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49 Cards in this Set

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Heres a picture of GI circulation

Liver functions

1. Carb, protein, and lipid metabolism


2. Hormone metabolism


3. Detoxification


4. Storage


5. Bile production


6. Immune function

What is the biliary tract?


The organs and ducts that make and store bile and deliver it to the SI

The organs and ducts that make and store bile and deliver it to the SI


What are some species differences in the Biliary tract?

Ruminants/pigs: sphincter of Oddi is less defined = continuous secretion of bile



Horses: no gull bladder = continuous secretion of bile



Dogs/cats: intermittent secretion = meal dependent

What are the 3 'tubes' that make up the portal triad?

Hepatic artery


Portal Vein


Bile duct



**hepatic and portal vessels go towards central vein, bile dict is the opposite way

Hepatobiliary tract - What do hepatocytes do?

Bile synthesis from cholesterol

Hepatobiliary tract - What does the Canaliculus do?

Bile formation

Hepatobiliary tract - What does the ductules and ducts do?

Modification of bile


Absorption and secretion

Hepatobiliary tract - What does the gallbladder do?

Concentration


Storage


Delivery


Hepatobiliary tract - What does the sphincter of Oddi do?

Regulated delivery of bile to duodenum


Prevention of reflux

Explain the regulation of bile secretion...

Explain the regulation of bile secretion...

1. nutrients in SI cause release of Secretin from S cells (H+) and CCK from I cells (FA, peptides)


2. CCK can...


-neuro root stimulate the vagus to DVC to vagal efferents to release bile (via Ach)


-blood to DVC to vagal efferents to release bile (via Ach)


-blood to gall bladder


3. Secretin can act on liver to release bile?

What are the 3 types of bile acids?

1. Primary (pH=6)


2. Conjugated (pK=2-4)


3. Secondary (products of bacterial metabolism)

What are primary bile acids composed of?

-cholic acid, chenodeoxycholic acid (high hyocholic in pigs)


-Hepatic synthesis from cholesterol


What are the 2 ways that Primary bile acids can be formed through hepatic synthesis from cholesterol?

1. Classical (neutral) pathway (75-90%): in microsomes



2. Alternate (acidic) pathway: in mitochondria



**both have rate limiting enzymes

hat is the importance of conjugated bile acids?

-Decrease pK of bile acids = charged complexes (bile salts) in intestinal lumen (pH=6)


-Bile salts cannot be absorbed passively in upper intestine


-retained in intestinal lumen for fat digestion/absorption

What are the 2 conjugated bile acids?

Taurocholic (pK = 2) conjugated to taurine



Glycocholic (pK = 4) conjugated to glycine


Conjugated acids are actively absorbed in the ileum via what?

ASBT (Apical Sodium dependent Bile acid Transporter)



OST (Organic Solute Transporter - basolateral)

What are secondary bile acids?

Deoxycholic acid, ursodexoycholic and lithocholic acid


-formed in the colon by bacterial dehydroxylation


(some absorbed in colon BUT more excreted)

Function of bile acids with lipid and fat soluble vitamin digestion?

-lipid emulsification


-micelle formation


-lipid absorption

Function of bile acids with Cholesterol metabolism?

Bile acid synthesis and excretion


**eliminate cholesterol


Function of bile acids with protein digestion

Bile acids denature proteins


-accelerate digestion by pancreatic proteases

Function of bile acids with Antimicrobial effects

-Cholic acid and deoxycholic acid disturb membrane integrity


-leakage of H+ K+ into bacterial cell


==== CELL DEATH

Function of bile acids with Metabolic signalling molecules

improve glucose tolerance and diabetic control

Entero-hepatic circulation of bile...

Entero-hepatic circulation of bile...

-95% of bile acids are recycled via portal vein at distal ileum


-recirculated back to liver to negatively feed back to bile synthesis (inhibit)

Entero-hepatic circulation of bile - what do hepatocytes do?

1. take up conjugated and unconjugated bile acids into the blood (portal vein)


2. synthesize new bile acids from cholesterol


-unconjugated are conjugated with taurine or glycine


-conjugated transported across apical plasma membrane (canalicular) into bile duct



Entero-hepatic circulation of bile - what does the gull bladder do?

1. Stores bile between meals


2. Neuro-hormonal pathways cause contraction and relaxation of the sphincter of Oddi at the ampulla of Vater resulting in transfer of bile into intestines


Entero-hepatic circulation of bile - what does the intestine do?

1. Conjugated bile acids in SI are taken up by Apical Sodium dependent Bile salt Transporter (ASBT) in end ileum and Organic solute Transporter (OST)



2. Some bile acids are deconjugated in proximal SI by protease removal of glycine or taurine and absorbed passively

Entero-hepatic circulation of bile - what is the total bile acids pool?

-95% is recirculated from intestine


-5% lost in stool

Since bile acid synthesis can be up or down regulated depending on requirements, how is bile acid synthesis affected by ileal resection and feeding bile salts?

-Increased secretion usually increases rate of return of bile acids to the liver via portal blood (negative feed back on synthesis)

-Increased secretion usually increases rate of return of bile acids to the liver via portal blood (negative feed back on synthesis)


How is bile acid synthesis affected by ileal resection SPECIFICALLY?



-interruption of enterohepatic circulation?


-Increased bacterial overgrowth and beconjugation?


-Loss of ileal brake?

-interruption of enterohepatic circulation = increase in hepatic bile synthesis


-Increased bacterial overgrowth and beconjugation = bile acid malabsorption = bile and FA diarrhea


-Loss of ileal brake = increased motility

How is bile acid synthesis affected by bile acid feeding SPECIFICALLY?

Feeding bile acids suppresses the new synthesis of bile acids by hepatocytes

What is pathway that bile is secreted?

-hepatocytes in canaliculi


-Bile ducts


-hepatic duct


-common bile duct

What is bile acid composition?

-solutes 4-10%


-bile salts 64% = electrolytes, phospholipids, cholesterol, bile pigments, and protein

What are chlorites and what do they stimulate?

-secretin and CCK


-bile secretion

Where does majority of the secretions/absorption happen in Carnivores/omnivores?



Horses?

Duodenum and Jejunum



Ileum, caecum, colon

What 5 cells are present in the intestinal epithelium?

-Goblet cells


-Columnar absorptive cells


-Proliferative cells


-Entero endocrine cells


-Paneth cells

What is a key structure present on the villi in the intestines?

Microvilli

What are the 5 Electrolyte Absorptive Mechanisms?

1. Sodium absorption in villus


2. Chloride absorption in Villus


3. Bicarbonate absorption in crypt


4. Potassium absorption in crypt


5. Water absorption/secretion in crypt

Explain sodium absorption in the villus..

1. Na co-transport with organic molecules 
2. Couple Na-Cl absorption 
3. Simple diffusion (Na channels)

1. Na co-transport with organic molecules


2. Couple Na-Cl absorption


3. Simple diffusion (Na channels)

Explain Chloride absorption in the villus..

1. Paracellular transport (with Na co-transport) 
2. Coupled Na-Cl absorption 
3. Cl-HCO3 exchange (important for buffering in colon of hindgut fermentors)

1. Paracellular transport (with Na co-transport)


2. Coupled Na-Cl absorption


3. Cl-HCO3 exchange (important for buffering in colon of hindgut fermentors)

Explain Bicarb absorption in the crypt..

1. Absorbed via acid neutralization in stomach


2. Facilitated by Na-H exchanger

Explain potassium absorption and Water absorption/secretion in the crypts....

Potassium: simple diffusion 
 
Water absorption/secretion: osmosis - paracellular/transcelluar

Potassium: simple diffusion



Water absorption/secretion: osmosis - paracellular/transcelluar



Summary of electrolyte absorptive mechanisms... Where are transporters/absorption located?

Summary of electrolyte absorptive mechanisms... Where are transporters/absorption located?

Na co-transport = duodenum, jejunum (U) > jejunum (M), jejunum (L)


Cl-coupled Na absorption: Colon > Ileum > jejunum, duodenum


Cl-HCO3 exchange: Colon > Ileum


HCO3 absorption: Colon > Ileum


K absorption: Colon >> Ileum



What is diarrhea?

Frequent passage of fluid and voluminous feces (intestinal disease)

Small intestinal diarrhea signs....



Acute due to?

-slight increase in frequency of defecation


-increase in volume, flatulence, borborygmi



Acute = diet, infectious disease, intoxication, intestinal obstruction


Signs of large intestinal diarrhea...



Cause by?

-straining and frequent passage of small amounts of fece with mucus and blood



-caused by diseases (infection, inflammation, parasites) of cecum, colon, and rectum

What are the four mechanisms of diarrhea?

1. Osmotic - dietary overload, malabsorption


2. Exudative - mucosal inflammation, erosions, lymphatic hypertension


3. Secretory - bacterial endotoxins, deconjugated bile salts (irritable)


4. Hypermotility - Disease and agents that....


-decrease segmental contractions (slow)


-increase aboral giant contractions in proximal SI (amp/frequency)

What are the general mechanisms for causing diarrhea?

What are the general mechanisms for causing diarrhea?

-Decreased Na+ absorption (Na+ H+ transporter)


-Decreased Na+ glucose AA absorption


-Increased Na+ paracellular permeability (into lumen)


-Increased Cl- secretion (CFTR normally closed)


-Decreased Cl- absorption (Cl- HCO3- transporter)


-Decreased H2O absorption (aquaporins disrupted)


What are examples of 2 diseases (and mechanisms) that can cause infectious diarrhea?

E.coli in calves (toxigenic)


-no Na+ H+ transport (Na+ out of lumen SI)


-no HCO3- Cl- transport (Cl- out of lumen SI)


-Increased Cl- Secretion (in crypts)



Cryptosporidium in calves (inflammatory)


-no Na+ H+ transport (Na+ out of lumen SI)


-no HCO3- Cl- transport (Cl- out of lumen SI)


-No glucose AA Na+ transporter