Respiratory System Pathophysiology and therapeutics

The primary function of the lungs is gas exhange. The lungs receive deoxygenated blood from the heart and put oxygen in it, send it back to the heart and then to the rest of the body. The lungs take this oxygen from the atmosphere and remove the carbon dioxide from the blood and expel it from the body. The lungs contain alveoli or air sacs that have 1 cell-thick walls and are the site of gas exchange for the blood supply. 

Restrictive - The lungs are unable to expand properly and take in as much air. This is an intake respiration problem. The lungs become stiff and hard, this creates restriction in the inhalation process meaning less oxygen is taken in and the system becomes less efficient. This can occur due to fibrosis - scar tissue formation. Chest diseases that effect lung expansion. Deposits in the lung tissue e.g. amyloidosis - protein gets studded into the ungs making it hard to expand. 

Obstructive - there is problems in the expiration of air in the lungs. This means the lungs are unable to collapse and expell the air back out to the atmosphere. This can be due to a mucous plug, craches collapse as they have lost the elastic quality structure, COPD, which is emphysema - lungs losing elasticity and chronic bronchitis - irritation causing mucous secretion. Asthma - airways spasms and prevents the air from getting out.

Ventilation - Pulmonary oedema - fluid building up in the alveoli creates an environment where oxygen cannot diffuse as quickly to the blood supply and carbon dioxide cannot be expelled as well. The blood then leaves the alveoli with barely an oxygen and more carbon dioxide than it should. This will cause shortness of breath. This can occur with infection e.g. pneumonia

Perfusion - the lungs are unable to get blood where it needs to go e.g. blood clot. The oxygen cannot be put into a blood supply that isnt there. This is called a pulmonary embolism. 

The trachea breaks off into the right and left bronchi that further branch off into bronchioles leading to the alveoli air sacs. Asthma is an obstructive disease where air cannot be expelled from the lungs efficiently. If a cross-section of a bronchiole is taken it contains a wall (connective tissue, glands and smooth muscle layer etc) and lumen where the air passes. In asthma the main feature is how the smooth muscle constricts the airway. The smooth muscle contracts and clamps down on the lumen of the airway preventing airflow. This also causes fluid secretion due to inflammation and this is secreted into the lumen also. This happens in all the bronchioles and airway tubes of the lungs in asthma making it very difficult to expel air. The process of inhalation has a power to it and the process of exhalation is passive so air can enter the lungs a little easier than leave. 

Smoking can be a huge trigger for asthma, as well as pollution, foreign material e.g. asbestos and stress etc. Wheezing in the lower airway due to the popping and reformation of air bubbles is characteristic of asthma. This causes shortness of breath. 

Asthma through observation seems to be related to eczaema - dry pathches of the skin - and allergies. If you have 1 you are likely to have the other two especially in children. 

For example if an allergen was to be inhaled. The immune system reacts to any foreign material that enters the body. The allergens are targetted by antibodies which tend to be IgE. Depending on how many times the foreign body has enterred the body it results in a quicker time to generate new IgE antibodies as the immune system remebers them. The IgE collects the foreign material and gos to find a mast cell that carry stores of histamine which are the central materials in an allergic reaction. The IgE/foreign material complex attach to a mast cell and allow it to release its histamine stores into the blood stream. This causes a myriad of symptoms e.g. sneezing, runny eyes/nose, rashes. The effect histamin has in the lungs is to cause mucous secretion and smooth muscle constriction, it fills the constricted lumen with more fluid than should be there making it far more difficult to breathe.

methacholine test. This is inhaled and reaction observed. Methacholine causes the airways to constrict in all people. This effect is enchanced in patients with asthma causes a huge constriction and very large reduction in lumen space compared to an individual without asthma.

Pulmonary function test - a machine records the volume speed of air going in and out of the lungs. FEV1 is the amount of air that comes out in the 1st sec divided by the total vital capacity - all the air you expelled should be equal to or greater than 80%. If it is less than 80% then it is an obstructive disorder like asthma. This is an example of spirometry. 

Peak flow test- this is personalised to each individual. 80-100% of the max is good and no meds are required the machine will show green. The next colour is yellow and some symptoms may be occurring and the patient should be caredul -50-80% of max, meds should be taken. Red means stop and is below 50% of max and should get medical attention. 

Xray - should be normal and rules outother disease e.g. pneumonia or pneumothorax. 

Stress test for the lungs for stress or exercise related asthma.

NO test  - tests the effectiveness of asthma treatments. will corticosteroids work? these should dilate the airway and relax the smooth muscle. 

an asthma attack occurs and sends the patient to hspital. The things that usually work e.g. beta2 agonist, nebuliser or steroid inhaler hasnt worked for the patient at the onset of the attack. Oxygen would be given en route to the hospital to help with providing the body with oxygen. 

A the hospital the patient would be given the same drugs they used at home but intravenously to provide a more rapid effect. Magnesium sulfate can also be given which opens up the airways or adrenaline to start the fight or flight response and open the airways but will feel panicked e.g. heart palpitations. Oxygen will also be given. 

Intubation is next to breathe for the patient and requires sedation. This is a last resort. 

Avoiding triggers is a huge preventative method e.g. smoking, allergens, NSAIDs

the goal is to control symptoms and reduce the frquency of attacks. Well controlled is less than 2 a week and only 1 a day. The meds are working. The next level is not well controlled more than 2 a week or more than one a day. Poorly controlled is worse. This requires an increase in medication.

Nebuliser - evaporated medication is inhaled with oxygen as a mist for around 10 mins. multiple medications can be used. To decrease inflammation - steroids, leukotriene inhibitors, 

Inhaler (with spacer) - the medication needs to travel with air so a spacer is good to use and takes 30 secs max and is easily carried. multiple medications can be used - bronchodilators e.g. beta agonist, theophyline (toxic?) 

Emphysema ocurs in the alveoli. Each alveolus is separated by a wall. In COPD the elastin in the airways gets destroyed. The elastin is important from insuring the lungs can relax and snap back to their normal size in order to expel air after expansion. The walls of the alveoli become destryed as their is nor elastin to support structure and the alveoli clusters and the end of the airway branches becomes an amorphous blob structure rather than like a bunch of grapes. On top of this the airway itself that the alveoli are on collapses as well causing a physical obstruction in the airwya preventing airflow. 

Emphysema often exists with chronic bronchitis.

There is now air trpped in the morphed alveoli in a collapsed airway. The gas exchange can only be half done as oxygen can go in but carbon dioxide cannot get out. There are over 2 million alveoli in the lungs so emphysema causes overinflation of the lungs and the ribcage and tissue of the chest changes shpe to accomadate giving the look of a barrel-chest. This is very uncomfortable. This creates the pink puffer characteristic. They dont lack oxygenated blood and have pursed lips due to the collapsed airways creating obstruction. If you breath slower it prevents the air from getting trapped and keeps the airway open longer. They breathe more breaths per minute however. 

This often exists with emphysema. Chronic bronchitis is characterised by an overproduction of mucous.  This is caused by constant inflammation of the lungs. The airway becomes to occluded with mucous creating difficulty in gas exchange and inhalation and exhalation of air. Smoking, pollution, allergies can cause this. 

Blue bloaters refers to the characteristic that deoxygenated blood cannot be delivered due to mucous build up. Blue tint to nail beds, skin, lips, eyes etc. This is due to low oxygen (lower 90s and below). Bloater refers to shape as patients will take lower bigger breaths, increasing the diameter of the chest. Leaving a bloated and hypoxic look.They will have a nagging cough for 3 months of the years for 2 years in a row to diagnose chronic bronchitis. The cough occurs because the tissue of the smooth muscle in the airway walls spasms to get rid of irritants and exageration causes a cough.

It can have acute flare-ups when ill e.g. cold, flu etc. The cough gets works an increases the irritation in the lungs and increases mucous production. The bacteria build up in this mucous build and cause infection. If there is a blockage due to mucous it is very likely to be bacterial and makes it harder to clear an infection. The infection could be pneumonia. 

In any opening of the body where irritants can get in, there is goblet cells that produe mucous to encapture these irritants and flush them out. This is phlegm in the lungs. It also triggers a cough reflex as the walls of the lungs are lined with smootgh muscle. When these spasm you cough. Over production of mucous in chronic bronchitis. An irritant enters and the mucous is produced in a normal reaction however in chronic bronchitis the mucous keeps building up and may clog branches of the lung and prevent gas exchange in that portion of the lungs. This happens over a long period of time. Tissue changes and the goblet cells over grow. The lumen is surrounded by goblet cells to secret a mucous layer to catch irritants in a normal patient. The Reid index is a way to calculate the ratio of the thickness of the glands to the whole wall. It is normally less than 40%, however, in chronic bronchitis the thickness of the goblet cell layer grows to keep up with mucous production and begin to grow toward the smooth muscle in the airway wall and becomes over 50%. This cannot be done in living patients. 

Elastin looks like a coil and when stretched it snaps back. This is how it works in the alveoli to inhale and exhale air. If destroyedin emphysema this esatin is destroyed. When air is inhaled this expands but cannot produce any force to expel the air hence obstructive. 

Elastin is broken down by elastase to cleave elastin and grow new tissue. The elastase is inhibited by alpha-1 antitrypsin that is made in the liver and therefore allows there to be more elastin. In emphysema there is too much elastase which therefore will break down more elastin. If there is inflammation in the body, there are neutrophils present and neutrophils are responsible for making elastase. There fore, if there are neutrophils there is lots of elastase, more elastase means more destruction of elastin which equals emphysema. Another cause of excess elastase is an alpha-1 antitrypsin deficiency which results from a genetic mutation in the SERPINA1 gene which causes it to get trapped in the liver so it can have no effect on elastase in the lungs. This causes elastase to degrade elastin without being controlled. This mutation also causes liver disease. 

Stop smoking - stops disease worsening as it causes emphysema.

Drug therapies manage symptoms.

Chronic therapies - bronchodilators (open airway by dilating smooth muscle layer of airways allowing more air through. Beta1 agonists work on beta 2 receptors in the sympathetic nervous system and stimulating them (fight or flight response) opens lungs - albutarol. Anticholinergics (opium),) Leukotriene inhibitors - leukotrienes are the final stage of the inflammation cascade so inhibiting tones down inflammation. This reduces neutrophils and less elastase is produced. 

Acute therapies - a flare up. Antibiotics (infection or for prophylaxis to prevent infection) As a general rule if there is a build up of trapped air, in exacerbation this gets worse due to infection. There is bacteria in lungs at all times nd once the air is stagnant this becomes a breeding ground and creates a high risk of infection resulting in exacerbation of emphysema. Steroids for infammation to prevent the inflammation cascade midway. The rest of the immune system also stops working and immunocpromises the patients. Oxygen in emphysema patients. Respiratory drive - gas exchange is very sensitive, if theres extra CO2 chronically the brain adapts and creates new normals. The lack of oxygen encourages them to breath and adding more oxygen can decrease emphysema patients drive to breathe.  

X-ray - hyper-inflated lungs, presses on diaphragm making it hard to breath. The muscles of the neck and abdomen may be exagerated. 

FET - same test as for asthma. FVC goes down. FEV1 goes down further than FVC. This gives an idea of severity.

Blood test - alpa-1 antitrypsin deficiency. blood gas - expensive and painful - determines oxygen and co2 levels in the blood. Complete blood count - bicarbonate measured if increased there is too much co2 which is characteristic of emphysema. 

Remove irritant - stop smoking stops the progression of disease. Pollution - moving. Occupation - coal, asbestos. Allergens 

Inflammation treatment. bronchodilator (beta2 agonist, anticholinergics), steroids and leukotriene inhibitors 

Mucous treatment - suppresents are not given. Coughing is good for cleaaring mucous. 

Lung function - Oxygen ( same as emphysema, carefully given) Steroids and antibiotics if acute attack (same as emphysema)