Functional development of GI tract Flashcards
Mammals at birth
-an immediate change from amniotic fluid to milk
-at weaning, a gradual or immediate change from milk to solid food
Mammals in utero
-weight of fetus increases dramatically during the last 1/3 of gestation which is linked to growth of GIT
-adrenal gland rapidly develops during last 1/3rd of gestation which is linked to cortisol production as it is known to play a role in GI development
-development of gastric function includes stomach acid and gastrin secretion, and enzymes (chymosin, pepsin, amylase, lactase, aminopeptidases)
Mammals stomach development
-thickening of glandular region and maturation of chief cells (secrete zymogens)
-Pepsin and HCl increases gradually following birth
-pH at birth is high at birth, and HCl secretion begins a couple days after birth
Mammal small intestine development
-increases in length and diameter from birth to adulthood
-early on, it is permeable to large molecules
-crypts and villi organized and functioning at birth
-enzymes present at birth (lactase levels are higher in neonate than adult; alkaline phosphatase activity minimal at birth and increases gradually)
Intestinal weight growth (piglet)
-allometric
-small intestines grow drastically compared to other tissues (as long as they are actually suckling)
Intestinal growth in dogs
-decrease in length, weight, and surface area when weaned
-also a decline in villus heigh and increase in crypt death following weaning
**don’t see overall increase in s. intestine growth like you see in piglets
Enzymes during post-natal development of dogs
-observed trypsin, amylase, lipase, chymotrypsin
-low protease activity at birth , allowing for acquisition of passive immunity
-lipase, amylase and ribonuclease activity is low initially. Important so they can digest milk properly. note consequence of milk replacers
Alterations in piglet small intestines structure at weaning
-provide some food (creep food) to help with weaning transition. Hope is that they see some food before complete weaning
-saw that there was a decrease in villi heigh/crypt depth due to weaning regardless of access to creep
can’t tell which animals were eating the creep or how much they were eating
Lactase activity in dogs during development
-enzyme activity in proximal part of intestines is highest
-decrease in lactase activity proximal to distal and at weaning
Peptidases activity in dogs during development
-less of an effect due to intestinal segment
-tendency of dipeptidases IV to increase with age
Pancreatic enzymes in pigs
-increase prior to weaning, then sudden decrease at weaning and then increase in amylase (starch digestion)
-shows impact of weaning on enzyme development
Barrier Function of GIT
-controls entry into the animal of substances that may be toxic/infectious if they could freely enter
-forms a barrier to the outside (inside GIT can be considered outside animal)»_space;achieved by epithelial cells joined together by tight junctions
Tight junctions
-formed by proteins (occludens, claudens, junctional adhesion molecules) that act as a permeability seal and facilitate communication between cells
Intestinal barrier
-consists of an apical and basolateral barrier
-has many different entry mechanisms (diffusion, and transporters)
Dysfunction of intestinal epithelial barrier
-results in leaky gut
-associated with intestinal disorders such as IBD, Crohn’s disease, ulcerative colitis, diabetes, COPD
Main components of intestinal barrier
-epithelial barrier
-mucus barrier
-lamina propria
Epithelial monolayer of GIT
-single layer of absorptive enterocytes interspersed with goblet cells (mucous production)
-Intestinal Epithelial Cells phagocytose bacteria and neutralize toxins
-Paneth cells- secrete anti-microbial peptides
-Enterochromaffin cells (neuroendocrine cells)
-Stem cells
Mucus barrier
-above epithelial barrier layer; first barrier to pathogens
-composed of mucin, secretory and IgA dimers and antibacterial peptides
Lamina Propria
-Subepithelial region
-has innate and adaptive immune cells
Parts of intestinal barrier
-microbiota
-chemical
-physical
-immune
Chemical components of intestinal barrier
-microorganisms
-IgA
-mucins
-antibacterial peptides
Physical components of intestinal barrier
-intestinal epithelial cells
-goblet cells (make mucins)
-paneth cells
-intestinal stem cells
Microflora of GIT
-competes with pathogens for nutrients
-metabolizes proteins and CHO and synthesizes vitamins
-produce metabolic products (ex. short chain fatty acids) that communicate with the gut and the brain and the immune system
Mucus of GIT
-varies throughout the intestine
-thin layer that facilitates absorption in small intestine (glycoproteins, secretory IgA, antimicrobial peptides)
Intestinal epithelium
-tight junctions
-monolayer of cells
-immune functions
Cell junctions of the intestinal epithelial cells (IEC)
-Tight junctions
-Adherens junctions
-Desmosomes
-gap junctions
Adherens junctions of intestinal epithelial cells
-important for cell signaling
-regulation of these junctions associated with actin cytoskeleton
-stabilization of cell-to-cell adhesion
-participate in cell proliferation, establishment of polarity, remodeling of actin skeleton
Desmosomes of intestinal epithelial cells (IEC)
-intercellular junctions allowing for intercellular signaling
-leaky, not really acting as a barrier
-mechanical strength
Gap junctions of intestinal epithelial cells (IEC)
-6 transmembrane proteins (connexins)
-channels to allow the transport of small molecules and communication between cells
-important for regulatory role in cell growth and differentiation
Tight junctions of intestinal epithelial cells (IEC)
-selectively limit diffusion of molecules, water, ions
-protection against inflammation and infection
What regulates tight junctions?
-regulated by the arrangement of actin with the interaction of transmembrane proteins such as occludins, claudins, and junctional adhesion molecules (JAMs) to form a tight seal
What strengthens tight junctions?
-complex strengthened by zona occluden proteins (ZO-1, ZO-2, ZO-3) which bind to actin filaments
What allows for the opening and closing of tight junctions?
-phosphorylation of occluding proteins is responsible for opening and sealing tight junctions
Leaky gut
-tight junctions are damaged in response to stressor allowing for LPS (lipopolysaccharides), pathogens, and non-digested food particles allowed to enter the bloodstream
>weaning also plays a role in damage/leaky gut
-results in activation of immune system and inflammation. This then leads to metabolic and inflammatory disorders (obesity, inflammatory bowel disease) and loss of barrier function
Probiotics
-shown to be effective for maintenance of intestinal integrity by changing the microbiome
-anti-inflammatory
Dietary fiber and short chain fatty acids (SCFA) affecting barrier function
-dietary fibre needed for SCFA
-deficiency of SCFA’s has been shown to impair barrier function
Factors affecting intestinal barrier integrity
-drugs/antibiotics
-Environmental stress
-Genetic susceptibility
-Pathogens
-Western Diet/high fat diet
**most of these factors related to immune response/inflammatory response
Which diets are linked with leaky gut?
-diets high in sucrose, refined CHO, Polyunsaturated fatty acids (omega-6) and low in fibre
