7.1: The Intestines

Question 1

Describe the condition of chyme leaving the duodenum

*3 things

Answer 1

1. Isotonic (water)
2. Neutral (bicarbonate)
3. Digestion nearly complete

Question 2

How is absorption throughout the intestines accomplished structurally?

Answer 2

1. A large surface area is achieved via villi, microvilli, plicae circularis and the general long length of the SI
2. Slow movement for absorption to take place

Question 3

Is absorption in the intestine primarily active or passive?

Answer 3

Mostly active

Question 4

Describe how the intestinal mucosa is constantly renewed

Answer 4

Cells multiply in the crypts between the villi and migrate up towards the tips, maturing as they go. They then acquire the capacity to absorb and contribute to the micro-villi. They are eventually shed from the villus tips

Question 5

Describe the composition and the job of the ‘unstirred layer’ of the intestine

Answer 5

Cells of the villi are active and secrete enzymes into the brush border, forming the ‘unstirred layer’. Here, almost digested nutrients are able to diffuse into the layer where the trapped enzymes complete digestion. Small molecules are released slowly out of the unstirred layer for absorption

Question 6

Describe the two main components of starch

Answer 6

1. Amylose; straight chains with a-1-4 bonds

2. Amylopectin; branched chains with a-1-6 bonds at branches

Question 7

Describe the role of a-amylases. Where are they secreted from?

Answer 7

Salivary amylase breaks down the a-1-4 bonds in starch, and pancreatic amylase continues a-1-4 bond breakdown

They yield glucose and maltose from amyloses and a-limit dextrins from amylopectins

Question 8

Name four brush border enzymes and how they continue carbohydrate digestion

Answer 8

1. Isomaltase: breaks down branched molecules at a-1-6 bonds
2. Maltase: breaks down maltose (a disaccharide) into two glucose molecules
3. Sucrase: breaks down sucrose into glucose and fructose
4. Lactase: breaks down lactose into glucose and galactose

Question 9

How do glucose, galactose, fructose and lactose enter the mucosal cells?

Answer 9

Glucose: is absorbed actively into the mucosal cell via the Na+/glucose cotransporter SGLT1 (glucose is going against its concentration gradient). The Na/K ATPase on the basolateral side is important in maintaining a low Na+ concentration inside the cell for SGLT1. (There is also a K+ channel to balance the Na/K ATPase and allow the K+ back into the ECF)

SGLT1 also transports galactose

Fructose and lactose enter by facilitated diffusion (not linked to Na+)

Question 10

How does glucose leave the mucosal cell and enter the ECF?

Answer 10

Facilitated diffusion on the basolateral side via the GLUT2 transporter

Question 11

Describe how Oral rehydration works

Answer 11

By giving a mixture of glucose and sodium, this stimulates further uptake of sodium chloride, glucose and water into the body causing rehydration

Question 12

Describe the enzymes involved in the digestion of proteins

*Including three main peptidases

Answer 12

1. Stomach: pepsin from chief cells (likes the bond near aromatic acid side chains)
2. Further peptidases released from the pancreas into the duodenum (as zymogens needing to be activated);
   A) Trypsin (breaks down bonds near basic side chains)
   B) chymotrypsin (breaks down bonds near aromatic side chains)
   C) Carboxypeptidase (cleaves C terminal amino acids)

Question 13

Which enzyme activates trypsinogen into trypsin and where?

Answer 13

Enterokinase in the brush border of the duodenum

Question 14

How does the absorption of proteins change from a neonatal individual to an adult?

Answer 14

Adults can absorb amino acids and small peptides, whereas neonatals can absorb proteins such as IgG from breast milk to help develop their immune system

Question 15

How are amino acids actively absorbed?

Answer 15

There are 5 active Na+/amino acid co transporters (mechanism exactly like the uptake of glucose) with different affinities for different amino acids

Question 16

How are dipeptides and tripeptides absorbed?

Answer 16

Active mechanism: Performed with Cotransport with protons; protons are first pumped out into the lumen to acidify the area around that brush border which can be used to uptake the small peptides and the proton

Question 17

How are electrolytes and water absorbed?

Answer 17

Sodium is taken up via diffusion into the cell and active transport across the basolateral membrane. Cl- follows (negative attracted), and the osmotic gradient formed by the absorption of ions leads to the uptake of water

Question 18

How much of the mineral calcium is absorbed a day?

Answer 18

~700 mg/day

Question 19

Describe the process of how the mineral calcium is absorbed from the diet, how much of the ingested amount is absorbed? What does this process depend on and what is it stimulated by?

Answer 19

Only 10% from diet absorbed. Since calcium has a low intracellular concentration, it enters the cell via facilitated diffusion. Ca2+ ATPase constantly pumps calcium across the basolateral membrane.

Depends on Vitamin D (active version, calcitriol), as this acts as a transcription factor that activates the expression of genes that perform the facilitated diffusion and Ca2+ ATPase, and is stimulated by PTH

Question 20

One issue with iron absorption is its lack of solubility, which substances are important in fixing this and where are they secreted from?

Answer 20

The stomach secretes gastric acid which helps free iron from where its bound and put into a solution.

Oxyntic cells in the gastric mucosa secrete Gastroferrin (a protein) which helps iron maintain its soluble form

Question 21

Once iron has been made more soluble, how is it absorbed and transported throughout the body?

Answer 21

1. Mucosal cells secrete transferrin which iron is able to bind to in the lumen
2. The complex is taken into the cell by endocytosis
3. Inside the cell Fe2+ is liberated again and is exported into the blood where it binds to transferrin to be transported around the body to tissues with a transferrin receptor

Question 22

How are water soluble vitamins largely absorbed? Name two examples

Answer 22

Passive diffusion, Vit C and B vitamins

Question 23

What’s necessary for the absorption of Vit B12?

Answer 23

Vit B12 is absorbed with a co-factor ‘intrinsic factor’ which is secreted by parietal cells in the stomach mucosa and acts as transporter for B12 until the whole complex (B12 intrinsic factor complex) is absorbed in the terminal ileum

Question 24

Name two conditions that could hinder your ability to absorb B12 and a potential consequence of this

Answer 24

1. Any stomach damage which disables parietal cells (intrinsic factor releasing cells) or
2. Removal of the terminal ileum (where B12 is eventually absorbed).

A consequence of this is pernicious anemia. Since B12 is important in nucleotide synthesis in erythropoiesis, a deficiency results in RBCs that can’t develop properly and become larger than normal

Question 25

Describe how contents move through the small intestine | *Include an explanation of the intestinal gradient

Answer 25

Process called ‘segmenting’, very slowly with gentle agitation (not quite peristalsis) to maximize chances of absorption. The intestinal gradient is created by intestinal pacemakers that are located at intervals along the length of SI, with their frequency being highest at the stomach end (depolarize quicker here). This creates a more rapidly moving cephalic segment and gradual caudal progression. Each pacemaker triggers an AP that travels through gap junctions and triggers the surrounding NS - so often it’s a combination of pacemaker + other inputs causing the final intermittent contraction. After a few seconds the contractions relax and the next pacemaker fires. In the portions where the muscle isn’t contracting, contents are mixed and brought into contact with the brush border. *segmenting does not propel contents but mixes them, however there is a slow net movement of material in a caudal direction

Question 26

Describe how contents move through the large intestine | *The two main processes

Answer 26

1. Haustral Shuttling; the colon is divided into segments known as haustra. Contractions of smooth muscle (including the 3 bands of taenia coli replacing the longitudinal layer) shuffle contents back and forth with gentle progression towards the sigmoid colon. This works in combination with a slow absorption of the remaining water and salts, forming feces. 2. Mass movement; A peristaltic propulsion from the transverse-descending colon and forcing feces rapidly into the rectum that happens 1-2 times/day. This process is induced by the gastrocolic reflex triggered by eating, expansion of the stomach, and the absorption of some products (likely fats) in the SI and induces the urge to defecate (but it can also occur at fixed times of the day)

Question 27

Describe why someone feels the urge to defecate?

Answer 27

Once the rectum has been filled by mass movement, pressure receptors cause waves of contraction in the rectal muscle forcing feces towards the anus

Question 28

What causes relaxation of the internal anal sphincter?

Answer 28

Activated pressure receptors in the rectum trigger the parasympathetic system to relax the smooth muscle of the sphincter

Question 29

What causes relaxation of the external anal sphincter?

Answer 29

The external anal sphincter is voluntary striated muscle, and must be relaxed voluntarily. However, if rectal pressure becomes too high sacral reflexes will eventually trigger defecation

Question 30

``` Describe how the following elements of the innate immune system/first line of defence normally prevent infection in the large intestine A) physical barrier B) physiological barrier C) chemical barrier D) biological barrier ```

Answer 30

A) physical: epithelium of mucous membrane lining the bowel provides a physical barrier. The mucous membrane contains goblet cells that secrete mucous which helps protect underlying tissues from damage by digestive enzymes and to propel microorganisms through the GI tract B) physiological: Diarrhea (which can also be caused by the bacteria) expels unwanted products and pathogens C) chemical: GI tract has many digestive enzymes that affect pathogens. Specialized cells such as defensins also produce specific microcidal molecules D) Biological: many non-pathogenic bacteria in the normal flora which compete for attachment sites and resources and inhibit the ability of potential pathogens to multiply and cause disease

Question 31

What is the second line of immune defence in the large intestine?

Answer 31

The epithelial lining containing cells of the immune system such as macrophages which can phagocytosis pathogens

Question 32

What is the mechanism of disease production by C.difficile?

Answer 32

Major contributing factors are 1. Alteration of normal intestinal bacterial flora 2. Toxin produced (at time where C. difficile is rapidly growing and other, normal intestinal organisms are suppressed) which causes epithelial damage resulting in sloughing of the epithelium. Toxin A enterotoxin also produces an intense inflammatory response and formation fo an exudate 3. Age-related susceptibility; increased incidence of C.difficile toxin-positive stools in 60+

Question 33

What is a pseudomembrane and how might a C.difficile infection cause one?

Answer 33

A pseudomembrane is a layer of exudate that resembles a membrane C. Difficile releases - Toxin A: enterotoxin causing excessive fluid secretion and inflammation on the lining of the bowel wall - Toxin B: disrupts protein synthesis and is therefore cytotoxic The necrotic epithelium and inflammatory exudate together form the pseudomembrane.

Question 34

How does the large intestine pathology differ between C.difficile and cholera?

Answer 34

In cholera the colon is oedematous without any other pathological changes, and although cholera is also a toxin-mediated disease there is no epithelial destruction

Question 35

What element of the innate immune system normally prevents an infection occurring with regards to bacteria in the large bowel?

Answer 35

Probiotics GALT

Question 36

Name two antibiotics that are frequently associated with a C.difficile infection

Answer 36

Cephalosporin, amoxicillin

Question 37

C.difficile is a part of the group of clostridium bacteria, name the two other bacteria in this group and the diseases they might cause

Answer 37

C. Tetani - tetanus | C. botulinum - botulism