- Created by: Katherine
- Created on: 01-05-14 16:31
The role of mucus in the lungs
The lungs allow rapid gas exchange between the atmosphere and the blood. Air is drawn into the lungs via the trachea due to low pressure in the lungs, created by the movement of the ribs and diaphragm. The trachea divides into two bronchi which carry air to and from each lung. Within each lung there is a tree-like system of tubes ending in narrow tubes, bronchioles, attached to tiny balloon-like alveoli. The alveoli are the sites of gas exchange.
What are Epithelial cells?
Epithelial cells form the outer surface of many animals including mammals. They also line the cavities and tubes within the animals, and cover the surfaces of internal organs. The cells work together as a tissue known as epithelium.
The epithelium consists of one or more layers of cells sitting on a basement membrane. This is made of protein fibres in a jelly like matrix, There are several different types of epithelia.
The epithelium in the walls of the alveoli and capillaries is squamous (or pavement) epithelium. The very thin flattened cells fit together like crazy paving. The cells can be less than 0.2um thick.
In the small intestine the epithelial cells extend out from the basement membrane. These column-shaped cells make up columnar epithelium. The free surface facing the intestine lumen is normally covered in microvili, which greatly increase the surface area.
In the trachea, bronchi and bronchioles, there are ciliated epithelial cells with cilia on the free surface. These cilia beat and move substances along the tube they line. The ciliated columnar epithelium of the gas exchange airways appears to be stratified (composed of several layers), but in fact, eahc cell is in contact with the basement membrane. It appeas to have several layers becasue some cells have their nucleus at the base of the cell while in others it is in the centre, giving the impression of different layers. This epithelium is therefore known as pseudostratified.
How sticky mucus increases the chances of lung inf
Microorganisms become trapped in the mucus in the lungs. Some of these can cause illness - they are pathogens. The mucus is normally moved by cilia into the back of the mouth cavity where it is either coughed out or swallowed, thus reducing the risk of infection. Acid in the stomach kills most mictoorganisms that are swallowed.
With CF, the mucus layer is so sticky that cilia cannot move the mucus. Mucus production still continues, as it would in a normal lung, and the airways build up layers of thickened mucus. There are low levels of oxygen in the mucus, partly because oxygen diffuses slowly through it, and partly becuase the epithelial cells use up more oxygen in CF patients. Harmful bacteria can thrive in these anaerobic conditions.
White blood cells fight the infections within the mucus but as they die, they break down releasing DNA which makes the mucus even stickier. Reperated infectionc can eventually weaken the body's ability to fight the pathodens, and cause damage to the structures of the gas exchange system.
How sticky mucus reduces gas exchange:
Gaes such as oxygen cross the walls of the alveoli into the blood system by diffusion. To supply enough oxygen to all the body's respiring cells, gas exchange must be rapid. The fine structures of the lungs helps to maximise this.
The effect of increase in size on surface area:
Living organisms have to exchange substances with their surroundings. For example, they take in oxygen and nutirents and get rid of waste materials such as carbon dioxide. In unicellular organisms, the whole cell surface membrane is the exchange surface. Substances that diffuse into or out of a cell move down a concentration gradient (from a high to a low concentration). The gradients are maintained by the cell continuously using the substances absorbed and producing waste. For example, oxygen diffusing into a cell is used for respiration which produces carbon dioxide.
The larger an organism, the more exchange has to take place to meet the organism's needs. Larger multicellular organisms have more problems absorbing substances because of the size of the organism's surface area compared with its volume. This is known as the surface area to volume ratio, calculated by dividing an organism's total surface area by its volume.
Gas Exchange Surfaces:
Within the lungs, alveoli provide a large surface area for exchange of gases between the air and the blood. Features of gas exchange in the alveoli and the blood:
Large surface area of the alveoli,
Numerous capillaries around alveoli,
Thin walls of the alveoli and capillaries meaning a short distance between the alveolar air and blood in the capillaries.
Diffusion Across The Alveolar Wall:
The body's demand for oxygen is enormous, so diffusion across the alveolar wall needs to be rapid. The rate of diffusion is dependent on three properties of gas exchange surfaces:
Surface area - Rate of diffusion is directly proportional to the surface area. As the surface area increases the rate of diffusion increases.
Concentration gradient - rate of diffusion is directly proportional to the difference in concentration across the gas exchange surface. The greater the concentration gradient the faster the diffusion.
Thickness of the gas exchange surface - rate of diffusion is inversely proportional to the thickness of the gas exchange surface. The thicker the surface the slower the diffusion.
Rate of diffusion= Surface area x difference in concentration thickness of the gas exchange surface
The large surface area of the alveoli, the steep concentration gradient between the alveolar air and the blood (maintained by ventilation of the alveoli) and the thin walls of the alveoli and capillaries combine to ensure rapid diffusion across the gas exchange surface.
How sticky mucus might affect gas exchange:
The sticky mucus layer in the bronchioles of a person with cystic fibrosis tends to block these narrow airways, preventing ventilation of the alveoli below the blockage. This reduced the number of alveoli providing surface area for gas exchange. Blockages are more likely at the narrow ends of the airways. These blockages will often allow air to pass when the person breathes in but not when they breathe out, resulting in over inflation of the lung tissue beyond the blockage. This can damage the elasticity of the lungs.
People with CF find it difficult to take part in physical exercise because their gas exchange system cannot deliver enough oxygen to their muscle cells. The oxygen is needed for the chemical processes of aerobic repsiration, which release the energy used to drive the contraction of the muscles during exercise. People with CF become short of breath when taking exercise but exercise is very beneficial to them.
Protein Structure is Key to Protein Function:
Proteins have a wide range of functions in living things. Antibodies, enzymes and many hormones are all protein molecules. Various proteins make upmuscles, ligaments, tendons and hair. Proteins are also components of cell membranes and have important functions within the membrane. All proteins are composed of the same basic units: amino acids. There are 20 different amino acids that occur commonly in proteins. Plants can make all these amino acids whereas animals can only make some, obtaining others through their diet.
Two amino acids join together in a condensation reaction to form a dipeptide, with a peptide bond forming between the two subunits. This process can be repeated to form polypeptide chains which may contain thousands of amino acids. A protein is made up of onne of more of these polypeptide chains. The sequence of amino acids in the polypeptide chains is known as the primary structure of a protein.
The chain of amino acids may twist to form an a - helix. Within the helix, hydrogen bonds form between the C=O of the carboxylic acid and the -NH of the amine group of different amino acids, stabilising the shape.
Several chains may link together, with hydrogen bonds holding the parallel chains in an arrangement known as a B pleated sheet. Within one protein molecules, there may be ssections with a helices and other sections that contain B pleated sheets.
Tertiary and Quaternary Structure:
A poly peptide chain often bends and fold to produce a precise three dimensional shape. Chemical bonds and hydrophobic interactions between R groups maintain this final tertiary structure of the protein.
An R group is polar when the sharing of the elctrons within it is not quite even. Polar R groups attract other polar molecules, like water, and are therefore hydrophilic. The non polar groups are hydrophobic. Non polar, hydrophobic R groups are arranged so they face the inside of the protein, excluding water from the centre of the molecule.
A protein may be made up of several polypeptide chains held together. For example, haemoglobin, the protein found in red blood cells that carries oxygen, is made up of four polypeptide chains held tightly together in a structure known as the quaternary structure. Only proteins with several polypeptide chians have a quaternary structure; single chain proteins stop at the tertiary level.
Globular & Fibrous Proteins:
Proteins can be divided into two distinct groups: Globular Proteins & Fibrous Proteins.
In globular proteins, the polypeptide chain is folded into a compact spherical shape. These proteins are soluble due to the hydrophilic side chains that project from the outside of the molecules and are therefore important in metabolic reactions. Enzymes are globular proteins. Their three-dimensional shape is cucial to their ability to form enzyme-substrate complexes and catalyse reactions within the cells.
The three dimensional shapes of globular proteins are critical to their roles in binding to other substances. Examples include transport proteins within membranes and other oxygen transported pigments haemoglobin and myoglobin. Antibodies are also globular and rely on thier precise shapes to bind to the microorganism that enter our bodies.
Fibrous Protein do not old into a ball shape but remain as long chaines. Several polypeptide chains can be cross linked for additional strangth. These insoluble proteins are important structural molecules. Keratin is hair and skin, and collagen in the skin, tendons, bones, cartilage and blood vessel walls, are examples of fibrous proteins.
Cell Membrane Structure:
A Phospholipid Bilayer:
CF = caused by faulty transport protein in the surface membrane of the epithelial cells.
There is a bilayer of about 7nm wide, seen when using an electron microscope. The basic structure is two layers of phospholipids.
A phospholipid molecule has two distinct sections: the hydrophilic head and the hydrophobic tails.
The phosphate head of the molecule if polar; one end is slightly positive and the rest is slightly negative. This makes the phospate head attract other polar molecules, like water, and it is therefore hydrophilic. The fatty acid tails are non polar and therefore hydrophobic. When added to water phospholipids arrange themselves to avoid contact between the hydrophobic tails and the water. They may form a layer on the surface with their hydrophobic tails directed out of the water, arrange themselves into spherical clusters called micelles or form a bilayer.
Cell Membrane - Diffusion
Diffusion is the net movement of molecules or ions from a region where they are at a higher concentration to a region of their lower concentration. Diffusion will continue until equilibrium, when the substance is evenly spread throughout the whole volume. Small uncharged particles diffuse across the cell membrane, passing between the lipid molecules as the move down the concentration gradient. Small molecules, like oxygen and carbon dioxide, can diffuse rapidly across the cell membrane. Carbon dioxide is polat but its small size still allows rapid diffusion.
Cell Membrane: Facilitated Diffusion
Hydrophilic molecules and ions that are larger than carbon dioxide cannot simply diffuse through the bilayer. They are insoluble in lipids, the pydrophobic tails of the phopholipids providing an impenetrable barrier to them. Instead, they cross the membrane with the aid of proteins in a process called facilitated diffusion. They diffuse through water filled pores within channel proteins that span the membrane. There are different channel proteins for transporting different molecules. Each type of channel protein has a specific shape that permits the passage of only one particular type of ion of molecule. Some channels can be opened or closed depending on the presence or absence of a signal, which could be a specific molecule, like a hormone, or a change in potential difference (voltage) across the membrane. These channels are called gated channels.
Some proteins that play a role in facilitated diffusion are not just simple channels but are carrier proteins. The ion or molecule binds onto a specific site on the protein. The protein changes shape and, as a result, the ion or molecule crosses the membrane. The movement can occur in either direction, with the net movement being dependant on the concentration difference across the membrane. Molecules move from high to low concentration due to move frequent binding to carrier proteins on the side of the membrane where the concentration is higher. Some proteins that play a role in facilitated diffusion are not just simple channels but are carrier proteins. The ion of molecule binds onto a specific site on the protein. The protein changes shape and as a result the ion or molecule crosses the membrane. PASSIVE TRANSPORT.
Osmosis is thenet movement of water molecules from a solution with a lower concentration of solute to a solution with a higher concentration of solute through a partially permeable membrane.
Cell Membrane: Active Transport
If substances need to be moved across a membrane against a concentration gradient (from low to high concentration) then energy is required. As with facilitated diffusion, specific carrier proteins are also needed. The energy comes from respiration and is supplied by the energy transfer molecule ATP. The substance to be transported binds to the carrier protein. Energy from ATP changes the shape of the carrier protein, causing the substance to be released on the other side of the membrane.
Active transport or pumping of substances across membranes occurs in every cell. E.g. transport of ions across epithelial cells, plant cell roots, muscle cells and nerve cells. It also occurs between compartments within a cell, for example between mitochondria and cytoplasm.
Exocytosis and Endocytosis:
Sometimes very larege moleucles or particles need to be transported acros cell surface membranes. This is achieved by exocytosis and endocytosis, which rely on the fluid nature of the membrane. Exocytosis is the release of substances, usually proteins of polysaccharids, from the cell as vesicles (smalle membrane bound sacs) fuse with the cell membrane. E.g. Insulin (the hormone produced by certain cells in the pancreas) is released into the blood by exocytosis. Neurotransmitter substances are also released in this way from nerve endngs.
Endocytosis is the reverse process: substances are taken into a cell by the creation of a vesicle. Part of the cell mmbrane engulfs the solid or liquid material to be transported. In some cases the substance to be absorbed attatches to a receptor in the membrane and is then absorbed by endocytosis. This is how cholesterol is taken up into the cells. White blood cells ingest bacteria and other foreign particles by endocytosis.
Regulating water in the mucus - Excess Water:
1.) Na+ (Sodium ions) is actively pumped across the basal membrane.
2.) Na+ diffuses through sodium channels in the aprical membrane.
3.) Cl- diffuses down electrical gradient.
4.) Water is drawn out of cells by osmosis due to the high salt concentration in the tissue fluid.
5.) Water is drawn out of the mucus by osmosis.
Regulating water in the mucus - Too Little Water:
1.) Cl- is pumped into the cell across the basal membrane.
2.) Cl- diffuses through the open CFTR channels.
3.) Na+ diffuses down the electrical gradient into the mucus.
4.) Elevated salt concentration in the mucus draws water out of the cell by osmosis.
5.) Water is drawn into the cell by osmosis.
Regulating water in the mucus - CF
1.) CFTR channel is absent or not functional.
2.) Na+ channel is permanently open.
3.) Water is continually removed from mucus by osmosis.
In a person who has CF, the CFTR protein may be missing, or not functional. When there is too little mucus in the mucus, Cl- cannot be secreted across the apical membrane, and there is no blockage of the epithelial sodium ion channels. Since the Na+ channels are always open, there is continual Na+absorption by the epithelial cells. The raised levels of Na+ draw chloride ions and water out of the mucus into the cells. This makes the mucus more viscous, which makes it harder for beating cilia to move it, so the mucus is not effectively cleared up and out of the lungs. Sticky mucus builds up in the airways. This mucus frequently becomes infected with bacteria, causing a downward spiral of airway inflammation and damage.
The effect of CF on the digestive system:
Usually, most of the chemical breakdown of food molecules and the subsequent absorption of the soluble products into the bloodstream occurs in the small intestine. Glands secrete digestive enzymes into the lumen of the gut, where they act as catalysts to speed up the extracellular breakdown of food molecules. A wide range of enzymes are produced by exocrine glands outside the gut, e.g. salivary glands, the liver and the pancreas. Enzymes are also built into the membranes of the gut wall.
Groups of pancreatic cells produce enzymes that help in the breakdown of proteins, carbohydrates and lipids. These digestive enzymes are delivered to the gut in pancreatic juice released through the pancreatic duct.
In a person with CF, the pancreatic duct becomes blocked by sticky mucus, imparing the release of digestive enzymes. The lower concentration of enzymes within the small intenstine reduces the rate of digestion. Food is not fully digested, so not all the nutrients can be absorbed. A higher proportion of partially digested and undigested food means energy is lost in the faeces. This is called malabsorption syndrome.
An additional complication occurs when the pancreatic enzymes become trapped