Gastro Week 2: Digestion and Absorption in the GI tract

List ways of mechanical digestion

• chewing

• swallowing

• peristaltic mixing

• retropulsion and propulsion

• segmental mixing

What is chemical digestion?

• chemical digestion is using enzymes to breakdown food by breaking chemical bonds

Explain how carbohydrates are broken down in the mouth?

1. carbohydrates begin digestion in the mouth and oesophagus through chewing and salivary amylase (starch/glycogen —> maltose/maltotriose/dextrins) Amylase breaks the 1,4-glycosidic bond via hydrolysis.

Explain how carbohydrates are digested in the stomach:

- chemical carbohydrate digestion stops in the stomach but retropulsion and propulsion physically breakdown carbs.

Explain how carbohydrates are broken down in the small intestine:

1. Once in the duodenum, pancreatic enzymes like maltase, lactase and sucrase further breakdown carbs into glucose, fructose and galactose.

Explain how carbohydrates are absorbed?

• once digested, carbohydrates are either in the form of glucose, sucrose or fructose.

• Enterocytes uptake glucose from the intestinal lumen of the small intestine via secondary active transport

• Specifically through the apical membrane using SGLT1 transporter proteins.

• This process requires energy to move glucose/galactose against its gradient, facilitated by a Na+/K+ ATPase pump that creates a sodium gradient. 

• Glucose then exits the cell into the blood via passive diffusion using GLUT2 transporters on the basolateral membrane.

• Fructose is absorbed by the GLUT5 transporter into the cell and by GLUT2 out of the cells (so is not dependent on the SLGT1 transporter).

What is the SGLT1?

The SGLT1 is a symporter, meaning it moves two different things in the same direction at the same time. It works like a revolving door that requires two specific "keys" to turn:

1. The Keys: To function, the SGLT1 must bind two Sodium ions and one Glucose molecule.

2. The Action: Once all three are attached, the protein changes shape and "flips" them from the inside of the gut (the lumen) into the intestinal cell.

3. The Result: From inside the cell, the sodium and glucose are then moved into the blood.

Give some clinical examples of when SGLT1 dependent- carbohydrate absorption goes wrong:

• glucose/galactose malabsorption due to patient having defective intestinal D glucose and D galactose absorption

• In neonates with this condition they will present with very severe watery diarrhoea → death unless you restore water and electrolyte balance quickly

• They will not eat foods with high glucose/galactose but they can eat food with fructose 

List the 3 ways glucose is made from polysaccharides:

1. starch/glycogen → maltose → glucose (via matlase)

2. starch/glycogen → sucrose → glucose + fructose (via sucrase)

3. starch/glycogen → lactose → glucose + galactose (via lactase)

How does the amylase enzyme breakdown carbs in the mouth?

• amylase breaks the 1.4 glycosidic bonds of the starch molecules through hydrolysis

Define short bowel syndrome:

• having less than 180-200 cm of remaining small bowel

• causes malabsorption of nutrients

• sodium concentration in bowel lumen is lowered so water absorption into enterocytes decreases

• to counteract this, patients are given high sodium fluids

Where is fibre digested?

• large colon

What are the 2 types of fibre and how are they broken down?

1. soluble fibre; dissolves into a gel-like substance

2. insoluble fibre; ferments via bacteria → short chain fatty acids

Give 3 examples of short chain fatty acids that come from insoluble fibre being fermented:

1. acetate

2. propionate

3. butyrate

What function do these short chain fatty acids have?

• buytrate can be used as an energy source for isolated colonocytes

• SCFAs are also readily absorbed and can be used by the liver and muscles as an energy source

What is dietary protein broken down into and by what enzyme:

protein → di + tri peptides + amino acids (via pepsin)

How are dipeptides, tripeptides absorbed by the small intestine?

• PEPT1 transporter

• Na+ dependent or independent transporter

Once the di and tri peptides are in enterocytes, what do they become?

• amino acids

What is special about protein absorption in newborns?

• immediately after birth, the intestinal epithelial cells can absorb some peptides larger than 3 amino acids by transcytosis (this is how passive immunity passes from mother to baby)

• this ceases at 6 months

Name a disease which affects amino acid transport and uptake across the apical membranes and its symptoms:

1. Hartnup disease

2. leads to skin changes, cerebral attacks and psychiatric anomalies

Describe how whole proteins are digested in the stomach:

• after being chewed and swallowed

• HCl denatures proteins, unfolding their 3D structure to reveal the polypeptide chain

• pepsin → shorter polypeptides

Which enzymes continue protein digestion in the small intestine?

1. trypsin

2. chymotrypsin

3. proteases

What is the name given to pancreatic digestive enzymes?

• pancreatic zymogens

How do pancreatic zymogens travel to the SI from the pancreas?

• enzymes travel through the pancreatic duct to the duodenum

What activates pancreatic zymogens once they enter the duodeum?

• enterokinase (enzyme found on the brush border of the cells of duodenal mucosa)

What is the inactive form of trypsin?

trypsinogen

How are the other pancreatic zymogens activated once in the SI?

• trypsinogen → trypsin via enterokinase

• trypsin activated ALL other pancreatic zymogens

What happens when you get inappropriate activation of trypsinogen?

• pancreatitis

• trypsin digests pancreatic tissue

• triggers an inflammatory response

How does the pancreas protect itself from its own enzymes@

• acinar cells in the pancreas synthesise and secrete SPINK1 a trypsin inhibitor that acts as a safeguard against trypsin activation

• trypsin also has a mechanism of AUTOLYSIS or self digestion which prevents it from becoming active inappropriately

Which cell type expresses pepsinogen?

• chief cells in the stomach

How does pepsinogen become activated in the stomach?

• hydrochloric acid secreted by parietal cells creates an acidic environment

• this allows pepsinogen to enfold and cleave itself → forms pepsin

When can pepsin become inactivated?

• high pHs

Give the pathway of fat digestion:

1. fats are chewed and saliva begins digestion

2. mechanical digestion of fats occurs in stomach and triacylglycerols → diglycerides + fatty acids

3. diglycerides + fatty acids are mixed with bile in SI

4. bile emulsifies these products → become smaller and smaller

Explain how fats are broken down in the small intestine:

1. emulsification by bile; large fat droplet → emulsified fat droplets

2. enzymatic digestion; triglyceride → monoglyceride + FAs via pancreatic lipase

3. fatty acids → micelles

Describe the structure of micelles:

• tiny self-assembled clusters of fatty acids

• spherical in shape

• form in water

• hydrophobic core and hydrophilic shell

What is the function of micelles?

• micelles allow fats to be transported into enterocyte cells in small intestine epithelium

What happens to short-medium length fatty acid chains and glycerol once in the enterocyte?

• absorbed into blood via capillary

What happens to long-chain fatty acids and monoglycerides once in the enterocyte?

• fatty acid chain form into triglycerides

• form chylomicrons via golgi apparatus

• travel into LYMPH vessels → processed in liver

How do chylomicrons get into the lymphatic system?

• Apoprotein B48 (chylomicrons → lymph → blood)

What happens to chylomicrons once in the blood?

• apoprotein C2 activates lipoprotein-lipase

• enables triglycerides to turn into fatty acids in the adipose tissue

• chylomicron remnants are then transported to the liver

What happens to chylomicron remnants in the liver?

• apoprotein E mediates their re-uptake into the liver where the remnants can be used for further energy generation

• cholesterol remnants → go to blood

Describe the structure of chylomicrons:

• phospholipid outer layer

• embedded apolipoproteins

• triglycerides

What is the name for the condition when fat absorption goes wrong?

• steatorrhoea → oily poo