blood gas transport and regulation

why do we need O2 3

• O2 in bloodstream diffuses to mitochondria of all cells where it is needed for the production of ATP via oxidative phosphorylation 

• ATP is energy currency, no storage so is needed in continuous supply 

• Catabolism of macromolecules yields FADH + NADH which are oxidised by protein complexes in the mitochondria inner membrane 

what 2 things do redox reactions produce

E,E

• Electrons

They are transported along the protein complexes until they react with O2 and H+ in the matrix to generate H2O

Without O2 as the final electron acceptor, electron flow would stop 

• Energy 

Redox reaction generates a small amount of energy allowing H+ to be pumped into the mitochondria inter-membrane space  

The H+ gradient created across the inner membrane, powers ATP synthase -> generates large amts of ATP 

alveolar partial pressure

pCO2, O2, air

• how much O2 is dissolved in plasma

pO2 - 100mmHg

pCO2 - 40mmHg

pAir - 760mmHg

• 15mL O2/min (henry’s law/ dissolved O2 in plasma = alveolar pO2xO2 solubility) - insufficient to meet body’s needs

protein bound O2

• how much O2 is transported bound to Hb

• what is the graph shape of O2-Hb dissociation curve, why

• what is in each Hb molecule 4×2

• what is the role of Hb 2

• what are the two conformations T,R (what is the affinity for O2 in each)

• 98%

• The sigmoidal shape of the oxygen-haemoglobin dissociation curve is due to cooperative binding of O2 to Hb

Each Hb molecule contains:

• 4 globin proteins: 2 alpha and beta chains 

• 4 hemes: a Fe2+ ion bound to a porphyrin ring 

Roles:

• Reversible O2, CO2 transport in the blood, buffering agent 

2 conformations:

• Tensed (T) state has LOW affinity for O2

• Relaxed (R) state has high affinity for O2

light absorbance of Hb

• what is the difference between Hb and Hb-O2 light absorbance

• why is this useful clinically

• what conditions would affect readings

• how does skin tone affect this

• Hb-O2 and Hb absorb red and infrared light differently, this is compared to a standard curve

• oximetry, finds clinical signs of hypoxaemia, determines spO2

• CO poisoning, abnormal Hb, sickle cell

• darker skinned people might have overestimated oxygen saturation

why is the Hb-O2 dissociation curve SIGMOIDAL

• what state is Hb in at low pO2

  • what is the affinity for oxygen

• as pO2 rises, what happens to the probability for O2 to bind to Hb

• what happens to Hb when O2 binds

• what does disrupting salt bridges do to the subunits

• what does this mean for the oxygen binding sites

• what happens to the Hb form and affinity as pO2 rises

• what happens when Hb is saturated

• T (tense) state, low affinity for O2

• probability for O2 to bind Hb increases

• O2 binds to a subunit and causes a conformational change in the SU

• conformational change causes it to pull on non-covalent salt bridges, linking all the subunits together and change to the R (relaxed) form

• O2 binding sites are more exposed and increases the affinity of Hb

• T state to R state and affinity increases

• max affinity for O2 but all O2 binding sites are saturated, no more O2 can bind to Hb

respiring tissues

• how do they get O2 from Hb

• in low pO2, Hb has a low affinity for O2

• this triggers it to unload its O2

• respiring tissues have low pO2 and high CO2

the bohr effect

• what conditions facilitate unloading of O2 3

• how does this happen

• what does this effect allow

• how does this appear on a graph

• increase in temperature, increase in pCO2 level, reduction in pH

• CO2 and H+ react with Hb causing a decrease in Hb affinity for O2

• allows for increased delivery of O2 in metabolically active tissues

• right side shift in Hb-O2 dissociation curve

• where does CO2 come from in our bodies

• what does RQ tell us, what is it

• by-product of macromolecule catabolism in mitochondria, diffuses out the cell and into the blood

• ratio of O2 consumed and CO2 released = respiratory quotient

  • tells us which macromolecule is being used as a metabolic source

• what are the 3 forms CO2 can be transported as in the body + %

D, B, CC

10%

• dissolved CO2

70%

• bicarbonate

20%

• carboamino compound

CO2 as bicarbonate

• what enzyme catalyses conversion of CO2 into carbonic acid H2CO3

• what happens to carbonic acid (turns into ion)

• what does this ion bind to

• what happens at the lungs

• what is the chloride shift

• carbonic anhydrase

• H+ ion

• binds to Hb to buffer the process

• reverse: H+ dissociates and combines with bicarbonate to make carbonic acid → h2o+co2

• exchange of bicarbonate HCO3- and Cl- across RBC (co2 can diffuse but hco3- needs a protein to leave and exchanged cl-, helps remain charge)

carbamino compounds

• how are they formed

• what is the haldene effect

• why does it happen 2

• CO2 combined with Hb

• describes the ability of deoxygenated Hb to carry more CO2 than oxy-Hb

  • deoxy-Hb forms carbamino complexes more ready with CO2 (this is how it can carry CO2)

  • it is a better buffer than O2-Hb, of H+ ions

in the lungs

• the blood has a high amount of what dissolved 2

• what binds to Hb in the alveoli

• what does this reduce the affinity of

• CA (enzyme) works to do what

• dissolved bicarbonate HCO3-, H+, CO2

• O2 binds to Hb

• reduced affinity for Hb for H+ and CO2 so they unbind

• carbonic anhydrase helps remove co2 from lungs

respiratory centres of the brain

• what type of innervation is responsible

• how is rhythmic activation of resp. skeletal muscles activated

• what 2 inputs modulate ventilation

• where are the neurons in the respiratory centre in the brain

  • DRG

  • VRG

• somatic motor

• intrinsic periodic AP firing by neurons in the brainstem (central pattern generator)

• sensory and voluntary

• medulla

  • dorsal respiratory group neurons are active during normal inspiration

  • ventral respiratory group neurons are active during forced in/expiration

factors modulating ventilation

• emotions

  • where in the brain does it act through

• sensory inputs

  • 3 examples

• voluntary behaviour

  • what part of brain is involved

emotions

• emotional stimuli acts through hypothalamus

sensory input

• pain, temp acts through hypothalamus

voluntary behaviour

• cerebral cortex

what are the two types of chemoreceptors

central and peripheral

central chemoreceptors

• what are they

• where are they located

• why can they only respond to CO2

• where is carbonic anhydrase and what does it do

• how does reduced pH of CSF directly activate central chemoreceptors

• specialised cells that monitor arterial blood gases (PaO2 and PaCO2) and pH levels

• In the medulla oblongata

• dissolved CO2 penetrates the blood-brain-barrier (while H+ and HCO3- cannot)

• in CSF, catalyses the formation of HCO3- and H+ (from CO2 and H2O)

• the H+ made in the reaction stimulates AP firing of chemosensitive neurons

peripheral chemoreceptors

• what are carotid bodies

  • location, which CN

• what are aortic bodies

  • location, which CN

• what is the metabolic rate and blood flow like for peripheral chemoreceptors

CAROTID BODIES:

• Located at the bifurcation of each common carotid artery 

• Afferent fibres of glossopharyngeal nerve CN IX 

AORTIC BODIES:

• Located on the underside of the aortic arch 

• Afferent fibres of the vagus nerve CN X 

Peripheral chemoreceptors have high metabolic rate and high arterial blood flow 

• They are complex structures made of glomus cells, arterioles sinusoids, afferent and efferent neurons 

peripheral chemoreceptors

• what do they mainly sense (condition of blood)

• what increases sensitivity of carotid bodies

• what do glomus cells detect

  • how

• They mainly sense hypoxaemia, a decrease in blood pO2

• a decrease in pH and increase in pco2

Glomus cells detect changes in PaO2 

• Receptor activates and closes K+ membrane channels 

• Depolarisation 

• VG Ca2+ channels -> ca2+ influx -> exocytosis of NT 

• Sensory neurons activated -> AP 

what are short term compensations for a drop in pO2 or rise in pCO2

• firing of AP

• ventilation

• heart rate

• cardiac output

1. Fall in Pao2/ rise in pco2 

2. Increased firing of chemoreceptors 

3. Increased ventilation, increase o2 (decreases arterial pco2 and increase lung stretch)

4. Inhibition of cardio-inhibitory centre in medulla -> tachycardia -> increase cardiac output 

long term adaptations of low O2/ high CO2

• erythrocyte production

  • what detects hypoxaemia

  • what hormone is produced

  • what is a result

• O2 unloading

  • what does low pO2 stimulate in RBC

  • what does 2,3-DPG bind to and do

  • what unloading is increased

Increased erythrocytes production 

• Hypoxaemia is detected by fibroblast-like cells in the renal cortex 

• Activation of hypoxia inducible factor HIF

• Increased transcription erythropoietin EPO 

• EPO stimulates erythrocytes production in bone marrow 

• Increases O2 carrying capacity of blood 

But, can increase blood viscosity and risk of thrombus 

Enhanced O2 unloading at the tissues 

• Low pO2 stimulates glycolysis in erythrocytes and ^ production of 2,3 DPG

• 2,3-DPG binds to Hb and lowers Hb affinity for O2 (right shift in Hb-O2 dissociation curve) 

• Increased O2 offloading 

name:

• inspiratory reserve volume

• tidal volume

• inspiratory capacity

• vital capacity

• expiratory reserve volume

• total lung capacity

• functional residual capacity

• residual volume