Gastro Block 6: Gut Fluid Balance

Give the two main functions of epithelial cells in relation to fluid balance:

• Secrete water and electrolytes (they transport these substances from the blood into the gut lumen)

• Absorb water and electrolytes (transport these substances from the gut lumen into the blood)

How much water do we typically ingest per day?

• 2 litres

How much saliva do we typically secrete a day?

1.5L

How much secretion does the stomach produce a day?

2L

How much secretion does the pancreas produce per day?

1.5L into the small intestine

How much fluid does the gall bladder secrete each day?

0.5 L into the small intestine

How much secretion does the small intestine produce each day?

1.5L

How much fluid goes into the small intestines each day?

about 9L

How much fluid do we lose in excrement per day?

• 100ml

Describe the role of the SI and colon in water absorption?

• SI can absorb 8.5L per day

• colon absorbs about 400ml of water (90% of what comes into it) and controls whether we get malabsorption of water aka watery stools

Overall, how much fluid is reabsorbed by the body from the gut?

• about 9L

How does water move from one area to another? (no energy)

• osmosis: water moves down osmotic gradients from an area of low osmolarity (low solute conc) to an area of high osmolarity (high solute conc)

• requires no energy

• aims to balance solute concentrations on both sides of the membrane

How do electrolytes move from one area to another? (no energy)

• electrolytes move down their electrochemical gradients

• an area of high conc to an area of low conc via passive diffusion

How do you move solutes against their concentration gradient?

• requires energy

• energy is supplied by sodium gradients (generated by sodium pump) and by proton gradients

Which pump is found on the basal lateral membrane of epithelial cells?

• Na+/K+ ATPase pump

List the two routes by which water is transported from the gut into the bloodstream:

1. Paracellular route

2. Transcellular route

Describe the Paracellular route of water transport:

• passive movement of water between adjacent epithelial cells

• water moves through tight junctions and intercellular spaces

• movement is driven by osmotic of hydrostatic pressure

What is the difference between hydrostatic pressure and osmotic pressure?

• hydrostatic pressure is the physical, outward-pushing force exerted by a fluid against a container wall due to gravity or pumping → typically forcing fluid OUT of capillaries

• osmotic pressure is the inward-pulling pressure required to STOP water from moving across a membrane → typically drawing fluid in.

Explain the transcellular route of water transport:

• movement of water directly through cells

• passing across both the apical and basolateral plasma membranes

• mechanism is driven by osmosis and facilitated by aquaporins

What makes up the Intestinal Mucosa?

1. epithelial layer

2. lamina propria

3. muscularis mucosae

Give the function of the intestinal mucosa?

• it acts as a selective, semipermeable barrier for nutrient/water absorption while protecting against pathogens via mucus, immune cells and antimicrobial proteins

Describe the structure of the gut epithelium:

• a single layer of cells (enterocytes, goblet cells)

• has villi and microvill = maximise surface area for absorption

Describe the structure of the lamina propria:

• connective tissue layer containing blood vessels, nerves, and immune cells

Describe the structure of the muscularis mucosae

• a thin layer of smooth muscle

Give 2 other structures found in the mucosa layer of the gut:

1. Crypts of Lieberkuhn

2. Stem cell niche

Where are the crypts of lieberkuhn found?

• located between villi

• they extend down to muscularis mucosae

Where are stem cell niches found?

• located at the base of crypts of lieberkuhn

What is the function of the stem cell niche?

• stem cells divide here constantly, sending new cells up to the crypt to differentiate into

• enterocytes

• goblet cells

• enteroendocrine cells (nutrient sensing cells)

What happens to stem cells the further up the crypt:

• the cells become more differentiated into absorptive function

How are damaged stem cells removed in the crypts?

• apoptosis

• old cells are shed at the tip of the villus

How long does it take for a stem cell to move from the base of the crypt to the tip of the villus?

• about 3 to 6 days

What is always true about fluid balance in the intestinal mucosa?

• Absorption of water and nutrients across villus enterocytes always exceeds the level of secretion from within the crypts of Lieberkuhn

List the 5 factors that affect absorption in the gut?

1. number and state of enterocytes

2. blood and lymph flow (clearance rates of nutrients)

3. nutrient intake (e.g. fibre)

4. gastric motility (stomach)

5. intestinal motility (SI)

List 3 factors that affect secretion from goblet cells?

1. irritants

2. bacterial toxins

3. bile

List 3 factors affecting both secretion and absorption in gut?

1. hormonal

2. paracrine factors

3. neural factors

Describe how water is taken up by enterocytes from the gut lumen?

1. SGLT-1 transporter at apical aspect of enterocytes takes in 1 glucose with 2 sodium ions into cell - using energy generated from Na+/K+ATPase gradient which maintains low intracellular Na+ levels.

2. water follows the flow of ions via osmosis, thrugh leaky tight junctions (paracellular route)

3. chloride ions follow to maintain electroneutrality

In what conditions can this way of water uptake occur?

• can occur without the presence of nutrients but it takes a very long time

How efficient is this way of water uptake?

• extremely efficient

• 260 molecules of water for every glucose taken up

List 3 other transporters that support transcellular water uptake in the intestine:

1. Aquaporins (10+3)

2. NHE3 (sodium/hydrogen exchanger)

3. DRA (Cl-/HCO3- exchanger)

How is fructose absorbed in the gut?

• fructose is not dependent on the sodium-glucose transporter

• fructose is taken up on the apical surface of enterocytes by GLUT5

• fructose then enters the blood stream via GLUT2 but also can be GLUT5

• fructose is rapidly cleared to the blood, keeping the effective circulating concentration low

Why do goblet cells (and also enterocytes but to a lesser extent) secrete mucus?

1. dilute food hypertonic contents

2. dilute secreted enzymes

What activates fluid secretion in the gut?

1. Ach - released from gut nerves → stimulated by stretch of smooth muscle in gut → causes release of mucus from goblet cells

2. VIP - released from gut nerves and blood → stimulated by fats/proteins in lumen → drives secretion of fluid from goblet cells in the crypts

List the 3 overarching ways in how gut secretion in the SI is regulated:

1. neural regulation (enteric + autonomic)

2. hormonal regulation

3. paracrine control

How does the nervous system regulate gut secretion?

1. distension of stomach → Ach secretion from vagus nerve → Ach binds to muscarinic receptors (M3) on epithelial cells, goblet cells and parietal cells → activates intracellular signalling cascade → increases calcium levels → triggers exocytosis of mucus

How do hormones regulate gut mucus secretion?

1. acidic chyme enters duodenum → triggers secretin release from S cells → stimulates bicarb rich secretion from pancreas (then goes into duodenum)

2. fats and proteins enter duodenum → CCK released from I cells in pancreas → INDIRECTLY supports secretion in SI

3. GIP → reduces gastric activity and therefore intestinal secretions

What paracrine controls are there that regulate gut secretion?

1. Histamines → enhances secretion by binding to H1 and H2 receptors on epithelial cells → signalling cascade

2. Prostaglandins → promote mucus and bicarb secretio → protects mucosa