Gastrointestinal Secretions and Absorption

Function of saliva in digestion

provides mucus for lubrication and water to balance osmolarity

alkaline to allow for neutralization once reaches stomach

Ingesta is ______ and needs to be ______ before it reaches the stomach

hyperosmotic

isotonic

What does saliva contain?

amylase to break down starch

lipase to break down fats

antimicrobial substances to control bacterial populations in oropharynx

Esophageal stomach

nonglandular stratified squamous epithelium

Cardiac stomach

invaginations of submucosa form short glands lined by columnar epithelium

produce thick mucus and buffer used to protect lining to prevent damage from enzymes and stomach acid

Fundic stomach

produce acid, proteolytic enzymes, hormones, and mucus

Pyloric stomach

moderately deep glands that produce mucus and buffer

Enteroendocrine G-cells produce

gastrin in response to distension

Gastric pits

forms thick gel that stick to gastric pit to protect from acid and enzymes

incorporates a Na+ bicarbonate buffer to provide further protection

Gastric gland

extends a long distance to reach submucosa

has chief cells, enterochromaffin cells and parietal cells

also produces intrinsic factor → binds vitamin B12 and carries to ileum

Chief cells

secrete proteolytic enzyme precursor pepsinogen

secreted as inactive to avoid digestion of cells

cleaved by HCl

also produce rennin- helps digest milk in neonates

Parietal cells

produce HCL which aids in hydrolytic breakdown of diet components and kills bacteria

Enterochromaffin cells

produce hormones that are endocrine and paracrine to control acid and enzyme production

among chief and parietal and in lamina propria

Parietal cells and acid secretion

absorbs Cl- from blood and actively pump into lumen of stomach

movement into lumen requires expenditure of energy and active transport processes to pump Cl- across apical membrane

When greater acid secretion is needed, hormonal and parasympathetic efferent innervation

increase activity of various Cl- pumps

K+ pumps can also be activated when needed to increase

What are the 3 factors to activate mechanisms to increase Cl- secretion into and Na+/K+ removal to increase acidity?

histamine from enteroendocrine cells at base of glands when pH of fluid rises too high

gastrin secreted into blood in response to distension of pylorus or rise in pH

vagus nerve; afferents can detect stretch of stomach or alterations in osmolarity of stomach contents and transmit info to medulla

Reducing histamine/gastrin secretion and vagal tone reduces

acid production

If lining of stomach is damaged from too much acid, what is produced?

prostaglandin (PG)E1, PGE2, PGI2

this diffuses through basal lamina to reduce histamine and gastrin secretion by enteroendocrine cells new damage

Secretin does not inhibit parietal cell acid production, instead it works to

correct low pH in duodenum by increasing production of alkaline secretions by salivary glands, pancreas, and duodenal submucosal (Brunner’s) glands to neutralize or buffer acid

Lipids absorbed during digestion are packaged by

chylomicrons

where they are then taken up by lympathic circulation and reach the liver via hepatic artery

What is the liver’s role in digestion?

detoxify poisons and waste products via biotransformation and excretion into bile for elimination

acts as a site of storage for lipids and vitamins A, D, and E

What does the hepatic arteriole do?

brings in highly oxygenated blood and chylomicrons containing lipids

What does the portal venule do?

brings poorly oxygenated blood to lobule along with sugars, volatile fatty acids (VFAs), and amino acids

What do hepatocytes do?

remove some portion of nutrients from mixed portal and hepatic arteriole blood in sinusoids

it can return nutrients to sinusoid in form of new proteins or glucose

Space of Disse

small space between sinusoid endothelial layer and hepatocytes

ions and nutrients leaving sinusoids much cross space before they can reach hepatocytes

where stellate cells exist

Stellate cells

produce fibrous scar tissue to wall of area to prevent spread of disease

Triglycerides produced in the liver can be packaged with

apolipoproteins to form VLDL (very low density lipoproteins) for export

Sinusoidal endothelium has

large fenestrae to allow large proteins and lipoprotein particles made in hepatocytes to move into blood

Canaliculi

small spaces between adjacent hepatocytes

Toxins/wastes 2 phases process

Compound undergoes an oxidation reaction → adds 1 or more hydroxyl groups to various points in molecule → changes its structure sufficiently so no longer a danger

Use cytochrome P450 monooxygenases → insert 1 atom of O2 into aliphatic position of an organic substrate

In phase 2 of bile secretion, the compound is conjugated to

glucuronide of sulfate molecule by enzymes in hepatocyte which makes molecule much more water soluble and permits it to remain soluble in bile as it moves through bile ductules

Bile salts

formed within hepatocytes by conjugating an amino acid with cholesterol

Taurine

1 of amino acids most commonly used and when bound to cholesterol, forms bile salt taurocholic acid

Salts are highly polar molecules and very water-soluble, they have

hydrophobic end provided by cholesterol

also have hydrophilic end provided by amino acid

this allows them to form micelles within intestine that aid in fat digestion and absorption

Choleresis

secretion of bile and is continuous process

Many species collect bile in gallbladder to

be released after meals

What species do not have gallbladders?

horses and rats

Bile production by hepatocytes and contraction of gallbladder can be stimulated by

hormone CCK

Cells of ductules function to

increase alkalinity of pancreatic secretion

does this by secreting Na+ and some K+ into fluid being secreted and remove Cl- from secretions → sits closer to 7.8

Influence of duodenal hormone secretion causes

amount of Cl- removed to be increase of pH to 8.2

this plays a major role in neutralizing low-pH chyme from stomach which protects mucosa and optimizes enzyme activity

Villi and crypts increase

surface area available for digestion/absorption

Brunner’s glands

typical compound tubular glands with acinar structures with a duct system → conveys secretions to base of crypts

acinar cells secrete mucus and duct cells add Na+ and K+ to while also removing Cl- from secretions to make it alkaline

used to flush crypts and villi to neutralize acid

controlled by secretin (released from enteroendocrine cell in duodenum)

Crypt stem cells

at base of crypt and helps regenerate many of the cell types in crypts

Crypt enterocytes

have microvilli at apical surface; secrete Cl-, Na+, and water to help with absorption; and migrate from bottom of crypt to villus using lamellipodia (actin monomers extending from basolateral membrane)

Goblet cells

also migratory and more common in duodenum; secrete mucus; shed shortly after reach villus tip

Enterendocrine cells

stay near base of crypt and have contact with lumen on apical surface

monitors pH, osmolarity, and ingesta composition

Paneth cells

stay in base of crypts, relatively long-lived that provide protection for crypt stem cells

produce antibacterial lysozyme, phospholipase, and defensins

in cows and horses, not in cats, dogs, and pigs

M-cells/dome cells

origin unknown, interspersed among enterocytes, common to find over top Peyer’s patches; capture particles and pass them unchanged to dendritic cells and lymphocytes within lamina propria

Villous absorptive enterocytes

derived from secretory enterocytes, produce enzymes within apical membrane microvilli (brush border), and enzymes help with digestion; also will express transport proteins to help with absorption

undergo apoptosis when reach tip and are sloughed off after <4 days

1 Crypt contains ______ enterocytes and goblet cells while a villus usually need _____ cells to cover basal lamina

~250-300

3,000

How many cells slough off of a villus tip each day?

~1400

stem cells have to produce an equal number to make up for the loss

Why are villous tips important?

important in absorption processes and do so in relatively O2 poor environment

What are the 2 critical functions of enterocyte secetions?

Na+ excreted into lumen of crypts provides electrochemical force needed to allow absorption of amino acids, sugars, phosphate, and other nutrients

Water secreted into lumen acts to reduce osmolarity of digesta → ensures it remains sufficiently moist to solubilize ions, sugars, and amino acids

Secretory piece

special proteins that extend from basolateral surface of enterocytes and act as IgA receptors

Once dimer binds to secretory piece, it

stimulates endocytosis of IgA dimer bound to piece

Mucosa of cecum and colon contain

crypts but no villi

lined mostly with goblet cells that secrete alkaline mucus; has small amount of absorptive epithelial cells and some crypt stem cells

Nondissociated state has

both water and lipid-soluble parts and have no charge so can freely cross lipid bilayer

Dissociated state has

a charge that makes them soluble only in water

Each ion or particle within a solution acts as

an osmotic particle, regardless of charge

Osmolarity of compartment or solution is determined by

concentration or # of moles of particles in solution

Solvent drag

small solutes can be swept from 1 compartment to another by bulk flow of water

Very large or highly charged particles can be moved across membranes by

endocytosis

Pinocytosis is used to

absorb immunoglobulins, especially in colostrum

Paracellular absorption

tight junction composed of proteins that seal cells against pathogens and large molecules that have been ingested

prevents passage of small ions and water but can be overcome if electrochemical forces driving ions to opposite side are great enough

Paracellular transport

absorption of solute across tight junction between enterocytes from lumen into ECF

Transport proteins

facilitate passive diffusion or allow active transport of solute against its electrochemical gradient at expense of ATP

involves moving solute from lumen to cytosol of enterocyte across apical membrane and movement of solute from cytosol to ECF across basolateral membrane

Electrogenic pump

3 Na+ ions will be pumped out of cell in exchange for 2 K+ ions moving into cell (Na+/K+-ATPase pump

Na+/Cl- pump

Na+ and Cl- can be actively pumped across basolateral membrane at expense of an ATP

used primarily in lower intestine

Chloride absorption in apical membrane

Cotransported with Na+ to maintain electrical balance- all sections of intestine

1 Cl- ion is brought into cell in exchange for 1 HCO3- ion moved into lumen to maintain electrical neutrality; requires ATP and important in colon where luminal concentration low

Na+/K+/2CL- cotransporter

electromotive force of Na+ moving down its electrochemical gradient helps move K+ and Cl- across membrane

Chloride absorption in basolateral membrane

moves to ECF against its concentration but with its electrical gradient

Cl-/K+ cotransporter

K+ moves into ECF down its concentration but against its electrical gradient; combined force of K+ moving down concentration gradient and Cl- moving down its electrical gradient allows both molecules to overcome resistance

Cl- pump

can be actively pumped across membrane with use of ATP

used primarily in lower intestine

Na+/Cl- pump

Na+ and Cl- actively pumped across membrane with use of ATP

used primarily in lower intestine

What concentration is very high in the uppermost duodenum?

Cl-

Bulk of K+ absorption occurs across

tight junctions

K+ absorption in apical membrane

lumen K+ must cross membrane against its concentration with but with its electrical gradient

K+ absorption in basolateral membrane

K+ moves down its concentration but against its electrical gradient

Ca2+ channels

production of these channels within membrane depends on stimulation of epithelial cells by hormonal form of vitamin D (1,25-dihydroxyvitamin D3 or 1,25(OH)2D)

Ca2+ absorption in apical membrane

Ca2+ will move across membrane down its concentration and electrical gradient BUT membrane is impermeable to Ca2+

Free Ca2+ ions within cytosol can have many effects on cell since free Ca2+ are utilized as second messenger by many G protein-coupled receptors

Ca2+ absorption in basolateral membrane

Will have to exit enterocyte against its concentration and electrical gradient

Ca2+/3Na+ exchange ATPase pump

another 1,25(OH)2D-dependent protein

uses ATP and electrochemical force provided by allowing 3Na+ ions into the cell to drive a Ca2+ atom into ECF against a hug concentration gradient

Paracellular Ca2+ transport

2nd mechanism for vitamin D-independent Ca2+ absorption; movement from lumen of intestine to ECF between intestinal epithelial cells

driven by concentration of soluble Ca2+ reaching epithelial cells

mechanism only a factor when dietary Ca2+ is high and only in upper duodenum

both passive and active mechanisms occur in rumen

Phosphate (transcellular HPO4-) in apical membrane

Will move against its concentration and electrical gradients

HPO4-/2Na+ coupled transporter

several different types of cotransporter protein can perform this function; most efficient is produced in enterocytes on stimulation by 1,25(OH)2D

without it, cannot absorb phosphate well from low-phosphate diet

driving force for phosphate absorption is provided by entry of 2 Na+ cotransported with phosphate anion

Phosphate absorption in basal membrane

Moves down concentration and electrical gradients

Phosphate absorption in basal membrane (paracellular transport)

Dietary phosphate can cause intraluminal phosphate concentration to be higher than extracellular concentration

Large amount can cross tight junctions and enter extracellular fluid

60-80% of dietary phosphate is absorbed paracellularly when animals are fed typical diet

Pepsinogen

secreted from chief cells in inactive form to prevent autodigestion

acid mixes with it and cleaves off a fragment to form pepsin; pepsin cleaves peptide bonds next to hydrophobic amino acids with aromatic side chains

Rennin

secreted by chief cells that cleaves between phenylalanine and methionine residues on proteins

Dipeptides and tripeptides can be transported by

special active transport proteins that do not require Na+ but do need ATP