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Gas Exchange Asthma Notes

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Semester 2 Case 2: Peak Performance

* How does gas transport & gas exchange occur?
Dalton's Law & Partial Pressures Air we breathe: N2 = 78.6%, O2 = 20.9%, CO2 = 0.04%, and the rest is mainly water molecules. Atmospheric pressure is caused by the collision of these gas molecules. Atmospheric pressure = 760mmHg = 100kPa. Each gas contributes to pressure relative to its abundance. This relationship is known as Dalton's Law. The partial pressure of a gas is the pressure contributed by a single gas in a mixture of gases. PN2 + PO2 + PH2O + PCO2 = 760mmHg. Henry's Law (Diffusion Between Liquids & Gases) At a given temperature, the amount of a particular gas in solution is directly proportional to the partial pressure of that gas. When a gas under pressure contacts a liquid, the pressure tends to force gas molecules into (& out of) solution. At a given pressure, the number of dissolved gas molecules will rise until an equilibrium is established. The actual amount of a gas in solution at a given partial pressure & temperature depends on the solubility of the gas in that particular liquid. E.g. In body fluids, CO2 is highly soluble, O2 is somewhat less soluble, and N2 has very limited solubility. Composition of Alveolar Air In the nasal cavity, inhaled air becomes warmer & the amount of water vapour increases. In the pharynx, trachea, & bronchial passageways, humidification & filtration continue. At alveoli, incoming air mixes with air remaining in the alveoli from the previous respiratory cycle. Therefore, alveolar air contains more CO2 and less O2 than does atmospheric air. Inhaled air: N2 = 80kPa, O2 = 21kPa, CO2 = 0.04kPa, H2O = 0.49kPa. Alveolar air: N2 = 76kPa, O2 = 13kPa, CO2 = 5.3kPa, H2O = 6.3kPa. Exhaled air: N2 = 75.9kPa, O2 = 15.5kPa, CO2 = 3.7kPa, H2O = 6.3kPa. Gas exchange at the respiratory membrane is efficient because:
- The differences in partial pressure across the respiratory membrane are substantial.
- The distances involved in gas exchange are small.
- The gases are lipid-soluble.
- The total surface area is large.
- Blood flow & airflow are coordinated. Partial Pressures In Alveolar Air & Alveolar Capillaries Blood arriving in the pulmonary arteries has a lower PO2 & a higher PCO2 than does alveolar air. Diffusion between the alveolar air & the pulmonary capillaries increases PO2 & decreases PCO2. By the time it reaches the alveolar venules, it has reached equilibrium with the alveolar air. Hence, when blood departs the alveoli PO2 = 13.3kPa, PCO2 = 5.3kPa. Partial Pressures In The Systemic Circuit As blood enters pulmonary veins, it mixes with blood that flowed through capillaries around conducting passageways of the lungs. Gas exchange only occurs at alveoli, so blood leaving conducting passageways carries relatively little oxygen. Therefore, in pulmonary veins, PO2
= 12.7kPa. No further changes in partial pressure occur until blood reaches peripheral capillaries. Normal interstitial fluid: PO2 = 5.3kPa. As a result, oxygen diffuses out of capillaries &
carbon dioxide in, until capillary partial pressures are the same as those in adjacent tissues. Inactive peripheral tissues: PCO2 = 6kPa, whereas blood entering peripheral capillaries has PCO2 = 5.3kPa. So CO2 diffuses into blood as oxygen diffuses out. Gas Pickup & Delivery Oxygen & carbon dioxide have limited solubilities in blood plasma. When plasma oxygen or carbon dioxide concentrations are high, the excess molecules are removed by RBCs. When plasma concentrations are falling, the RBCs release their stored reserves. Oxygen Transport

98.5% of O2 in the blood is bound to haemoglobin - specifically to the iron ions in the centre of heme units. Each haemoglobin molecule can bind 4 oxygen molecules, forming oxyhaemoglobin (HbO2). Haemoglobin with no oxygen bound is called deoxyhaemoglobin. The % of heme units containing bound O2 at any given moment is called the haemoglobin saturation. The shape & functional properties of haemoglobin change in response to the PO2 of blood, blood pH, temperature, & ongoing metabolic activity within RBCs. These changes can affect oxygen binding. The poisonous effect of carbon monoxide stems from its competition for the oxygen binding site. PO2: At equilibrium, O2 molecules bind to heme at the same rate that other O2 molecules are being released. If PO2 increases, the reaction shifts to the right & more O2 gets bound to haemoglobin. If PO2 decreases, reaction shifts to the left & more O2 is released by haemoglobin. The shape of the Hb molecule changes when an O2 molecule binds to it, making it easier for the next O2 to bind. Because each arriving O2 increases affinity of Hb for the next O2, the slope rises rapidly after the first O2 binds. A very small change in PO2 would result in a large change in %
saturation. % then plateaus. Hb will be >90%
saturated if exposed to an alveolar PO2 of
>8kPa. When oxygenated blood arrives in peripheral capillaries, the blood PO2 declines rapidly as a result of gas exchange with the interstitial fluid. This decline causes haemoglobin to give up its oxygen. pH: Active tissues generate acids, which lower the pH of interstitial fluid. When pH drops, shape of Hb changes & release their oxygen reserves more readily, so saturation declines. This is the Bohr effect. Primary compound responsible = CO2. When CO2 diffuses into the blood, it rapidly diffuses into RBCs. In the RBCs:

When PCO2 rises, more H+ is produced, lowering pH. Temperature: As temperature rises, Hb releases more O2. As temperature declines, Hb holds onto O2 more tightly. Temperature effects are significant only in active tissues in which large amounts of heat are being generated. BPG: RBCs that lack mitochondria produce ATP by glycolysis, in which lactic acid is formed. BPG is also formed. Normal RBCs always contain BPG. For any PO2, the higher the concentration of BPG, the more O2 released by Hb, but there's improved O2 delivery to tissues. BPG levels can be increased by thyroid hormones, GH, adrenaline, androgens, &
high blood pH. Foetal haemoglobin has greater affinity for O2 than adult haemoglobin. Carbon Dioxide Transport CO2 is generated by aerobic metabolism in peripheral tissues. After entering the blood stream, CO2 is then either; converted to a molecule of HCO3, bound to the protein portion of Hb molecules, or dissolved in plasma. All 3 reactions are reversible: HCO3 Formation (70% of transport)

In peripheral capillaries, this reaction proceeds vigorously, and reaction continues as CO2 diffuses out of the interstitial fluids. Most of the H+ binds to Hb. The HCO3- move into

surrounding plasma & is exchanged for Cl-. The result is a mass movement of Cl- into RBCs, called the chloride shift. Binding to Hb (23% of transport) CO2 attaches to exposed amino groups of the Hb molecules. Resulting molecule is called carbaminohaemoglobin. Transport in Plasma (7%) Plasma becomes saturated with CO2 quite rapidly, which is why only 7% is transported in this way.

* What is asthma?
[2, 3] Asthma

is a common chronic inflammatory condition of the lung airways. The course isn't yet completely understood. Features

* Chronic Desquamating Eosinophilic Bronchitis

* Bronchial hyperresponsiveness

* Acute reversible airways obstruction

* Excessive mucus secretion

* NO irreversible lung damage Symptoms Clinical features vary according to the severity of asthma (classified from mild to severe &
either intermittent or persistent). Principle symptoms of asthma are wheezing, attacks, &
episodic shortness of breath. Symptoms are usually worst during the night. Cough is a frequent symptom. Other symptoms include chest tightness. Acute severe asthma in adults is diagnosed if:

* Patient cannot complete sentences in one breath,

* Respiration rate [?]25 breath/minute,

* Pulse [?] 110 beats/minute,

* PEFR (Peak Expiratory Flow Rate) [?]50% of predicted or best. Life-threatening asthma is characterised by:

* PEFR <33% of predicted or best,

* Silent chest & cyanosis,

* Bradycardia or hypotension,

* Exhaustion, confusion, or coma,

* PaO2 <8kPa. Asthma is a major cause of impaired quality of life with impact on work, recreational, as well as physical activities & emotions. Epidemiology In many countries, the prevalence of asthma is rising, particularly in the second decade of life where this disease affects 10-15% of the population. 5% of the adult population are receiving treatment at any one time. Asthma is common in more developed countries, some of the highest rates being in New Zealand, Australia, & the UK. It's much rarer in Far Eastern countries such as China & Malaysia, and in Africa, and Central & Eastern Europe. Evidence suggests that the disease may become more frequent as individuals become more 'westernised'. Classification of Asthma Extrinsic Asthma: Implying a definite external cause. It occurs most frequently in atopic individuals who show positive skin prick reactions to common inhalant allergens. Positive skin prick tests to inhalant allergens are shown in 90% of children & 50% of adults with persistent asthma. Childhood asthma is often accompanied by eczema. An over-looked cause of late-onset asthma in adults is sensitisation to chemicals in biological products in the workplace. Intrinsic Asthma: AKA: Cryptogenic. This is when no causative agent can be identified. IT often starts in middle age. Nevertheless, many patients with adult-onset asthma show

positive skin tests & on close questioning give a history of respiratory symptoms compatible with childhood asthma. Non-atopic individuals may develop asthma in middle age from extrinsic causes such as sensitisation to occupational agents, or aspirin intolerance, or because they were given badrenoceptor-blocking agents for concurrent hypertension or angina. Pathogenesis Atopy Term is best used to describe individuals who readily develop antibodies of IgE class against common materials found in the environment. There is a link between serum IgE levels and both the prevalence of asthma & airway hyperresponsiveness. Serum IgE levels are affected by genes & environment. Some genes associated with high serum IgE are:

* The IL-4 gene cluster on chromosome 5q31-33.

* The PHF11 gene on chromosome 2, which controls IgE synthesis.

* The ADAM33 gene on chromosome 20, associated with airway hyperresponsiveness
& the tissue changes of remodelling. As well as genetic factors, prevalence of asthma is affected by environmental influences in early life (e.g. maternal smoking, intrauterine nutrition, avoidance of dietary & environmental allergens in first few years of life - AKA: hygiene hypothesis). - These all effect IgE production. Components of bacteria, viruses & fungi are able to stimulate toll-like receptors (TLRs) expressed on immune cells to direct the immune & inflammatory response away from the allergic pathways. Therefore, early life exposure to inhaled & ingested products of microorganisms may be critical in helping shape the subsequent risk of atopy. The varying clinical severity & chronicity of asthma is dependent on interplay between airway inflammation & airway wall remodelling. The inflammatory component is driven by Th2-type T lymphocytes which facilitate IgE synthesis through production of IL-4 &
eosinophilic inflammation through IL-5. It's a TYPE 1 HYPERSENSITIVITY REACTION!

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