Overview of Gastrointestinal Tract

Mouth: chewing and hydrolysis (enzymatic breakdown) =bolus

Esophagus: propels bolus

Stomach: churning + hydrolysis + storage = chyme

Small intestine: hydrolysis + absorption

Large intestine (colon): absorption (of ions, water, vitamin K, not nutrients)

Rectum: storage of processed food until we expel it

Anus: expulsion

Mouth (oral/buccal cavity)

Goal of the mouth is to convert food into bolus, which we do in 2 steps:

1. Mastication (chewing)- accomplished by teeth and tongue

   1. tongue is made of extrinsic and intrinsic muscles

   2. extrinsic: causes elevation, depression, protrusion, and retraction

   3. intrinsic: (inside the tongue) shorten and widen, and lengthen and narrow

2. Break down of food particles by hydrolysis. The enzymes in our mouth that do this come from glands

   1. Glands release serous content (for enzyme breakdown/and cut food by hydrolysis) and mucinous content (wet the food so its easier to make bolus)

      1. Parotid glands: serous, release 25% of saliva content, release alpha amylase

      2. Submandibular: mostly serous, release 70% of saliva, releases alpha amylase

      3. Sublingual gland: mainly mucin, release 5% of saliva, releases alpha amylase

      4. Von Ebner gland: tip of tongue, serous, 5% of saliva

         1. also breaks down triglycerides with lingual lipase into free fatty acids, diglycerides, and monoglycerides

   2. Alpha amylase breaks down starches into smaller cards

Teeth

Mandible: lower jaw

Maxilla: upper jaw

There is symmetry on both left and right sides as well as between mandible and maxilla

28% of people have:

• 4 central incisors, 4 lateral incisors, 8 premolars, and 12 molar teeth

• 72% have the third molars (wisdom teeth) removed due to inadequate space within the mouth which can lead to tearing and inflammation within the gums (becomes impacted)

Esophagus

There are sphincters- circular localizations of muscle- at the very top and very bottom of the esophagus. These keep food moving in one direction

• Upper esophageal sphincter: voluntary, made of skeletal muscle

• Lower esophageal sphincter: its actually the diaphragm, looks like a sheet of muscle between the thoracic cavity and the abdominal cavity and helps lungs expand and breathe

  • forms a ring around the base of the esophagus and holds it in place

  • over time, humans can get a hernia where the esophagus moves up through the diaphragm and causes acid reflux

• Works as a passageway for food and doesn’t do much except for peristalsis

• Muscle-makeup is split into thirds:

  • top third: all skeletal muscle, voluntary control

  • middle third: combination of skeletal and smooth

  • bottom third: all smooth muscle, involuntary control

Stomach

Stomach is responsible for 3 steps:

1. receives bolus of food

2. churns bolus/breaks down food even more

3. hydrolysis (enzyme assisted breakdown) of bolus

The end product is chyme, which sits there for a little bit (stomach stores up to 4L of food at a time) before moving on to the small intestine

Stomach is lined with many infoldings (rugae) of the gastral wall that help increase surface area. The folds are lined with gastric glands and goblet cells:

• Gastrin hormone causes the secretion of HCl, pepsinogen and increases stomach motility

• Goblet cells: found along the entire GI tract and secretes mucus

  • Mucus in the stomach protects the stomach wall from pepsin and HCl

• Gastric glands

  • Parietal cells: release HCl (pH of stomach is about 2)

  • Chief cells: release pepsinogen (turns/activates into pepsin due to HCl presence)

    • pepsin breaks down proteins by cleaving peptide bonds, thus protein is the only type of molecule to be broken down in the stomach

    • Pepsinogen is a type of zymogen (inactive forms that are activated by proteolytic cleavage by another enzyme) BUT PEPSINOGEN AUTCLEAVAGES ITSELF BY ACIDIC PROTEOLYSIS

Small intestine

Chyme enters the small intestine by the pyloric sphincter

• stomach emptying can be inhibited if the small intestine is already full or if there is excess acidity, which is mediated by nerves and the hormone cholecystokinin, secreted by epithelial cells into the bloodstream to causes pancreatic bicarbonate (high pH) and water secretion to adjust pH

The small intestine is divided into 3 segments:

1. Duodenum: receives chyme from the stomach. Most of the digestion occurs here

2. Jejunum: most absorption happens here

3. Ileum: absorbs important things like vitamins

Duodenum is very with with four key processes:

• receives chyme and HCl from the stomach

• liver and gallbladder send bile to the duodenum

• pancreas also delivers some important enzymes

• the duodenum itself has brush border enzymes, which are important for absorption and for enzyme activity

  • brush border are in-foldings on the wall of the duodenum called villi

    • each villus is even more in-foldings, microscopic projections called microvilli

    • all these increase surface area for absorption and digestions, because the projections have enzymes

Digestion in the Duodenum

Protein is broken down by several enzymes in the small intestine into constituent amino acids

• peptidase is found on the brush border

• the pancreas sends trypsinogen and chymotrypsinogen, which an enzyme called enteropeptidase turn into their active forms of trypsin and chymotrypsin

Carbohydrates are broken down by amylase and lactidase (can only break apart lactose, found on brush border)

• when you have a stomach bug it can inflame the duodenum and actually knock off some of the lactidase enzymes, thus you become temporarily lactose intolerant

• eventually left with monosaccharides

Nucleotides are broken down by nucleosidases on the brush boarder which cleave the base-pentose bond

Fat is broken down by lipase, released by the pancreas and cleaves the triglycerides into glycerol and 3 fatty acids

• bile released by the liver/gallbladder to organize the fatty acids

Absorption (Mostly in Jejunum)

After digestion, monomers are present (A.A’s, monosaccharides, nucleobases, fatty acids, etc.)

Amino acids are funneled into intestinal cells with primary active transport (uses ATP) and eventually enters a blood capillary

Sugar monosaccharides are funneled into and eventually out of the intestinal cells with secondary active transport (uses ion like sodium to flow down the concentration gradient to enter or exit to allow the monosaccharide to go the opposite direction)

P-pentose and nitrogenous base also enter/exit the cell with primary active transport and end up in the blood capillary

Fatty acids can just diffuse across the membrane into the enterocyte (intestinal cell) where they are organized into chylomicrons which are absorbed into the lymphatic capillary (lacteal) where they are further digested into smaller bits and then get into the veins and blood capillaries

Liver

Responsible for 4 main things:

1. metabolism- involves catabolism and anabolism

2. storage

   1. carbs are stored a glycogen and cats can be stored as lipoprotein and triglycerides

   2. protein aren’t stored but are turn into molecules like albumin which can be sent into the blood stream until they’re needed and retrieved back to the liver

3. detoxification- achieved mainly by cytochrome P450

   1. can take many different kinds of substrates and react with them

   2. causes a problem when we take medications because it decreases drug efficacy

4. bile production- needed for fat absorption

The liver has two separate blood supplies going to it, and one that leaves it. These vessels make up the portal triad

• the portal vein supplies the liver with nutrient rich blood (nutrients absorbed in the intestinal tract which go through circulation and end up in the portal vein (turns excess nitrogen from proteins into urea)

• proper hepatic artery supplies liver with arteriole, oxygen rich blood

• hepatic vein carries away nutrient and oxygen poor blood

  • this blood then travels to the heart to be oxygenated, goes past the intestines to gain nutrients, then re-enters liver through portal vein

The other output from the liver is bile, which leaves through the common hepatic duct

Hepatic lobule

The portal triad is important to identify in surgery, and easy to identify when we look at pieces of the liver called hepatic lobules

• in the hepatic lobule, there are many liver cells or hepatocytes, and around them are three distinct branches that make up the portal triad. There are actually bunches of portal triads surrounding hepatocytes- this leads to 6 distinct sides of the hepatic lobule

  • the portal vein is how we get nutrient rich blood to enter the hepatic lobule (portal vein branches are call sinusoids) where hepatocytes then break those nutrients down for storage or whatever is needed. The proper hepatic artery beings in oxygen to the hepatic lobule.

• once those have been extracted, the blood collects in the center of the hepatic lobule into the central vein which then becomes the hepatic vein, which sends the blood back to the heart and intestines

Biliary tree

Bile is composed of bile pigments and bile salts (helpts emulsify fat into micelles, which can be absorbed in the ilium)

Bile thats made in the live travels through the common hepatic duct into the cystic duct which leads to temporary storage in the gallbladder

• gallbladder is used to store bile, its the organ’s only focus

Cholecystokinin (CCK) is a hormone that causes bile to be released from the gallbladder though the organ contracting and squeezing the bile into the cystic duct to go to the common bile duct

• the common bile duct then goes to the duodenum where the bile is released and fats are emulsified

• bile salts are then absorbed by the ileum to circulate back to the liver to repeat the process

Exocrine Pancreas

The pancreas sits below and behind the stomach, and sort of hugs the duodenum of the small intestine

• some say its in a different part of the body, the retroperitoneum (along with some big blood vessels) and not in the peritoneum (where the abdominal cavity rests)

The pancreas releases powerful enzymes that digest lots of macromolecules. Its also unique cause it’s un-encapsulated. (its just a slurry of cells, which is difficult especially for surgeons operating nearby)

Many consider the pancreas to the the ‘lion’ of the abdomen because of its importance and power

There are two main components to the pancreas:

• the exocrine pancreas: takes salts an enzymes and releases them in the duodenum

• the endocrine pancreas: releases hormones

The exocrine pancreas releases four main things:

1. Bicarbonate: neutralizes gastric acid (HCl with chyme from the stomach)

2. Amylase: breaks down starch into monosaccharides

3. Lipase: breaks down triglycerides into free FAs, monoglycerides, diglycerides, and glycerol

4. Proteolytic enzymes: includes trypsinogen and chymotrypsinogen

   1. Trypsinogen is turn into its active form typsin by anteropeptidase enzyme in the duodenum and then chymotryspinogen is turned into its active form chymotrypsin by trypsin

   2. if trypsinogen ends up turning into trypsin while in the pancreas… it would travel around and digest all sorts of proteins (in membranes, food, organs, not good)

The endocrine pancreas is more famous: it releases hormones rather than enzymes and salts. Those enzymes enter the bloodstream and move all over the body

The endocrine pancreas is composed of many islet cells that sit in “islands”

3 main types of islet cells:

• alpha islet cells: release glucagon (breaks molecules, turns glycogen into glucose)

• beta islet cells: release insulin (stores molecules, turns glucose into glycogen)

  • Also the hormone responsible for diabetes “eye, nerve, and kidney disease” , which is caused by too much glucose in the body because insulin isn’t working

  • Type 1: no insulin

  • Type 2: insulin receptors are broken

• delta islet cells: release somatostatin (stops the effect of other hormones in GI tract)

Colon, Rectum, and Anus

After foot is absorbed in the small intestine, it travels to the large intestine (larger in diameter but shorter in length)

At the end of the small intestine/beginning of the large intestine is the ileocecal valve

The first main part of the large intestine is the cecum (with the appendix tail hanging off), then the ascending colon, transverse colon, and the descending colon. The last part of the large intestine is the sigmoid colon (has an S shape to it)

The large intestine is most responsible for absorbing:

• Water

  • absorb too much water=constipation

  • absorb too little water= diarrhea

  • The disease cholera attacks certain proteins/receptors in the intestinal lining that cause tremendous fluid loss and eventually leads to death by dehydration

    • keeping a person very hydrated through the whole disease manifestation will lead them to eventually passing the bacteria and being okay

• Inorganic Ions- potassium and sodium

  • absorbed through transport mechanisms like the kidney

  • inorganic ion absorption is more important in the kidneys, so you’ll be okay with you have a colonectomy in terms of ion absorption

The large intestine is also home to lots of micro-organisms that assist in digestion of things like carbs, making byproducts of methane, and dihydrogen sulfide

Rectum is after the sigmoid colon and it’s main function is storage- it holds onto stool until it is excreted

The anus is composed of 2 sphincters:

• internal anal sphincter: smooth muscle, involuntary

• external anal sphincter: skeletal muscle, voluntary

The internal anal sphincter releases to allow stool to move to allow us to know it is time for defecation. Defecation occurs once external sphincter opens

Hormonal Control of Appetite

When the stomach is empty, gastric cells produce the hormone ghrelin to stimulate appetite.

When the colon is full, the jejunum produces peptide YY to reduce appetite

The hormone leptin, produced by white adipose tissue is an appetite suppressant that acts as an ‘adipostat’ (maintains stable lipid content in the adipose tissue)

• Leptin is secreted in response to increased triglyceride levels and works to suppress appetite until appropriate levels are store

• Leptin is a focus on obesity research, in humans obesity is often associated with high levels of leptin but a lack of appetite suppression, which suggests the hypothalamus has become resistant to leptin due to down-regulation of receptors