Describe the flow of pancreatic secretions.
Pancreatic secretions flow into larger intralobular ducts & into the main pancreatic duct–>duodenum
What are the 4 types of pancreatic secretions?
What are examples of proteolytic enzymes?
Tyrpsin, chymotrypsin, carboxypolypeptidase
What is the main carbohydrate enzyme & what does it do?
pancreatic amylase: breaks glycogen, starch & carbs into di & trisaccharides
What does pancreatic lipase do?
hydrolyzes neutral fat to fatty acids & monoglycerides
What does cholesterol esterase do?
hydrolyzes cholesterol esterases & phospholipases so that fatty acids can be separated from phospholipids
How do you activate trypsinogen?
enterokinase (released from mucosa when it contacts chyme)
How do you activate chymotrypsinogen?
What is the purpose of the trypsin inhibitor?
it is released from glandular cells in the pancreas & prevents the trypsinogen from being activated in the secretory cells, acini or pancreatic duct…otherwise it would eat the pancreas! Sad.
What happens in the pancreatic acinar cell?
protein synthesis happens in the RER.
proteins are collected in the cisternal cavity
the enzymes are condensed into vacuoles
there they are concentrated into zymogen granules
the zymogen granules fuse w/ the apical membrane & rupture to release their contents
Where are bicarb ions & water secreted from in the pancreas?
from the epithelial cells of the ducts of the acini
**when stimulated to release zymogen granules, also releases the bicarb & water
How do the conc’n of the ions in this secretion compare to that of plasma? What pH is created by the bicarb ions?
Na+ & K+ similar to plasma
Cl- less than plamsa
HCO3- produces a pH of 8.2
What are the 2 proposed mechanisms for how bicarb is secreted?
I. Acinar cells secrete stuff w/ Na+ & K+ & the duct cells secrete stuff w/ a ton of bicarb.
II. Acinar cells secrete stuff rich in bicarb. Duct cells exchange the bicarb for Cl-. When flow is fast, less bicarb can be exchanged.
What is HCO3- secretion from duct cells dependent on?
the amount of luminal Cl- ions to exchange with!!
exchanger on the apical membrane
HCO3- made by CA from the CO2 diffused from blood
What are the 4 basic stimuli that are critical in determining pancreatic secretions?
When is ACh released?
from parasympathetic vagal nerve terminals & from other cholinergic nerves in the enteric nervous system
When is gastrin released?
it is released during the gastric phase of the stomach
When is CCK released?
when food enters the SI…it is released from the duodenal mucosa
When is secretin released?
secreted when low pH products enter the SI
Which of the stimuli cause the pancreatic acinar cells to prepare the digestive enzymes?
**but no fluid secretion!!
What does secretin do?
Thankfully, secretin stimulates large secretions of bicarb soln from ductal cells in the pancreas, but doesn’t affect enzyme secretions.
During the cephalic phase of digestion…what is released? Does this cause pancreatic enzyme secretion?
ACh released @ pancreas. Causes enzymes to be secreted in acini. But NO real secretions b/c of lack of fluid to flow that stuff thru the duct.
During the gastric phase of digestion…what is released? Does this cause pancreatic enzyme secretion?
There still aren’t really secretions from the pancreas b/c of the lack of fluid…
During the intestinal phase of digestion…what is released? Does this cause pancreatic enzyme secretion?
Secretin & CCK are released…
This is stimulated by the chyme when it enters the duodenum…
These 2 substances travel in the blood & stimulate the pancreas to secrete enzymes. With the secretin stimulating the duct cells to release bicarb & water…it can actually flow into the SI.
Let’s focus in on secretin release. What cells release it? What 2 substances really stimulate its release? What pH makes it ideal to release? What 2 things potentiate its release?
Secretin is released from S cells. HCl/Gastric acid & long chain fatty acids stimulate this release. The HCl creates a lower pH…when it gets to like 4.5 secretin is released. CCK & ACh potentiate the release of secretin.
Let’s focus in on CCK. What cells release it? What 2 things prompt its release?
I cells in the duodenal mucosa & upper jejunal mucosa release it.
Proteoses & peptones prompt its release. These are products of long chain fatty acid digestion.
The bicarb released in the duodenum is a part of a protective mechanism to get rid of extra HCl. This protects the intestinal mucosa from being destroyed! Describe this mechanism.
HCl + NaHCO3- –> NaCl + H2CO3 –>H2O + CO2
The CO2 is absorbed in the blood & expired in the lungs. This gets rid of extra acid.
Aside from a protective mechanism…what else does bicarb do in the SI that’s awesome?
The HCO3- raises the pH of the lumen to around 8. This is ideal for the function of pancreatic enzymes.
What are the 2 main functions of bile?
- emulsify large fat particles into small fat particles that can be broken down by pancreatic lipases. Furthermore, bile salts help transport these break down products thru the SI mucosa.
- helps w/ excretion of waste products from the blood (like bilirubin & excess cholesterol)
T/F Bile consists of both organic & inorganic compounds.
Bile acids are mainly conjugates of what 2 things? What are the 4 main acids found in bile?
mainly conjugates of taurine & glycine Cholic Acid Chenodeoxycholic acid Deoxycholic acid Lithocholic acid
Of the 4 main bile acids…which are primary derivatives of cholesterol? Which are secondary derivatives of bile acids thru the action of microorganisms?
Primary Derivatives of Cholesterol: Cholic acid Chenodeoxycholic acid Secondary Derivatives: Deoxycholic acid Lithocholic acid
What happens to bile acids when they are in low conc’n? What about when they are in high conc’n?
Low conc’n: not much interaction amongst themselves
High conc’n: formation of micelles!! How exciting!
Aside from bile acids, what are the other components that make up bile?
Phospholipids, mainly lecithins Cholesterol Bile Pigments (like bilirubin) Inorganic ions (Na+, K+, Ca2+, Cl-, HCO3-) Proteins Fatty Acids
Of the components of bile, which are involved in micellar formation?
What is the one organic component of bile that isn’t a part of micellar formation? What is its special function?
It can help to indicate how well the liver is functioning…
T/F Bile is isosmotic.
Describe how bile gets from inside the liver to inside the duodenum.
collects in bile canaliculi (b/w hepatocytes) to terminal bile ducts to hepatic duct to common bile duct either to cystic duct to be stored in the gallbladder OR to the ampulla of Vater to Sphincter of Oddi to the DUODENUM!! What a journey.
T/F Bile is only secreted in response to chyme.
False. It is secreted continually throughout the day. The rate varies, however. It is recycled 3-16 times/day. Less than 5% is lost to the colon & 500 mg is lost from the body.
Explain how the bile is recycled.
thru enterohepatic circulation
the small intestine, especially the ileum absorbs the bile & thru portal venous return takes it back to the liver to be recycled & re-secreted.
What are the 3 mechanisms involved in enterohepatic circulation?
- passive diffusion
- The major one: terminal ileal absorption thru active carrier
- Deconjugation of bile salts into bile acids in the terminal ileum & the colon
How is bilirubin formed basically?
Thru the breakdown of old RBCs in the reticuloendothelial system (mainly spleen). The hemoglobin is broken down into unconjugated bilirubin.
How is unconjugated bilirubin disposed of?
some bilirubin ends up in the kidneys & is excreted in the urine as urobilin
most of it is taken into the liver via active anion transport & is conjugated w/ glucuronic acid
This goes thru the biliary system & is put in the SI. In the SI it is broken down by bacterial proteases to urobilinogen. Most of this is excreted in the feces as stercobilin.
How are bile salts secreted into the bile?
via salt transport pumps
What are the 2 major categories by which electrolytes are secreted?
Bile Acid Dependent
Bile Acid Independent
Describe the bile acid dependent secretion of electrolytes.
Bile acids secreted in the liver creates an osmotic gradient. Water flows down this gradient & grabs with it electrolytes. This is a passive process.
Describe the bile acid independent secretion of electrolytes.
Na+ actively transported by hepatocytes.
In the bile ducts, bicarb secretion is active. NaCl is absorbed by the duct cells.
What are 4 causes of gallstone formation?
- too much absorption of water from bile
- too much cholesterol in the bile, leading to precipitation
- too much absorption of bile acids from bile
- inflammation of the epithelium
What are Brunner’s glands? Where are they found? What do they secrete?
These are submucosal glands found in the duodenum b/w the pylorus & ampulla of Vater.
They secrete mucus in response to certain stimuli. This is important mucus b/c it protects the SI mucosa.
What are the 4 stimuli that can stimulate secretion of mucus from Brunner’s glands?
- tactile stimuli
- irritating stimuli
- vagal stimulation
- GI hormones, like secretin
What is something that can inhibit the secretion from Brunner’s glands? What happens if this happens too often?
Sympathetic stimulation can inhibit secretion from Brunner’s glands. Duodenal peptic ulcers can result.
What happens in the crypt of Lieberkuhn in the SI?
They secrete ECF w/ a pH of about 8. The villi then reabsorb this fluid w/ other nutrients.
So…bicarb & Cl- are actively secreted in the crypts.
Then Na+ moves down its gradient.
Water passively follows the party.
What kind of stuff is secreted in the large intestine? Where is it secreted from? What is its function?
Mucus w/ a bunch of bicarb is secreted from crypts of Lieberkuhn in the LI. Note: no villi in LI.
Its fcn is to protect the mucosa from acid from feces. Also, it helps the fecal material to form.
What prompts the release of mucus from LI crypts? What is the mechanism?
Parasympathetic stimulation increases it.
NaCl cotransport into the intestinal cell on the basolateral side. Cl- secretion from the apical membrane dependent on cAMP. cAMP levels regulated by VIP. VIP is secreted after a meal.
What causes cholera? What happens early on when you get it?
Early on: abdominal pain & diarrhea & vomiting.
What happens in the late stages of cholera?
Later on: extreme diarrhea! Dehydration Tachycardia Fever Dry Skin **diarrhea has white flakes that are GI cells If not treated, 50% death rate. Responsible for SO many deaths. Sad.