GI - Mulroney Flashcards by William Leake

Path/structures of the GI tract:
Mouth
- 2 glands are.....
Esophagus
- 2 structures are......
Stomach and Duodenum
- \_\_\_\_\_\_ Sphincter
- contributing organs =
- duodenum length ~ \_\_in
Intestinal tract = 
Anus
- Anal sphincters =

Parotid and Salivary
Upper esophageal sphincter (UES) & Lower (LES)
Pyloric
Liver/Gallbladder, Pancreas
12in
Jejunum (~8ft), Ilium (~10ft), Ileocecal sphincter, Ascending colon, transverse colon, descending colon
Internal and External anal sphincters

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The GI tract is composed of smooth muscle, except in ______, upper __________ and _______________.

mouth, esophagus, external anal sphincter

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The diverse cell types in the small intestine allow ________, ________, ________ of motility and secretion.

digestion, protection, regulation

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The splanchnic circulation encases the intestines; blood flows from the ________ through the _____ vein to the ____. This is the ____ ____ effect.

intestines, portal, liver

first pass

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What are the functions of the GI tract?
D
E
E
P

M
A
S
S

Digestion– Enzymes and HCl (*HCl does not actually digest, it makes chunks smaller, increasing surface area?)
Endocrine– LOTS of hormones which act on GI tract and other tissues
Elimination– rids body of undigested waste
Protection– HCl, IgAs, opsonins, and other immune cells
Motility– propels and mixes chyme
Absorption– of almost everything you eat
Secretion– buffers mucus, hormones (into blood), enzymes
Storage– stomach and colon

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Fluid intake is ~_ L/day

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You may only ingest _ liters of fluid a day, but the GI tract SECRETES - LITERS. This means it has to absorb _-_LITERS of fluid each day!

2, 7-8, 9-10

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The secretions help _______, ________, and _____ the chyme.

lubricate, digest (HCl, enzymes), and buffer (HCO3 buffers the acid)

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The movement of fluids and gases in and out of the intestines can be heard sometimes. These sounds are called ___________.

borborygmi

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Changes in __ through the tract are important to GI function.
Stomach acid ~
Chyme in jejunum ~

pH
1
7 (pH where enzymes can function)

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Regulation of the GI tract:
▪ Enteric Nervous System
- _________ plexus (muscle/movement)
- _________ plexus (secretions)
▪ ____________ Nervous System (mainly vagal to transverse colon, then pelvic nerves to anus)
▪ ____________ Nervous System (post-ganglionic adrenergic fibers from celiac, superior and inferior mesenteric and hypogastric plexes)
▪ ___
▪ Lumenal ______-, ______- and ____receptors (act on the enteric NS)
▪ _________

myenteric
submucosal
Parasympathetic (pro)
Sympathetic (slow)~running is good for motility by forcing GI to relax?
CNS~anticipatory response for pro!
chemo-, mechano- and osmo
Hormones

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What is the nervous system specific to the GI tract called?

What are the two nerve nets and what do they control?

Enteric Nervous System

myenteric plexus (muscle/movement)
submucosal plexus (secretions)

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The interdigestive state has a special type of motility:

The Migrating Myoelectric Complex, or MMC

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The MMC:
•Begins about ___ hours after you finish eating •Housekeeping movement– sweeps undigested material and bacteria into ______
•Is active from mid-stomach through the terminal ileum •Has 4 phases, with the main propulsive movements occurring during phase III (phases I, II and IV have minor, disregulated contractions): an entire cycle lasts 75-120 min.
•Phase III contractions only last about __min each cycle, but the series of contractions sweep material lower in the tract. Phase III is stimulated by the hormone ______, secreted into blood from the M cells of the small intestine.

3-4 hours
colon
10 min, Motilin

*MMC when have not eaten for a period of time?

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Moving down the GI tract–
Swallowing– begins as ________ action (remember the skeletal muscle in the upper esophagus/pharynx), and then is involuntary as the ________ and _________ nervous systems take over.
In the esophagus there are 2 types of propulsion, ______ and ________ esophageal peristalsis.

*Smooth muscle disorders in the GI tract can affect the enteric nerves…

voluntary
enteric (from mechanoreceptors) and autonomic
primary and secondary

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Receptive relaxation concept =

SEE SLIDE 7 of Motility lecture

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Principle of bariatric surgery is to reduce the ability of the stomach to _____________ food.

accommodate

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Gastric emptying…..see slide 9

Motility lecture

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How are contractions generated?

By electrical impulse.
Resting Membrane Potential = slow waves (stomach ~ 3min, small int ~ 10-12min).
RMP = Base Electrical Rhythm (BER)
Spike potential = > -40mV at peak of BER if there is a stimulus = Ca + Calmodulin.

*See slide 11 Motility lecture

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Depolarization by:

Hyperpolarization by:

stretch, ACh/parasymp, gastrin, serotonin, subst. P (tachykinin)

NE, sympathetics, Vasointestinal Peptide, NO?

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Peristalsis:

May be under more vagal/extrinsic control

*slide 12 motility helpful

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Segmentation:

May be under more intrinsic (enteric nerve) control

*slide 13 motility helpful

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Contraction of the gall bladder releases ____ into the _________, which facilitates ____ absorption. _____ stimulation relaxes the sphincter of Oddi (into the duodenum), and later in digestion (during the intestinal phase) the hormone ___(in addition to vagal stimulation) will stimulate gallbladder ___________.

bile, duodenum, lipid

Vagal, CCK, contraction

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In the colon, the_________ contract to make sacs in the colon (_______). This is _________ propulsion. It is SLOW, and designed for storage and dehydration of _____ to feces.

taneia coli
haustrae
segmental (NOT segmentation)
chyme

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Haustrae are formed by contraction of the __________.

taneia coli

Mass Movements: • These are peristaltic contractions that are stimulated by GI __________ and the ______ nerve, in response to ______ in the upper GI tract. (this works great in babies!) The haustrae smooth out into a tube, and the mass movement contractions force the feces into the descending colon and rectum. This will typically stimulate the defecation reflex (or rectosphincteric reflex).

hormones, vagus | chyme

Clinical Significance of GI Motility:

* Constipation * Diarrhea * Inflammatory Bowel Disease * Inflammatory Bowel Syndrome * Congenital disorders (eg, Hirschsprung’s d.)

Rectosphincteric reflex =

transient involuntary relaxation of the internal anal sphincter in response to distention of the rectum.

Gastrocolic reflex =

an increase in motility of the colon consisting primarily of giant migrating contractions, or mass movements, in response to stretch in the stomach and byproducts of digestion in the small intestine. Thus, this reflex is responsible for the urge to defecate following a meal. The small intestine also shows a similar motility response. The gastrocolic reflex's function in driving existing intestinal contents through the digestive system helps make way for ingested food.

Secretions through the GI tract: | Mouth =

Saliva Lingual lipase Salivary alpha-amylase R-Proteins = Transcobalamin-1 (TC-1)

Esophagus =

Electrolytes | mucus

Stomach =

``` HCl, intrinsic factor pepsinogens gastric lipase mucus, gastrin somatostatin histamines ```

Pancreas: | Exocrine glands =

``` buffers and enzyme (tripson, chymotrypsin, procarboxypeptidase, lipase, colipase, proelastase, alpha-amylase) monitor peptides (trypsin inhibitor; stimulates CCK) ```

Pancreas: | Endocrine Glands =

insulin glucagon somatostatin

Liver and gallbladder =

bile and buffers (electrolyte)

Small intestine =

``` Buffers (mucus and electrolytes) enterokinase brush border disaccharidases brush border peptidases secretin gastrin CCK VIP GIP motilin 5HT somatostatin ```

``` Hormones secreted by the GI tract: Gastrin Site of secretion = Stimuli = Actions = ```

G-cells in antrum of stomach and in the duodenum Stretch, peptides, amino acids, vagus (through GRP) Stimulate gastric H+, increased lower GI motility, increased gastric mixing

``` Hormones secreted by the GI tract: Secretin Site of secretion = Stimuli = Actions = ```

S-cells of the duodenum Acidic chyme increased pancreatic, biliary and intestinal buffers, decreased gastric H+

``` Hormones secreted by the GI tract: Cholecystokinin (CCK) Site of secretion = Stimuli = Actions = ```

I-cells of the duodenum and jejunum Small peptides, amino acids and fats increased pancreatic enzyme secretion, contracts gallbladder, relaxes Sph. Of Oddi

``` Hormones secreted by the GI tract: Glucose Insulinotropic Peptide (gastric inhibitory peptide, GIP) Site of secretion = Stimuli = Actions = ```

Duodenum and jejunum Fatty acids, glucose, amino acids increased pancreatic insulin secretion, (decreased gastric H+) ** GIP really doesn’t have physiologic effect on acid, only pharmacologic

``` Hormones secreted by the GI tract: Motilin Site of secretion = Stimuli = Actions = ```

M-cells of the duodenum Fasting Stimulates Phase III MMC contractions

``` Hormones secreted by the GI tract: Glucagon-Like Peptide (GLP)-1 and Peptide YY Site of secretion = Stimuli = Actions = ```

Mainly jejunum/lower SI Jejunum/ileum Chyme Satiety (decreased hypothalamic NPY)

``` Hormones secreted by the GI tract: Ghrelin Site of secretion = Stimuli = Actions = ```

Oxnytic cells of stomach Fasting Hunger (increased hypothalamic NPY)

Hunger: In the fasting state, _______ is secreted into blood from oxnytic cells in the stomach. In the arcuate nucleus of the ______________ ghrelin stimulates ___, an orexigenic peptide (stimuates _______).

ghrelin, hypothalamus, NPY, hunger

Satiety: When you eat, several peptides, including peptide __ and _____ are secreted into the circulation---they suppress ______________, decreasing appetite

YY, GLP-1 (glucagon-like peptide) | hypothalamic NPY

Satiety: Longer acting? [In addition to gut peptides…. ______ is produced in adipose (and other) tissues and is considered the counterpart of ______– when you eat, glucose and insulin increase circulating ______ which decreases appetite by suppressing ___ in the arcuate nucleus. ]

Leptin ghrelin leptin NPY

Daily Salivary Output: Parotid Glands serous fluid (w/amylase) Submandibular Glands mixed serous/mucous fluid Sublingual Glands mucous fluid

< | >

Saliva is ALWAYS __________ to plasma

hypotonic

``` Saliva: “Primary Secretion” •Contains _______ •{Na, K+, Cl-, HCO3-]similar to _______ •Modification of ____ content •Electrolyte concentration __________ proportional to flow of saliva ```

amylase plasma ionic directly

``` The PNS (through facial (_______ & ________ glands) and glossopharyngeal (______ glands) nerves) controls salivary flow: See slide 6, secretions!!! ```

submax & sublingual | parotid

``` Regulation of Salivary Flow: the following Increases or Decreases flow? • Parasympathetics, Ach • CNS (cephalic phase) • Nausea • Esophageal distension • Chewy, flavorful foods • Dry, acidic, alkaline foods • Meats, sweets, bitter foods ```

Increases

``` Regulation of Salivary Flow: the following Increases or Decreases flow? • Sympathetics, NE • Hormones (ADH, Aldo) • Sleep • Dehydration • Drugs • aging ```

Decreases

What does saliva do?

* Taste - adds to it due to digestion of some nutrients * Coagulation factors * Antimicrobial action (decrease saliva = more cavities) * Protection (cools hot food) * Digestion * Lubrication (mucus) * Oral hygiene (no saliva at sleep = bad morning breath, swallowing flushes bacteria out)

Gastric Secretions: into lumen to make chyme HCl = ________ cells (activated by vagal stimulation of food in stomach): starts a chemical rending of food to increase Stomach Acid (pH ___) before comes into the duodenum from the stomach. Not only under neural (vagus) control but also under intrinsic control via gastrin – a blood borne mediator and potent secretagogue. Intrinsic factor (IF) = _______ Cells: second line of defense for ________________________. B12 attached to ____ (which prevents it _______ from being digested by pepsins in stomach). IF binds to Vit B12 at a site to protect from pancreatic proteases in the small intestine. Pepsinogens = _____ Cells: Cleaved by HCl to pepsin (need an ______ environment to make pepsin. Pepsin breaks down proteins into smaller peptides). Start _______ digestion. _______ digestion starts in stomach. Rule of thumb ______% of digestion occurs preduodenal. Gastrin = ____ Cells in antrum of stomach and duodenum: ONLY secreted into ______: hormonal aspect of HCl secretion. Stim by vagus nerve (PSNS) in response to food/stretch in stomach. _________ HCl secretion from parietal cells. Lipase = _____ Cells: continues _____ digestion at ____ pH. Mucus = _______ Cells: lubricates & sticks to cell to trap _______________ Other = - Histamine (H1)– H1 receptors – ________ HCl - Somatostatin (SS) – modulates/________ HCl

HCl = Parietal cells (activated by vagal stimulation of food in stomach): starts a chemical rending of food to increase SA (pH 1.5) comes into the duodenum from the stomach. Not only under neural (vagus) control but also under intrinsic control via gastrin – a blood borne mediator and potent secretagogue. Intrinsic factor (IF) = Parietal Cells: second line of defense for vit B12 (B12 is essential and necessary for RBC maturation, no B12 = pernicious anemia). B12 attached to TC-1 (which prevents it from being digested by pepsins in stomach). IF binds toVit B12 at a site to protect from pancreatic proteases in the small intestine. Pepsinogens = Chief Cells: Cleaved by HCl to pepsin (need an acidic environment to make pepsin. Pepsin breaks down proteins into smaller peptides). Start protein digestion. Protein digestion starts in stomach. Rule of thumb 20-30% of digestion occurs preduodenal. Gastrin = G-Cells in antrum of stomach and duodenum: ONLY secreted into blood: hormonal aspect of HCl secretion. Stim by vagus nerve (PSNS) in response to food/stretch in stomach. Increases HCl secretion from parietal cells. Lipase = Chief Cells: continues lipid digestion at low pH. Mucus = Epithelial Cells: lubricates & sticks to cell to trap bicarbonate HCO3- Other = - Histamine (H1)– H1 receptors – increase HCl - Somatostatin (SS) – modulates/decreases HCl

Bariatric Surgery. They take a part of the body of stomach and get rid of it so it can’t accommodate (expand). Now we lose a lot of ___ production and __. So you could need _________ shots. _________ is stored in the liver for long time so you don’t need shots all the time.

HCl IF vitamin B12 vitamin B12

Stimulation of Acid Secretion: slide 11 secretions Spaghetti-like fingers are tubulovesicles (where the __________ pump is). During inter-digestion phase, the tubulovesicles invert and go into the cell = __________. When secretions are stimulated, the tubulovesicles come out and (increase/decrease) surface area for secretions significantly. 3 things that control Acid secretion at level of Parietal cells: aka Inserting proton pumps: 1. __________ (local) – Found in the ECL cells. Stimulates acid production through adenylate cyclase and cAMP. 2. _____ stimulation – ACH can act directly on a Muscarinic receptor of parietal cell or indirectly to stimulate ECL -> Histamine -> cAMP -> proton pump. 3. _____ – secreted by ___ Cells. Works directly on parietal cell or indirectly through the ECL -> Histamine -> cAMP -> proton pump.

``` H/K ATPase no active secretions increase Histamine Vagal Gastrin, G- ```

Parietal cell HCl production: slide 12 secretions How H is made in the HCl - Cellular metabolism -> ___ production -> ___ + (Carbonic Anhydrase)+H2O = Carbonic acid -> breaks down into __ and _____ - __ is used in the H/K ATPase pump in exchange for _ - _ leaks out and becomes ___ - _____ goes into blood via the _________ exchanger. How Cl is made in HCl - _________ exchanger on the blood side gets __ into the parietal cell - Actively secreting stomach – _____ is being reabsorbed into the blood = blood coming out of the stomach is _______. ***[Na+] decreases as the parietal cells become more active -> relatively high [K+] in the gastric “juices” So.....Chronic vomiting not only is there alkalosis, but it can also make the person ___________. Which can lead to problems with conduction.

CO2, CO2, H+ and HCO3- H+, K, K, KCl HCO3-, Cl-/HCO3- Cl-/HCO3-, Cl Bicarb, alkaline hypokalemic

Helicobacter pylori and ulcer formation: - ________ to person transmission (gastro-oral) - Helicobacter in stomach releases - > _______ (produces NH3?) -> buffers acid environment - > _______________ -> allow colonization and adhesion to gastric mucosa - > where they release factors that ________ tissue damage via inflammatory and immunologic mediators * **NSAIDs decrease H2 -> decrease acid secretion?

Person urease virulence factors promote

Regulators of Gastric HCl Secretion | Stimulates acid secretion:

* Parasympathetics, ACh * Gastrin * Histamine

Regulators of Gastric HCl Secretion | Inhibits acid secretion:

• Secretin (duodenal hormone, decreases gastrin) • Somatostatin (local?) • Peptide YY (jejunum satiety hormone) • prostaglandins (local acting on parietal cells to decrease histamine H2 release) ** GIP really doesn’t have physiologic effect on acid, only pharmacologic

Rate limiting step of HCl production = | ____________ pump

H+/K+ ATPase pump (Proton Pump)

__ receptor antagonists will suppress the majority of the acid – but if you go a step further you can use ___ and this basically takes out 99% of acid secretion.

H2 | PPI

______ traps bicarbonate and neutralizes any acid that comes into that layer. Every _-_ days all the cells are replaced. *Slide 15, secretions

Mucus | 3-6 days

Neural Control of Acid Secretion: Cephalic phase: Food is in the _____. The ______ plays a large role during this phase. It stimulates the secretion of ___ and increase of ______ later in the tract.

mouth vagus HCl motility

Neural Control of Acid Secretion: Gastric phase: Food is in the ______. There is not only ______ activity, but ______ circulating in the bloodstream to increase the secretion of ___. When stomach is empty – _____ stimulation STOPS.

``` stomach vagus gastrin HCl vagus ```

Neural Control of Acid Secretion: Intestinal phase: Food is in the _________. The chyme enters the _________ and there is feedback to decrease ___ secretion and ______ emptying. When _________ is empty – everything shuts off à Only ___ ensues, controlling motility & absorption.

``` duodenum duodenum HCl gastric duodenum ENS ```

Crypt cells (and cells in the colon) have the ____ – chloride channel. CF occurs when CFTR is malfunctioning or not present. CFTR maintains ____/_____ balance. When malfunctioning, __ gets trapped in cells -> _____ cannot hydrate the cellular surface causing _____ to become thick/sticky), which secretes __ into the lumen of the gut. __ and ___ follow. The __________ senses the composition of chyme entering it and determines what is needed for digestion.

``` CFTR (cystic fibrosis transmembrane conductance regulator) salt/water Cl- (salt\component) water mucus Cl- Na+ and H2O duodenum ```

Brush border villus cells – aid in further __________ and _________ of nutrients

digestion, absorption

Crypts of Liberkuhn – secrete _______ into the ______

buffer, lumen

Endocrine cells – secrete _________ into the ___________ to affect other parts of the GI tract

hormones, bloodstream

Duodenal hormone release into the?

blood

Gastrin – (increases/decreases) HCl, motility (increases/decreases) in _____ GI.

increases increases lower

Secretin – _________ pancreatic and intestinal buffers.

increases

Cholecystokinin (CCK) – increases __________ enzymes needed for digestion of carbs/lipids/proteins in chyme and continue digestion down until it reaches the brush border or is able to be diffused in (lipids). Stimulates ___________ contraction to secrete bile.

pancreatic | gallbladder

Glucose-insulinotropic peptide (GIP) – increases ______ at the ________ (travels via blood) preparing for when glucose enters the blood ... so as soon as glucose enters, your _______ levels are already elevated and ready.

insulin pancreas insulin

Digestive enzymes in upper GI handle __% of digestion needed for processing in small intestine. __% happens via pancreatic enzymes (before the brush border absorption)

25-35% | 75%

Pancreatic Acini secrete ?

enzymes and buffers

Acinar cells make up the Acinar Sac (secretes into a duct making it an ________ gland) – secrete ?

exocrine | enzymes

Centroacinar Cells secrete ?

buffers

Hormones will synergize – ___ helps potentiate the effects of the buffers

CCK

Exocrine cells secrete: 1. Buffers – stimulated by 2. Enzymes- stimulated by

secretin | CCK

Pancreatic Enzymes: __% of digestion happens in the small intestine via pancreatic enz (__% preduodenally)

75,25

Pancreatic Enzymes: Proteases secreted as zymogens: • _____________ in duodenum converts trypsinogen -> trypsin. • ! trypsinogen can _____________ activate to trypsin and can start chewing up that area of the pancreas causing pancreatitis. • ______ inhibitor (in the pancreas) -> breaks down the trypsin to prevent pancreas damage. ______ inhibitor in the duodenum is called “_______ peptide”, here it stimulates CCK? Activated by trypsin:

``` Enterokinase spontaneously Trypsin Trypsin monitor ``` * chymotrypsinogen * pro-carboxypeptidase * pre-co-lipase

End of the meal.... When the chyme is lower in the tract, pancreatic secretions ______. This is occurs from the reduction in ______ stimulation (no food/chyme in the upper GI tract), as well as from multiple _____________, including somatostatin (SS), glucagon, pancreatic polypeptide, and peptide YY, which _________ pancreatic exocrine secretions. In the ileum, there is secretion of _ and ____. _____ and ____ are reabsorbed. ____ is secreted to buffer the _ that is secreted. In the colon ____ is reabsorbed and _, _, and _____ are secreted.

cease vagal secretogogues decrease H+ and HCO3- Water and NaCl HCO3-, H+ NaCl K+, H+, and bicarbonate

Secretion of H+ and HCO3- into the lumen in the ileum... helps reclaim __, __ and ___ back into the ECF: Lumen side - Na+/H+ antiport – allows reclamation of Na. - Cl/HCO3- antiport – allows Cl to come back in to the ECF (green side) In the lumen H+ and HCO3- turns into H2o and CO2. H2o & CO2 will diffuse into the cells – which then turn back into H+ and HCO3- to keep the transporters working to keep getting the Na+ and Cl- in.

sodium, chloride and water

Secretion of HCO3-, and K+ into the lumen in the colon: Reclaim ____ into the ECF, ____ comes in via HCO3/Cl exchanger and ____ is excreted – the ____ stays in the feces here. ____ also secreted into the lumen (via concentration gradient) All that is left in the lumen now are (will exit via feces)? *everything else was reclaimed into the ECF.

``` Na+ Cl HCO3 HCO3 K+ ``` H2o, HCO3-, K+

Bile: Why do we need it? - As chyme gets near the intestinal wall the flow slows down. The ___________ are secreting Mucus and HCO3 that protect the cells and SLOWS the flow near the cell = ? - _________________ only becomes a problem with ______ – pool together and can’t get through the unstirred water layer to enter the enterocytes. - Lipids need a carrier = Bile! Bile + Lipids = _______ (like an uber). _______ are formed in the small intestine through process of ____________ of lipid by the bile and co-lipaze binding to bile allowing pancreatic lipase to hydrolyze the lipids = micelle formation. This micelle (__________ outer shell) takes the lipids through the unstirred water layer to the enterocyte -> lipids absorption can now occur.

Enterocytes, unstirred water layer Unstirred water layer, lipids (hydrophobic) micelle Micelles, emulsification, hydrophilic

1. Bile is necessary for efficient absorption of lipids

True

2. Bile forms the structure of a micelle

True (this micelle acts like an uber to bring lipids to the | enterocytes)

3. There are specific transporters for lipids on enterocytes

False (lipids are lipophilic and can readily | diffuse once at the enterocyte)

4. Lipids are readily absorbed in the small intestine

False (Hydrophobic and cannot readily cross the | unstirred water layer. Lipase digests them into monoglycerides, free fatty acids etc)

5. The unstirred water layer results solely from laminar flow

False (not only due to laminar flow. Small | intestine secrete mucus which slows down flow)

Bile Formation: Synthesized by ___________ of the liver. Primary Bile – (main type of bile) starts as Cholic Acids w/ a __________ backbone (from diet, and synthesis): o Synthesis of Cholesterol – happens in hepatocytes by enzyme HMG CoA Reductase becomes polar on the side of the amino acids (polar = _________) while the rest of it stays non-polar (________) = ? o Bile ______ lipid Secondary Bile – Bile that has been acted on by __________ lower in the intestinal tract, mainly in colon. NOT ___________, much more ___________ and has a harder time getting through to the enterocytes.

hepatocytes cholesterol statins excess phospholipids, bilirubin-one of the key ways we remove bilirubin from the body hydrophilic, lipophilic, amphipathic emulsifies (think of a big chunk of fat in water, adding dish soap disperses the lipids and emulsifies it) intestinal bacteria amphipathic lipophilic

1. Only 50% of primary bile is conjugated with taurine or glycine.

False (all primary bile is conjugated with taurine/glycine. Becomes amphipathic – amino acid ends are hydrophilic while the interior will remain lipophilic.

2. Bile is synthesized in hepatocytes.

True

3. Bile secretions are hypotonic.

False (Bile is near isotonic to plasma. Bile is an osmotic agent and pulls water as it is secreted into the bile canaliculi. This exerts solvent drag, pulling solutes with it and making a great buffer)

4. Cholic acids are primary bile acids.

False

5. Primary bile acids are made from cholesterol and they are lipophilic.

True

6. When secreted, bile acts as a detergent and emulsifies lipid droplets.

True

7. Secondary bile is a product of bacterial action on bile in the lower GI tract (mainly the colon).

True

Secretion and Recycling of Bile: -Secreted by hepatocytes INTO the ________. Bile is ______ = will pull water with it = as water is pulled ______ are pulled (these solutes are sodium bicarb which are ______!). -________ Drag - when bile secreted through bile ducts down into the liver and drags buffers with it. When you activate the ______ nerve (food in stomach) 1. Starts (increasing/decreasing) bile production in liver 2. _____ the Sphincter of Oddi. -As chyme enters the duodenum, hormones are released in the duodenum (especially ___). ___ will contribute to more bile production + relax Sphincter of Oddi + start rhythmic contractions of the gallbladder. Bile is spurted into the duodenum to get ready for the lipids. -In the _________ there are sodium dependent co-transporters that recognize the primary bile and allow bile into the enterocytes back into the liver = _______. Each _____ contains multiple cycles of secretions of bile in this manner (keeps recycling) – this continues as long as chyme is coming down - With each cycle, __% of bile is lost into feces and not recycled -This loss is how we rid body of ?

bile ducts osmotic solutes buffers Solvent Vagus increasing Relax CCK, CCK terminal ileum, recycled meal, 10, Cholesterol & bilirubin

bile ducts osmotic solutes buffers Solvent Vagus increasing Relax CCK, CCK terminal ileum, recycled meal, 10, Cholesterol & bilirubin reduced, closes, gallbladder

Gallstones: Because the gallbladder stores bile, the bile & salts can form accretions -> ______ bile ducts -> ______/______ = ___________ surgery. -Treatment with surgical removal of gallbladder – you _____ live without a gallbladder, you need modifications: -Low ___ diet prescribed (don’t need as much bile) -Liver _____ make more bile

blocks, sepsis/toxicity, emergency can fat, can

1. Micelles form in the liver.

False (Micelles form in small intestine

2. Bile recycling occurs throughout the small intestine.

False (Very last part of Terminal ileum)

3. What duodenal hormone stimulates bile production, gall bladder contraction and the opening of the sphincter of Oddi?

CCK

4. The excretion of bile in feces removes some cholesterol, bilirubin, and random waste products from the body.

True

5. During each cycle ~10% of secreted bile passes into the colon and is excreted in feces.

True

Functions of the Liver: Regulation of ______, ___________, and _____ metabolism ◦ The liver receives newly absorbed nutrients through the _____ vein, along with the contents of systemic blood, and processes them according to need. ◦ The liver produces:

Protein, carbohydrate, and lipid portal albumin, fibrinogen, immunoglobulins, binding proteins, cholesterol, lipoproteins, bile, and other important molecules.

Functions of the Liver: Regulation of ___________ production and excretion ◦ The body requires _________, and although this substance can be synthesized by many cells in the body, the liver can produce it at a high rate when necessary (with hydroxymethylglutaryl–coenzyme A [HMG- CoA] reductase being the first enzyme used in this process) ‣ This is the enzyme that________ work to inhibit. Would reduce the body's ability to make _________, effectively lowering __________ levels. ◦ __________ is also used to synthesize bile, and thus when bile is excreted in the feces, cholesterol is removed from the body.

cholesterol, cholesterol STATINs, cholesterol, cholesterol

Functions of the Liver: β-Oxidation of __________ ◦ Although many tissues use β-oxidation of _________ as an alternate energy source when glucose is not present, the liver has a _____ capacity for β-oxidation during the _____________ period. --> gluconeogensis?

fatty acids fatty acids high interdigestive

Functions of the Liver: Bile acid production ◦ Bile is necessary for efficient lipid absorption, because lipids alone cannot efficiently pass through the water that bathes the enterocytes. Bile is polar [b/c of ______ and ______], allowing it to incorporate lipids into micelles; the micelles can move the lipids through the unstirred water layer adjacent to the enterocytes. Without bile, the bulk of the hydrophobic lipids would not be able to get near the brush border.

glycine and taurine

Functions of the Liver: Degradation of hormones ◦ Endocrine functions: - The hepatocytes produce and secrete hormones into blood, including ? - Participates in activation of vitamin _ (see Chapter 31 ?)

insulin-like growth factor–1 (IGF-1), hepatocyte growth factor, angiotensinogen, and cytokines. It converts thyroxine to active triiodothyronine (see Chapter 28 ?) D

Functions of the Liver: Detoxification and excretion of drugs and toxins ◦ The liver contains reticuloendothelial cells, known as ________ cells , that are fixed ____________ in the endothelial lining of hepatic sinusoids. As blood passes through the liver, ____ and __________ erythrocytes undergo phagocytosis by Kupffer cells (take care of ~ __ % of the bacteria entering the portal blood from the intestines) ◦ Hormones, drugs, and other chemicals are metabolized by the ____________.

Kupffer macrophages old and damaged 99 hepatocytes

Functions of the Liver: Vitamin storage ◦ The liver stores several elements crucial to normal body functions = ◦ Vitamins can be stored for _______ to ________, providing a source of the vitamin if the dietary supply is depleted. ◦ The liver is also the site of large _____ stores, bound to the protein ferritin (the liver contains __% of the body's iron). When needed, the _____ is released into the blood and enters the bone marrow for the production of ___________.

vitamin B12, folic acid, and iron weeks to months iron, 25, iron (bound to transferrin), hemoglobin

The primary functions of the liver can be separated into 3 major components: ________- storage and filtration of blood ◦ Liver is a sponge. ________- carbohydrate, lipid and protein metabolism ________- bile formation and secretion

Vascular Metabolic Secretory/excretory

Blood Flow to Liver: The blood supply to the liver comes from the ______ artery and ______ vein. The systemic arterial blood from the hepatic artery enters the liver at a rate of ∼___ mL per minute. The portal vein carries venous blood from the intestines (∼_L per minute), and the arterial and venous blood intermingles in the sinusoidal capillaries. Total blood flow through the liver represents approximately __% of the cardiac output. As the blood from the ______ vein enters the liver, nutrients, bacteria, and foreign bodies are processed, which is the “___________” effect, allowing the absorbed materials to be “cleared” by the liver before the blood leaves through the ______ vein into the systemic circulation. Although not all such substances will be cleared or metabolized in one pass, the bulk of the substances will be handled.

hepatic artery and portal vein 450 mL, 1L, 30% portal, first pass, hepatic

Blood Flow to Liver: Path = ?

Intestines ---> Portal Vein + Hepatic Artery ------> Liver (first pass effect) ---> Hepatic Vein -> vena cava --> systemic circulation

Blood Flow to Liver: The hepatic v. drains into the __________, and pressure averages ____. This is important--pathology develops when pressure rises: ascites = hepatomegaly =

vena cava zero fluid in peritoneum enlarged liver

Blood Flow to Liver: Portal Hypertension = *Can be before the liver, at the liver, or after the liver. Pre-Hepatic = Intra-hepatic = Post-hepatic =

Back up of pressure to the Portal vein/intestine system. portal vein thrombosis. Thrombosis in portal vein draining the blood to the liver. Leads to back up of blood -> portal hypertension. cirrhosis, fibrosis, scarring, Wilson's disease, biliary atresia? Liver is diseased and becomes the place of obstruction. Leads to back up of blood -> portal hypertension. Hepatic vein thrombosis, CHF, pericarditis. The obstruction is after the liver, thrombosis in hepatic vein. CHF. Back up of blood -> portal hypertension.

Blood Flow to Liver: Blood flow through the liver is critical to homeostasis, and obstruction of blood flow can result in several symptoms including _______ -> fluid is pressed out of liver (which is like a sponge) into peritoneal space. Overwhelms greater momentum, unable to absorb the fluid. ____________ -> liver is swollen with blood r/t post liver obstruction. (Liver is like a sponge, can expand) ________ -> unable to excrete bilirubin via bile. Build up of bilirubin.

Ascites Hepatomegaly Jaundice

Lymphatics are EVERYWHERE in | the liver--Lymph removes fluid and proteins from the ______________, and drains the fluid into the venous blood.

Space of Disse

Bilirubin is the end-product of ______ degradation, and is incorporated into bile, and excreted in feces (metabolite is also excreted by the kidneys).

RBC

Obstructive jaundice =

obstruction of the bile ducts (cirrhosis, gallstones, biliary atresia, cancer). In each case, the bilirubin that is usually incorporated into bile enters the blood, instead.

Hepatic jaundice =

acute or chronic hepatitis, drug hepatotoxicity and cirrhosis. This reduces the ability of the cells to metabolize bilirubin (to incorporate it into bile)

Hemolytic jaundice** =

extra-hepatic results from anything that increases hemolysis of RBCs (eg, malaria, sickle cell anemia, genetic disease (spherocytosis)), and increases bilirubin production faster than bile can excrete it. ◦ Not a problem of the liver.

Neonatal jaundice =

``` usually is not pathologic, but results from metabolic changes, as the liver and GI tract start to function appropriately after birth (common, usually fine) • Congenital pathologic conditions such as G6PD deficiency and spherocytosis can also cause neonatal jaundice. ```

Primary jaundice =

hepatic dysfunction, as seen with obstructive liver disease (cirrhosis), blockage of bile ducts (by tumor or gallstones), or inflammation (hepatitis C)

Secondary jaundice =

extrahepatic causes, such as abnormal lysis of RBCs (hemolytic disease). In most cases, when the cause of the jaundice is treated, the jaundice will abate as the excess bilirubin eventually clears (through fecal and urinary excretion). ***An important distinction is that with secondary jaundice, liver function is normal.

Basic Liver Metabolism: Carbohydrates The liver acts as a blood glucose reservoir, storing glucose as glycogen and releasing it when blood levels are ___. Carbohydrates are absorbed in the intestine as monosaccharides and are carried in the portal blood to the liver. _____ of the glucose passes through the liver rapidly and is released into the systemic blood, where elevated insulin will facilitate its entry into tissues. In the liver, excess monosaccharides (not only extra glucose) are handled by the following processes: • Conversion of other monosaccharides to _______: Fructose and galactose can be converted into _______. • ________ synthesis and storage: Excess glucose is polymerized and stored as ________. Stored hepatic ________ can provide glucose for __ to __ hours during fasting. When blood glucose levels are ___, glucagon and other hyperglycemic hormones such as epinephrine and growth hormone stimulate glycolysis to break down glycogen and release glucose into the blood. If the glycogen stores are not used, excess glucose (which is not released into the blood) will eventually be converted to triglycerides (TGs) and transported to ____________ for storage. ** Excess blood glucose is converted to glycogen by __________. Epinephrine and glucagon can stimulate phosphorylase, releasing molecules of glucose into the _______ when needed. • Gluconeogenesis: The liver (and to a lesser extent, the kidney) has the ability to make glucose from substrates such as glycerol, pyruvate, and the amino acids glutamine and alanine. Gluconeogenesis provides an alternate energy source and occurs primarily during _______ and _______. • Formation of chemical compounds: Excess glucose can also be converted into other chemical compounds (e.g., pyruvic acid, lactic acid, and acetyl CoA) that can be used in metabolic pathways such as the ____________. Big Picture: This helps maintain blood glucose levels. If the liver can’t do this, blood glucose can rise _X higher than normal! Also, think energy. (The liver has GLUT2 family transporters which are insulin-____________, and allow for high capacity transport. These transporters are also found in brain, pancreas, kidneys and basolateral side of enterocytes.) - Allow entry of glucose without ______.

``` low Most glucose glucose Glycogen glycogen glycogen 12 to 17 low adipose tissue glucokinase blood fasting and starvation citric acid cycle 3 independent insulin ```

Basic Liver Metabolism: Lipids • Most lipids are packaged into chylomicrons in the enterocytes (see Chapter 26 ?). The first entry of absorbed lipid into the liver is from the _________, not _________, circulation. • Liver lipid metabolism includes the following: ‣ β -Oxidation of fatty acids: very ____ in the liver. ‣ Formation of most lipoproteins: ____, ____, and ____ are formed in the liver. ____ and ____ transport TGs and cholesterol to tissues. ____ is implicated in development of cardiovascular disease because it is incorporated into atherosclerotic plaques. ____ transports lipids from tissues to the liver and is considered beneficial in terms of cardiovascular health.

systemic, portal high, Very low density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), VLDL and LDL, LDL, HDL

Basic Liver Metabolism: Lipids • VLDL: • LDL: • HDL: ◦ So if you are highly metabolic, low fat diet, takes fat out of lipid stores and brings fat back to liver to repurpose it. Constantly going on with HDLs.

* VLDL: high TGs, some chol & PLs--take TGs to adipose tissue. * LDL: high chol & PLs, little TGs (these are bad guys) * HDL: 50% protein, less chol & PLs

Basic Liver Metabolism: Lipids ‣ Synthesis of cholesterol and phospholipids: Cholesterol and phospholipids are necessary for making __________, and cholesterol is also the precursor for ______ hormones and ____. Because of these important functions, the liver ensures a supply of these substrates by forming them from other lipids. A liver enzyme, HMG-CoA reductase, catalyzes the rate-limiting step in cholesterol synthesis, and pharmacologic intervention by statins (cholesterol-lowering drugs) inhibits this enzyme. ‣ Conversion of unused glycogen to TGs: When liver glycogen is not used, it is converted to TGs which are transported to adipose tissues in ____s. Big Picture: This provides another energy source, provides the building blocks for membranes, intracellular structures, as well as steroid hormones, and can bulk up your fat stores (ouch!)

membranes steroid hormones and bile VLDL

Basic Liver Metabolism: Proteins Protein metabolism in the liver is essential for survival; the liver processes dietary __________ for systemic use and participates in the processing of ________ wastes for excretion. The major functions of the liver are: • Deamination of amino acids: Deamination is the first step in removal of excess amino acids; aminotransferases remove the amino group from the amino acids, creating ___________. • Production of urea: The NH 3 (ammonia) combines with CO2 to form _____, thereby buffering NH 3 , a toxin, and allowing urinary excretion. • Synthesis of plasma proteins: About __% of plasma proteins are made in the liver. These proteins include: ‣ _______, which contributes to oncotic pressure of plasma. ‣ _____________, which contribute to immune functions. ‣ _________, which is necessary for blood clotting. ‣ Interconversion of amino acids: Needed amino acids are ____________ from other available amino acids. Big Picture: This is ABSOLUTELY ESSENTIAL for survival. If the liver can’t do this efficiently, you could die within days from toxicity. ---> from _________?

``` amino acids, nitrogen ammonia (NH 3 ) urea 90, albumin, immunoglobulins, fibrinogen, synthesized ammonia ```

Which is more serious to remove and why, the gallbladder or ilium?

ileum because No recycling of bile! * Bile secreted by the gallbladder and liver will be excreted in feces. (All of it, not just 10%) * When the Sphincter of Oddi closes, the bile in the ducts is “vacuumed” into the gallbladder and stored. Overall the liver has to produce much more bile, since there is no recycling. * Although the increased sodium and water entering the colon will increase sodium (and water) reabsorption, overall, the increase in bile and motility will cause diarrhea.

Bilirubin metabolism/excretion: • Colonic bacteria remove the acid moiety and bilirubin is coverted to ____________. •About 10-20% of the urobilinogen is recycled into portal blood (from the colon) and then systemic circulation, where it is filtered, converted to _______ (_______ color) and excreted in _______. • The unabsorbed urobilinogen is further oxidized by bacteria to _______ (_______ color) excreted in ______.

urobilinogen (So the 10% of bile that gets past terminal ileum and into colon will encounter this colonic bacteria and become urobilinogen) urobilin (yellow color), urine stercobilin (brown color), feces