Week 11: Accessory Organs/Regulation of Digestive Tract

What is the pancreas/function/structure

organ with essential endocrine and exocrine functions. Connected to the upper portion of the small intestine via two ducts where the pancreativ juscies come into contact with the chyme. 

How do exocrine secretions move through/out of the pancreas?

• Exocrine secretions come from a few different cells within the epithelial clusters in the pancreas. 

• Exocrine secretions made by the pancreatic cells are moved through the body of the pancreas via the pancreatic duct which joins to the common bile duct which connects to the liver and gallbladder.  

What is the hepatopancreatic sphinter (Oddi) ?

needs to open to allow the exocrine secretions (from pancreas/gallbladder/liver) to enter into the duodenum. 

What is the pancreatic duct?

also allows for the secretions of the pancreas to enter into the first part of the small intestine. 

What make exocrine versus endocrine secretions in the pancreas?

The acinar cells (secrete types of enzymes/zymogens) and ductal cells (secrete bicarbonate and water) make exocrine secretions while cells within the pancreatic islets make endocrine secretions.  

What to acinar cells secrete and in what enviornment do these function best?

enzyme pancreatic amylase which digests starch (component of starch called amylose) and the enzyme pancreatic lipase which digests triglycerides.  

Both enzymes function best in a more alkaline environment, so it is important that the acidic chyme coming from the stomach into the duodenum be neutralized by bicarbonate. 

Function of ductal cells

secrete bicarbonate to help create alkaline environment for acinar secretions and water which helps liquify the solution so it can move through small ducts.

How are the zymogens secreted by acinar cells activated?

activated once they enter the lumen of the small intestine due to a cascade of events that begin with the activity of the brush border enzyme enterokinase also called enteropeptidase 

Tripsinogen and chymotryptinogen are zymogens from acinar cells (protein digesting in active form) and once in the lumen of small intestine enterokinase can activate trypsinogen into trypsin. 

From there the rest of the zymogens are converted into active enzymes by the activity of trypsin which cuts all of these zymogens into enzymes

pancreas protected since activation occurs in small intestine

What is procolipase/colipase?

Also included in this mix of zymogens is the inactive protein procolipase – when activated colipase. not an enzyme but an enzyme helper – helps the enzyme pancreatic lipase digest triglycerides more efficiently. 

List all the enzymes/zymogens produced by the acinar cells of the pancreas and what they do

• 1) pancreatic amylase = an enzyme that digests starch, amylose (active when secreted) 

• 2) pancreatic lipase = enzyme that digests lipids triglycerides (active when secreted) 

• 3) trypsinogen =  zymogen converted into enzyme trypsin digests proteins 

• 4) chymotrypsinogen = zymogen converted into enzyme chymotryptin digests proteins. 

• 5) procarboxypeptidase = zymogen converted into enzyme carboxypeptidase digests proteins 

• 6) proelastase= zymogen that is converted into enzyme elastase digests proteins 

• 7) prophospholipase = zymogen converted into enzyme phospholipase digests phospholipids. 

• 8) procolipase = inactive protein that is converted into coenzyme colipase which helps pancreatic lipase more efficiently digest triglycerides. 

What are the functions of the liver?

accessory digestive organ, removes waste products, converts ingested nutrients into other usable forms. 

What is metabolism?

biotransformation of waste products for excretion, or converting absorbed carbohydrates into other useable forms like lipids

What is the main cell type of the liver and what does it do?

Hepatocytes - makes bile solution

What ducts collect bile in the liver and what do they combine to?

• bile is collected within the liver by ducts called hepatic ducts. 

• The two main left and right hepatic ducts connect together to form the common hepatic duct.  

What is the cystic duct?

The liver is connected to the gallbladder via the cystic duct.

What makes up the common bile duct and what happens here?

The cystic duct and common hepatic duct join together to form the common bile duct. Secretions from the pancreatic duct connect to the common bile duct (at the very end other than that travels independently)

Bile solution concentrates here until contracted then solution goes to small intestine. 

What is the hepatopancreatic sphincter?

When the hepatopancreatic sphincter opens, the secretions collected in the common bile duct can enter into the duodenum. 

What is unique about the blood vessels of the liver and what does this allow for?

Two blood vessels bring blood to the liver; one is the hepatic artery carrying oxygenated blood, and the other is the hepatic portal vein (deoxygenated) that brings nutrient rich blood from the gastrointestinal tract. 

Cells of the liver can then process the contents of the blood before it exits the liver via the hepatic vein (also deoxygenated but nutrient dense to deliver to rest of the body).

What are sinusoids?

Where hepatic artery and portal vein pool their contents together into permeable capillaries.

What is a liver lobule

basic structural unit of the liver, organized in a hexagonal shape. The hepatocytes make up most of the lobule allowing them to make bile solution.

What are at the corners of the liver lobule and what is at the center?

at the corners are three different vessels: a branch of the hepatic artery, a branch of the hepatic portal vein, and a branch of the bile duct.  

At the center of each lobule is a central vein, which collects the blood that has passed through the sinusoids. 

What are bile canaliculi?

bile solutions that is made by hepatocytes are collected by small vessels called bile canaliculi which collects into the bile duct. 

How are hepatocytes organized and how does this help with absorption/bile secretion?

into a single plate of cells that are exposed to both blood via sinusoids and bile canaliculi. 

sinusoids are so leaky hepatocytes have good exposure to the mixed arterial-portal venous blood and can therefore easily absorb and metabolize nutrients.  

Hepatocytes also take waste products in blood and produce/secrete bile solution – containing bile salts (help solubilize the lipids we ingest) is secreted into small spaces between hepatocytes which are the bile canaliculi vessels (not across sinusoidal because not going into the blood). 

When the hepatocytes metabolize the mix of blood from hepatic artery and portal vein they decide if those items go back into the blood or can make different secretions. 

What are the two different membranes

hepatocytes membrane that faces the sinusoids is called the sinusoidal membrane - as microvilli (increased surface area) and there are lots of different transporters to allow for items to enter hepatocyte. 

hepatocyte membrane that faces these bile collecting vessels is called the canalicular membrane. 

Where does bile solution go?

Bile solution is not secreted into the blood – goes to bile canaliculi. 

What is the gallbladder and function

pear-shaped sac made up of smooth muscle that lies beneath the liver. Function is to store and concentrate bile solution that is produced by the liver until it is needed. 

What does the gallbladder do when chyme solution enters the duodenum?

When chyme solution enters into the duodenum, the gallbladder will be stimulated to squeeze and contract pushing the bile solution out of the gallbladder through the cystic duct down the common bile duct and into the duodenum. 

What does bile solution do?

aids in the metabolism of lipids but also functions as a vehicle to excrete waste products like bilirubin which is the breakdown product from hemoglobin. 

What are bile salts and what is function?

Bile salts are amphipathic molecules (have both hydrophobic and hydrophilic regions) made by hepatocytes - function as detergents to solubilize lipids

How does the composition of bile solution change as it is transported through bile ducts?

composition of bile solution changes as it is transported through the bile ducts, becoming more alkaline by the addition of bicarbonate from the cells that line the bile ducts. 

What is a cholecystectomy?

removal of gallbladder for those who experience attacks when bile solution has crystallized into gallstones. Can live without gallbladder. 

How do digestive organs communicate?

Through neural and hormonal messages

How is the digestive tract regulated

by the ENS which is mostly due to the activity of the myenteric plexus neurons within the muscularis externa layer of the digestive tract (where the neuron bodies of the ENS are found) - but can also be regulated by both divisions of ANS

Difference in function between submucosal plexus and myenteric plexus?

submucosal plexus extend to the epithelial cells of the mucosa layer of the digestive tract and can stimulate what is secreted and how much secretions are made.

myenteric regulates motility patterns

What sensory neurons of the ENS are part of the submucosal plexus?

• 1) Mechanoreceptors: sensory neurons that can detect how much the digestive tract organ is stretching or if there are contents within the lumen of the digestive tract, or can detect how solid versus liquid the lumen contents are.  

• 2) Chemoreceptors: sensory neurons that can detect the contents of the bolus or chyme, including the nutrient density and the types of macronutrients such as proteins, amino acids and lipids 

• 3) Nociceptors: sensory neurons that can transmit pain, identifying damaging events such as injury or inflammation 

What are short loop reflexes?

local reflexes can begin and end within the wall of the GI tract these are defined as the short loops reflexes of the ENS. Since sensory neurons are located within the submucosal plexus, lumen contents are detected and this results in an output that usually involves increasing motility/increasing secretions within the lumen of the gut. 

What are some short loop reflexes?

can induce secretions of enzymes, but also can stimulate the secretion of acid as in the example of the stomach to improve chemical digestion (in response to sensory receptors in ENS)

Short loop efferent neurons can cause neurons from the submucosal plexus to stimulate secretion of epithelial cells of the mucosa, and change the activity of neurons in the myenteric plexus to change smooth muscle for contraction and dilation patterns. 

What are long loop reflexes?

incorporate the CNS – information can be sent to the CNS and the sensory information can be integrated by the brain and result in action.  

What type of sensory information does long loop reflexes respond to?

• sensory information can originate within the digestive tract, such as the presence of food - but can also be outside the digestive tract such as the smell/sight/thought of food.

What is the role of the vagus nerve in long loop reflexes - what branch does it belong to?

• The vagus nerve can bring sensory information back to the brain. 

• The vagus nerve also contains efferent neurons (and afferent) so that the CNS can control neurons within the myenteric and submucosal plexus. This will stimulate motility patterns and control secretions. 

• Vagus nerve is part of the parasympathetic NS – activated during rest/digest 

How to long and short loop reflexes interact?

Long loop reflexes help reinforce short loop reflexes – CNS sends signals that makes changes which triggers short loop reflexes. 

List the 5 digestive hormones that act on the tract (endocrine organ)

• 1) Gastrin: peptide hormone secreted by G cells of the stomach, triggered for release due to activation by the neurotransmitter ACh stretching of the stomach due to a bolus and the presence of proteins or amino acids. 

• 2) Somatostatin: peptide hormone secreted by D cells of the stomach, triggered for release due to low pH 

• 3) Cholecystokinin (CCK): a peptide hormone secreted by I cells of the small intestine, triggered for release due to the presence of protein or lipids in chyme. 

• 4) Secretin: a peptide hormone secreted by S cells of the small intestine, triggered for release due to low pH. 

• 5) Glucose Dependent Insulinotropic Peptide (GIP): a peptide hormone secreted by K cells of the small intestine, triggered for release due to the presence of carbs, lipids, and proteins in chyme. 

What in the mouth is under neural control?

In the mouth only neural control exists for the control of salivary production and flow rate - hormones can modify composition but not production/rate of flow. 

How do branches of ANS regulate salivary secretion - what are the effects?

Both branches of the ANS both positively regulate salivary secretion, unlike the typical antagonistic control on most other organs. 

PSYN will initiate a large volume of saliva, while stimulation by SYN will also cause saliva production, although the composition may have more mucus and less enzymes (both positive but different composition and volume). 

Which salivary glands receive innervation from what branches of the ANS

• Each salivary gland receives PSYN and SYN innervation. 

• PSYN innervation of the parotid gland is by the glossopharyngeal nerve, while the submandibular gland and sublingual gland are inntervated by the facial nerve. 

• The SYN innervation of each of the glands (carotid/submandibular/sublingual) is by the thoracic spinal nerves (T1-T3) 

• PSYN innervation typically produced during times of eating food 

What do the interstitial cells of the muscularis externae layer of the stomach regulate motility - what has to reach threshold for this to happen?

These are pacemaker like cells that generate an electrical signal that spreads through the connected smooth muscle cells, without any neural or hormonal input. 

If the self-generating electrical signals, also called basal electrical rhythms (BERs) reaches threshold, than a muscle contraction can occur

What happens to interstitial cells when a bolus is present?

When a bolus does enter the stomach, the self-generating electrical waves of the interstitial cells are halted, and the stimulus of a bolus will generate the mixing patterns to assists with the liquefaction of a bolus to a chyme solution. (MMC only occurs in fasted state but BERs always occur but do not reach threshold when eating)

Instead long/short loops and gastrin regulate contractions/motility patterns.

What is the role of gastrin in acid secretion?

G cells are stimulated to release gastrin due to the presence of amino acids or small peptides (found in bolus), distension of the stomach that causes a short loop reflex, or the vagus nerve activation. Binds to its receptor on parietal cells to secrete acid.

Gastrin release can be caused by neural stimulation via the neurotransmitter gastrin releasing peptide (from enteric NS neurons) in response to stretching

What other two stimuli are required for maximal acid secretion?

Maximal levels require more reinforcing signals – the other two stimuli for acid secretion is the chemical messenger histamine and the neurotransmitter ACh. If one or two of these are present acid is still secreted but at a lower volume

Where does histamine come from and what causes this release?

Histamine comes from the enterochromaffin like (ECL) cells which are located in the mucosa layer near parietal cells (stomach). ECL cells are stimulated to release histamine because of gastrin (have these receptors), but also because of neural activation (due to stretch causing ACh release).   

What is the role of ACh in acid regulation and how is this activated?

ACh (neurotransmitter made by enteric neurons) – stimulated by vagus nerve in response to thinking about food (long loop) or due to presence of food (short loop). 

What inhibits acid release from parietal cells and what are the three ways this is triggered?

one is somatostatin release from D cells - stimulated by low pH of the stomach (2)

Other factors that promote release from D cells include the hormones cholecystokinin (CCK) and secretin. somatostatin binds to G cells to stop release of gastrin. 

What are the 4 neural/hormonal regulations of gastric emptying?

• 1) increased vagus nerve activity – causes more pyloric sphincter opening/increases gastric emptying. 

• 2) Gastrin in circulation – causes more opening/emptying 

• 3) increased sympathetic nerve activity – less opening/emptying 

• 4) CCK in circulation – causes less opening/ decreases gastric motility 

What regulates pancreatic secretions of acinar and ductal cells (hormonal and neural)

CCK stimulates the secretions by acinar cells and secretin increases bicarbonate and water secretion by ductal cells. 

efferent neurons from the vagus nerves (parasympathetic) are also involved in activation of acinar and ductal cells. 

What neural/hormonal regulates bile secretion

CCK stimulates gallbladder contraction and relaxation of the hepatopancreatic sphincter and stimulates the production and secretion of bile salts from hepatocytes. 

PSYN activation of the gallbladder is another stimulus from gallbladder contraction. 

Secretin stimulates the secretion of bicarbonate and water from the ductal cells that line the common bile duct – as bile solution goes into small intestine it neutralizes acidic chyme. 

How are bile salts recycled? When does bile solution increase in volume?

• Unlike enzymes bile salts need to be available in large amounts to solubilize lipids – it is efficient that the bile salt pool is recycled so that the liver does not need to produce as much for bile solution (reabsorbed in ileum) 

• The amount of bile solution released will increase in volume during the absorption and digestion of a meal. 

What are the three phases of regulatory events for the secretions and motility of the gastrointestinal tract?

Cephalic, gastric, and intestinal phase

What happens in the cephalic phase?

taste/thought/smell of food is sufficient to stimulate the cephalic phase. 

Higher order neural centers in the cerebral cortex in the hypothalamus are activated which then activated regions in the medulla oblongata - activates facial/glossopharyngeal/vagus nerves (PSYN) to stimulate submucosal/myenteric plexus regulating secretions and motility.

Some responses to neural activation = increased salivary secretions, acid secretion, and motility of the stomach. 

What occurs in the gastric phase?

Once the bolus has entered the stomach, the gastric phase begins.  

Stretching detected by stretch receptors (sent to ENS/CNS) and pH increases are detected by chemoreceptors.

Both sensory inputs trigger short loop refleces activating parietal cells to secrete acid/mucus

hormonal control = amino acids/peptides stimulate G cells to secrete gastrin and increases further acid/motility/emptying (open pyloric sphincter)

increases in both stomach/intestine

What occurs in the intestinal phase?

Once chyme has begun to enter the duodenum the intestinal phase. Large overlap between the gastric and intestinal phases as chyme can begin entering the duodenum when there is still a bulk of contents in the stomach. 

Chemoreceptors and stretch receptors activate short loop reflexes to increase secretions/motility of small intestine.

Secretions of pancreas and liver stimulated by long loop reflexes where the vagus nerve can stimulate the pancreatic fluid secretions and bile solution from the liver. 

Acid in the duodenum stimulates S cells to release the hormone secretin, while partially digested macronutrients like lipids and peptides stimulate the release of the hormone CCK – also K cells (GIP) 

What do we see increased secretions of during the intestinal phase?

• Increased secretion from: intestine (mucus) 

• Pancreas: bicarbonate from ductal (S cells), digestive enzymes from acinar cells (CCK) and insulin from beta cells (GIP). 

• Increased motility in the intestine (segmentation/peristalsis) 

• CCK stimulates contraction of gallbladder causing release of bile solution into duodenum and causes hepatopancreatic sphincter to open allowing secretions from the pancreas, liver, and gallbladder to empty into the small intestine. 

How does the intestinal phase impact the gastric phase?

Intestinal phase can slow the gastric phase by a neural long loop reflex called the enterogastric reflex. 

When the duodenum is stretched by chyme solution, this information is sent up to the medulla which will inhibit the PSYN pathway to the stomach, but will instead activate SYN innervation in the stomach.  

decline in gastric secretions and motility, and decreased opening of the pyloric sphincter = slows gastric emptying