Physiology of the Gastrointestinal Tract and Introduction to Gut Microbiome Flashcards
Big picture functions of the GI Tract?
- Transporting food by-products
- Breaking down and absorbing food by-products
- Decontaminating the food and maintaining appropriate relationship with live non-human cells
3 basic movements that take place along the GIT?
- Peristalsis
- Segmentation
- Migrating motor complex (MMC)
Waves of smooth muscle contraction that propel food bolus throughout entire GI tract?
Peristalsis
What produces rhythm of peristalsis? Where is it located?
Interstitial cells of Cajal (ICC) - in myenteric plexus
Peristalsis involves _____ behind (proximal) the food bolus and _______ in front (distal) of the food bolus
Contraction; Relaxation
Function of peristalsis?
Propel food further along the GI tract
Some problems with Peristalsis? (3)
- Esophageal spasms
- Atonic colon
- Gastroparesis
Coordination of smooth muscle cells and interstitial cells of Cajal?
Segmentation
Where does segmentation occur?
Within the Small and Large Intestines
Function of segmentation?
Promotes mixing food particles to increase their interaction between villi and promotes absorption
Small movement, almost a vibration, that occurs predominantly during fasting 1.5-2 hr intervals
Migrating motor complex (MMC)
Where does MMC occur mainly?
Stomach and Small Intestine
What is MMC movement promoted by?
Motilin - secreted by Mo-cells in teh duodenum
Function of MMC?
Self-cleaning mechanism = dislodges food and bacteria from walls
What may a lack of MMC cause?
SIBO
What are the “pacemakers of the GI Tract”?
Interstitial Cells of Cajal (ICC)
Where are ICC’s found?
Throughout the entire GI Tract
ICC’s form a network with each other and smooth muscles via _______, as well as ______
Gap junctions; enteric motor neurons
What triggers smooth muscle contractions of ICCs?
Spike potentials
Additional factors that can increase the excitability of smooth muscle? (3)
- Muscle stretch (distention)
- Acetylcholine
- Other GI hormones
What can decrease excitability of smooth muscles? What does it cause?
Norepinephrine - causes hyperpolarization
What is the enteric nervous system composed of?
Sensory, motor, and interneurons
What is the enteric nervous system organized into? (2)
- Submucosal plexus and Myenteric plexus
Where is the Submucosal plexus located?
Located between the layers of submucosa and circular muscle (only present in SI and LI)
Function of the submucosal plexus? (4)
- Regulate motility
- Regulate local blood flow
- Regulate secretions
- Regulate epithelial cell function
Where is the Myenteric plexus located?
Between longitudinal and circular muscles (entire GI)
What is the function of the myenteric plexus?
Regulate motility
Nerves that connect the ENS and CNS? (3)
- Vagus Nerve
- Pelvic Splanchnic Nerves
- Thoracic Sympathetic Trunk
Secretions promoting motility? (5)
- I-cells = CCK
- Enterochromaffin cells = serotonin
- G-cells = gastrin
- Mo-cells = motilin
- Beta-pancreatic cells = insulin
Secretions reducing motility? (4)
- S-cells = secretin
- D-cells = somatostatin
- Pancreatic cells = Pancreatic peptide YY
- Alpha-pancreatic cells = glucagon
What is digestion?
Breaking down macromolecules into smaller molecules to increase absorption
Two types of digestion?
- Mechanical
- Chemical
What is mechanical digesiton?
Physically chewing/cutting/crushing/churning food to decrease vol and increase SA
Parts of the GI tract that help with mechanical digestion?
Mouth and Stomach
What is chemical digestion?
Chemical processes that allows absorption of food particles
Two types of chemical digesiton?
- Enzymatic digestion
- Lipid solubilization
What is enzymatic digestion?
Enzymes break macronutrients down into smaller and smaller particles through the process of hydrolysis
What is lipid solubilization?
Emulsifiers secreted by the liver emulsify ingested lipids so that enzymes can break them down to smaller, absorbable molecules
Enzymes/secretions present in the mouth to aid in digestion? (3)
- Salivary amylase
- Mucus
- Water
Contributing organs/structures for digestion in the mouth? (2)
- Salivary glands
- Teeth
What is being digested in the mouth?
Carbohydrates (all other are being broken down into smaller particles)
Enzymes/secretions present in the stomach to aid in digestion? (3)
- HCl
- Lipase
- Pepsin
Contributing nerve for stomach digestion?
Vagus nerve promotes HCl release
What is being digested in the stomach?
Proteins, fats, carbs - limited digestion other than proteins
What is the most important site of chemical digestion?
Small intestine
Enzymes/secretions present in the small intestine to aid in digestion? (3)
- Bile acids
- Pancreatic enzymes
- Brush border enzymes
Contributing organs/structures to small intestine digestion?
- Liver contributes bile
- Pancreas releases numerous enzymes including lipase and amylase
What is being digested in the small intestine?
- Proteins (bb enz. Pancreatic enz.)
- Carbs (bb enz. and amylase)
- Lipids (lipase and bile acids)
The movement of any substance across the mucosal epithelium of the alimentary tract and into the bloodstream (most substances) or lymphatics (lipids)?
Absorption
What is absorption largely dependent on?
The health of the villus and microvilli of enterocytes in the small intestine
What occurs in carbohydrate digestion?
Polysaccharides are broken down into monosaccharides
What monosaccharides can be transported across the epithelial cells of the small intestine? (3)
Galactose, Glucose, Fructose
How are glucose and Galactose transported into the enterocyte?
Na+/glucose (galactose) co-transporter (SGLT1)
What does SGLT1 depend on?
High [Na+] in the lumen to power transport of hexose
How is fructose transported into the enterocyte?
GLUT-5 = passive transporter
How are the monosaccharides transported out the basolateral side of the enterocyte?
GLUT-2 and GLUT-5
Where are majority of proteins absorbed?
The duodenum and jejunum
Transporters for individual amino acids?
Na+ symporters
How are dipeptides and tripeptides transported into the enterocyte?
PepT1 Transporter
What does the PepT1 transporter rely on?
H+ concentration gradient
What happens to di- and tripeptides in the enterocyte?
They’re hydrolyzed into amino acids
Nucleic acids are broken down into sugars, purines, and pyrimidines - how are the bases absorbed?
Nucleoside transporters
What fatty acids can passively diffuse through enterocyte (unmodified)?
FFAs that are 10-12 C long
What happens to fatty acids that are > 10-12 C long?
They’re re-esterified once in the enterocyte
How is cholesterol transported into the enterocyte?
NPC1L1 transporter
What are FFA’s and cholesterol that are coated with proteins, more cholesterol and phospholipids
Chylomicron
Why does chylomicron enter the lymphatics?
Too large to pass between endothelial cells into blood stream
Impaired fat digestion and absorption resulting in high amount of fat in the stool
Steatorrhea
What are the fat soluble vitamins? What do they depend on for absorption?
A,D,E,K
Depend on incorporation into micelle
Where are most vitamins and nutrients absorbed?
Duodenum
Where is Vitamin B12 absorbed?
Ileum
What do most B vitamins and Vitamin C require for absorption?
Na+ co-transporter
Where does Iron absorption occur? Via what?
Occurs within duodenum via divalent metal transporter 1 (DMT1)
How is iron transported out of the enterocyte?
Ferroportin 1 and hephaestin
In the plasma Fe2+ is converted to Fe3+ and is transported by _____
transferrin
What is the microbiome?
The collection of all organisms living on and in a given environment or habitat
What organisms are most/least prevalent in the microbiome?
viruses > bacteria > fungi
What is the distribution of microbiota determined by? (4)
- pH
- O2 access
- temperature
- tropism
Most common bacteria in mouth?
Spirochaetes
Most common bacteria in the Esophagus?
Streptococci and Lactobacilli
Most common bacteria in the stomach?
H. pylori
Most common bacteria in the small intestine?
Lactobacilli
Most common bacteria in the large intestine?
- Bifidobacteria
- Lactobacilli
- Enterococci
Where is the most diversity in the microbiome in the body?
Large intestine
93.5% of gut bacteria belong to what phyla? (4)
- Firmicutes
- Bacteroidetes
- Proteobacteria
- Actinobacteria
What 2 bacteria contribute most to the gut microbiome?
Firmicutes and Bacteroidetes
Examples of Firmicutes? (2)
- Lactobacillus
- Enterococcus
Examples of Bacteroidetes? (2)
- Bacteroides
- Prevotella
Examples of Proteobacteria? (5)
- Helicobacter
- E. coli
- Shingella
- Salmonella
- Yersina
Example of Actinobacteria? (1)
- Bifidobacterium
8 functions of gut microbiome?
- Harvesting energy
- Strengthen gut integrity
- Shape intestinal epithelium
- Regulate immune function
- Regulate intestinal motility
- Protection against pathogens
- Production of some nutrients
- “Endocrine organ”
Gut microbiome development if C-section?
- Less Bacteroides
- More clostridium
Gut microbiome development if vaginal birth?
More characteristic of mothers microbiota
Gut microbiome development if breastfed?
Bifidobacterium high
Gut microbiome development if formula-fed?
- Bifidobacterium low
- higher diversity and altered ratios of other bacteria
Gut microbiome development if under-fed?
Increased entero-pathogens
What happens with a childs gut flora by 2.5 years old?
Composition, diversity, and functional capabilities similar to that of an adult
What factors can influence the composition of the gut microbiota?
- Genetics
- Diet
- Medications
Dietary impact on gut microbiome of diet rich in starch, fiber, and plants vs. sugar, starch, animal proteins
Starch/fiber/plant = Prevotella present
sugar/starch/animal = prevotella largely absent
Why is Prevotella important?
Produces short chain fatty acids (SCFA’s)
Microbiome metabolites? (4)
- Short-chain fatty acids (SCFAs)
- Trimethylamine (TMA)
- Bile acids
- Indoles
Examples of SCFAs produced? (3)
Acetate, Propionate, Butyrate
When are SCFAs’ produced?
During fermentation of indigestible carbohydrates (fibers)
How do SCFAs promote intestinal integrity? (4)
- Regulating luminal pH
- Regulate mucus production
- Produce fuel for the epithelial cells
- Modify mucosal immune function
How do SCFAs influence overall metabolism? (4)
- Appetite regulation
- Energy expenditure
- Glucose homeostasis
- Immuno-modulation
Microbiome metabolite that has been linked to increasing RF for atherosclerosis and thrombosis?
Trimethylamine (TMA)
Microbiome metabolite that has been correlated to changes in energy metabolism?
Bile acids
Microbiome metabolite that is produced by Trp metabolism and maintains intestinal barrier and influences immune function?
Indoles
What can be metabolized into TMAs?
- Choline
- Phosphatidylcholine
- L-carnitine
Healthy/Beneficial changes made by non-pathogenic E. coli?
Increase epithelial mucus secretion and reduce epithelial permeability
Healthy/Beneficial changes made by non-pathogenic Lactobacillus rhamnossus?
Increase expression of occludin and
ZO-1 proteins
Healthy/Beneficial changes made by non-pathogenic L. rheuteri?
Increase epithelial cell proliferation
Pathogenic changes in Salmonella entetica?
Reduced ZO-1 and occludin proteins and tight junction complexes
Pathogenic changes in Clostridium difficile?
Reduced mucin production
Pathogenic changes in Enterovirus E11?
Direct cytotoxicity
Bacteria increased when constipated? Decreased?
I: Bacteroides and Enterobacter
D: Bifidobacterium and Prevotella
Bacteria increased in diarrhea? Decreased?
I: Prevotella
D: Bifidobacterium, Bacteroides, Lactobacillus
Mechanism of action interferes with bacterial cell activity (including replication) without directly causing death
Bacteriostatic
Mechanism of action directly kills the bacteria
Bactericidal
Antibiotic is able to effect different types of bacteria’s including gram positive, gram negative, and others (spirochetes, atypical)
Broad spectrum
Negative effects of antibiotics on gut microbiome? (3)
- Reduce species diversity
- Altered metabolic activity
- Select the antibiotic-resistant organisms
When does antibiotic associated diarrhea (ADD) typically occur?
Initially during treatment or up to 2 months following discontinuation