Respiratory

Question	Answer
Gas in air is a mix of:	78% nitrogen 21% oxygen 0.46% water vapour 0.1% argon 0.04% carbon dioxide Total =100% = atmospheric pressure = 760mmHg Daltons Law: Total pressure = sum of all pressures Each gas contributes its partial pressure = part of the total
Gas in the alveoli	BUT Inspiration does not provide ‘fresh air’ to the alveoli Alveolar air is affected by dead-space & alveolar ventilation After breathing out the maximum possible, there is still air filled passageways & partly inflated alveoli = residual volume. All of the air in the upper respiratory tract and most of the lower respiratory tract cant be used for gas exchange and is termed ‘ dead space’. Dead space is part of the residual volume. Inspired air mixes with expired air remaining in the dead space.
Breath arrives at the Alveoli	Total lung capacity = 5.9L (m) 4.4L (f) Tidal volume = 500mL. Cannot over stretch lungs = Hering Breuer reflex
Alveolar ventilation	=the amount of air entering alveoli with each breath = (TV – dead space ) = 350mL 500mL is breathed in but only 350ml is new air Rate and depth of breathing alters alveolar ventilation Rapid shallow breathing may move same amount of air as normal but little of it may reach the alveoli
Alveoli	600 million alveoli Large surface area of about 70 -100m² for gas exchange Alveoli are made of simple squamous epithelium on basement membrane. Covered by capillaries also simple squamous epithelium on a basement membrane Gases need to diffuse through just two thin cells = respiratory membrane. Septal cells: (produce surfactant to lower surface tension and stop alveoli collapse) Macrophages: phagocytize any bacteria that have not been trapped by the mucus Water: diffuses from the alveoli cells into the alveoli so that they are constantly moist. Oxygen dissolves in this water before diffusing through the cells into the blood.
Breath arrives at the alveoli	Ventilation is greatest at the base of the lungs getting 2.5 times the air of the apex Alveoli pores allow air to move from one to the next alveolus, evenly through lungs The base of the lungs has higher ventilation due to higher compliance and that the lung weight pulls the apex away from the wall increasing the pleural space and increasing the negative pressure. Hering Breuer reflex a reflex triggered to prevent over-inflation of the lung. Pulmonary stretch receptors present in the smooth muscle of the airways respond to excessive stretching of the lung during large inspirations.
Blood arrives at the pulmonary capillaries	Blood flow into capillaries = Perfusion An auto-regulation system ensures blood only goes to capillaries of the alveoli that are ventilated At rest, some alveoli are not being used so little blood is sent to them.
Ventilation –perfusion coupling	At the lung apex ventilation exceeds perfusion At the lung base perfusion exceeds ventilation This results in decreased O2 & increased CO2 at base Local changes keep ventilation and perfusion matched Ventilation is altered by changing bronchiole diameter Perfusion is altered by changing pulmonary arteriole diameter
Ventilation-perfusion coupling	Bronchioles dilate or constrict in response CO2 in air Arterioles dilate or constrict in response to CO2 or O2 blood These controls ensure air and blood go to the same area
Gases diffuse down their concentration gradient Equilibrium is never quite reached	Breathing keeps alveolar PCO2 & PO2 fairly constant even though O2 is leaving & CO2 is entering Amount O2 & CO2 in alveoli stays constant The gas levels in blood leaving the lungs will be almost the same as gas in the alveoli
Rate of diffusion	The rate of diffusion across the respiratory membrane is dependent on: large surface area thinness (0.5 m) partial pressure difference across the membrane gas characteristics e.g. solubility the adequacy of the pulmonary circulation
Transport of oxygen; first step	O2 diffuses into the plasma 1.5% of oxygen is dissolved in plasma. Measured as PO2 = Partial pressure of oxygen PaO2 = oxygen dissolved in arterial blood plasma PaO2 is determined by alveolar PO2 and the state of the alveolar-capillary interface Normal Arterial = 90-105 mmHg Normal venous = 40 mmHg
Transport of oxygen; second step	O2 is poorly soluble in plasma so most quickly moves into the erythrocytes 98.5% of oxygen is bound to haemoglobin Erythrocytes contain haemoglobin (Hb) Each Haemoglobin molecule contains 4 polypeptide globin molecules and 4 heme molecules with iron (Fe++) atoms Fe++ has a strong affinity for O2
Oxygen Transport	The amount of O2 attached to hemoglobin = SaO2 = saturation = as a % SaO2 is determined by the PaO2 Normal Arterial = 95-98% Normal venous = 75% Neither PO2 or SaO2 tells us how much oxygen in total When Hb is 98 - 100% saturated, it is called oxyhaemoglobin (HbO2). Each Hb holds 4 O2 If each Hb only carries 1-3 O2 molecules it is “partially saturated” Hb in venous blood is about 75% saturated creating an oxygen reserve to supply extra demand
Hemoglobin	Hemoglobin transports 3 substances: O2 attached to haem, CO2 attached to globin & H+ attached to globin. The binding or release of one changes the shape of the Hb. This influences its ability to bind or release the other 2
Transport of oxygen At alveoli at tissue	At the alveoli One O2 binds causing Hb to change shape so that the next O2 can bind more easily, with the 4th binding most easy. At the tissue One O2 unloads causing Hb to change shape The next O2 can unload more easily, with the 4th unloading most easy.
Easier oxygen unloading from:	↑ Temperature ↑ [H+] = ↓ pH = Bohr effect ↑ CO2 = Haldane effect All lower Hb affinity for O2 CO2 & H+ diffuse into RBC making O2 unloading easier Makes unloading easier in the working cells & tissues
Carbon dioxide transport	Cells create CO2 from conversion of glucose to ATP Remember from HAP I? Glucose + O2 → CO2 + H2O + ATP It diffuses down its concentration gradient from cell into interstitial fluid into plasma 8% dissolved in plasma. Most quickly moves from plasma into erythrocytes.
CO2 transport: In the red blood cell:	20% bound to the globin of hemoglobin as carbaminohemoglobin (HbCO2) The higher the PCO2, the more bound to globin Haldane effect: The less O2 on the heme, the more readily CO2 binds on globin and the more Hb can buffer H+ 70% combines with water to form carbonic acid H2O + CO2  H2CO3 (H2CO3 = Carbonic acid) This requires the enzyme carbonic anhydrase Carbonic acid dissociates into hydrogen ions and bicarbonate ions which leave the RBC. H2CO3 H+ + HCO3- (HCO3- = bicarbonate ion) Bicarbonate ion (HCO3-) moves to plasma to act as a buffer Exchanged for a chloride ion The hydrogen ions attach to haemoglobin 70% of CO2 is carried as bicarbonate ions in plasma
Neural control of breathing	Breathing rate = 12 – 20 breaths / min Control is both voluntary & involuntary Voluntary control from cerebral cortex Respiratory centres in Medulla & Pons over-ride voluntary control Involuntary breathing is established by ventral respiratory group (VRG) in the Medulla Oblongata
Control of Respiration	Medulla = rhythm centre VRG = Ventral respiratory group is rhythm generating. VRG inspiratory neuron APs trigger external intercostal muscles & diaphragm contraction, via phrenic & intercostal nerves VRG expiratory neurons stop inspiratory neurons, then muscles relax Dorsal respiratory group (DRG) integrates signals from chemoreceptors (chemical factors) & peripheral stretch receptors.
Peripheral stretch receptors	are proprioceptors, baroreceptors and irritant receptors
Neural control of Respiration	Pons alters rate & depth of breathing Influences VRG to create a smooth transition between inspiration & expiration Allows talking and breathing smoothly
Control of Respiration	The nervous system controls the volume changes in the thoracic cavity that control respiration via the: VRG & DRG in the medulla & the pontine RG in the Pons Cerebral cortex Stretch receptors in the lungs Pulmonary irritant receptors Receptors in muscles and joints Chemical factors like CO2, O2, & H+ Hypothalamus
Chemoreceptors	Arterial/peripheral chemoreceptors; stimulated by hypoxia (low oxygen. PO2 of 60mmHg or less), increasing CO2 (hypercapnia) & decreasing pH (increasing acidity) Central chemoreceptors in Medulla; stimulated by very small increases in CO2 (& are slightly sensitive to pH) in CSF
Autonomic Nervous system controls perfusion & ventilation NOT rate & depth	Sympathetic Dilates bronchioles β2 adrenergic receptors to increase ventilation Increases rate and force of contraction to increase perfusion to lungs Parasympathetic Constricts bronchioles to reduce dead-space
Acid-base balance	pH plasma = 7.35- 7.45 Above this = alkalosis Over excited nervous system Twitching, tingling, respiratory paralysis Below this = acidosis Depressed nervous system Confused, disoriented, coma A pH below 7 or above 8 = dead
Acids & Bases or Alkalise	Acid: A molecule or ion that donates a proton (= H+) pH = 1 – 6.9 Destroys body tissue Base: A molecule or ion that accepts a proton pH = 7.1 - 14 Destroy body tissue HCO3- + H+ ↔ H2CO3 Bicarbonate ion + proton ↔ carbonic acid
pH	A Measure of the concentration of free H+ H+ + OH- H2O Acid + base salt + water Negative logarithmic scale pH1 = 10-1 = 0.1M of H+/L
pH balance	Normal metabolism produces H+ + CO2 Remember from HAP I? Glucose + O2 → CO2 + H2O + ATP These must be removed 3 systems Buffer system Respiration Kidneys
Buffers	Resist changes in pH Provide protection against drastic changes in pH React very quickly Are limited in their capacity Excess acids / bases not removed from the body Come as a pair = A weak acid and a weak base Excess H+ combines with the weak base to form water H+ + OH- → H2O
3 buffer systems	Bicarbonate buffer system Phosphate buffer system Protein buffer system
Bicarbonate buffer system	Most measured buffer Predominant buffer in ECF Buffer pair = HCO3- (weak base) & H2CO3 (weak acid) H+ + HCO3- ↔ H2CO3 If excess acid, equation moves out If excess base equation moves in
Other buffers	Phosphate buffer system ICF buffer Especially important in cytosol & kidney tubules Protein buffer system Intracellular buffers includes haemoglobin which buffers H+ as it journeys from cell to lungs
Respiratory effect on pH	Maintains pH by altering amount of CO2 breathed out H2CO3 -> H2O + CO2 Chemoreceptors in the medulla monitor [H+] in CSF & adjust breathing H+ + HCO3- -> H2CO3 -> H2O + CO If more H+ produced, pH decrease & equation moves ->
Kidney effect on pH	Most important in long term pH maintenance Slowest of the 3 systems to work Kidneys can: Secrete H+ if acid or HCO3- if alkaline Reabsorb HCO3- Synthesise HCO3- Usually eliminating H+ & conserving HCO3-
Effect of Kidney function on pH	CO2 diffuses from blood into kidney tubule cell CO2 is converted to H+ & HCO3- HCO3- is reabsorbed back into blood H+ swapped for Na+ in urine H+ in urine is buffered by ammonia & phosphate ions NH3 + H+ NH4+ (ammonia  ammonium ion) HPO42- + H+ H2PO4- NH4+ (as NH4Cl) & H2PO4- are lost in urine

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	Created by Jonathan Cash almost 8 years ago