones, etc.) • bile is produced by the parenchyma cells (75%) and by the epithelium (25%) lining the bile ducts the latter secretes electrolytes • sinusoids with large-pored endothelium, between them one-cell-thick parenchyma sheets – between neighboring hepatocytes bile canaliculi, surrounded by tight junctions – if damaged bile enters circulation • bile is concentrated in the gallbladder, emptied three times a day (20-30 ml) • 95% of bile acids are reabsorbed from the gut • bilirubin is transformed by bacteria to stercobilin giving the brown color of the stool

20. Digestion and absorption I. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-35. 20/23 • carbohydrates completely, while lipids and proteins up to more than 90% are digested and absorbed from the gut • digestion of carbohydrates and proteins is a two-step process: luminal digestion is completed by enzymes (oligosaccharidases, exopeptidases) on the surface (glycocalyx) of enterocytes • absorption is mostly energized by the Na+ gradient that in turn is rebuild by the K+-Na+-pump in the basolateral membrane • carbohydrates: • -amylase can break the 1-4 bond, but not the 1-6 • it is unable to break the -glycosidic bond in lactose, this bond gets broken by the lactase (-galactosidase) – the lack of this enzyme leads to lactose intolerance • uptake of glucose and galactose is accomplished by a Na+ cotransporter, fructose enters the cell using GLUT-5 – it is slower, as it is a passive process • all sugars are transported through the basolateral membrane by GLUT-2  • part of the plant fibers (cellulose) are fermented by bacteria – not much usable energy is released, but huge amount of CH4, CO2 is produced

21. Digestion and absorption II. 21/23 • proteins: • luminal endopeptidases (pepsin, trypsin, chymotrypsin, elastase) and exopeptidases (carboxypeptidases) digest proteins to amino acids and smaller peptides • enterocyte glycocalyx: different membrane peptidases • membrane transport as amino acids (70-75%) or di-, and tripeptides (25-30%), mainly by group-specific Na+ cotransporters (active transport), partly through facilitated diffusion • at the basolateral membrane: facilitated diffusion • vitamin B12: • absorbed in protein-associated form • demand: 1-2 microgram/day – reserves in liver are sufficient for several years • B12 binds to R-protein in the stomach, R is digested in the duodenum, B12 binds to intrinsic factor • in the ileum, receptor induced endocytosis, in blood transported by transcobalamin II • B12 is needed for erythropoiesis – anemia is most frequently caused by the lack of the intrinsic factor

22. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-36. 22/23 Digestion and absorption III. • lipids: • hydrophobic character, digestion is only possible at the lipid-water border – micelles formed with the help of bile acids • most important enzyme: pancreatic lipase; in general it cuts off 1,3 fatty acids • fatty acids, 2-monoglycerids enter the enterocytes from the micelles • micelles also contain lipid-soluble vitamins (DEKA) – lack of bile acids leads to low vitamin K levels and disturbances in hemostasis • lipids are reformed in the endoplasmic reticulum of enterocytes and form lipoproteins containing triglycerides, phospholipids, cholesterol and its esters as well as apolipoproteins • lipoproteins are classified according to their density: VLDL, LDL, HDL – the largest are the chylomicrons • lipoproteins are transported from the Golgi to the lymphatic vessels through exocytosis  • lipoproteins are also produced in the liver

23. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-37. 23/23 Digestion and absorption IV. • calcium: • reabsorbed partly by paracellular diffusion, but mostly by active transport • regulation: parathormone and calcitriol (1,25-dihidroxi-D3-vitamin) • entrance by unknown mechanism – calcium binding protein – active transport through the basolateral membrane • iron: • stored in the enterocytes in the form of ferritin, transported in the blood bonded to transferrin – if the enterocyte is saturated absorption stops • demand: in men 1 mg/day, in women (because of blood loss during menses) 2-3 mg/day – iron is needed mainly because of the renewal of enterocytes • water and NaCl: • Na+ channels in the apical membrane (their number is regulated by aldosterone) - Na+-pump in the basolateral membrane • Cl– and water follows passively 

24. End of text

25. Reactor types Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-13.

26. Parts of the digestive tract Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-15.

27. Monogastric stomach Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-18.

28. Anatomy of the small intestine Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-20.

29. Structure of a villus Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-21a,b.

30. Brush border Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-21c,d.

31. Colon and cecal fermenters Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-22.

32. Behavioral control The Far Side Gallery 3, G.Larson, Andrews and McMeel, Kansas City. 1994, p..21.

33. Digestive systems in vertebrates Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-17.

34. Cross-section of the intestine Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-22.

35. Motility of the intestine Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-24.

36. Basic membrane potential rhythm Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-25.

37. Autonomic innervation Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-26.

38. Gastrointestinal hormones Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-34.

39. Digestive secretions Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-29.

40. Rinsing function of saliva The Far Side Gallery 3, G.Larson, Andrews and McMeel, Kansas City. 1994, p..24.

41. Production of saliva Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-28.

42. HCl secretion in the stomach Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-32.

43. Pepsin secretion in the stomach Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-33.

44. Sugar transport in the intestine Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-35.

45. Lipid transport in the intestine Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-36.

46. Digestive fluidmovements Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-37.