O2/CO2 transport and acid base balance

blood gas transport

• combination of O2 and Hb in the lungs

  • loading

• release of O2 from hemoglobin at tissues

  • uploading

→ reversible runs

• CaO2 = (SaO2 x Hb x 1.37) + PaO2 × 0.003

  • SaO2: arterial O2 saturation

  • PaO2: partial pressure of O2

    • pressure is important ot maintain arterial components

• partial pressure of O2 dictates affinity of O2 to Hb

  • drop favours unloading of O2 on Hb

• decrease in pressure nad increased unloading ti increase O2 at tissues

  • relationship between partial pressure of O2 in blood and relieve satiation of haemoglobin with O2

    • oxygen-hemoglobin dissociation curve

  • steep portion of curve up to PO2 values of 40mm Hg

    • gradual rise to palteau

O2 dissociation change with pJ

• impairs O2 delivery to tissues

• as we exercise we decrease pH and increase uploading at tissues 

  • use of glycolysis ot deliver O2 and favour transport into system 

O2 dissociation change with temperature

• increased temp increases O2 release at molecular level

  • alters affinity of O2 carrying capacity 

CO2 movement from tissues into the blood 

• CO2 is released from cells and moves into the blood

• transported in 3 forms

  • dissolved CO2

  • CO2 combined with Hb → HbCO2

    • transports through pressure gradient quickly → carbinohemoglobin 

      • shifted along important buffering pathway 

  • bicarbonate

    • as HCO3 moves out of the RBC, Cl moves into the RBC to maintain a balanced change in the cell

• increase PCO2 causes CO2 to combine with H2) to form carbonic acid

  • catalyzed by carbonic anhydrase found in RBC

  • carbonic anhydrase then dissociates into a H+ and HCO3= ion

    • H+ binds ot Hb and HCO3- diffuses out of RBC into the plasma

movment of CO2 form blood into alveolus of the lung

• at time of CO2 release in lung there its ‘reverse chloride shift” and carbonic acid dissociated into CO2 and H20

• removal of negatively charged molecules is avoided by the replacement of bicarbonate with Cl which diffuses from plasma into RBC

  • exchange on anions occurs in RBC as blood moves through th tissue capillaries nad s called chloride shift

Carbond Anhydraze

• converts H+ to carbonic acid 

• blacks estimation increased rate of breating 

  • ventilation remains high 

• low O2 sitmulates chemoreceptors 

  • decreases CO - chemorecpeotrs also influence 

rest to work transitions

• icnrease metabolic work 

  • increased VE

  • increased  PCO2 

    • muscle working anaerobically 

  • decreased O2 

    • taken out of arrival system - not sufficient 

  • increase CO2 production 

• arterial pressure of PCO2 and PO2 are relatively unchanged during steady-state sub maximal exercise 

  • arterial PO2 decreases and arterial PCO2 tends ot increase slightly in transition from rest to steady state exercise 

• increase in alveolar vneitaltion at start of trnaotions 

ventilation during incremental exercise

• ventilatory threshold is difference in trained and untrained indivudals 

  • pH response increases as buffering system increases 

    • can exercise at rate when pH drops even more

• PO2 values differ in trained and untrained 

  • efficiency to use O2 at tissue levels 

• decreased VE at given or similar relative intensity 

  • preserves VQ match

• in both subjects, ventilation increases as a linear function of O2 uptake up to 50-70% of VO2 max where VE begins to rise exponentially

  • VE inflection point has been called ventilatory threshold 

PO2 in untrained individual during incremental exercise 

• able to maintain arterial PO2 within 10-12 mmHg of normal resting value

PO2 in trained individual during incremental exercise 

• decrease of 30-40 mmHg during very heavy exercise 

• drop in arterial PO2 viewed in athlete is similar to that observed in exercise of patients with severe lung disease 

  • only 40-50% of elite male endurance athletes show this marked hypoxemia 

    • the degree of hypoxemia observed in these athletes during very heavy exercise varies considerably among individuals 

      • the reason for the subject differences is unclear 

• female endurance athletes also develop exercise-induced hypoxemia 

  • incidence at a higher rate than males

CO2 ventilatory threshold

• VE increase at a linear function of arterial PCO2 with each increase in exercise

  • 1 mmHg rise in PCO2 results in a 2L/min increase in VE

  • increase in VE that results from a rise in arterial PCO2 is likely due ot CO2 stimaution of both carotid bodies and central chemoreceptors

O2 ventilatory threshold

• point of the PO2/VE curve where VE begins to rise rapidly is called hypoxic threshold

  • usually occurs around an arterial PO2 of 60-75 mmHg

  • chemoreceptors responsible for the increase in VE following exposure to low PO2 are carotid bodies because the aortic and central chemoreceptors in humans do not respond to change in PO2

motor control of ventilation 

• motor control of respiratory muscles is controlled by respiratory control centres in the 

  • breathing centres regulate ventilation so that it matches metabolic rate

  • change ventilatory rhythm and rate 

• amount of CO2 produced and mount of O2 required for metabolism 

  • afferents 3 + 4 modulate response of rate 

    • as we exercise brain interacts with all of this

• clusters of neurons located in medulla oblongata of brain stem controls both rate and depth of breathing

• normal rhythm of breathing occurs via interaction of all 3 regions

• interaction between respiratory neurons to control breathing involves feedback from a variety of locations to achieve precise control of breathing

PreBotC

• PreBotzinger complex

• neural inspiratory pacemaker

  • primary resting pacemaker

• stimulates motor neurons responsible for activating diaphragm and external intercostal muscles

RTN/pFRG

• regulated expiratory ventilation

• controls active expiration

• activates rectus abdomens and internal intercostals

  • expiatory muscles

pons

• pontine respiratory centre that fine tunes breathing 

  • ie. neuron cluster

• communicates with both preBotC and RTN/pFRG to fine tune breathing by regulating both rate and patterns of breathing

ventilatory regulation at rest

• inspiration and expiration produced by contraction and realization of diaphragm during quiet breathing 

  • occurs by accessory muscles during exercise 

• direct ontrol by somatic motor neurons on SC 

• motor neuron acitvity is directly controlled by respiratory control centre located in medulla oblongata 

• rhythm of breathing dominated by pacemaker neurons in preBotC 

• expiration is largely passive due elastic properties of lungs and chest walls 

ventilatory regulation during exercise

• preBotC interacts with pontine respiratory centre and RTN.pFRG regulate breathing ot match metabolic requirements

input to respiratory control centre

• input from both high brain centres and afferent neural signals from several locations 

• neural and humoral input 

  • neural input from higher brain centres or afferent input ot respiratory centre from enrols excited by other factors 

  • humoral input to respiratory control centre is influenced by blood borne stimuli reaching specialized chemoreceptors 

    • react to strength of stimuli and sends appropriate message to medulla

peripheral chemoreceptors

• arotic bodies 

• carotid bodies

aortic bodies

• located in arctic arch and bifurcation of common carotid artery

• response ot changes in pH and PCO2 

• capable of sensing changes in blood CO2 

  • role in control of breathing both at rest and during exercise 

carotid bodies

• what is going into the brain 

• response to change in pH, PaCO2 and PaO2 

• sensitive to increase in blood potassium levels, NE, decrease in arterial PO2 and increase temp 

  • more important in control of breathing during exercise 

Central chemoreceptors

• pRFG/RTN - respond to changes in PCO2 and pH in the CSF

• increase in either PCO2 or H+ of CSF results in central chemoreceptors sending afferent input into respiratory centre to increase ventilation 

• no O2 receptor - more concerned with CO2 

  • increased CO2 in brain neurons produce CO2 building up arterial CO2 reducing diffusion along a gradient 

    • need to slow cerebral metabolism

    • acidosis provokes neuronal degradation

      • stimulates breathing and improves O2 intake nad CO2 outage

neural input ot respiratory control centre

• impulses from motor cortex can activate skeletal muscle to contract and increase ventilation in proportion to exercise being performed 

• neural impulses originating in motor cortex passes through medulla and “spills over” causing an increase in ventilation reflecting number of MU recruited 

• additional input to respiratory control centre comes from stretch receptors in the lungs 

• these receptors are sensitive to strength in the the lungs and responsible for Hering-Bruer equation 

  • limits dept of inspiration 

  • limits inflation of the lung 

  • depends upon stitch receptors within walls of bronchi and bronchioles of the lungs 

  • action potentials generate in stretch receptors when lungs are inflated and passed along the inspiratory neurons in medulla oblongata 

    • single inhibits inspiratory centre and expiration outflows 

ventilation control centres

• central command initiated VE increase during moderate intensity exercise through afferent neural pathways 

  • increase VE prior to exercise 

• respiratory control centre 

  • modulation of signals 

• increased E and NE stimulate carotid bodies to increase VE 

  • ie. ventilatory drift

• respiratory muscles

  • stretch of muscles

• labrous breathing affects signal to brain

• increase in ventilation during moderate intensity exercise occurs through interaction of neural and chemoreceptor input ot respiratory control centre

  • efferent neural mechanisms from higher brain centres produce initial drive ot breath during exercise

  • humoral chemoreceptors and neural feedback from working muscles precisely match ventilation with amount of CO2 produced via metabolism

  • redudancty in control mechanisms due ot importance of repsiration in maintaining steady state during exercise 

• chemoreceptors (group 3 +4 afferent fibres) and mechanoreceptors 

influences of training on ventilation

• training lowers ventilation at similar relative intensistke to pre training

  • lower acidosis 

  • lower CO2

  • less afferent feedback from working muscles

  • lower O2 demands

• trialing effect due ot changes in aerobic capacity of locomotor skeletal muscles

  • results in less production in H+ loss (reduced acidosis) and less afferent feedback which reduced stimaution to breathe

acid

• brown-stead Lowry definition: molecules that can donate H+

  • acids increase the H+ [] in a solution

• lactic acid is a strong acid

  • acids that give up H+ more completely

base

• brown-stead lowly denenfition: molecule capable of combining with H+

  • decreases H+ [] a solution 

    • increases pH 

• bicarbonate is a strong base 

  • ionize more completely 

acid producers

Exercise induced production fo CO2 and H2CO3 in working skeletal muscles

• CO2 is end product of oxidation of CHO, fats and proteins

  • Acid due to abiltiy to react with water ot form H2CO3 which in turn dissociaed to form H+ and HCO3

Exericse induced production of lactic acid in working muscle

• Production of lactic acid in muscle during heavy, very heavy and severe exercise is key factor cuasing decrease in muscle pH

Exercise induced ATP breakdown in working muscles

• Breakdown of ATP do energy during mm contraction results in rleease of H+ ions

  • ATP + H2O -> ADP + HPO4 + H+

 

Contracting muscles can produce H+ from several sites

Cause of exercise indued aciosis due ot production of H+ ions from several different souruces

acid buffers

• intracellular buffers

  • cellular proteins

  • histidine dipeptide - carnoside

  • phosphate groups 

  • bicarbonate 

• extracellular buffers 

  • bicarbonate 

  • hemoglobin 

  • blood proteins

cellular proteins

• contain histidine with ionizable group that can accept H+

  • combination of H+ with cellular toeing results in formation of weak acid protecting against a decrease in cellular pH

carnosine

• dipeptide anserine - methylated analogue of carnoside

  • carnoside is important buffer of muscle fibres

phosphate groups

• dihydrogenphosphate - H2PO4-

• monohydrogenphosphate (HPO4-2) → weak base

  • important in beginning of exercise

bicarbonate

• both intra- and extracellular buffer

• useful during exercise 

• most important extracellular buffer 

  • increase in bicarbonate results in better performance outcomes 

  • CO2 + H20 ←> H+ + HCO3

hemoglobin

• major blood duffer during resting conditions 

• 6x buffer capacity of plasma proteins due to high []

• deoxygenated hB is better buffer than oxygenated Hb 

  • after deoxygenated in capillaries better ability to bind to H+ ions when CO2 enters blood to form tissues 

    • minimize pH changes caused by loading CO2 in the blood 

blood proteins

• Hb is the greatest contributor

• album is also used to maintain pH in blood via alteration of H+ ions

Henderson-hasselbalch equation

• Abiltiy of biocarb and carobic acid to act as buffer system described by equation

• pKa is dissocation constant for H2CO3 and cosntant valeu of 6.1

• pH of a weak acid solutation determined by ratio of [] of base in solution to [] of acid

• Normal pH of arteiral blood is 7.4

• Normal ration of bicarbonate to carbonic acid is 20 to 1

muscle pH Homeostasis

• Regulated by transport of hydrogen ions from muscle fibers into intrsitial space

  • H+ ions then buffered by ECF and blood buffers

• NHE and MCT move H+ across the sacrolemma

  • NHE moves Na2+ into the muscle nad hydren ions out of th muscle into the intersitiaitl space

    • Moves 1 H+ out for 1 Na2+ ion

  • MCT - human sk. Mm. has two MCTs MCT1 and MCT 4

    • 1-to-1 co-transport of lactate and H+ out of the muscle fibree

    • Carry one lactate molecule and one H+ ions across sacolemma

  • Important in regualtion of muscle pH udring high intensity exercise

respiratory buffering

• carbonic acid dissociation equation

  • CO2 + H20 ←> H2CO3 ←> H+ + HCO3

• when pH decreases

  • H+ increases

  • reaction moves to the left

  • CO2 is “removed” by lungs eliminating and stabilizing pH if CO3 buffering and expiration exceeds production of CO2 and H+

• Ve increases as linear function of arterial PCO2

  • 1mm Hg rise in PCO3 results in a 2l/min increase in Ve

  • Increase in Ve that results from a rise in arterial PCO2 is likely due to CO2 stimulation of both carotid bodies and central chemoreceptors

renal buffering

• important in long term acid base balance 

  • kidneys do not play a key role in acid base balance during exercise 

  • blood flow decreases during exercise 

    • therefore not able to constantly regulate 

• kidneys contribute at rest through regulation of bicarbonate concentration in blood 

  • when blood pH decreases bicarbonate excretion is reduced 

  • when blood pH increases bicarbonate excretion increases 

  • longer process in response to chronic shifts in acidosis and alkalosis 

    • chronic hypoxia stimulates carotid, increasing ventilation and reducing CO2 

      • this causes a “yo-yo” in ventilation 

•  Kidneys reghualte H+ [] by increasing or dec reasing bicarbonate []

  • When pH decrease in body fluids the kiney responds by reducing rate of bicarobonate excretion

    • Results in increase in blood bicarbonate []

      • Assists in buffering the increase in H+ ions

• When pH of body fluids rises (H+ ion [] decreases) the kindeys increase rate of bicarb excretion

  • Changes amount of buffer present in body fluids

    • Kidneys aid in regualtion og H+ ion concentration

• This mechanisms located in the tubule and acts through a series of reactions and active transpost across tubular wall

• Takes a long time to respond - several hours therefore too slow to be a benefit during exericse

buffering during exercise

• buffering of H+ in the muscle

• buffering of lactic acid in the blood

buffering of H+ in the muscle

• 60% by intracellular proteins 

• 20-30% by muscle bicarbonate 

• 10-20% by intracellular phosphate groups 

buffering of lactic acid in the blood

• bicarbonate is major buffer

  • increases in lactic acid accompanied by decreases in bicarbonate and blood pH 

• hemoglobin and blood proteins play a minor role

changes in pH during exercise

• better removal of CO2 through extracellular buffering

• changes in blood and muscle pH during incremental exercise test 

• blood pH follows similar trends during exercise but muscle pH remains around 0.4 to 0.6 pH units lower than blood pH 

• Gradient in pH from muscle to blood occurs because muscle hydrogen ion [] is higher than that of blood and muscle buffering capacity is Lowe than that of blood 

changes in arterial acid base and pH during exercise

• bicarbonate is stable until 60% VO2 max

  • bicarbonate decreases as turining into carbonic acid

• at 50-60% of VO2 max blood levels of lactate begin to increase nad blood pH declines due to rise in H+ ions in the blood 

• increase in blood H+ [] stimulates central chemoreceptors in medulla nad peripheral chemorecpetrsd on carotid bodies 

  • then signal the respiratory control centre to increase alveolar ventilation 

    • ie. ventilatory threshold 

• increase in alveolar ventilation results in reduction of blood pCO2 and acts to reduce acid load produced by exercise

respiratory compensation

• process of respiratory assistance in buffering lactic acid during exercise

buffering during exercise

• control of acid base balance uniting very heavy and severe exercise is important 

• high intensity- above lactate threshold 

  • contracting sk mm produces significant amount of hydrogen ions 

• first line of deference against exercise indued acidosis resides in muscle fibre 

  • ie. bicarbonate, phosphate and protein buffers 

• limited muscle fibres buffering capacity 

  • additional buffer systems are required to protect body against exercise 

    • induced acidosis 

• second line of defence against pH shifts during exercise is blood buffer system

  • ie. bicarbonate, phosphate and protein buffers 

• increase in pulmonary ventilation during intense exercise assists in eliminating carbonic acid by “blowing off CO2” 

  • respiratory compensation to excise-induced acidosis plays important role against pH change during intense exercise 

• first and second line defence protect body against exercise induced acidosis 

• during exercise we improve MCTs which stimulates production of carbonicanhydrase which helps to buffer 

supplementation and acid-base regulation 

• diets low in acids can increase plasma pH but do not improve performance during very heavy or severe exercise 

• some sports regulatory agencies have banned use of sodium buffers during competition 

• exercise period of 2 weeks → 2 week washout period → 2 week exercise period 

  • exercise people either determination of Critical power or intervention period 

    • randomized order 

    • deterrmined CP

    • placebo or sodium bicarbonate 

• comparison of NaHCO3 over 5 days

  • not much change

  • except for plasma volume 

• comparison of placebos

  • VO2 - no diference

  • VCO2 - small change

  • RER - not really lower 

  • HR - HR was slightly lower

• most change occurs between 0 + 1 days 

  • does not look like much change overtime 

  • day 3 - plasma volume hadn’t changed much

supplementation with sodium citrate

• improves extracellular buffering capacity and can improve performance during high intensity exercise

  • lasting 120-140mins

• large dosses can cause alkalosis and promote nausea/vomiting

supplementation with beta-alanine

• precursor to carnosine synthesis 

• carnosine serves as an intracellular buffer and can icnrease time ot exhaustion during high intensity exercise 

  • lasting 1-4miins 

• only known side effect is parenthesis 

  • tingling of skin 

  • rapid capillary vasodilation 

• increased intake may alter blood flow to muscles and BP