Digestion + Absorption

Question 1

What are the 7 stages of the digestive process?

Answer 1

-Ingestion
→ breakdown and mixing of food via chewing

-Secretion
→ of enzymes and acid to break down macromolecules

-Mixing
→ helps break down food

-Propulsion
→ moves food along

-Digestion
→ breaks down macromolecules

-Absorption
→ of nutrients

-Excretion
→ of products that couldn’t be digested

Question 2

MOUTH + OESOPHAGUS:

1- What stages of the digestive process happen here?
2- How much absorption occurs?
3- How does food enter oesophagus?
4- How is food prevented from re-entering the oesophagus?

Answer 2

1- Ingestion, mixing, secretion

2- Little absorption in mouth/ No absorption or digestion in oesophagus

3- Peristalsis and gravity moves food into the oesophagus and continues to mix food with saliva

4- Cardiac sphincter opens in response to peristalsis and prevents food re-entering oesophagus

Question 3

What is saliva?
What enzymes are found in saliva? What do they digest?

Answer 3

• Slightly acidic watery solution containing electrolytes, mucus, bicarbonate and enzymes:
  > Lysozyme = proteins
  > Amylase = Complex carbohydrates are partially digested in the mouth (hydrolysis of a-1,4 links)
  > Lingual lipase = fats

Question 4

STOMACH:

1- Mechanical action of the stomach due to 3xlayers of muscles helps the separation of food to…

2- How does chyme pass out of the stomach?

3- What happens to the undigested foodstuff during the mechanical digestion and breakdown of food?

Answer 4

1- Mix food via segmentation into
Chyme = partially digested foodstuff

2- Passes into the pyloric antrum and along the pyloric canal where opening of the pyloric sphincter expels the chyme into the duodenum
> regulated by hormonal and neural signals

3- Bulk of undigested food stored in the Fundus

Question 5

STOMACH:

1- What happens to different enzymes in the stomach?

2- How much starch is digested in stomach?

3- What initiates protein digestion in stomach?

4- What is absorbed in the stomach?

5- How much gastric juice is secreted by the stomach per day?

Answer 5

1-
-some salivary amylase gets denatured
-lingual lipase and other digestive enzymes continue to function

2- 50% of dietary starch

3- Secretion of HCL + Proenzymes e.g. pepsinogen

4- Water + other substances e.g. ethanol and salicylic acid

5- 2L

Question 6

STOMACH: Gastric secretory cells

1- What is the mucosa layer of the stomach folded into?
2- What do mucous cells release? Why?
3- What do parietal cells release?
4- What to enterochromaffin-like cells release?
5- What do chief cells release?
6- What do endocrine cells release?

Answer 6

1- Gastric pits

2- Thick mucus to prevent autodigestion and bicarbonate to regulate PH

3- HCL + Intrinsic factor

4- Histamine

5- Pepsinogen, chymosin, gastric lipase

6- Gastrin (G cells) and somatostatin (D cells)

Question 7

STOMACH:

1- Pepsinogen is an inactive precursor (zymogen) of…
2- What catalyses the reaction of pepsinogen to pepsin? How?
3- What are the 3 main proteolytic enzymes involved in digestion of proteins?
4- What type of proteolytic peptidase is pepsin? What does it do?

Answer 7

1- Pepsin

2- Acidic pH of stomach > partial denaturation of the zymogen allowing autocatalysis to yield the active pepsin > autocatalysis increases the concentration of pepsin

3- pepsin, trypsin and chymotrypsin

4- Endopeptidase > cleaves longer amino acid chains into shorter chains

Question 8

STOMACH: Regulaton of gastric acid secretion

1- What stimuli cause gastric acid to be secreted by parietal cells?

2- What do these stimuli then activate?

Answer 8

1-
- presence of food in stomach or intestine
-taste, smell, sight, thought of food

2-
-histamine from H2 receptors
-acetylecholine from Muscarinic M3 receptors
-gastrin from CCK2 receptors
> In basolateral membrane of parietal cell which initiates signal transduction pathways that converge on the activation of H+/K+ ATPase.

Question 9

STOMACH: Regulaton of gastric acid secretion

1- What happens if proton pump is inhibited?

2- Histamine antagonist can be prescribed to control gastric HCL, Why are PPI preferred.

Answer 9

1- Reduces acid secretion independently of how secretion is stimulated

2- Inhibition can be overcome by food-induced stimulation of acid secretion via gastrin or acetylcholine receptors.

Question 10

1- What kind of drug is Omeprazole?

2- How does omeprazole inhibit activity of H+ K+-ATPase?

3- Why does omeprazole have few side effect?

Answer 10

1- Proton pump inhibitor
> Pro drug converted into active form in acidic environments.

2-
1. Weak base so specifically concentrated in the acidic secretory canaliculi of parietal cell.
2. Where it is activated by a proton-catalysed process to generate a sulphenamide
3. Sulphenamide interacts covalently with the sulphydryl groups of cysteine residues (in particular Cys 813)
- In the extracellular domain of the H+K+-ATPase
- inhibiting H+/K+-ATPase activity

3- Specific concentration of PPI in the secretory canaliculi of the parietal cell

Question 10

STOMACH:

1- Why is it important to regulate HCl secretion?

2- What 6 factors control the secretion of HCl? How do they affect HCL secretion?

Answer 10

1- Maintains optimum pH for pepsin

2-
-histamine from enterochromaffin-like cells +ve
-acetylecholine from innervation to stomach +ve
-gastrin secreted from G cells +ve
-presence of food +ve
-low pH -ve
- somatostatin released from neighbouring D cells -ve

Question 11

Where are G and D cells located?

Answer 11

• Pyloric glands along pyloric canal

Question 12

Gastric Emptying into duodenum:

1- How does the pyloric sphincter open and close?
2- How does Nervous control control pyloric sphincter?
3- How does endocrine control pyloric sphincter?

Answer 12

1- In response to to nervous and endocrine control

2- When the duodenum becomes full, it is distended and the sphincter is close

3- Hormones Secretin and choleocystokinin (CCK) released by the small intestine (duodenum) inhibit opening
> Hormone release is controlled by acidic chyme and high fat content

Question 13

Where is CCK (Cholecystokinin) produced? What does it stimulate?

Answer 13

• Produced in the duodenum and jejenum and stimulates secretion of bile and pancreatic juice.

Question 14

What important role does the secretin GIP (gastric inhibitory polypeptide) have ?

Answer 14

• Important role in insulin secretion from endocrine pancreas

Question 15

THE INTENSTINAL TRACT:
1- What does the duodenum (0.3m) account for mainly? What do the submucosal glands secrete?
2- What does the jejunum (1-2m) account for mainly?
3- What does the ileum (1.5m) lead into? At what?
4- What tissue found at the ileum and colon is important in controlling resident microflora?
5- What vein delivers nutrients to liver?

Answer 15

1- Primary site of digestion > Bicarbonate-rich mucus to help neutralise the acidity of chyme

2- Majority of the absorption of macronutrients

3- Large intestines at illeo-cecal calve

4- Lymphoid tissue

5- Hepatic portal vein

Question 16

1- What percentage of chemical digestion and absorption takes place in small intestines?

2- Describe the speed of food movement through small intestines.

Answer 16

1- 95%

2- Slow > 3-5hrs

Question 17

PANCREAS:

1- What do the exocrine cells of the pancreas secrete?

2- What does pancreatic juice contain?

3- What are the proteolytic enzymes in pancreatic juice?

4- How does pancreatic juice empty into the duodenum?

Answer 17

1- Pancreatic juice

2- Pancreatic juice: bicarbonate; carbohydrases; lipase; nucleases; proteolytic enzymes , endocrine hormones

3- trypsin , chymotrypsin , carboxypeptidases

4- Pancreatic duct penetrates duodenal wall at Major duodenal papilla

Question 18

LIVER:

1- What is the primary secretion of liver? How many litres?

2- What colour is this primary secretion? What is it composed of?

3- What does the Gall bladder store?

Answer 18

1- Bile > 0.8L per day

2- Green/yellow = bile salts, bilirubin, water and electrolytes

3- Concentrated bile to be released during each meal in the presence of fat

Question 19

What happens to the digested macromolecules? How by what 3 processes?

Answer 19

• Their nutrients, electrolytes and vitamins are absorbed by the intestinal epithelium Via:

1-Passive diffusion. (e.g. short chain fatty acids), conc gradient
2-Facilitated diffusion - Protein channels, conc gradient , co-transporters
3-Active transport - ATP

*dependant on the different distribution of transport machinery at the luminal and contraluminal membranes.

Question 20

What is the difference between luminal and contraluminal sides of enterocyte cells?

• Morphological appearance
• Enzymes?
• Transport systems

Answer 20

Question 21

What is Km?

Answer 21

• The affinity a transporter has for the protein it is transporting.
  > Lower the Km means transporter works at lower concentrations

Question 22

Glucose transporters:

• Where are GLUT1/2/3/4/5 found? What is their Km? What do they do?
• Where is SGLT1 found? What is its Km? What does it do?

Answer 22

• GLUT > work across concentration gradient
• SGLT > work against concentration gradient

Question 23

Electrochemical gradients drive nutrient uptake:

How are most nutrients absorbed into enterocytes? What does this require? How?

Answer 23

Against a concentration gradient requires active transport
> Uses the energy from ATP to indirectly drive an electrochemical gradient. = Secondary active transport

Question 24

- What membrane is Na+/K+ ATPase present? What is it responsible for?

Answer 24

- **Contraluminal** membrane of the enterocyte and is responsible for removing Na+ from the cell (3x Na+ out for 2x K+ in) to maintain an **electrochemical gradient**

Question 25

What is the significance of the Na+/K+ ATPase maintaining an electrochemical gradient? (3 points)

Answer 25

1- allows for the absorption of **NaCl** in both the small and large intestine 2- Allows for **glucose** and **amino acid** absorption in the SI enterocytes 3- **NaCl/bicarbonate secretion** by intestinal crypt cells and secretory cells of the pancreas

Question 26

ABSORPTION OF CARBOHYDRATES: 1- How is Lactose, starch and sucrose broken down and absorbed?

Answer 26

1- Begins with amylase 2- Other key enzymes on the **brush boarder membrane** yield free monosaccharides which can be absorbed 3- Facilitated diffusion into the enterocyte by **GLUT2** initially = equilibrium ... then later by active transport through **SGLT1**: this is ‘co transport’. > Purpose of SGLT1 active transport processes serves to ensure that almost all available sugars are removed. 4- **GLUT5** is the fructose transporter. 5- Glucose, Galactose and fructose move via facilitated diffusion into capillary via GLUT2 channel

Question 27

1- The intracellular concentration of glucose and other sugars must be high in order to maintain a concentration gradient for GLUT2, How do enterocytes do this? 2- What is some of the intracellular glucose used for?

Answer 27

- **Maintain a pool of ‘free’ glucose** 2- > Some glucose is used by enterocytes for ATP production (required by the Na/K ATPase to maintain the Na+ gradient) > Some being metabolised to lactate (this is also released into the portal vein and is delivered to the liver).

Question 28

ABSORPTION OF AMINO ACIDS: 1- How are polypeptides broken down and absorbed?

Answer 28

1- Through digestive tract beginning with gastric secretion, pepsin. 2- Then via pancreatic enzymes entering duodenum to break down protein to free amino acids and oligopeptides 3- Oligopeptides are digested by brush border enzymes to yield di/tri peptides and amino acids which are absorbed 4- Free amino acids are co-transported with Na+ which enters the cell down the electrochemical gradient, driven by indirect active transport maintained by the Na+/K+ exchanger. 5- Di- and tri-peptides are co-transported with H+ the driving force for this is powered by an Na+/H+ exchanger 6- Amino acids move via facilitated diffusion into capillary

Question 29

1- What transporter drives absorption of NaCl (and water) into the small intestine and large intestine? 2- Where is majority of NaCl absorbed? What happens to the rest? 3- What forces drive water absorption?

Answer 29

1- Na+/K+ ATPase 2- Small intestines > scavenged in large intestine depending on bodies needs 3- Osmotic forces

Question 30

Defects of Na/K ATPase driving absorption of NaCl and Water is associated with inflammatory bowel disease. Why? How is it treated?

Answer 30

- Reduced activity (<70%) of the Na+/K+ exchanger and collapse of electrochemical gradient = Reduced absorption of Na+ and Cl- leads to decreased water uptake, contributing to diarrhoea > Glucocorticosteroids

Question 31

Defects of Na/K ATPase is associated with cystic fibrosis. How?

Answer 31

- Na+/K+ ATPase **also powers NaCl secretion** from intestinal crypts and pancreas > Driving force for secretion of bicarbonate and enzyme-rich fluid into duodenum *This isn't functional with cystic fibrosis

Question 31

1- What is the basic structure of fatty acid? 2- What are the 3 ways fatty acids are classified? 3- Industrial hydrogenation results in fat production, how?

Answer 31

1- **Long C-C** chain with a carboxylic acid group > Carboxyl end > Methyl end or ‘Ω/ω-carbon’ 2- 1.**Length** (short-, medium-, long-) 2.**Saturation** (no. of C=C double bonds) 3.**Shape** (cis-, trans-) Trans fats present normally in small amounts 3- Industrial hydrogenation of **cis-unsaturated fatty acids** results in some trans fat production…..

Question 32

1- How are triglycerides formed? (Include the enzyme in your answer) 2- What are DAG important as?

Answer 32

1- Formed sequentially in **condensation reactions** MAG > DAG > TAG > **Diglyceride acyltransferase (DGAT)** catalyses the formation of TAG from DAG > The committed step of TAG synthesis 2- Signalling molecules

Question 33

How are lipids digested and absorbed?

Answer 33

1- TAG droplets are emulsified partly by the stomach first to smaller emulsion droplets 2- Mixed micelles are formed by bile acids and other lipase enzymes (pancreatic) 3- Hydrolysis of TAG to FFA and monoacylglycerol within the lumen 4- Uptake of FFA and MAG via specific ***FAT and FATP1** transport proteins, re-esterified to TAG. 5- TAG packaged into chylomicrons which enter the lacteal and lymphatic circulation. Medium chain fatty acids directly enter capiliary

Question 34

CHYLOMICRONS: 1- What are chylomicrons? 1-a - Why do we need to package fatty acids into lipoproteins? 2- Why do they have a phospholipid monolayer? 3- What varies between different lipoproteins? 4- What surface protein is unique to chylomicrons? 5- What do lipoproteins activate? 6- What do lipoproteins acquire in circulation?

Answer 34

1- Dietary Lipids (fatty acids/TAG and cholesterol/cholesterol esters) are transported round the body as **lipoproteins** 1-a- Lipids are either **insoluble or sparingly soluble** in water which creates problems of transport and delivery. 2- Allows tight packing of highly **hydrophobic TAG** 3- **Surface proteins = apolipoproteins** > dictate the fate of lipoprotein 4- B-48 5- Activate **receptors for uptake or hydrolysis of stored TAG** 6- **Apo-CII** in circulation

Question 35

What is the difference in blood between a fasting person, and 2-4 hours after a fatty meal, caused by? > Relate to how alcohol may affect fat metabolism.

Answer 35

- **Chylomicrons in the blood after a fatty meal** * Alcohol consumption affects fat metabolism so that the arrival and clearance of chylomicrons is delayed – so light scattering by **chylomicrons can be seen more than 4 hours after a fatty meal.**

Question 36

LARGE INTESTINES/ COLON (1.2m) 1- What is the primary role of colon? 2- What are undigested carbohydrates broken down by in colon?

Answer 36

1- Convert chyme to faeces > absorbs water from the chyme converting it from liquid to solid 2- **Resident microflora** by fermentation > Produces a **number of short chain fatty acids** which are used as energy sources by colonocytes > Some also diverted to liver. * Process serves to ‘scavenge’ any remaining energy that may otherwise be lost in the faeces.