Digestion and Absorption

Question 1

What are the two seemingly paradoxical tasks of the intestinal epithelial barrier (IEB)? How is this multitasking permitted? How is regulation of the IEB modulated?

Answer 1

1. Enable the absorption of nutrients (permeable)
2. Control the passage of pathogens or toxins (Impermeable)

• This multitasking ability is permitted by the structural organization and compartmentalization of the intestinal epithelium.
• Regulation of the IEB is highly modulated by components of its:
  o ‘outer’ microenvironment (microflora, chyme…)
  o ‘inner’ microenvironment (immune cells, fibroblasts or the enteric nervous system [ENS] and extrinsic nerve fibers).

Question 2

How are the functional structures of the enterocytes (to allow for permeability) built up?

Answer 2

• The functional structures of the enterocytes (to allow for impermeability) are built up by specialized cytoskeletal proteins
  (see diagram in notes)

Question 3

What is the surface area of the gut versus the skin? What is the reason for this?

Answer 3

Skin = 25 metres squared
Mucosae = 32 metres squared
- Reason for large surface area: 95% of absorption of nutrients occurs in the small intestine

Question 4

What are the rates of fluid into the digestive system? And of fluid out?

Answer 4

In:

• ingested water (2 liters)
• liver and pancreatic secretions (2 liters)
• salivary gland secretions (1.5 liters)
• secretions by glands of the stomach and small intestines (3.5 liters).

Out:

• Small intestines absorbs ~ 8.5 liters
• Colon (400ml)
• feces (100 ml)

Question 5

What can stem cells in the intestinal crypt give rise to? What happens to dead cells in the intestine?

Answer 5

• Stem cells in crypt (ditch in gut lining) can give rise to enterocytes or goblet cells, etc
• Dead cells get extruded (discarded) out into intestine (migrate out of crypt)

Question 6

Where does most of absorption happen?

Answer 6

• Most of absorption happens in duodenum and jejunum

see diagram for what happens where

Question 7

What is absorbed in the ileum?

Answer 7

Water and sodium (moderate amount)
B12
Intrinsic factor
Bile acids reabsorbed for recycling to the liver

Question 8

What is absorbed in the colon?

Answer 8

Water absorbed (small amount)
Electrolytes absorbed (small amount)
Bile acids reabsorbed (small amount)

Question 9

What is the structure of the small intestine and colon walls?

Answer 9

See diagram in notes

Question 10

What are the 3 phases of normal digestion and absorption?

Answer 10

1. ‘Luminal Phase’: The ingested food is broken down by acid in the stomach, alkali in the small intestine and a panel of substrate-specific enzymes secreted by the gastric and small bowel mucosa and the pancreas.
2. ‘Mucosal Phase’: Pre-digested nutrients are selectively taken up at the brush border membrane of the enterocytes and then enter the intestinal cells.
3. ‘Post-absorptive Phase: Transport of absorbed nutrients via lymphatics and the portal circulation to the rest of the body (e.g. liver).

Question 11

Why is water required in the digestive system?

Answer 11

o Hydrolysis reactions of digestion
o Facilitation of absorption (brings products of digestion into close proximity to microvilli)
o Facilitation of propulsion of gut contents
o Combination with mucin granules to make mucus

Question 12

Which 4 types of nutrients may be absorbed in the gut?

Answer 12

• Carbohydrates and complex carbohydrates
• Lipids
• Proteins
• Vitamins

Question 13

What are the features of the phases of digestion of carbohydrates and complex carbohydrates?

Answer 13

• Luminal phase:
  o Split into shorter molecules by salivary (trivial – stops working in low pH so is useless once food reaches the stomach) and pancreatic (important) enzymes (e.g. maltase, amylase).
  o = disaccharides + limit dextrins

-	Mucosal phase:
o	Brush border enzymes complete digestion.
o	Brush border enzymes:
	 Sucrase
	 lactase
	 maltase
	 limit dextrinase
	glucoamylase
o	Glucose and galactose enter epithelial cells via sodium-linked secondary active transport across the apical membrane. Fructose enters by facilitated diffusion. 

• Post-absorptive phase:
  o The sugars exit the cells across the basolateral membrane by facilitated diffusion to the portal vein.

Question 14

What are the features of the phases of digestion of lipids?

Answer 14

• Luminal phase:
  o Lipid digestion begins in the mouth with lingual lipases and continues in the stomach where gastric lipase is added to the mixture.
  o With the help of Bile salts, pancreatic lipase digests triglycerides into free fatty acids, and monoglycerides.
  o Micelles: contain fat soluble vitamins and cholesterol
• Mucosal phase:
  o Fatty acids and monoglycerides enter the enterocytes by simple diffusion.
  o Inside the enterocytes the molecules are reassembled into triglycerides and are packaged into large particles called chylomicrons.
• Post-absorptive phase:
  o The chylomicrons are secreted across the basolateral membrane by exocytosis.
  o The chylomicrons enter lymphatic capillaries (as they are too big to enter the bloodstream). The flow of lymphatic fluid then carries the chylomicrons to the bloodstream.

Question 15

What is enterohepatic circulation (VERY IMPORTANT)?

Answer 15

o Bile salts enhance the digestive action of lipases by breaking down fat globules into smaller droplets = emulsification. The bulk of the bile salts are absorbed in the ileum and recycled by the liver (otherwise will end up in colon and cause diarrhea).

Question 16

How do commensal bacteria (microbiome) act as key regulators of digestion?

Answer 16

o A dynamic equilibrium exists between diet-gut microbiome-bile acid pool size/composition. (bile acid pool consists of primary and secondary bile acids and can be efficient or not depending on its composition)

Question 17

Why are conjugated bile acids more efficient in emulsifying fats? How do microbial enzymes make them less efficient?

Answer 17

• Conjugated bile acids are more efficient in emulsifying fats because at intestinal pH they become more ionized than the unconjugated bile acids.
• Microbial enzymes deconjugate bile acids! (make them less efficient)

Question 18

What are the features of the phases of digestion of proteins?

Answer 18

• Luminal phase:
  o Begins in the stomach with the action of pepsin. In the stomach, chief cells release pepsinogen. This zymogen is activated by hydrochloric acid (HCl), which is released from parietal cells in the gastric pits.
  o Protein digestion is completed in the small intestines by enzymes secreted by the pancreas.
• Mucosal phase:
  o Trypsinogen is converted into trypsin by enterokinase, a brush border enzyme.
  o Trypsin can then activate:
   chymotrypsinogen -> chymotrypsin
   procarboxypeptidase -> carboxypeptidase
  • (pro-enzymes -> enzymes)
  o Amino acids enter epithelial cells via sodium-linked secondary active transport across the apical membrane. (JUST LIKE SUGARS)
• Post-absorptive phase:
  o Amino acids are then transported across the basolateral membrane by facilitated diffusion.

Question 19

What are pro-enzymes?

Answer 19

• Zymogen (pro-form) = enzyme cannot act yet (so as not to digest yourself by mistake)
• Enzyme = active form

Question 20

Why do vitamins need to be absorbed by food? What are the two types of vitamins? Why is B12 more complex and how is it absorbed?

Answer 20

• Vitamins can’t be manufactured by the body, so they need to be absorbed from the food.
  1. Fat soluble vitamins A, D, E and K
• Absorbed with lipids as they readily dissolve in lipid droplets, micelles and chylomicrons.
  2. Water soluble vitamins
• Most water-soluble vitamins (B, C) follow the flux of water from the gut lumen through the mucosa.
• B12 has a complex absorptive pathway. It can be absorbed only in the terminal ileum, and must first be complexed with stomach-derived intrinsic factor.
  o B12 (cobalamin) has a complex absorptive pathway:
  o Binds to Haptocorrin produced in the salivary glands.
  o Must be complexed with stomach-derived intrinsic factor (IF).
  o Transported into the portal circulation. The vitamin is then transferred to transcobalamin II (TC-II/B12), which serves as the plasma transporter
  o Absorbed in the terminal ileum.

Question 21

What are the main causes of generalised malabsorption?

Answer 21

• Commonly results from small intestine disease.
• Though it can also result from pancreatic disease or conditions in other organs (cholestatic liver disease…)
• Malabsorption in mucosal phase:
  o Small intestinal mucosal disease = reduced absorptive area
   Coeliac disease, post-infectious malabsorption, Crohn’s disease
• In the economically developed world, the most common cause of malabsorption is coeliac disease.

Question 22

What is coeliac disease? Who does it occur in? What gene causes it?

Answer 22

• Autoimmune disorder of the small intestine. Occurs in genetically predisposed people: Over 95% of people with coeliac have the isoform of DQ2 or DQ8 of the human leukocyte antigen HLA-DQ protein.
• HLA stands for: Human Leukocyte Antigen. It is the name given to the Major Histocompatibility Complex (MHC) in humans.

Question 23

What are common causes of generalised malabsorption in the developing world?

Answer 23

• In the developing world: Acute or chronic infection probably underlies many cases of malabsorption. Post-infectious malabsorption and tropical sprue
• Similar conditions may affect travellers returning from developing countries (e.g. postinfectious malabsorption, travellers’ diarrhoea).
  o may be initiated by a viral infection
  o may be associated with chronic bacterial infection of the upper gastrointestinal tract.

Question 24

What is specific malabsorption and what are some common specific malabsorptive states?

Answer 24

-	Specific malabsorption is the failure of the processes governing absorption of one class or type of nutrient. 
o	Example: genetic or acquired failure to absorb dissacharide sugars (ie: lactase deficiency) or vitamin B12 (pernicious anaemia).
-	Disaccharidase deficiencies are generally genetic and most of the world’s population is lactase deficient.

Question 25

What mutation causes lactase deficiency and how?

Answer 25

• Mutation in the gene LCT: Affecting the ‘mucosal phase’ of dissacharides absorption (lactase is in the brush border).

Question 26

How does glucose-galactose malabsorption occur (what mutations are involved)?

Answer 26

• Mutation in the gene SLC5A1:
• SLC5A1 encodes a member of the sodium-dependent glucose transporter SGLT1 (Sodium dependent GLucose Transporter one). Mutations in SLC5A1 cause Glucose-galactose malabsorption.

Question 27

What are the consequences of disaccharide malabsorptive states?

Answer 27

• Unabsorbed disaccharides reaching the colon adds to the osmotic load and causes watery diarrhoea. Fermentation of sugars in the intestine causes gaseous distension and adds to the watery diarrhoea.
  (see diagram in notes)