Sc04 L04 Gaseous Diffusion and Transport 2

02 February 2012 17:03

How does increased CO2 or lactic acid affect haemoglobin? decreases haemoglobin’s affinity for O2

Decreases pH which

With increases in CO2 or lactic acid, pH decreases. This changes haemoglobin’s affinity for O2 (decreases). Hyperventilation doesn’t improve O2 delivery to blood. Doesn’t change saturation.

As arterial blood flows into the tissue capillaries the haemoglobin is exposed to a reduced PO2 and this causes the haemoglobin to release oxygen. increase in temperature. so that at any given PO2 the oxygen saturation reduced. aiding unloading of oxygen. temperature What does this result in? Changes in affinity of haemoglobin for oxygen How does increased PCO2 shift the curve? Towards the right.3-DPG Why is this beneficial as arterial blood flows into tissue capillaries? Haemoglobin exposed to reduced PO2 and decreased pH. pH rises and temperature falls. reduced pH and if the tissue is metabolising heavily (e. This is reflected by a 'rightward' shift of the oxyhaemoglobin dissociation curve. skeletal muscle in exercise) there will also be an increased temperature. With haemoglobin. pH. ‘Bohr shift’ What else can cause this shift? Fall in pH. How does the graph change with anaemia and CO poisoning? With anaemia. known as the 'Bohr shift'. an increase in temperature and a rise in the red cell metabolite 2. increase in 2. less sigmoidal. These changes will reduce the affinity of haemoglobin for oxygen. increased temperature.g. there is a sigmoid curve which steepens because the 2nd haem group binds O2 more readily due to conformational change due to previous binding.What affects the quaternary structure of haemoglobin? PCO2. pH rises and temperature falls. aiding the oxygen uptake that is occurring as the blood is exposed to increased PO2 in the alveolus Double pressure doubles dissolved oxygen (in plasma). In the lungs the reverse changes happen as PCO2 falls. shifts down. At the same time the haemoglobin is also exposed to increased PCO2. still sigmoidal. Affinity of haemoglobin for oxygen rises aiding oxygen uptake What is the haemoglobin graph shaped like and why? Sigmoid curve which steepens because the 2nd haem group binds O2 more readily due to conformational change caused by previous binding Notes on oxyhaemoglobin dissociation curve shifts The quaternary structure of haemoglobin is altered by changes in PCO2. The affinity of haemoglobin for oxygen rises. shifts down. With CO poisoning. A fall in pH. steeper curve at lower O2 content . pH and temperature and this in turn affects the affinity of haemoglobin for oxygen.3 diphosphoglycerate also cause a rightward shift of the oxyhaemoglobin dissociation curve. Increased PCO2 reduces the affinity of haemoglobin for oxygen. etc (in active muscle) and so affinity for oxygen is reduced and oxygen is released Why is this beneficial in the lungs? Reverse changes happen as PCO2 falls.

high enough to match O2 needs – exercise intolerance.No O2 saturation scale as patients would have different saturations. What does normal HbA consist of? 2alpha. 2beta protein chains What about HbF? 2alpha. no cooperative binding What is cyanosis? Blue tinge in a tissue due to high conc of deoxyHb What is peripheral cyanosis? Reduced blood flow to regions Arterial O2 content is decreased in this. T/F?False. it may be normal. fine at rest. What are the causes of cyanosis? Local obstruction or (more commonly) low CO What does cyanosis depend on. high percentage or high content of deoxyHb? Absolute concentration What is central cyanosis? Arterial hypoxaemia – buccal mucosa and lips are best sites How much deoxygenated haemoglobin would the arterial blood contain for cyanosis to be observable? >15-20g/l At what O2 saturation does this occur? About 85-90% if [Hb] is normal (150g/l) In what patients does it appear more easily (at higher O2 sat)? In polycythaemic patients Why is central cyanosis impossible in severe anaemia? It would require an O2 saturation incompatible with life Cyanosis is a blue tinge in a tissue due to a high concentration of deoxygenated Hb Peripheral cyanosis = reduced blood flow to region(s) Arterial O2 content may be normal . 2gamma protein chains What about myoglobin? Single haem group and protein chain ‘Hyperbolic’. breathlessness in exertion. At point B.

. Occurs when O2 saturation = about 85-90% if [Hb] normal (150g/l) It appears more easily (higher O2 saturation) in polycythaemic patients.Usually low CO rather than local obstruction High absolute concentration of deoxyhaemoglobin. In severe anaemia central cyanosis is impossible as it would require an O2 saturation incompatible with life. When the arterial blood contains >15-20g/l of deoxygenated haemoglobin cyanosis is observable even in well-perfused tissues.buccal mucosa and lips are best sites. Central cyanosis = arterial hypoxaemia . it isn’t the percentage that matters.

Fortunately. Normal tissue PO2 is about 2-5kPa (15-40mmHg) The process of delivering oxygen from the air (PO2 about 21kPa to the tissues and their mitochondria involves a series of step falls in PO2 as shown in the diagram. (Life on earth emerged in a very low PO2 atmosphere.) Rightward reaction aided by buffering of [H+] by Hb Bicarbonate formed within the RBC diffuses out down its concentration gradient into the plasma in exchange for Cl.ml-1 Carbonic acid .0052 ml.bicarbonate    Reaction 1 is slow in plasma but fast in RBC because of presence of carbonic anhydrase (c.a. they evolved to work in quite a low PO2 environment and need local tissue PO2 to be kept above about 0. PCO2 = 5.0274 ml.kPa-1 Ie.(the chloride shift) . Carbon dioxide carriage Dissolved CO2 Solubility CO2 = 0. it may be a necessary process to 'step down' the PO2 to provide the correct tissue PO2 and protect the cells from the effects of a PO2 that is too high.3kPa (2mmHg) to keep working. 20 times more soluble than O2 In normal arterial blood.) However.High O2 levels damage lungs = toxic Notes on 'The Oxygen Cascade' One of the main roles of the cardiovascular and respiratory system is to deliver oxygen to the mitochondria of the tissue cells where it is used.ml-1. too low a PO2 is also obviously harmful and the diagram also helps us understand the places where problems may lead to tissue hypoxia. Previously viewed as the inevitable inefficiency of the system.3 kPa Therefore dissolved CO2 = 0.

g. Due to: 1. lysine. Hb is a better buffer when deoxygenated. little affected by PCO2 CO2 not competing with O2 Haldane effect = at any given PCO2 the quantity of CO2 carried is greater in deoxygenated blood than in oxygenated blood.diffuses out down concentration gradient Carbamino Compounds RNH2 + CO2 <=> RNHCOOH e. arginine side chains Mostly formed with haemoglobin (Hb) a little with plasma proteins Reaction affected by oxygenation of Hb. Hb forms carbamino compounds more readily when doxygenated 2. HCO3. Therefore increased formation of HCO3Relative importance of mechanisms of CO2 carriage Of the CO2 evolved at the mouth. about: 60% comes from HCO330% comes from carbamino compounds 10% comes from dissolved CO2 .

alveolar and therefore arterial PCO2 is determined by the balance between CO2 production and alveolar ventilation: Hypercapnia = high PaCO2 due to hypoventilation (possible causes of hypoventilation are head injury. chronic lung disease) . anaesthetics. drugs.Breathing air (CO2-free).

The effects of a high PCO2 are:  Flushed skin  Full pulse. acidosis. still muscles. tetany (all especially in hands and feet) Mechanisms:  Low PaCO2 --> Cerebral vasoconstriction --> Cerebral hypoxia  Low PaCO2 --> alkalosis --> ↓plasma *Ca2++ --> ↑ nerve and muscle excitability . excessive mechanical ventilation) Symptoms:  Dizziness. visual disturbances. pins and needles. pain. increases PaCO2)  Death Hypocapnia = low PaCO2 due to hyperventilation (caused by: anxiety. extrasystoles  BP often raised  Muscle twitching. low PaO2. 'hand flap' Very high PaCO2 (>10kPa or 75 mmHg) result in:  Confusion  Convulsions  Coma  Depressed ventilation (positive feedback.