Genes and health 2.2 CF and sticky mucus

Question 1

In cystic fibrosis, what is missing that makes the mucus sticky?

Answer 1

Sufficient water due to a faulty CFTR

(cystic fibrosis transmembrane conductance regulator)

Question 2

What causes a reduction of water in the mucus in cystic fibrosis patients?

Answer 2

Abnormal levels of Na⁺Cl^- (sodium chloride) in epithelial cells

Question 3

What are all proteins made from?

Answer 3

Amino acids

Question 4

To review proteins, go to Biological Molecules - Proteins section

Answer 4

Ok…

Question 5

What are cell membranes made of? ( 4 pts)

Answer 5

1. Phospholipid bylayer (see lipids quiz)
2. Proteins
3. Cholesterol
4. Glycoproteins

Question 6

What is on the outside and the inside of a cell?

Answer 6

cytoplasm

(lit. ‘cell gel’)

Question 7

What is the fluid mosaic model? (5 pts)

Answer 7

1. This describes the nature of the cell membrane:
2. some proteins are fixed within the layer
3. some float around the layer

Question 8

What are peripheral proteins?

Answer 8

Proteins loosely attached to the cell membrane

Question 9

What are integral proteins?

Answer 9

They are fully embedded within the phospholipid bilayer

Question 10

What experiments indicated support for the fluid mosaic model?

Answer 10

Some proteins (peripheral) could easily be separated from the membrane by raising ionic strength of a solution; others (integral) required adding a detergent to loosen them

freeze-fracture process showed a smooth surface between the lipid layers consistent with lipid tails that was interspersed with larger molecules (integral proteins)

mouse and human membrane proteins were flouresced green and red respectively which indicated an intermixing of the proteins, diffusing through membranes

experiments ‘labelling proteins’ indicated that some proteins only attach to the outer surface of the membranes (e.g., lectin labelled with ferritin)

Question 11

What increases the fluidity of a membrane? (3pts)

Answer 11

1. More phospholipids containing unsaturated fatty acids to saturated fatty acids.
2. The hydrocarbon tails are always kinked, which prevent a ‘packing together’, and which allows movement.
3. Cholesterol between the phospholipids also maintain fluidity

Question 12

By what processes do substances pass through cell membranes?

(5 pts)

Answer 12

1. diffusion
2. osmosis
3. active transport
4. exocytosis
5. endocytosis

Question 13

What do the cells lining airways produce?

Answer 13

mucus

Question 14

Why must the mucus produced in the airways maintain a constant relatively runny viscosity?

Answer 14

To enable the cilia to flush away particles

Question 15

How is excess water removed from mucus (making it too runny)? (10 marker)

Answer 15

If the mucus is too runny, the epithelial cells detect excess water

Excess water in the mucus cause carrier proteins in the basal membranes of the epithelial cells pump out sodium ions Na⁺ creating a positvely charged environment in tissue fluid

This firstly reduces the relative ratio of sodium ions in the cell, causing sodium ions to cross the opposite apical layer through sodium channels from the mucus into the cell.

Secondly, the positively charged tissue fluid attracts negatively charged chloride ions to diffuse out of the mucus - they are diffused by the potential difference (- attracts +) between the epithelial cells.

The higher ratio of Na+ and Cl- in the tissue fluid now prompts water to diffuse out of the cells and into the tissue fluid by osmosis

In turn, the reduced water content of the cells prompts an osmosis from the mucus across the apical layer and into the cell thereby reducing water content in the mucus.

Question 16

What is the pathway for too little water in the mucus (which may become too sticky)? (10 points)

Answer 16

Chloride ions cross the basal membrane into the epithelial cell.

This raises the concentration of chloride in the cell relative to those in the mucus above the apical layer

This prompts the cystic fibrosis transmembrane conductance regulator (CFTR) protein channels to open

Chloride ions now diffuse out into the mucus

Chloride ions are negative, so this produces an electrical gradient between the mucus and tissue fluids

Sodium Na⁺ ions are now attracted to the mucus and pass between the epithelial cells

The movement of ions into the mucus now draws water out of the cells by osmosis so preventing the mucus becoming too sticky

Question 17

What is the function of the CFTR (cystic fibrosis transmembrane conductance regulator)? (2pts)

Answer 17

1. CFTR helps regulate the levels of salts and water on the surfaces of the airways (apical membrane of the epithelial cells)
2. When functioning properly, H2O and Cl- ions flow in and out;
3. when it is not, ions and water cannot flow freely causing the mucus to become sticky

Question 18

What happens to water regulation in people with cystic fibrosis? (4pts)

Answer 18

1. CFTR may be missing or not functioning properly, inhibiting the flow of ions and water across the apical membrane of epithelial cells.
2. When mucus water levels drop, chloride ions cannot be secreted across the apical membrane;
3. while sodium ions continue to flow into the epithelial cells;
4. this action draws more chloride ions and water out of the mucus by osmosis, making it even stickier

Question 19

Why is sticky mucus a problem?

Answer 19

1. The cilia cannot move so well
2. and so cannot move the mucus and hence clear out the airway of pathogens
3. so the mucus becomes infected
4. Phagocytic cells come to clear up the bacteria in hordes and as they die their debris adds to the viscosity of the mucus…
5. Alveoli efficiency reduces; airways become inflamed and lung damage ensues.