Gastrointestinal Physiology Flashcards

1
Q

Functions of the Gastrointestinal Tract (GIT)

A

Transfer digested organic nutrients, minerals and water, from the external environment into the internal environment:

involves digestion and absorption

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2
Q

What is digestion?

A

Process of forming absorbable molecules from food through GIT motility, pH changes, and biological detergents/enzymes

ie breakdown food into absorbable molecules

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3
Q

What is absorption?

A

Movement of digestive food from the intestine into the blood or the lymphatic system

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4
Q

How does the GIT function in excretion?

(ie what is excreted from GIT)

A

Non-absorbable components of food, bacteria, intestinal cells, and hydrophobic molecules (drugs), cholesterol and steroids are excreted

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5
Q

How does the GIT function in host defense?

A
  • Lumen of the GIT is continuous with exterior of body = outside considered to be outside the body
  • The GIT forms a barrier with the outside environment and contains a highly developed immune system
    • The GIT can inactivate harmful bacteria or other microorganisms
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6
Q

What are the 6 components of the GIT and what are the 3 accessory organs of the GIT?

A

6 components:

  1. Mouth
  2. Pharynx
  3. Esophagus
  4. Stomach
  5. Small intestine (duodenum, jejunum, ileum)
  6. Large intestine

3 Accessory Organs

  1. Pancreas
  2. Gall Bladder
  3. Liver
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7
Q

The top third of the esophagus is composed of _________ muscle and the rest is ________ muscle

A

The top third of the esophagus is composed of Skeletal muscle and the rest is smooth muscle

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8
Q

What are the three subsections of the mucosa?

A
  1. Epithelium - very thin layer of cells
  2. Lamina Propria
  3. Muscularis mucosa - very thin smooth mm layer
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9
Q

What are the four layers of the GIT?

A
  1. Mucosa (has three sublayers:
    • Epithelium
    • Lamina propria
    • Muscularis mucosa
  2. Submucosa
  3. Muscularis externa
  4. Serosal layer
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10
Q

The connective tissue layer of the GIT is ________ and the outer muscular layer is the _______

A

The connective tissue layer of the GIT is serosal layer and the outer muscular layer is the muscularis externa

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11
Q

The epithelial cells of the mucosa are polarized, what does this mean?

A

They have a basolateral surface and apical surface

*there are different transport proteins on each surface

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12
Q

Which surface of epithelial cells is closest to the blood surface, facing away from the tube?

A

Basolateral surface

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13
Q

Which surface of the mucosal epithelium inserts the inside of the tube or lumen of the tube

A

Apical surface

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14
Q

What is the function of the epithelial layer of the mucosa (layer of the GIT)

A
  • Selective uptake of nutrients, electrolytes and water
  • Prevent passage of harmful substances
  • stem cells in crypts produce daughter cells
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15
Q

Epithelial surface area is increased by presence of _______ and ______

A

Epithelial surface area is increased by presence of villi and crypts

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16
Q
  • Villus contains a _________
  • Crypt is a region which _______ into the _______
A
  • Villus contains a single layer of epihelial cells containing microvilli
  • Crypt is a region which invaginates into the lamina propria
    • ​has stem cells
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17
Q

The ______ is the air passage between the pharynx and trachea

A

The larynx is the air passage between the pharynx and trachea

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18
Q

The _______ is the area around the vocal cords where air travels through

A

The glottis is the area around the vocal cords where air travels through

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19
Q

The _______ is a tissue flap that covers the trachea during swallowing

A

The epiglottis is a tissue flap that covers the trachea during swallowing

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20
Q

Swallowing is a series of ______ initiated by ______ receptors in the wall of the ________

A

Swallowing is a series of reflexes initiated by pressure receptors in the wall of the pharynx

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21
Q

How is swallowing initiated?

A

Pressure receptors in the pharynx are initiated by food or liquid entering the pharynx. The receptors send signals to the swallowing centre in the brainstem which signals muscles in the pharynx, the esophagus and respiratory muscles

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22
Q

What is happening at each letter in the image?

A

a) Tongue pushes food (bolus) to the back of the pharynx
b) Soft palate elevates to prevent food entering the nasal passages

  • Impulses from the swallowing centre:
    • inhibit respiration, raise the larynx, and close the glottis

c) Epiglottis covers the glottis to prevent food/liquid entering the trachea
d) Food descends into the esophagus

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23
Q

What is the upper esophageal sphincter composed of and where is it located relative to the pharynx?

A
  • Upper esophageal sphincter is composed of a ring of skeletal muscle
  • Found just inferior to the pharynx
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24
Q

What is the Lower Esophageal Sphincter composed of?

Where is it located?

A

Composed of a ring of smooth muscle

Found where the esophagus joins the stomach

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25
At rest, are the esophageal sphincters open or closed?
Closed (both are closed except when swallowing, vomiting or burping)
26
What type of tissue is the esophagus composed of?
Stratified squamous epithelium
27
In upper third of the esophagus is _______ mm and the lower two thirds is ______ mm
In upper third of the esophagus is _skeletal_ mm and the lower two thirds is _smooth_ mm
28
What is secreted in the esophagus to lubricate and aid in the passage of food?
Mucus
29
What happens during the esophageal phase of swallowing?
1. Upper esophageal sphincter relaxes = allows food to pass through 2. sphincter closes and glottis opens to breathe again 3. Peristaltic waves move the food bolus down the esophagus towards the stomach (~5-9seconds) 4. Lower sphincter at the stomach opens and allows food to pass through 5. Lower sphincter closes
30
What is the main force for the esophageal phase of swallowing?
Peristalsis (gravity assists but is NOT necessary eg can still swallow when in space or upside down)
31
What aids the lower esophageal sphincter in preventing gastric contents from entering the esophagus?
Equal pressure of the lower esophagus and the stomach = no pressure gradient forcing the gastric contents out
32
What happens when small amounts of acid enter the esophagus?
1. Stimulation of peristalsis to push the acid back out 2. increased salivary secretion * aids with neutralization of the acid with saliva and clearance of the acid out of the esophagus
33
What three scenarios might lead to heartburn?
Lower esophageal sphincter doesn't close properly A big meal Pregnancy
34
What are 5 functions of the stomach?
1. Storage of food 2. Mechanical breakdown of food 3. Chemical breakdown of food 4. Control rate at which food enters sm intestine 5. Secretes **intrinsic factor** critical for absorption of Vit B12 in the ileum
35
What are 2 chemicals secreted by the stomach?
1. Pepsinogen * cleaved to form the enzyme **pepsin** * initiates protein digestion 2. HCl * dissolves food and partially digests macromolecules in food
36
Vitamin B12 is required for:
Red blood cell formation
37
Failure to absorb Vit B12 might result in:
Pernicious anemia and RBC deficiency
38
Which region of the stomachhas the most muscle?
Fundus and Body each have a thin layer of smooth mm Antrum has a thicker smooth muscle layer
39
What is different between the three regions of the stomach?
* Fundus and Body * thin layer of smooth mm * secretes * mucus * pepsinogen * HCl * Antrum * Thicker smooth mm layer * Secretes * Mucus * Pepsinogen * Gastrin
40
What controls the emptying of the stomach?
Pyloric Sphincter
41
A chemical messenger secreted into ducts then on to an epithelial surface without passing into blood?
Exocrine secretion
42
What are three major exocrine secretions in the stomach?
1. Mucus * protective coating to avoid self-digestion 2. HCl * Hydrolysis of proteins into AA, dissolving food and digesting macromolecules and sterilizing food 3. Pepsinogen * precursor to pepsin which is important for protein digestion
43
What are four **minor** secretions of the stomach?
1. Intrinsic factor * Vit B12 absorption 2. Gastrin (endocrine) * important for stimulating HCl production and increasing stomach motility 3. Histamine (paracrine) * Stimulates HCl production 4. Somatostatin (paracrine) * Inhibits HCl production
44
What is the function of the following four stomach secretions: 1. Intrinsic factor 2. Gastrin 3. Histamine 4. Somatostatin
What is the function of the following four stomach secretions: 1. Intrinsic factor * absorption of Vit B12 2. Gastrin * Endocrine * hormone important for stimulating HCl production * Increases stomach motility 3. Histamine * Paracrine * stimulates HCl production 4. Somatostatin * ​Paracrine * Inhibits HCl production
45
A generalized gastric gland has what five types of cells? Include role and where they are mostly found
1. Mucous cell 2. Mucous neck cell 3. Parietal Cell * secretes intrinsic factor and HCl * Found mostly in the Body/Fundus 4. Chief Cell * Secretes pepsinogen 5. Enteroendocrine cell * G-cells * Secrete Gastrin * Found mostly in the antrum
46
Where are chief cells found? What do they secrete?
In gastric glands in all regions of the stomach Secrete Pepsinogen (inactive precursor to pepsin) Pepsinogen is cleaved by HCl into pepsin which accelerates protein digestion
47
Where are enteroendocrine cells found? What are they also known as? Secrete?
* Where are enteroendocrine cells found? * gastric glands of **antrum** * What are they also known as? * G-cells * Secrete? * Gastrin (hormone) * stimulates HCl production and GI motility
48
Which cell type would you find at the luminal end of the gastric gland?
Mucous cell
49
Which cell type would you find in the body and the fundus of the stomach but NOT in the antrum?
Parietal cell
50
What is zymogen?
Precursor for a protein that is not active and some type of chemical reaction needs to occur to make it active
51
What are enterochromaffin-like cells? Where are they found? What do they secrete?
* What are enterochromaffin-like cells? * Found in gastric glands in all regions (more in the **antrum**) * Secrete **histamine** * **​**Stimulates HCl release/production
52
Where are D-cells found and what do they secrete?
Found in gastric glands in all regions of the stomach but are more numerous in the Antrum Secretes **somatostatin** -regulator that **negatively** regulates HCl production
53
What is another name for parietal cell?
Oxyntic cell
54
What feature of parietal cells increases their surface area to maximize secretion into the stomach lumen?
Canaliculi
55
As the parietal cell is activated, what happens to the canaliculi?
Canaliculi become more defined, * movement of membrane to the canaliculi * distends them and greatly enlarges them * **proton pumps** are inserted
56
Why is it important for parietal cells to have many mitochondria?
Need lots of ATP for active acid secretion
57
How does the lumen pH of the stomach compare to the cytosol pH?
Lumen pH = 1 Cytosol pH = 7
58
The ______ surface of the parietal cell faces the stomach lumen.
The _Apical_ surface of the parietal cell faces the stomach lumen.
59
What are 7 mechanisms involved in acid secretion from the parietal cell?
1. Na+/K+ ATPase 2. H+/K+ ATPase 3. Carbonic anhydrase 4. Cl-/HCO3- exchanger 5. K+ channels 6. Cl+ channels 7. HCl
60
Describe the secretion of acid from the parietal cells and include why each of the following are important: * Na+/K+ ATPase * H+/K+ ATPase * Carbonic anhydrase * Cl-/HCO3- exchanger * K+ channels * Cl+ channels * HCl
Describe each of the methods of transport of the parietal cell: * Na+/K+ ATPase * Pumps 3 Na+ out and 2 K+ in for every molecule of ATP hydrolyzed * establishes electrochemical gradients with a high concentration of K+ inside the cell and a high [Na+] outside the cell * H+/K+ ATPase * Apical/luminal membrane of the parietal cell * Pumps out a proton (acid) into the lumen * Primary ACTIVe Transport (ATP is hydrolyzed) * As acid is leaving, the cell becomes more basic * other mechanisms must prevent the cytosolic pH of the parietal cell from becoming too basic * Carbonic anhydrase * Parietal cell gets rid of base by removing bicarbonate * catalyzes the formation of H2CO3 (carbonic acid) from H2o and CO2 * H2CO3 dissociates into H+ for secretion into lumen and HCO3- * Cl-/HCO3- exchanger * HCO3- is pumped out in exchange for a chloride ion (Cl-) secondary active transport * K+ channels * As protons are pumped out through the apical primary active transporter, K+ levels increase in the cytosol * K+ channels in the apical surface open and allow K+ to leave down concentration gradient * Loss of positive with every K+ means we must lose a negative charge to compensate thought he loss of Cl- channels * Cl- channels * Apical membrane * Cl- lost into lumen of stomach as diffuses through Cl- channel * compensates for loss of positive charge through K+ channels * HCl * Secreted into the lumen of the stomach as a proton leaves the cell tthough the apical H+/K+ ATPase and Cl- through the Cl- channel
61
How do chemical messengers regulate acid secretion?
Chemical messengers regulate the insertion of the H+/K+ ATPase into the plasma membrane of the parietal cell
62
What are four chemical messengers that regulate the insertion of H+/K+ ATPase into the membrane of parietal cells to regulate acid secretion?
1. Gastin 2. Acetylcholine 3. Histamine 4. Somatostatin
63
How do each of the four chemical messengers control insertion of H+/K+ ATPase into the membrane of parietal cells? (to regulate acid secretion) 1. Gastin 2. Acetylcholine 3. Histamine 4. Somatostatin
1. Gastrin * Gastric hormone released by G cells * Stimulates insertion of the H+/K+ ATPase into the membrane, stimulating HCl secretion 2. Acetylcholine * Neurotransmitter * Increased Parasympathetic activity causes the release of Ach * increases insertion of H+/K+ ATPase into the membrane, stimulating HCl production 3. Histamine * Paracrine released from the ECL-Cell * Stimulates insertion of the H+/K+ATPase into the membrane , stimulating acid secretion 4. Somatostatin * Paracrine released from D-cells * Inhibits the release of HCl, gastrin and histamine
64
Histamine potentiates the effects of _______ and ________ to stimulate acid production
Histamine potentiates the effects of _gastrin_ and _acetylcholine_ to stimulate acid production
65
Secretion of pepsinogen from ________ cells is stimulated by \_\_\_\_\_\_\_
Secretion of pepsinogen from _chief_ cells is stimulated by _the enteric nervous system_
66
The release of pepsinogen from the chief cell parallels:
The release of Acid from parietal cells:
67
What happens once pepsinogen enters the lumen?
It is cleaved and activated to **pepsin** by acidic pH in the stomach
68
What is the advantage of inactive precursor secretion (pepsinogen instead of pepsin)
Prevents digestion of self
69
What happens to pepsin once it enters the small intestine?
It is **irreversibly inactivated**
70
Regulation of stomach secretion is divided into what three phases?
1. Cephalic Phase * stimulation in the brain 2. Gastric Phase * when food reaches the stomach 3. Intestinal Phase * when food that has been partially broken down by the stomach enters the Sm Int.
71
What is the **cephalic** phase of gastric secretion? * Stimulation? * Nerve? * Response?
What is the cephalic phase of gastric secretion? * Stimulation? * sight, smell, taste of food provides excitatory stimulation mainly via the: * Nerve? * **Vagus Nerve** to the **stomach** * Response? * Vagal nuclei in the brain cause the Parasympathetic nerve to release ACh at the *parietal cells* = stimulation of acid production
72
What is the Gastric Phase of Gastric Secretion? * Major phase for regulating \_\_\_\_\_\_\_ * Stimulatory phase mediated mainly via the release of \_\_\_\_\_\_ * Food in the stomach causes ______ to release ______ into the blood which has what result:
What is the Gastric Phase of Gastric Secretion? * Major phase for regulating _acid production_ * Stimulatory phase mediated mainly via the release of _gastrin_ * Food in the stomach causes _G-Cells_ to release _gastrin_ into the blood which has what result: * Gastrin interacts with the parietal cell to increase acid production
73
What is the intestinal phase of gastric secretion? * _______ phase * Mainly ______ due to presence of \_\_\_\_, \_\_\_\_, _____ products and ________ in the \_\_\_\_\_\_- * Mediated by:
What is the intestinal phase of gastric secretion? * _Inhibitory_ phase * Mainly _inhibitory_ due to presence of _acid, fat, digestion_ products and **_hypertonic sol'n_**s in the _duodenum_ * Mediated by: * Gastrointestinal hormones including **secretin** and **CCK**
74
Where are secretin and CCK secreted from and what effect do they have on Gastric Secretion?
CCK and Secretin are GI hormones secreted from epithelial cells of the Small Intestine Enter the blood and have a negative influence on gastrin production
75
What four chemical messengers regulate the insertion of H+/K+ ATPase into the plasma membrane of the parietal cell?
1. Gastrin 2. ACh 3. Histamine 4. Somatostatin
76
What three chemical messengers stimulate the parietal cell to release acid?
ACh Histamine Gastrin
77
Starvation would occur without the \_\_\_\_\_\_\_\_ a) stomach b) salivary glands c) pancreas
Starvation would occur without the _pancreas_
78
What are four families of enzymes produced by the pancreas?
1. Proteases * protein into peptides and AA 2. Amylolytic enzymes * starch into sugars 3. lipases * triglycerides into fatty acids and monoglycerides 4. nucleases * digest nucleic acids into free nucleotides
79
What are acinar cells?
Cells of the pancreas that synthesize and package pancreatic enzymes (as pro-enzymes) into **zymogen granules** that are stored at the apical pole of the cell
80
What stimulates exocytosis of zymogen granules (containing pancreatic enzymes) into the lumen of the pancreatic duct?
Neurohormonal input
81
What enzyme embedded in the luminal membrane of the duodenum cleaves **trypsinogen** into **trypsin**?
Enterokinase - activates proenzymes from the pancreas
82
What is trypsin?
protease that also activates other proteases
83
What does the pancreas secrete to antagonize any prematurely activated trypsin?
a variety of trypsin inhibitors
84
What is notable about trypsin that is activated prematurely (prior to reaching the intestine)?
It can degrade itself
85
Proteases secreted by the pancreas **Trypsinogen** * Activated by: * Active enzyme: * Action * End products
Proteases secreted by the Pancreas: **Trypsinogen** * Activated by: * Enterokinase * Active enzyme: * Trypsin * Action * Endopeptidases (hydrolyze interior peptide bonds of proteins and polypeptides) * End product * Mixture of peptides and AA
86
Proteases secreted by the pancreas **Chymotrypsinogen** * Activated by: * Active enzyme: * Action * End products
Proteases secreted by the pancreas **Chymotrypsinogen** * Activated by: * Trypsin * Active enzyme: * Chymotrypsin * Action * Endopeptidases (hydrolyzes interior peptide bonds of proteins and polypeptides) * End products * Mixture of peptides and AA
87
Proteases secreted by the pancreas **Pro-elastase** * Activated by: * Active enzyme: * Action * End products
**Pro-elastase** * Activated by: * Trypsin * Active enzyme: * Elastase * Action * Endopeptidases (hydrolyzes interior peptide bonds of proteins and polypeptides) * End products * Mixture of peptides and AA
88
Major Proteases secreted by the pancreas **Pro-carboxy peptidase A & B** * Activated by: * Active enzyme: * Action * End products
Major Proteases secreted by the pancreas **Pro-carboxy peptidase A & B** * Activated by: * trypsin * Active enzyme: * Carboxypeptidase A & B * Action * Exopeptidases (hydrolyze bonds at the C-terminal) * End products * Mixture of peptides and AA
89
What are four major proteases secreted by the pancreas? Are they endopeptidases or exopeptidases?
1. Trypsinogen - endopeptidases 2. Chymotrypsinogen - endopeptidases 3. Pro-elastase - endopeptidases 4. Pro-carboxypeptidase A & B - exopeptidases Endo = hydrolyzes interior peptide bonds of proteins and polypeptides Exo = hydrolyzes bonds at the C-terminal end
90
What is the amylolytic enzyme secreted by the pancreas? Function and end products?
* Pancreatic amylase * Function * Cleaves starches to sugars * End-product: * Maltose, maltriose, and alpha-limit dextrins
91
What are three Lipolytic enzymes secreted by the pancreas?
1. Prephospholipase A2 (inactive) 2. Lipase (active) 3. Cholesterolesterase (active)
92
What is different between the breakdown of amylose by pancreatic amylase vs salivary amylase?
Nothing, identical process
93
Relaxation of the stomach is mediated by the __________ to the \_\_\_\_\_\_\_\_
Relaxation of the stomach is mediated by the _parasympathetic nerves_ to the _Enteric nervous system_
94
Lipolytic enzymes secreted by the pancreas: **Prephospholipase A2** * Activated by * Active Enzymes? * Action? * End-Products?
Lipolytic enzymes secreted by the pancreas: **Prephospholipase A2** * Activated by? * Trypsin * Active Enzymes? * Phospholipase A2 * Action? * hydrolyzes phospholipids * End-Products? * Free fatty acids and lysophospholipids
95
Lipolytic Enzymes secreted by the pancreas: **Lipase** * Activated by? * Active Enzymes? * Action? * End-Products?
Lipolytic Enzymes secreted by the pancreas: **Lipase** * Activated by? * secreted in active form * Active Enzymes? * already active as **lipase** * Action? * Hydrolyzes triglycerides * End-Products? * Free fatty acids and 2-monoglycerides
96
Lipolytic Enzymes secreted by the pancreas: **Cholesterolesterase** * Activated by? * Active Enzymes? * Action? * End-Products?
Lipolytic Enzymes secreted by the pancreas: **Cholesterolesterase** * Activated by? * secreted in active form * Active Enzymes? * Cholesterolesterase * Action? * Hydrolyzes cholesterol-esters * End-Products? * Free fatty acids and cholesterol
97
Where is the pyloric sphincter?
Between the antrum (of the stomach) and the duodenum (of the sm int)
98
Why are stomach contractions weaker in the body of the stomach than in the antrum of the stomach?
The antrum has a thicker smooth mm layer than the body
99
What causes the pyloric sphincter to close?
peristaltic wave in the body of the stomach and a stronger force of contraction in the antrum causes the pyloric sphincter to close
100
The stomach has _______ cells in the smooth muscle layer that lead to spontaneous slow waves of depolarization and repolarization
The stomach has _pacemaker_ cells in the smooth muscle layer that lead to spontaneous slow waves of depolarization and repolarization (basic electrical rhythm)
101
What is the basic electrical rhythm of the stomach?
Spontaneous slow waves produced by the pacemaker cells in the smooth mm layer of the stomach (depolarization and repolarization)
102
Why doesn't the basic electrical rhythm cause any contractions in the absence of neural or hormonal input? What is their purpose?
Why doesn't the basic electrical rhythm cause any contractions in the absence of neural or hormonal input? * depolarizations are too small What is their purpose? * allows the timing of contractions
103
What determines the strength of stomach contraction and what determines the timing of stomach contraction?
What determines the strength of stomach contraction and what determines the timing of stomach contraction? * Strength = amount of stimulus from neurotransmitters or excitatory hormones * Timing = basic electrical rhythm (pacemaker cells of stomach)
104
Where is the "vomiting centre" located in the brain?
Medulla oblongata
105
What are the 5 steps of vomiting?
1. Nausea, salivation, breath held in mid-inspiration 2. Glottis closes off trachea 3. Lower esophageal sphincter and esophagus relax 4. Diaphragm and abdominal mm contract 5. Reverse peristalsis moves upper intestinal contents into the stomach 6. Stomach contents move up through the esophagus and out through the mouth (soft palate is raised)
106
What are two benefits to vomiting?
1. Remove harmful substances before they are absorbed into your body 2. Nausea and feeling bad associated with vomiting are negative conditioning so that if you experience these, they may prevent you from consuming the noxious substance again
107
What are four negative consequences of vomiting?
1. Dehydration 2. electrolyte imbalance 3. metabolic alkalosis = pH tissue is elevated beyond normal range due to loss of acid from stomach 4. Acid erosion of tooth enamel
108
What is a peptic ulcer?
Damage to or erosion of the GIT mucosa * occurs in regions which are acidic such as the esophagus, stomach or the duodenum
109
What causes an ulcer? (3)
1. Imbalance of aggressive factors (acid and pepsin) and protective factors (mucus and bicarbonate) 2. Most common: bacterium *Helicobacter pylori* * *​​*results in inflammation of the lining and irritation and eventually chronic inflammation and erosion 3. Non-bacterial factors: * NSAIDS * smoking * alcohol * gastrinomas (rare tumour)
110
What problems might occur if you have a very small stomach or a stomach removed (as in gastric bypass)
* Reduction in the release of intrinsic factor = inability to absorb B12 = anemia * Stomach is useful for reducing bacteria in your system * Stomach regulates how much food enters the SI
111
What are the exocrine functions of the pancreas?
* vital for digestion * produces secretions that enter the GIT * Source of the majority of enzymes required for digestion of carbs, proteins, fats and nucleic acids * Secretes bicarbonate into duodenum to neutralize HCl from stomach
112
What must happen in the duodenum for pancreatic digestive enzymes to be functional?
The stomach acid from the stomach must be neutralized by bicarbonate from the pancreas. Pancreatic enzymes are inactive in acidic pH
113
The __________ from the pancreas joins the ________ from the liver to become the _______ just before entering the duodenum
The _Main pancreatic duct_ from the pancreas joins the _common bile duct_ from the liver to become the _hepatopancreatic sphincter (or sphincter of oddi)_ just before entering the duodenum
114
What regulates the release of both liver and pancreatic contents into the SI?
Hepatopancreatic sphincter (Sphincter of Oddi)
115
What is different between the secretions from the exocrine pancreas and the endocrine pancreas?
* Endocrine: * ductless gland * secretion occurs across the *epithelial basolateral* surface for diffusion into the blood * Endocrine cells surround capillaries * Pancreatic Islets * Exocrine: * secrete substances into ducts that drain onto the epithelial surface (or the *apical surface*) and converge into the pancreatic duct * Secretions ultimately enter the Sm Int
116
Pancreatic ducts have _\_\_\_\_\_\_\_\__ cells at the end portion of the duct
Pancreatic ducts have _acinar_ cells at the end portion of the duct * Acinar cells produce and secrete digestive enzymes * exocytosis of vesicles within the acinar cells
117
* Acinar cells found at the ______ portion of the ________ produce and secrete \_\_\_\_\_\_\_\_\_ * Ductal cells secrete _________ and \_\_\_\_\_\_\_\_\_
* Acinar cells found at the _end_ portion of the _pancreatic ducts_ produce and secrete _digestive enzymes_ * Ductal cells secrete _bicarbonate_ and _water_
118
What are two primary types of cells found in pancreatic ducts?
1. Acinar cells * secrete digestive enzymes 2. Ductal cells * secrete bicarbonate and water
119
What is pancreatic juice composed of?
* Isotonic and alkaline (because of bicarbonate) * Electrolytes * High in HCO3- and low in Cl- * [Na+] and [K+] are the same as in the plasma (hence isotonic) * Digestive enzymes
120
How do the ductal cells of the pancreas produce bicarbonate and water (alkaline watery sol'n)
1. Cl- channel (**CFTR**) at the **apical** surface of the ductal epithelium allows Cl- to diffuse out of the duct cell into the lumen 2. Cl- that has diffused out of the duct cell is then exchanged for HCO3- 3. in the pancreas, HCO3- (*base*) leaves the cell 4. **Carbonic anhydrase** catalyzes the formation of **carbonic acid** (H2CO3) 5. H2CO3 dissociates into HCO3- and H+. This HCO3- is the base that is moved into the duct lumen 6. Neutral pH of cytosol is maintained by the exchange of H+ (out) for Na+ (in) via **H+/Na+ exchanger** * secondary active transport pathway where the Na+ moving down its conc gradient supplies the energy to efflux H+ from the cell * Na+ gradient is provided by the Na+/K+ ATPase 7. Cl- gradient into the duct lumen draws Na+ and water paracellularly (between cells)
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What is the alkaline and acid tide?
**alkaline tide**: * After a meal, acid is being produced by the parietal cell and enters the lumen of the stomach * Base leaves the cell into the bloodstream as bicarbonate (HCO3-) * Whatever is moving into the blood = tide (therefore alkaline tide because base is moving) * Large amount of bicarbonate is pumped across the basolateral surface into the blood = Alkaline Tide **AT THE SAME TIME:** **Acid Tide:** * In the pancreas the duct cells are producing base as bicarbonate, which is moving into the lumen of the pancreatic ducts * Large amounts of acid (H+) are being pumped across the basolateral surface into the blood stream = *Acid Tide* Eventually, the base from the stomach and the acid from the pancreas meet up in the portal vein to maintain the acid-base balance of the blood stream
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What cells in the pancreas synthesize and package pro-enzymes and what are the "packages" called? Where are they stored?
**Acinar** cells synthesize and package pro-enzymes into **zymogen** **granules** that are stored at the **apical pole** of the cell.
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What are zymogens?
proenzymes (aka pre-cursor enzymes) Inactive enzymes
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What two types of secretory cells important in regulating pancreatic juice secretion are localized to the epithelium of the small intestine
S-cells - secretes secretin I-cells - secrete CCK
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What is happening at each number in the image: Regulation of pancreatic secretion is mainly regulated by \_\_\_\_\_\_\_\_\_
What is happening at each number in the image: Regulation of pancreatic secretion is mainly regulated by _food & acid entering the small intestine_ 1. Acid enters duodenum from the stomach which stimulates 2. **S-cells** to secrete **secretin** * Secretin is a hormone released into the blood which will eventually: 3. reach **pancreatic duct cells** and *stimulate the release of* **bicarbonate** * important in neutralizing the acid in the duodenum which would otherwise denature pancreatic enzymes 4. *AT the SAME TIME as 1-3* * *​​*Digested fat and protein in the Sm Int stimulates: * **I-cells to secrete CCK** into the blood 5. CCK acts on **acinar cells** in the *pancreatic duct* to stimulate 6. Zymogen granules to release enzymes into the lumen Finally, The **parasympathetic nerve** acts as a *minor regulatory pathway* and will cause the release of digestive enzymes when you are hungry and smell food
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* Fatty acids and amino acids in the Sm Int trigger the secretion of _____ from \_\_\_\_-cells in the small intestine into the blood * The circulating hormone released stimulates the pancreas to: * This stimulates the **gallbladder** to \_\_\_\_\_\_\_\_ * Release of _______ for fat breakdown * _______ relaxes * As fats and amino acids are absorbed, the stimuli for _____ release is removed as it is the fats and AA that trigger its secretion * Negative Feedback Loop
* Fatty acids and amino acids in the Sm Int trigger the secretion of _CCK_ from _I_-cells in the small intestine into the blood * The circulating hormone released stimulates the pancreas to: *increase the secretion of digestive enzymes* * This stimulates the **gallbladder** to _contract_ * Release of _bile acids_ for fat breakdown * _Sphincter of Oddi (hepatopancreatic sphincter)_ relaxes * As fats and amino acids are absorbed, the stimuli for _CCK_ release is removed as it is the fats and AA that trigger its secretion * Negative Feedback Loop8
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How does Secretin regulate pancreatic HCO3- Secretion? * _____ entering the duodenum from the stomach stimulates secretin secretion from ___ cells in the SI into the blood * Circulating secretin stimulates: * ______ cells in the pancreas to increase bicarbonate secretion * ______ cells in the liver to increase bicarbonate secretion * Stomach acid is ______ thus removing the stimulation for secretin release * Negative Feedback Loop
How does Secretin regulate pancreatic HCO3- Secretion? * _Acid_ entering the duodenum from the stomach stimulates **secretin** secretion from _S_ cells in the SI into the blood * Circulating secretin stimulates: * _Duct_ cells in the pancreas to increase bicarbonate secretion * _Duct_ cells in the liver to increase bicarbonate secretion * Stomach acid is _neutralized_ thus removing the stimulation for secretin release * Negative Feedback Loop
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What is the common function of both Secretin and CCK?
Both CCK and Secretin **inhibit gastrin secretion**: * Results in reduced stomach motility (slows stomach emptying) and reduced acid secretion
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As the stomach is emptying you do Not want to produce _____ at high levels, so _____ and ____ reduce this secretion
As the stomach is emptying you do Not want to produce _acid_ at high levels, so _secretin_ and _CCK_ reduce this secretion
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What are the three phases of Pancreatic Secretion?
1. Cephalic Phase * Stimulation in the brain * minor * Sight smell and taste of food stimulate pancreatic secretion via the **parasympathetic nerves** 2. Gastric Phase * Minor * Distension of the stomach will stimulate pancreatic secretion via the **parasympathetic nerves** 3. Intestinal Phase * MAJOR * Acid from stomach in duodenum = secretin release * Digested fat and protein in duodenum = CCK release
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The Cl- channel involved in bicarbonate secretion in the pancreas is the same channel that is mutated in the disease \_\_\_\_\_\_\_\_
The Cl- channel involved in bicarbonate secretion in the pancreas is the same channel that is mutated in the disease _cystic fibrosis_ * this channel creates optimal secretions in the lungs * Get thick mucus in the lungs
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Cystic fibrosis patients can suffer from "\_\_\_\_\_\_\_\_"
Cystic fibrosis patients can suffer from "_Pancreatic insufficiency_"
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Why can patients with cystic fibrosis still produce all of the digestive enzymes? Further, if they are still producing all of the digestive enzymes, why then can they have "pancreatic insufficiency" How can this me overcome?
* Digestive enzymes are produced in the **acinar region** (the Cl- channel is mutated in the Cl-/bicarbonate and water secretion (Duct cells)) * bicarbonate and water secretion is so minimal that the produced enzymes cannot be flushed from the duct and do not reach the intestine * Retained proteolytic (breakdown proteins) enzymes can result in **autodigestion** * Patients must receive supplements of digestive enzymes and antacids to allow for adequate nutrition
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* Where is the liver located? * Where is the gallbladder located
* Below the ribcage in the Right Upper Quadrant of the Abdominal cavity * Underneath the lobule of the liver
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The main pancreatic duct and the common bile duct join to form the _______ before releasing their contents into the \_\_\_\_. The release of their contents is controlled by:
The main pancreatic duct and the common bile duct join to form the _ampulla of vater_ before releasing their contents into the _duodenum_ The release of their contents is controlled by: the sphincter of Oddi (hepatopancreatic sphincter)
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Which two distinct routes supply the liver with blood? How much does each route supply? How does the make-up of blood differ between the two routes?
1. Systemic circulation (via the Hepatic artery) * ~25% of the blood volume entering the liver * oxygenated but **nutrient poor** 2. Hepatic portal circulation (via the Hepatic portal vein) * ~75% of blood * deoxygenated BUT **nutrient rich**
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The hepatic portal vein (venous blood) and the hepatic artery (arterial blood) mix within the ________ and blood then flows through the liver toward the _____ or ______ veins which unite to carry blood back toward the **inferior vena cava**
The hepatic portal vein (venous) and the hepatic artery (arterial) mix within the _hepatic sinusoids_ and blood then flows through the liver toward the _hepatic_ or _central_ veins which unite to carry blood back toward the **inferior vena cava**
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What is the functional unit of the liver?
Hepatic Lobule
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The hepatic lobule (functional unit of the liver) is a _______ structure with a ______ vein running through the centre and a ________ in each corner
The hepatic lobule is a _hexagonal_ structure with a _central_ vein running through the centre and a _portal triad_ in each corner
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What is the portal triad (of the liver)?
* Composed of branches of * A hepatic artery * A portal vein * A bile duct
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What are the epithelial cells of the liver called?
Hepatocytes
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What is 'unique' about the epithelial cells of the liver compared to the classic single-layered epithelial cells that you see lining the intestine for example? (include how bile ducts are formed)
* Hepatocytes: * form cell-to-cell junctions considered the **apical surface** of the cell * Form Tube-like structures called **canaliculi networks** * **​**conduct bile produced by hepatocytes * Join together to form the **bile ducts**
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What type of capillary are found in the liver?
Sinusoids: Thin-walled capillaries with large gaps = more permeable than other types of capillary
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The hepatocytes are bathed in _____ and take up ______ and _____ thereby acting as a \_\_\_\_\_\_
The hepatocytes are bathed in _blood_ and take up _nutrients_ and _toxins_ thereby acting as a _filter_
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Bile components produced by the hepatocytes are put into the _________ and flow towards the ______ (opposite direction of \_\_\_\_\_\_)
Bile components produced by the hepatocytes are put into the _Canalicular network_ and flow towards the _bile ducts_ (opposite direction of _blood flow_ which occurs on the other surface of the hepatocyte)
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The liver is an _____ gland that is important for the * secretion and production of \_\_\_\_ * ______ and ______ of nutrients * matches supply to demand * ________ and ______ (oral drugs, hormones, toxins) * Producing circulating \_\_\_\_\_\_
The liver is an _exocrine_ gland that is important for the * secretion and production of _bile_ * _metabolism_ and _storage_ of nutrients * matches supply to demand * _deactivation_ and _detoxification_ * Producing circulating _proteins_ * _​(eg_ blood coagulation factors and lipoproteins)
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What are the 6 major components of bile?
1. Bile acids * made from cholesterol within the hepatocyte * important for the emulsification of fats * amphipathic chemicals (not enzymes) 2. Cholesterol 3. Salts * sodium, potassium and bicarbonate as well as water 4. Phospholipids * important for breakdown of fat 5. Bile pigments (bilirubin) * bilirubin is important for the breakdown of heme 6. Trace metals
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Provide a function of each of the 6 major components of bile: 1. Bile acids 2. Cholesterol 3. Salts 4. Phospholipids 5. Bile pigments (bilirubin) 6. Trace metals
Provide a function of each of the 6 major components of bile: 1. Bile acids * made from cholesterol within the hepatocyte * important for the emulsification of fats * amphipathic chemicals (not enzymes) 2. Cholesterol 3. Salts * sodium, potassium and bicarbonate as well as water 4. Phospholipids * important for breakdown of fat 5. Bile pigments (bilirubin) * bilirubin is important for the breakdown of heme 6. Trace metals
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Bile works in consort with the pancreatic enzyme \_\_\_\_\_\_
Bile works in consort with the pancreatic enzyme _lipase_ * lipase is water soluble * only works on surface of lipid droplets * bile makes the droplets smaller via emulsification
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What is emulsification? What 3 things does it require?
* Process by which bile makes a fat globule into smaller globules to allow pancreatic lipase to work * Requires * Mechanical disruption (GI motility) * Emulsifying agent to prevent reaggregation (found in bile) * Amphipathic bile salts * Phospholipids
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Bile acids form _____ with phospholipids and products of lipase digestion (free fatty acid and monoglycerides)
Bile acids form mixed _micelles_ with phospholipids and products of lipase digestion (free fatty acid and monoglycerides)
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* Why are micelle's important?
* Fatty acids and monoglycerides are really insoluble in water * only a few molecules exist in solution and are free to diffuse into the enterocyte * Micelles keep monoglycerides and fatty acids in small soluble aggregates * Equilibrium between the micelle and free fatty acid and monoglycerides * free forms diffuse across the SI epithelium * Micelles are like a "holding station" for small, nonsoluble lipids
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* An emulsion droplet is held in solution and not allowed to re-aggregate due to the _____ and \_\_\_\_\_\_\_ * This increases the _____ for the water-soluble pancreatic ____ to have access to these fat droplets * Lipase breaks down the triglycerides into ______ and \_\_\_\_\_ * A small number of _____ and ______ can exist in an aqueous sol'n but are rapidly absorbed by the _______ while the majority of them exist in \_\_\_\_\_\_ * As _____ breakdown and reform, some of the ______ and ______ are released and this allows for their \_\_\_\_\_\_
* An emulsion droplet is held in solution and not allowed to re-aggregate due to the _bile salts_ and _phospholipids_ * This increases the _surface area_ for the water-soluble pancreatic _lipase_ to have access to these fat droplets * Lipase breaks down the triglycerides into _monoglycerides_ and _fatty acids_ * A small number of _monoglycerides_ and _fatty acids_ can exist in an aqueous sol'n but are rapidly absorbed by the _SI epithelium_ while the majority of them exist in _micelles_ * As _micelles_ breakdown and reform, some of the _monoglycerides_ and _fatty acids_ are released and this allows for their _absorption_
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What are the two main cell types in the liver important for the formation of bile?
1. Hepatocytes * Produce and secrete bile acids * also secrete phospholipids, cholesterol and bile pigments * into bile canaliculi 2. Bile duct cells * Add bicarbonate and other salts and water to the bile
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What is the role of each of the following in bile formation: 1. **Hepatocyte** 2. **Bile duct cells** 3. **Gallbladder**
1. **Hepatocytes** * Produce and secrete bile acids * also secrete phospholipids, cholesterol, and bile pigments * into bile canaliculi 2. **Bile duct cells** * Add bicarbonate and other salts and water to the bile 3. **Gallbladder** * stores and concentrates bile between meals and releases it when **chyme** enters the duodenum
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Recycling of bile acids occurs through:
Enterohepatic circulation
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Bile acids are produced by ________ in the liver and secreted into ________ networks
Bile acids are produced by _hepatocytes_ in the liver and secreted into _canalicular_ networks
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What are the steps for bile acid recycling?
1. Bile acids are released by the liver/gallbladder into the duodenum for fat digestion 2. Bile acids are reabsorbed across the small intestine (ileum) into the portal circulation 3. Bile acids are transported back into hepatocytes
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Step one of Bile acid recycling: * Bile acids are synthesized within the hepatocyte and move across the ______ surface of the hepatocyte * Transported via a __________ into the ________ (requires \_\_\_\_) * Then drain from _______ networks into _____ and then enter the gallbladder or directly into the SI
Step one of Bile acid recycling: * Bile acids are synthesized within the hepatocyte and move across the _apical_ surface of the hepatocyte * Transported via a _primary active transport pathway_ into the _canalicular network_ (requires A**_TP_**) * Then drain from _canalicular_ networks into _bile ducts_ and then enter the gallbladder or directly into the SI
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Step 2 of Bile acid recycling: * Reabsorption from the \_\_\_\_\_\_ * bile acids enter the small intestine lumen, digest the food and move through the SI to the *terminal portion* called the \_\_\_\_\_\_ * Bile acids move back into \_\_\_\_\_\_\_ * Bile acids are absorbed across the epithelial cell (\_\_\_\_\_\_) through a \_\_\_\_\_ * Required to allow the bile acids to move from a region that is dilute (the \_\_\_\_\_\_\_\_) to a region that is more concentrated (\_\_\_\_\_\_) * Bile acids then move by _________ across the ______ surface of the enterocyte and into the blood
Step 2 of Bile acid recycling: * Reabsorption from the _Ileum_ * bile acids enter the small intestine lumen, digest the food and move through the SI to the *terminal portion* called the _ileum_ * Bile acids move back into _portal circulation_ * Bile acids are absorbed across the epithelial cell (_enterocytes_) through a _Na+-dependent secondary active transport pathway_ * Required to allow the bile acids to move from a region that is dilute (the _intestinal lumen_) to a region that is more concentrated (_enterocyte_) * Bile acids then move by _facilitated transport_ across the _basolateral_ surface of the enterocyte and into the blood
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what is a way to prevent high cholesterol that is related to enterohepatic circulation?
Prevent reabsorption of bile acids
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Step 3: transport of bile acids from blood into hepatocytes * Bile acids are in the portal blood and are carried into the _\_\_\_\_\_\_\_\__predominantly through a _\_\_\_\_\_\_\_\_\_\__ * the cycle can start over again with the transport of _\_\_\_\_\_\__ from the hepatocyte into the bile through a \_\_\_\_\_\_\_\_
Step 3: transport of bile acids from blood into hepatocytes * Bile acids are in the portal blood and are carried into the _hepatocyte_ predominantly through a _secondary active transporter_ * the cycle can start over again with the transport of _bile acids_ from the hepatocyte into the bile through a _primary active transport pathway_
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Hepatobiliary secretion is predominantly regulated during the intestinal phase by which three methods?
1. Bile salts * As more bile salts are absorbed from the ileum and return to the liver, more will secreted back into the bile * Bile salt synthesis is reduced when the enterohepatic circulation is working well 2. Secretin * Controls *bicarbonate* production not only in the pancreas but also in the liver * Produced and released by the S-cells in the duodenum * Its production and release is stimulated by acid in the duodenum * Increases bicarbonate secretion by the bile duct cell sand also in the pancreas 3. CCK * Produced by I-cells in the duodenum and jejunum * Production stimulated by digested fats and proteins in the upper SI * Increases contraction of the gallbladder and relaxes the sphincter of Oddi * bile is released into the duodenum
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How do bile salts contribute to the regulation of hepatobiliary secretions during the intestinal phase?
* As more bile salts are absorbed from the ileum and return to the liver, more will be secreted back into the bile * Bile salt synthesis is reduced when the enterohepatic circulation is working well
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How does secretin contribute to hepatobiliary secretion during the intestinal phase?
* Controls bicarbonate production not only in the pancreas but also in the liver * Produced and released by the **S-cells** in the duodenum * Its production and release is stimulated by acid in the duodenum * Increases bicarbonate secretion by the bile duct cells and also in the pancreas
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How does CCK contribute to the regulation of hepatobiliary secretion during intestinal phase?
* Produced by I-cells in the duodenum and jejunum * Production stimulated by digested fats and proteins in the upper SI * Increases contraction of the gallbladder and relaxes the sphincter of Oddi * bile is released into the duodenum
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Gallstones are caused by excess \_\_\_\_\_\_\_\_
Gallstones are caused by excess _cholesterol_
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How are gallstones formed?
* Cholesterol is insoluble in water and kept in solution in the bile through the formation of micelles with bile acids and phopholipids * If the concentration of cholesterol in bile becomes high relative to bile acids, cholesterol starts to *precipitate out*, "nucleating" agent also required (ie protein, bacteria)
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How are pigment gallstones formed?
With excess red blood cell breakdown (hemolysis) the amount of bile pigments are increased Bile pigments are insoluble and concentrate in bile and form precipitates with calcium
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What are the three major functions of the duodenum?
1. Mixing of pancreatic digestive enzymes and bile with food 2. Absorption of nutrients, iron and calcium 3. Release of endocrine hormones **secretin** and **CCK**
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What is the major function of the jejunum?
Digestion and absorption * Most of the chyme entering the small intestine is digested and absorbed in the first 25% of the small intestine (duodenum and jejunum)
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What is the ileum primarily involved in?
Absorption of bile acids and Vitamin B12
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Where is the pyloric sphincter?
Between the stomach and small intestine
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In the lumen of the small intestine are folds of _______ (circular folds)
In the lumen of the small intestine are folds of _Kerckring_ (circular folds)
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The circular folds of the small intestine are covered in \_\_\_\_\_\_\_
The circular folds of the small intestine are covered in _villi_ * Villus is a projection of tissue into the lumen of the tube
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The surface of each individual villus in the small intestine is covered with a layer of epithelial cells whose surface membranes form small projections called \_\_\_\_\_\_\_
The surface of each individual villus in the small intestine is covered with a layer of epithelial cells whose surface membranes form small projections called _Microvilli_
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Projections in the opposite direction of villi in the small intestine are called:
Crypt regions - invaginations of the epithelium -Have stem cells
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Where are the stem cells found in the small intestine and what are four types of epithelial cells that they differentiate into?
In the Crypts 1. Paneth cells 2. Endocrine cells 3. Goblet cells 4. Enterocytes or absorptive cells
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Which type of epithelial cell in the small intestine has microvilli at the **apical** surface of the cell (this microvilli layer is called the "brush border membrane")
Enterocyte (Absorptive cell)
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Which type of small intestine epithelial cell is important for the secretion of mucus for the lubrication of the food and protection from acid?
Goblet Cell
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What type of epithelial small intestine cell is the hormone-producing cell and what are it's two subtypes?
Enteroendocrine cells 1. I cells 2. S cells
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Which small intestine epithelial cell secretes antibacterial peptides which protect the GIT from bacteria?
Paneth cells
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What is the brush border?
Small projections (microvilli) of epithelial cells covering the villi of the small intestine, major absorptive surface of the small intestine
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What is a brush border enzyme?
Enzyme anchored to the brush border with catalytic activity in the lumen eg enterokinase which activates trypsinogen to its active form trypsin
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Brush border enzymes are important for breaking down _______ and ______ into sugars and amino acids prior to transport across the \_\_\_\_\_\_\_
Brush border enzymes are important for breaking down _carbohydrates_ and _peptides_ into sugars and amino acids prior to transport across the _enterocyte_
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Digestion of Carbohydrates * Starch (\_\_\_\_\_ and \_\_\_\_\_\_) is broken down into \_\_\_\_\_, \_\_\_\_\_\_, and ______ by salivary and pancreatic amylases * _______ and _______ cannot be absorbed by the intestinal tract; only monosaccharides (glucose) can be absorbed * The products of amylases are further broken down by ______ \_\_\_\_\_\_\_ \_\_\_\_\_\_ * Maltose/maltotriose can be digested by \_\_\_\_\_\_, ______ or ________ to glucose * _alpha-limit dextrins_ are broken down by _______ to glucose
Digestion of Carbohydrates * Starch (_amylose_ and _amylopectin_) is broken down into _maltose, maltotriose_ and _alpha-limit dextrins_ by salivary and pancreatic amylases * _disaccharides_ and _trisaccharides_ cannot be absorbed by the intestinal tract; only monosaccharides (glucose) can be absorbed * The products of amylases are further broken down by _brush border enzymes_ * Maltose/maltotriose can be digested by _maltase, sucrase_ or _alpha-dextrinase_ to glucose * alpha-limit dextrins are broken down by _alpha dextrinase_ to glucose
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What is sucrose broken down into and by what?
Sucrose (disaccharide) broken down by brush border enzyme **sucrase** → glucose and fructose
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Lactose is broken down into what? By what enzyme?
 Lactose (disaccharide) broken down by brush border enzyme **lactase** → glucose and galactose
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What 3 monosaccharides are absorbed by the GIT?
Glucose, fructose, galactose
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How are glucose and galactose absorbed by the GIT (intestinal absorption of glucose and galactose)?
* Same transport pathway * Move from the intestinal lumen into the enterocyte through the *Na+ -dependent glucose transporter*, **SGLT** (apical membrane)  * *Secondary active transport* as it uses the Na+ gradient to drive uptake of sugar into the enterocyte * Na+ gradient generated by the Na+ /K+ ATPase * Glucose and galactose are transported across the **basolateral** surface of the enterocyte through a facilitated glucose transporter, **GLUT**
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How is Fructose absorbed in the GIT? (ie describe the intestinal absorption of fructose)
* Fructose moves into the *enterocyte* across the *apical* membrane through a *facilitated* carrier, **GLUT5** * Fructose is transported across the *basolateral* surface of the enterocyte through a *facilitated glucose transporter*, **GLUT2**
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Lumen of SI **pancreatic amylase** breaks down polysaccharides into 3 different products: \_\_\_\_\_\_\_\_\_, \_\_\_\_\_\_\_\_, __________ which are then further broken down by _________ into \_\_\_\_\_\_\_\_
1. maltose, 2. maltotriose and the 3. alpha-limit dextrins which are then further broken down by _brush border enzymes_ into monosaccharides (Fructose, **glucose**, galactose)
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* Fructose is carried into the enterocyte through a _\_\_\_\_\_\_\__carrier, _\_\_\_\_\_\_\__ * Glucose and galactose are carried into the enterocyte through a _**\_\_\_\_\_\_\_\_\_\_**_pathway, _\_\_\_\__ * All these monosaccharides are then absorbed across the basolateral surface of the enterocyte through a different member of the _\_\_\_\_\_\__ family (facilitated glucose transporter) * Only absorb ________ in the SI
* Fructose is carried into the enterocyte through a _facilitated_ carrier, _GLUT5_ * Glucose and galactose are carried into the enterocyte through a _secondary_ _active_ _transport_ pathway, _SGLT_ * All these monosaccharides are then absorbed across the basolateral surface of the enterocyte through a different member of the _GLUT_ family (facilitated glucose transporter) * Only absorb monosaccharides in the SI
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What are brush border enzymes?
Brush border enzymes in the SI break down carbohydrates, and peptides into amino acids
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*Protein Digestion and Absorption:* * Digestion of proteins begins in the _\_\_\_\_\_\_\__ * **Pepsinogen** is activated by _**\_\_\_\_\_\_\_\_**_to _\_\_\_\_\_\__, which breaks down proteins * In the small intestine proteins are broken down by **pancreatic proteases** (Major ones are _\_\_\_\_\_\_\__and _\_\_\_\_\_\_\_\_\__) * Further broken down to free amino acids by: * _\_\_\_\_\_\_\_\_\__ – pancreatic protease * _\_\_\_\_\_\_\_\__ – brush border enzyme * Many other _\_\_\_\_\_\_\_\_\_\__ * **Trypsin** and **chymotrypsin** can only cleave the _\_\_\_\_\_\_\__peptide bonds, while **carboxypeptidase** and **aminopeptidase** can cleave the _\_\_\_\_\_\_\_\__ and the _\_\_\_\_\_\_\_\_\__ peptide bonds * Free amino acids are absorbed by _\_\_\_\_\_\_\_\_\_\__coupled to _\_\_\_\__ (many different transport pathways) * Small peptides (dipeptides or tripeptides) can also be absorbed by _**\_\_\_\_\_\_\_\_\_**_coupled to _\_\_\__ (rather than Na+) * Once the peptides are absorbed by the cell, ___________ break down the peptides into individual **amino acids**
*Protein Digestion and Absorption:* * Digestion of proteins begins in the _stomach_ * **Pepsinogen** is activated by _stomach acid_ to _pepsin_, which breaks down proteins * In the small intestine proteins are broken down by **pancreatic proteases** (Major ones are _trypsin_ and _chymotrypsin_) * Further broken down to free amino acids by: * _Carboxypeptidase_ – pancreatic protease * _Aminopeptidase_ – brush border enzyme * Many other _brush border enzymes_ * **Trypsin** and **chymotrypsin** can only cleave the _internal_ peptide bonds, while **carboxypeptidase** and **aminopeptidase** can cleave the _amino-portion_ and the _carboxyterminal_ peptide bonds * Free amino acids are absorbed by _secondary active transport_ coupled to _Na+_ (many different transport pathways) * Small peptides (dipeptides or tripeptides) can also be absorbed by _secondary active transport_ coupled to _H+_ (rather than Na+) * Once the peptides are absorbed by the cell, _intracellular_ _peptidases_ break down the peptides into individual **amino acids**
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*Protein Digestion and Absorption:* * Amino acids undergo _\_\_\_\_\_\_\_\_\__across the _\_\_\_\_\_\__ surface of the enterocyte into the circulation * Many different _\_\_\_\_\_\_\__at the **apical** surface and _\_\_\_\_\_\_\_\__ transporters at the **basolateral** surface specific for different amino acids
*Protein Digestion and Absorption:* * Amino acids undergo _facilitated diffusion_ across the _basolateral_ surface of the enterocyte into the circulation * Many different _secondary active transporters_ at the **apical** surface and _facilitative_ transporters at the **basolateral** surface specific for different amino acids
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*Summary of Digestion and Absorption of Proteins:* * Proteins and peptides are acted on by in the stomach * is released by **chief** **cells** and then activated by the of the lumen of the stomach * continue to breakdown peptides into amino acids and smaller peptides in the **duodenum** * cleave peptides into amino acids * Amino acids can be reabsorbed and taken up by the enterocyte via a * Small peptides can also be taken up by a coupled to * Small peptides are cleaved within the cell by to amino acids * Amino acids can then undergo *out of the cell* into the interstitial space for absorption into the *bloodstream*
*Summary of Digestion and Absorption of Proteins:* * Proteins and peptides are acted on by _pepsin_ in the stomach * _Pepsinogen_ is released by **chief** **cells** and then activated by the _acidic pH_ of the lumen of the stomach * _Pancreatic proteases_ continue to breakdown peptides into amino acids and smaller peptides in the **duodenum** * _Brush border peptidases_ cleave peptides into amino acids * Amino acids can be reabsorbed and taken up by the enterocyte via a _Na+ - dependent process_ * Small peptides can also be taken up by a _secondary active transport_ coupled to _H+_ * Small peptides are cleaved within the cell by _intracellular peptidases_ to amino acids * Amino acids can then undergo _facilitated diffusion_ *out of the cell* into the interstitial space for absorption into the *bloodstream*
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\_\_\_\_\_\_\_\_ are composed of lipid molecules that arrange themselves in a spherical form in aqueous solutions
_Micelles_ are composed of lipid molecules that arrange themselves in a spherical form in aqueous solutions
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Micelles are formed by:
Formed from fatty acids, monoglycerides and bile salts during fat digestion in the SI
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Large fat droplets are composed mostly of \_\_\_\_\_\_\_\_
Large fat droplets are composed mostly of _triglycerides_
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* Lipid droplets are **emulsified** through the combined action of _\_\_\_\_\_\_\_\_\__and _\_\_\_\_\_\_\_\_\__ which allows _\_\_\_\_\_\_\_\_\__to release _\_\_\_\_\_\_\_\_\__ and _\_\_\_\_\_\_\_\_\__ * _\_\_\_\_\_\_\_\_\__is water-soluble and can only act on the surface of the _\_\_\_\_\_\_\_\_\__; large fat droplets must be broken down into smaller ones for _\_\_\_\_\_\_\_\_\__ to act * _\_\_\_\_\_\_\_\_\__and _\_\_\_\_\_\_\_\_\__ bind to the outside of the smaller droplets to keep them from **re-aggregating** * Pancreatic lipase can then break *triglycerides* into _\_\_\_\_\_\_\_\_\__and _\_\_\_\_\_\_\_\_\__; these products of lipase digestion are incorporated into micelles, which are in a dynamic state of breaking down and reforming
* Lipid droplets are **emulsified** through the combined action of _mechanical disruption_ and **_bile acids/phospholipids_** which allows _pancreatic lipase_ to release _free fatty acids_ and _monoglyceride_ * _Pancreatic lipase_ is water-soluble and can only act on the surface of the _fat droplets_; large fat droplets must be broken down into smaller ones for _pancreatic lipase_ to act * _Bile acids_ and _phospholipids_ bind to the outside of the smaller droplets to keep them from **re-aggregating** * Pancreatic lipase can then break *triglycerides* into _monoglycerides_ and _free fatty acids_; these products of lipase digestion are incorporated into micelles, which are in a dynamic state of breaking down and reforming
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Once the epithelial cells absorb the fatty acids and monoglycerides, they are processed by the _\_\_\_\_\_\_\_\_\_\__back into _\_\_\_\_\_\_\__
Once the epithelial cells absorb the fatty acids and monoglycerides, they are processed by the _endoplasmic reticulum_ back into _triglycerides_
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Why are fatty acids and monoglycerides resynthesized into triglycerides as they pass through the epithelial cell?
1. To maintain the diffusion gradient from the lumen of the small intestine to the epithelial cell, so that fatty acids and monoglycerides can be absorbed into the enterocytes by diffusion 2. To allow triglycerides to be further processed for absorption * Within the ER, triglycerides aggregate into lipid droplets that are coated with **amphipathic** **proteins**; the droplets of triglycerides are then packaged in the Golgi and secreted across the basolateral surface of the enterocyte through exocytosis
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Extracellular fat droplets known as “_\_\_\_\_\_\_\_\_\__”
Extracellular fat droplets known as “_chylomicrons_”
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Why are fatty acids and monoglycerides resynthesized into triglycerides as they pass through the epithelial cell? * To maintain the _**\_\_\_\_\_\_\_\_\_\_**_from the lumen of the small intestine to the epithelial cell, so that fatty acids and monoglycerides can be absorbed into the enterocytes by diffusion * To allow _\_\_\_\_\_\_\_\_\_\__ to be further processed for absorption * Within the _\_\_\_\_\_\_\_\_\_\__, triglycerides aggregate into _\_\_\_\_\_\_\_\_\_\__ that are coated with _\_\_\_\_\_\_\_\_\_\__; the droplets of triglycerides are then packaged in the _\_\_\_\_\_\_\_\_\_\__ and secreted across the _\_\_\_\_\_\_\_\_\_\__ surface of the enterocyte through exocytosis * Extracellular fat droplets known as “_\_\_\_\_\_\_\_\_\_\__”
Why are fatty acids and monoglycerides resynthesized into triglycerides as they pass through the epithelial cell? * To maintain the _diffusion gradient_ from the lumen of the small intestine to the epithelial cell, so that fatty acids and monoglycerides can be absorbed into the enterocytes by diffusion * To allow triglycerides to be further processed for absorption * Within the _ER_, triglycerides aggregate into _lipid droplets_ that are coated with _amphipathic_ _proteins_; the droplets of triglycerides are then packaged in the _Golgi_ and secreted across the _basolateral_ surface of the enterocyte through exocytosis * Extracellular fat droplets known as “_chylomicrons_”
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Chylomicrons contain (4)
1. triglycerides, 2. phospholipids, 3. fat-soluble vitamins and 4. cholesterol
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Chylomicrons are absorbed by the _\_\_\_\_\_\_\_\_\__via _\_\_\_\_\_\__
Chylomicrons are absorbed by the _lymphatic_ _system_ via _lacteals_
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Why are chylomicrons absorbed via lacteals instead of capillaries?
lacteals are leakier than capillaries Lacteal → lymphatic vessel in the intestinal villi
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Chylomicrons absorbed into the lymphatic system eventually enter systemic circulation through:
o The lymphatics eventually enter into the systemic circulation via the **thoracic** duct
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How are fatty acids and monoglycerides released from triglycerides in chylomicrons for absorption by tissues?
Components of fat move from the blood into the tissue; a **lipase** (lipoprotein lipase) found on endothelial cells of blood vessels then breaks down triglycerides present in chylomicrons to **monoglycerides** and **free fatty acids** to be taken up by tissues
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_\_\_\_\_\_\_\__iron or Fe2+ (_\_\_\_\_\_\__ iron)is absorbed by the GIT
_Divalent_ iron or Fe2+(_ferrous_ iron)is absorbed by the GIT
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How is divalent iron absorbed into the enterocyte? * Divalent iron is **actively** **transported** into the enterocyte through an **\_\_\_\_\_\_\_\_\_\_** * Once divalent iron is actively transported into the intestinal epithelial cells it binds with a protein called **\_\_\_\_\_\_\_** * _____ is a protein iron complex that acts as a **storage** **form** of iron * The absorbed iron that does not bind to ____ to be stored in the epithelial cell is *released* on the *blood side of the enterocyte* and transported in the blood attached to a *plasma protein* called **\_\_\_\_\_\_**
* Divalent iron is **actively** **transported** into the enterocyte through an **apical** **transport** **pathway** * Once divalent iron is actively transported into the intestinal epithelial cells it binds with a protein called **ferritin** * Ferritin is a protein iron complex that acts as a **storage** **form** of iron * The absorbed iron that does not bind to ferritin to be stored in the epithelial cell is *released* on the *blood side of the enterocyte* and transported in the blood attached to a *plasma protein* called **transferrin**
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*Absorption of Iron from the Intestine:* * Iron that remains in the enterocyte bound to ______ is excreted from the body when the enterocytes slough off of the villi tips * When body stores of iron are high, the production of ferritin is \_\_\_\_\_, resulting in: * When the intestinal cells are sloughed off, the iron is excreted in the feces * When there is a need for iron and iron stores are depleted, the enterocytes produce ___ ferritin resulting in:
* Iron that remains in the enterocyte bound to _ferritin_ is excreted from the body when the enterocytes slough off of the villi tips * When body stores of iron are high, the production of ferritin is _high_, resulting in: increased binding of ferritin in the epithelial cells and a reduction in the amount of iron released into the blood * When the intestinal cells are sloughed off, the iron is excreted in the feces * When there is a need for iron and iron stores are depleted, the enterocytes produce _less_ ferritin resulting in: less iron retained in the enterocyte and more will then be absorbed into the blood
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Which region of the GIT is responsible for the most fluid reabsorption?
The small intestine
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*Absorption and Secretion of Water: Generalizations:* * In the small intestine water absorption occurs at the _\_\_\_\_\__while secretion occurs at the _\_\_\_\_\__ * Intestinal epithelium establishes an _\_\_\_\_\_\_\_\__and water follows through _\_\_\_\_\_\_\__ (Paracellular transport) * The gradient has to be in the inward direction for _\_\_\_\_\_\__to occur and in the outward direction for _\_\_\_\_\_\_\__ to occur
*Absorption and Secretion of Water: Generalizations:* * In the small intestine water absorption occurs at the _villi_ while secretion occurs at the _crypts_ * Intestinal epithelium establishes an _osmotic gradient_ and water follows through _tight junctions_ (Paracellular transport) * The gradient has to be in the inward direction for _absorption_ to occur and in the outward direction for _secretion_ to occur
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It is important to understand electrolyte transport to understand water transport * _\_\_\_\_\__, _\_\_\_\_\__ and _\_\_\_\_\_\_\__ are important electrolytes for water transport
It is important to understand electrolyte transport to understand water transport * _Sodium_, _chloride_ and _bicarbonate_ are important electrolytes for water transport
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Absorption of Water in the Small Intestine predominantly depends on _\_\_\_\_\_\__ generated during secondary active nutrient uptake (_\_\_\_\_\_\_\_\_)_
Absorption of Water in the Small Intestine predominantly depends on _Na+ gradients_ generated during secondary active nutrient uptake (_glucose or amino acids)_
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Absorption of Water in the Small Intestine: * _\_\_\_\_\_\_\__generates a low intracellular Na+ concentration, pumping Na+ out of the cell; this Na+ gradient is used to move _\_\_\_\_\__ into the cell * In the case of glucose, glucose and Na+ are brought in by the _\_\_\_\_\_\_\_\_\__and then pumped out by the _\_\_\_\_\_\_\_\_\__ * The Na+ gradient from low to high results in _\_\_\_\_\__, a negatively charged ion, following the positively charged Na+ * Water then follows those two gradients
Absorption of Water in the Small Intestine: * _Na+ /K+ ATPase_ generates a low intracellular Na+ concentration, pumping Na+ out of the cell; this Na+ gradient is used to move _glucose_ into the cell * In the case of glucose, glucose and Na+ are brought in by the _Na+ -glucose transporter SGLT_ and then pumped out by the _Na+ /K+ ATPase_ * The Na+ gradient from low to high results in _Cl-_ , a negatively charged ion, following the positively charged Na+ * Water then follows those two gradients
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Water absorption in the LI is very similar to the SI, relying on the movement of _\_\_\__ from the lumen to the extracellular fluid * With what important difference\*\*\*\*\*\*
* Water absorption in the LI is very similar to the SI, relying on the movement of _Na+_ from the lumen to the extracellular fluid * Importantly, there are no nutrients (glucose) being absorbed in a healthy LI, so the transport pathway is a little different
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Secretion of Water in the SI predominantly depends on:
Secretion of Water in the SI predominantly depends on _Cl-_ gradients generated by secondary active _Na+ /K+ /2Cl- transporter (NKCC1)_
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*Secretion of Water in the SI:* * Depends on _\_\_\__gradients generated by _\_\_\_\__ * NKCC1 transports 3 ions: _\_\_\_\__, _\_\_\__ and _\_\__ * NKCC1 allows the accumulation of _\_\_\__in the enterocyte based on the inwardly-directed _\_\_\_\_\_\_\_\_\_\_\__ * _\_\_\_\_\__on the brush border membrane of the epithelial cell opens, to allow Cl- to move down its concentration gradient into the _\_\_\_\_\_\__ * _\_\_\_\__ will be attracted to the negative gradient of Cl- and water will follow, being secreted into the lumen * cAMP: * Stimulates the opening of _\_\_\_\_\__
*Secretion of Water in the SI:* * Depends on _Cl-_ gradients generated by _NKCC1_ * NKCC1 transports 3 ions: _Na+_ , _K +_ and _Cl-_ * NKCC1 allows the accumulation of _Cl-_ in the enterocyte based on the inwardly-directed Na+ electrochemical gradient * _CFTR_ on the brush border membrane of the epithelial cell opens, to allow Cl- to move down its concentration gradient into the _intestinal lumen_ * _Na+_ will be attracted to the negative gradient of Cl- and water will follow, being secreted into the lumen * cAMP: * Stimulates the opening of _CFTR_ \*CFTR = Cystic fibrosis transmembrane conductance regulator
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How does secretion of water by the LI differ to secretion of water in the SI?
They are identical: * Secretion of Water in the SI: * Depends on Cl- gradients generated by NKCC1 * NKCC1 transports 3 ions: Na+ , K + and Cl- * NKCC1 allows the accumulation of Cl- in the enterocyte based on the inwardly-directed Na+ electrochemical gradient * CFTR on the brush border membrane of the epithelial cell opens, to allow Cl- to move down its concentration gradient into the intestinal lumen * Na+ will be attracted to the negative gradient of Cl- and water will follow, being secreted into the lumen * cAMP: * Stimulates the opening of CFTR
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Most common motion in the SI during digestion is _\_\_\_\_\_\_\_\__
Most common motion in the SI during digestion is _segmentation_
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Why is segmentation important?
Allows for the mechanical breakdown of food (increase the surface area) and mixing of the food with digestive enzymes and water
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* Frequency of contraction set by _\_\_\_\_\_\_\_\__, driven by the _\_\_\_\_\__ cells in the *smooth muscle layers* * 12 contractions/min in _\_\_\_\__ * 9 contractions/min in _\_\_\_\__ * The contraction force of the smooth muscle is determined by _\_\_\_\_\_\_\__ * Results in a _\_\_\_\_\__ net migration towards the LI * Slow passage of food allows for _\_\_\_\_\_\_\_\_\_\__
* Frequency of contraction set by _basic electrical rhythm_, driven by the _pacemaker_ cells in the *smooth muscle layers*  * 12 contractions/min in _duodenum_ * 9 contractions/min in _ileum_ * The contraction force of the smooth muscle is determined by _neurohormonal_ _input_ * Results in a _very small_ net migration towards the LI * Slow passage of food allows for _digestion and absorption of nutrients_
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Peristaltic activity is referred to as the:
Peristaltic activity is referred to as the migrating myoelectric complex (MMC)
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Purpose of Migrating myoelectric complex (MMC)?
push undigested material from the SI into the LI and prevents bacteria from remaining in the SI
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What regulates the migrating myoelectric complex?
Intestinal hormone motilin * Initiates the MMC * When you eat, **motilin** release is **inhibited** to allow the segmentation contractions to occur
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What happens to motilin release when you eat?
**Motilin** is an intestinal hormone that initiates the MMC (peristaltic contractions). It's release is inhibited when you eat in order to allow segmentation contractions to occur
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What causes cholera? What are the symptoms? What is the physiological impact of the bacteria causing cholera?
* Cause * eating food or drinking water contaminated with the bacteria *Vibrio cholera* * Symptoms * Vomiting and excessive diarrhea * 20 litres of stool per day (normal 0.1 litres), dehydration, electrolyte imbalance, death * Physiological impact: * Vibrio cholerae produce a toxin that increases the production of **_cAMP_** * Increased cAMP stimulates the Cl- channel present in the SI epithelia to open, allowing large amount of Cl- into the intestinal lumen; water follows and is lost as diarrhea
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_\_\_\_\_\_\_\_\__: sphincter between the cecum and the ileum
_Ileocecal valve_: sphincter between the cecum and the ileum
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The ileocecal valve is _\_\_\_\__when the ileum contracts after a meal and _\_\_\_\__ when the LI is distended
The ileocecal valve is _open_ when the ileum contracts after a meal and _closed_ when the LI is distended; retains large intestine contents including bacteria
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Functions of the Ascending, transverse, descending, & sigmoid colon
* Re-absorption of water * Majority of water absorption occurs in the SI, but these regions do absorb water * Serve as a reservoir for the storage of waste and undigested materials prior to elimination by defecation * Absorb products of bacterial metabolism
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Anus: * Composed of two sphincters that control _\_\_\_\_\__ 1. Internal anal sphincter: _\_\_\_\_\_\_\_\_ (type of muscle)_ 2. External anal sphincter: _\_\_\_\_\_\_\_\_ (muscle?)_
Anus: * Composed of two sphincters that control _defecation_ 1. Internal anal sphincter: _smooth muscle_/_involuntary_ 2. External anal sphincter: _skeletal_ _muscle_/_under voluntary control_
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What is one reason why the surface area of the large intestine is much smaller than the small intestine?
The large intestine only has crypts (no villi) * crypts have stem cells
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4 different epithelial cells generated from the stem cells in the Large intestine:
Stem cells in the crypts of the LI differentiate into one of: 1. Absorptive cells (enterocytes) → similar to the SI but do not contain brush border enzymes 2. Goblet cells → abundant 3. Endocrine cells → very few 4. Paneth cells → very few
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What are three functions of the bacteria in the Large Intestine (colonic bacteria)?
1. Metabolize fiber into short chain fatty acids that are absorbed by diffusion 2. Can also produce vitamins (Vitamin K) that are absorbed 3. Produce gas
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Absorption of water in SI occurs predominantly over the _\_\_\_\__ surface whereas water absorption in the LI occurs predominantly in the \_\_\_\_\_
Absorption of water in SI occurs predominantly over the _villi_ surface whereas water absorption in the LI occurs predominantly in the _crypts (_no villi in large intestine)
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What are the two types of movement in the Large intestine?
1. Mixing: * **Segmentation** in the LI * Slower basal electrical rhythm than SI to allow retention in the colon 2. Propulsion: * Wave of propulsion or intense contraction (mass movement) spreads rapidly over the LI, pushing the contents towards the anus; this happens after eating and prior to defecation
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What initiates defecation?
Process of defecation initiated by the **mass movement** of the large intestine contents into the rectum
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Describe the defecation reflex:
1. Process of defecation initiated by the **mass movement** of the large intestine contents into the rectum 2. Rectum distends and activates **mechanoreceptors** o 3. A reflex is initiated: 1. Rectum contracts, *internal anal sphincter relaxes* and *outer anal sphincter contracts* (Initially) 2. Increased peristaltic activity in the sigmoid colon, increasing pressure results in *reflex relaxation of the external anal sphincter* 3. Feces voided * After toilet training, the brain can override this reflex relaxation of the **outer sphincter**, delaying defecation to a more socially acceptable time * Delay results in **reverse peristalsis** and rectal contents are moved back into the **sigmoidal** **colon** * Disadvantage of delay is more water absorption occurs and feces will become harder to void