Digestion

Types of digestion systems

• 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)

2/23

Alimentary canal in vertebrates

• 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

3/23

Headgut• 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)

4/23

Foregut• 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

5/23

Midgut I.• 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

6/23

Midgut II.• 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)

7/23

Hindgut• 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

8/23

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

Motility of alimentary canal II.• 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

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

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

Regulation of the intestines I.

• 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

Regulation of the intestines II.

• 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

Gastrointestinal hormones

cell

hormone stimulus stomach bile pancreas

G gastrin

peptides,amino acids

in the stomach

HCl producti

on, motility

up

CCK

cholecystokinin

lipids, proteins in the small intestine

motility, emptyin

g inhibite

d

emptying the

gall bladder

increased enzyme

production

S secretinacid in the

small intestine

emptying

inhibited

increased HCO3

- secretion

GIP

glucose-dependent

insulinotropic peptide

carbohydrates in the

small intestine

HCl producti

on, emptyin

g inhibite

d

glucose dependent

insulin secretion

15/23

Gastrointestinal secretions• 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

16/23

Secretion in the stomach

• 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

17/23

Secretion of the pancreas• 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

18/23

Functions of the liver• 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

19/23

Digestion and absorption I.• 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

20/23

Digestion and absorption II.• 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

21/23

• 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

Digestion and absorption III.

22/23

• 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

Digestion and absorption IV.

23/23

End of text

Reactor types

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

Parts of the digestive tract

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

Monogastric stomach

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

Anatomy of the small intestine

Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-20.

Structure of a villus

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

Brush border

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

Colon and cecal fermenters

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

Behavioral control

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

Digestive systems in vertebrates

Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-17.

Cross-section of the intestine

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

Motility of the intestine

Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-24.

Basic membrane potential rhythm

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

Autonomic innervation

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

Gastrointestinal hormones

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

Digestive secretions

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

Rinsing function of saliva

The Far Side Gallery 3, G.Larson, Andrews and McMeel, Kansas City. 1994, p..24.

Production of saliva

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

HCl secretion in the stomach

Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-32.

Pepsin secretion in the stomach

Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-33.

Sugar transport in the intestine

Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-35.

Lipid transport in the intestine

Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 15-36.

Digestive fluid movements

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