GI Tract Physiology and Intro to Gut Microbiome (Week 10) Flashcards

1
Q

Approximately how much food passes through the GI tract in an average lifespan?

A

60 tonnes

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2
Q

True or False: The GI tract is the largest interface between host, environmental factors, and antigens

A

True

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3
Q

What are the three types of movement that take place along the GI tract?

A

1) Peristalsis
2) Segmentation
3) Migrating motor complex (MMC)

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4
Q

What is peristalsis?

A
  • waves of smooth muscle contractions that propel the food bolus throughout the GI tract; involves contraction behind/proximal the food bolus and relaxation in front/distal the food bolus
  • involves the entire GI tract, starting @ esophagus
  • may be stimulated by distension (stretch) of smooth muscle cells
  • function is to propel food forward along GI tract
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5
Q

What is segmentation?

A
  • multiple contraction points produced by the coordination of smooth muscle cells and interstitial cells of Cajal (ICC)
  • occurs within small intestine and large intestine
  • function is to promote mixing of food particles to increase interactions between the villi of the enterocytes and various food particles to promote absorption
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6
Q

What is the migrating motor complex (MMC)?

A
  • small movements, almost a vibration, that occurs predominantly during fasting (in between meals);1.5-2hr intervals
  • occurs within stomach and small intestine (a few other locations too)
  • movement is promoted by motilin (secreted by Mo-cells), located in the duodenum
  • function is suspected to be a self-cleaning mechanism, as this movement causes small food particles and bacteria to be dislodged from the intestinal wall and prevents bacteria from travelling from LI to SI
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7
Q

What condition is a lack of migrating motor complex (MMC) associated with?

A

small intestinal bacterial overgrowth (SIBO)

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8
Q

What are considered the “pacemakers of the GI tract”?

A

interstitial cells of Cajal (ICC)

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9
Q

Interstitial cells of Cajal (ICC) form a network with each other and with smooth muscle via ______________, as well as enteric motor neurons

A

gap junctions

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10
Q

True or False: Interstitial cells of Cajal (ICC) are found in specific areas of the GI tract

A

False

ICC are found throughout the entire GI tract

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11
Q

ICC generate ________ (slow/fast) waves that do not typically lead to muscle contractions, and _____________ that do trigger smooth muscle contractions when there is an additional stimulus

A

slow,

spike potentials

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12
Q

What additional factors/stimuli can increase excitability of smooth muscle cells?

A
  • muscle stretch (distension)
  • acetylcholine
  • other GI hormones
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13
Q

What can decrease excitability?

A

norepinephrine

(causes hyperpolarization)

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14
Q

True or False: The enteric nervous system (ENS) is composed of sensory, motor, and interneurons

A

True

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15
Q

The enteric nervous system is organized into what two plexuses?

A

1) submucosal plexus (Meissner’s)
2) myenteric plexus (Auerbach’s)

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16
Q

Where is the submucosal plexus (Meissner’s plexus) located?

A

between the layers of the submucosa and circular muscle layer

Note: only present in small intestine and large intestine

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17
Q

Where is the myenteric plexus (Auerbach’s plexus) located?

A

between circular and longitudinal muscle layers

Note: this is through the entire GI tract

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18
Q

What is the function of the submucosal plexus/Meissner’s plexus?

A

to regulate motility, local blood flow, secretions, and epithelial cell function

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19
Q

What is the function of the myenteric plexus/Auerbach’s plexus?

A

to regulate motility

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20
Q

True or False: Although the enteric nervous system (ENS) can function independently, the CNS does innervate the GI tract in several places, providing additional regulation and modification of the ENS

A

True

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21
Q

Does the sympathetic nervous system stimulate or oppose GI motility?

A

oppose

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22
Q

Does the parasympathetic nervous system stimulate or oppose GI motility?

A

both (can stimulate and oppose; more complex)

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23
Q

What are some nerves that connect the CNS to the ENS?

A
  • vagus nerve
  • pelvic splanchnic nerves
  • thoracic sympathetic trunk
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24
Q

What cells and their secretions promote motility?

A

I cells –> cholecystokinin
Enterochromaffin cells –> serotonin
G cells –> gastrin
Mo cells –> motilin
beta-pancreatic cells –> insulin

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25
Q

What cells and their secretions reduce motility?

A

S cells –> secretin
D cells –> somatostatin
pancreatic cells –> pancreatic peptide YY
alpha-pancreatic cells –> glucagon

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26
Q

Breaking down macromolecules into smaller molecules to increase absorption is known as what?

A

digestion

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27
Q

What are the two major types of digestion?

A

1) mechanical digestion
2) chemical digestion

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28
Q

What is mechanical digestion?

A
  • physically cutting, crushing, and churning food so that the volume of each food particle decreases, therefore SA:volume ratio favours chemical digestion)
  • chewing (in the mouth)
  • segmentation (in the stomach)
  • food is broken down into smaller and smaller pieces as it is mixed with fluid secretions of the stomach
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29
Q

What is chemical digestion?

A
  • chemical processes that allow absorption of food particles; involves enzymatic digestion and lipid solubilization
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30
Q

enzymes break macronutrients down into smaller and smaller particles through the process of hydrolysis

A

enzymatic digestion

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31
Q

emulsifiers (bile salts, lecithin) secreted by the liver emulsify ingested lipids so that enzymes can break them down to smaller, absorbable molecules

A

lipid solubilization

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32
Q

Describe carbohydrate digestion

A

begins in the mouth with salivary amylase (minority of CHO digestion)

further broken down by pancreatic amylase and brush border enzymes within small intestine (majority of CHO digestion)

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33
Q

Describe fat digestion

A

begins in the stomach with HCl and lipase (minority of fat digestion)

further digested by pancreatic lipase and emulsified by bile acids released by the liver (majority of lipid digestion)

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33
Q

Describe protein digestion

A

begins in the stomach with HCL and pepsin

further digestion by pancreatic enzymes and brush border enzymes

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34
Q

What is the most important site for chemical digestion?

A

small intestine

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35
Q

Where do gut microbiota digest some of what hasn’t been digested yet?

A

large intestine

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36
Q

What is absorption?

A

movement of any substance across the mucosal epithelium of the alimentary tract and into the bloodstream (most substances) or lymphatics (lipids)

Note: absorption largely takes place in the small intestine

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37
Q

True or False: Absorption is dependent on the health of the villus and microvilli of enterocytes

A

True

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38
Q

Absorption is supported by ____________ to increase food bolus contact with microvilli and villi

A

segmentation

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39
Q

watery product of gastric digestion that needs to be mechanically and chemically digested before absorption can occur

A

chyme

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40
Q

In carbohydrate digestion, polysaccharides are broken into ____________

A

monosaccharides

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41
Q

True or False: Monosaccharides and disaccharides can be transported across the epithelial cells of the small intestine, but polysaccharides cannot be transported

A

False

Only monosaccharides can be transported

Disaccharides and polysaccharides cannot be transported

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42
Q

What are the monosaccharides that we can absorb?

A
  • galactose
  • glucose
  • fructose
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43
Q

Which transporter moves glucose and galactose (hexoses) from the lumen into the enterocyte (on its apical side)?

A

Na+/glucose (galactose) co-transporter (aka SGLT1)

Note: The SGLT1 transporter relies on high concentration of Na+ (sodium) within the lumen to power the transport of hexoses (Na+ moves down its concentration gradient)

Note: Therefore, Na+/K+ pump needs to continue to maintain low INTRACELLULAR Na+

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44
Q

Which transporter moves fructose from the lumen into the enterocyte via passive transport/facilitated diffusion (on its apical side)?

A

GLUT-5

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45
Q

Which transporters move glucose, galactose, and fructose OUT of the enterocyte (on the basolateral side) and into the blood stream/tissue?

A

GLUT-2 (and GLUT-5)

Note: Monosaccharides can now enter the hepatic portal vein

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46
Q

REVIEW: What does amylase break starch/glycogen (polysaccharides) into?

A

maltose, maltotriose, and dextrins (oligosaccharides/disaccharides)

which can be further broken down into glucose (monosaccharide) via enzymes glucoamylase, sucrase, and isomaltase

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47
Q

REVIEW: What does lactase break lactose into?

A

glucose and galactose

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48
Q

REVIEW: What does sucrase break sucrose into?

A

glucose and fructose

49
Q

Where is the majority of protein absorbed?

A

duodenum and jejunum

(very little left for ileum)

Note: only 2-3% of protein escapes digestion and absorption in healthy conditions

50
Q

True or False: Absorption of undigested protein by adults has been linked with allergic symptoms

A

True

51
Q

What transporter moves amino acids from lumen into enterocytes?

A

Na+ symporters (FYI: there are 5 different types)

Note: similar to SGLT1

52
Q

What transporter moves dipeptides and tripeptides from the lumen into enterocytes?

A

PepT1 transporter

Note: relies on H+ instead of Na+ concentration gradient

Note: peptides are hydrolyzed into amino acids by intracellular enzymes/peptidases (via cytosolic digestion) within the enterocyte

53
Q

Nucleic acids are broken into __________, which are further broken down into _____________

A

nucleotides,

nucleosides and phosphoric acid

54
Q

Nucleosides are further broken down into _____________

A

sugars and purines/pyrimidine bases

55
Q

What are purine and pyrimidine bases absorbed by?

A

nucleoside transporters (active transport)

56
Q

How do free fatty acids that are 10-12 carbons long or less (SCFAs and MCFAs) get absorbed?

A

passive diffusion

Note: these can pass through the enterocyte unmodified and enter portal circulation, remaining free and unesterified

57
Q

How do free fatty acids that are > 10-12 carbons (LCFAs) long get absorbed?

A
  • long chain fatty acids (LCFAs) require additional steps to diffuse across the membrane
  • first they must be emulsified by bile acids to form MICELLES (increases their water solubility)
  • micelles facilitate their passive diffusion across the brush border membrane
  • they are re-esterified into a triglyceride once they are inside enterocyte
  • cholesterol is also esterified and transported via the NPC1L1 transporter, in particular
  • cholesterol is either utilized by the enterocyte itself or turned into a chylomicron
58
Q

What is a chylomicron?

A

a large structure that includes FFAs and cholesterol, with a protein coat on the outside

59
Q

Do chylomicrons enter the blood stream?

A

No

They enter the lymphatic system instead (they are too big to pass between endothelial cells into the blood stream)

60
Q

What percentage of ingested fat gets absorbed in adults?

A

~ 95%

61
Q

What do we call the impairment of fat digestion and absorption resulting in a high amount of fat in the stool?

A

steatorrhea

Note: you can tell if the stool is floating

62
Q

What pathologies might present with steatorrhea?

A
  • pancreatitis* (lipases not working)
  • removal of gallbladder
  • biliary atresia (blocked or underdeveloped bile ducts)

among others

63
Q

REVIEW: What are the fat-soluble vitamins?

A

vitamins A, D, E, & K

Note: we can enhance the absorption of these vitamins by taking them with fat

64
Q

Where are majority of vitamins absorbed?

A

duodenum

Exception = vitamin B12 (in the ileum)

65
Q

True or False: Most of the B vitamins and vitamin C require Na+ co-transporters for absorption

A

True

66
Q

Where is iron absorbed?

A

in the duodenum via divalent metal transporter 1 (DMT1)

67
Q

What form of iron is absorbed?

A

Fe 2+ (ferrous form)

68
Q

How is iron transported out of the enterocyte?

A

ferroportin 1 and hephaestin

69
Q

Once in the plasma, Fe 2+ (ferrous form) is converted to __________

A

Fe 3+ (ferric form)

70
Q

In the plasma, Fe 3+ is transported by ___________

A

being bound to transferrin

71
Q

The collection of all organisms living on and in a given environment or habitat (such as the human body) is known as?

A

microbiome

(aka microbiota or commensal organisms)

72
Q

True or False: Bacteria outnumber viral and fungal composition of the human microbiome

A

False

Viral: Bacterial = 5:1
Bacterial: Fungal = 10:1

Therefore, viral > bacterial > fungal composition

73
Q

True or False: The composition of the human microbiome varies from person to person

A

True

74
Q

Approximately how many microbes are in the human microbiome?

A

~ 10^14 (100 trillion)

75
Q

bacteria present in oral cavity (mouth)

A

mostly Spirochaetes

FYI: 10^11/g (large amount but not a lot of variety)

76
Q

bacteria present in esophagus

A
  • Streptococci*
  • Lactobacilli*
  • other gram negative bacilli
77
Q

bacteria present in stomach

A

Helicobacter pylori

FYI: 10^3/mL

Note: less bacteria in the stomach due to acidic environment

78
Q

bacteria present in small intestine

A
  • Lactobacilli*
  • gram positive cocci
79
Q

bacteria present in large intestine

A
  • Bifidobacteria*
  • Bacteroides
  • Clostridia,
  • Peptostreptococci
  • Fusobacteria
  • Lactobacilli*
  • Enterobacteria
  • Enterococci*
  • Eubacteria
  • Methanogens
  • Sulphate reducers

FYI: 10^12/g

Note the vast amount + diversity in the large intestine

80
Q

93.5% of the gut microbiome belong to the following phyla:

A

1) Firmicutes (major)**
2) Bacteroidetes (major)**
3) Proteobacteria (minor)
4) Actinobacteria (minor)

81
Q

What are some genus examples that fall under the firmicutes phyla?

A
  • Lactobacillus
  • Clostridium
  • Enterococcus
82
Q

What are some genus examples that fall under the bacteroidetes phyla?

A
  • Bacteroides
  • Prevotella
83
Q

What are some of the functions of the gut microbiome?

A
  • harvesting energy (digesting and absorbing nutrients that we can’t utilize)
  • strengthen gut integrity
  • shape intestinal epithelium
  • regulation of immune function
  • regulate intestinal motility
  • protection against pathogenic microbes
  • production of some nutrients (e.g., vitamin K2, short chain fatty acids)
  • considered an “endocrine organ”
84
Q

How can a c-section influence an infant’s gut microbiome?

A

less Bacteroides and more Clostridium

Note: vaginal birth = more characteristic of mom’s microbiota

85
Q

How can breastfeeding vs. formula influence an infant’s gut microbiome?

A

breastfeeding = high Bifidobacterium

formula = low Bifidobacterium, higher diversity and altered ratio of E. coli, Clostridium difficile, and Bacteroides fragilis

86
Q

What does underfeeding an infant influence their gut microbiome?

A

increase in entero-pathogens, like Enterobacteriaceae

87
Q

By what age is the composition, diversity, and functional capabilities of a child’s gut flora similar to that of an adult microbiota?

A

2.5 years

88
Q

How can diet high in starch, fiber, and plants influence gut microbiome?

A
  • more Actinobacteria and Bacteroidetes
  • Prevotella present
89
Q

How can a diet high in sugar, starch, and animal protein influence gut microbiome?

A
  • less Actinobacteria and Bacteroidetes
  • Prevotella absent
90
Q

True or False: Short-chain fatty acids (SCFAs) are a microbiome metabolite, produced during fermentation of indigestible carbohydrates by gut microbiota

A

True

91
Q

What are examples of SCFAs produced by gut microbiota?

A
  • acetate
  • propionate
  • butyrate
92
Q

How do SCFAs promote intestinal integrity?

A
  • regulate luminal pH
  • regulate mucus production
  • produce fuel for epithelial cells/enterocytes
  • modify mucosal immune function
93
Q

How do SCFAs influence overall metabolism?

A
  • appetite regulation
  • energy expenditure
  • glucose homeostasis
  • immunomodulation
94
Q

Other than SCFAs, what are other microbiome metabolites?

A
  • trimethylamine (TMA)
  • bile acids
  • indoles
95
Q

TMA can be further converted into trimethylamine oxide (TMAO), which has been linked to increasing risk for what condition(s)?

A

atherosclerosis and thrombosis

96
Q

True or False: Bile acids have been correlated with changes in energy metabolism (specifically, related to cholesterol and insulin sensitivity)

A

True

97
Q

Indoles are produced by the metabolism of ___________

A

tryptophan

98
Q

What is the function of indoles?

A

maintain intestinal barrier and influence immune response

99
Q

What is a benefit of having non-pathogenic E.coli in the gut?

A

increase epithelial mucus secretion and reduce epithelial permeability

100
Q

What is a benefit of having Lactobacillus rhamnossus in the gut?

A

increased expression of occludin and ZO-1 proteins (both important for maintaining tight junctions)

101
Q

What is a benefit of having Lactobacillus rheuteri in the gut?

A

increased epithelial cell proliferation

102
Q

What is a pathological change that may occur with the presence of Salmonella entetica in the gut?

A

reduced ZO-1, occludin proteins, and tight junction complexes… leading to increased intestinal permeability (more leaky)

103
Q

What is a pathological change that may occur with the presence of Clostridium difficile in the gut?

A

reduces mucin production

104
Q

What is a pathological change that may occur with the presence of Enterovirus E11 in the gut?

A

direct cytotoxicity

(can kill enterocytes)

105
Q

True or False: Giving probiotics (live bacteria) to adults with constipation improves gut motility and increase of bowel movements per day

A

True

106
Q

True or False: Transplanting fecal flora from patients with constipation to germ-free mice does not result in constipation symptoms in the mice

A

False

Transplanting fecal flora to the mice leads to constipation in the mice

107
Q

True or False: SCFAs can increase serotonin production and acetylcholine activity (cholinergic neuron activity), which both can increase gut motility

A

True

108
Q

What is meant by the “bi-directional relationship” of the gut microbiome and intestinal motility

A

Changes in motility (e.g., constipation or diarrhea) influence the survival of different bacterial groups

109
Q

Constipation leads to changes in what bacteria?

A

increased = Bacteroides and Enterobacter

decreased = Bifidobacterium and Prevotella

110
Q

Diarrhea leads to changes in what bacteria?

A

increased Prevotella

decreased Bifidobacterium, Bacteroides, and Lactobacillus

111
Q

when the mechanism of antibiotic action interferes with bacterial cell activity (including replication) without directly causing death

A

bacteriostatic

Note: bacteriostatics do not directly kill bacteria but instead interfere with their growth so that our immune system has more time to “catch up”; therefore, a healthy host immune function is required to be able to clear the overgrowth

112
Q

What are some examples of bacteriostatic antibiotics?

A

macrolides and tetracyclines

113
Q

mechanism of antibiotic action directly kills bacteria

A

bactericidal

Note: usually comes with increased risk of adverse events compared to bacteriostatic antibiotics

114
Q

when the antibiotic is able to effect different types of bacterias including gram positive, gram negative, and others (e.g., spirochetes, atypical)

A

broad spectrum antibiotic

115
Q

What are some negative effects of antibiotics on the gut microbiome?

A
  • reduce species diversity
  • altered metabolic activity
  • selection for antibiotic-resistant organisms (can lead to C. difficile overgrowth –> resulting in antibiotic-associated diarrhea)

Note: In most cases, gut bacteria will recover to their baseline state within a few weeks after antibiotic is discontinued… however, long term dysbiosis has been reported in the literature

116
Q

True or False: Amoxicillin and nitrofurantoin (used for UTI) have very little impact on gut bacteria

A

True

117
Q

What percentage of patients develop antibiotic-associated diarrhea (AAD) during treatment and/or within 2 months after discontinuation?

A

5-30%

118
Q

What factors increase likelihood of developing antibiotic-associated diarrhea (AAD)?

A

age > 65 yrs

immunosuppression

ICU or prolonged hospitalization

119
Q

What bacteria accounts for 10-25% of antibiotic-associated diarrhea (AAD) cases?

A

C. difficile

120
Q

True or False: Antibiotic use (repeated; more than once) in childhood is associated with development of asthma, juvenile arthritis, type 1 diabetes, Crohn’s disease (IBD) and mental illness

A

True