2. Acid-Base Physiology Flashcards
What is a buffer
Solution to minimise changes in H+ concentration - when acid or base added
Physicochem process test tube / body
How does a buffer system work
Solution contains weak acid - HA mixed w/ salt of acid & strong base NaA
Salt provides a reservoir - A to replenish A- when removed by reaction with H+
Majority - capacity is maximal at pKa of weak acid
Majority buffering range pKa +-1
What is buffer power
effectiveness of diff buffer compared how much acid or base needs to be added to cause unit change in pH
Buffer power D[B+] / dpH
d{B+] - change conc base
dpH -refers to change pH
Major buffer systems
Extracellular
x 7
Extracellular -
- bicarbonate - highest conc
major ECF buffer - Hb - major buffer H= - prod red cell when HCO3 formed from Co2 & H20
- Deoxy hb >powerful buffer
o2 unloading assist increasing carriage of Co2 - Haldane effect - Plasma proteins - excell buffer - phosphate not important - low conc plasma
- ISF & CSF - low conc buffer
- Calcium bic in bone - signif excell buffer - prolonged disorder
- Urine - Phosphate concentrations are much high
Phos buffer - major titratable acidity urine - protein conc urine low &; protein non important
Intracellular
Proteins & phospates - signif conc & important
hb - intracelll
pKa of phosphate buffer
~~6.8 - very effective buffers - because
total con phos is significant
intracell ph is lower 6.8-7.1 - than excell pH - closer to pka
Why is bic effective buffer in plsam despite pKa far from physiological pH
pKa - bic 6.1 excell ph 7.4 - >1 pH away
‘Open at both ends
Both pCo2 & HCO3 - can be altered - minimising change HCO3/PCO2- henderson hasselbach
excretion Co2 - lungs mainta constant Paco2 - increases effective as a buffer -change co2 can occur rapidly
Why is Hb a more imporant
Hb 6x more important quantitatively
1. Conc x2 - proteins 150g v 70
- Each hb contains x3 histidine residues than acg plasma
imidazole group is the only AA provides buffering at phys Ph - average pKa 6.8 present proteins
Note bic cant act effective buffer H ion formed during formation of bic - hb predom buffer H= from source
Hb& bic can occur red cell
Bic aids vuffer metabolic acid ecf - transfer of bic out necessary Rc
Affects buffering capactiy hb
- pH solution
- state oxygenation - haldane
- Hb concentration higher Hb - more buffering capactiy per unit volume
More reduced Hb on venous circ - more buffering capacity - required increased H formed Co2 - bic carbino
Reduced hb is weaker acid
Deoxy hb 3.5 times more effective than oxyhb - formation carbamino compounds - increased formation of carbamino comp increased capacity buffer
No - carbamino compounds produced reaction Co2 - terminal amine groups each hb chanin
result production carbamic acid ;pw pka - plsam ph intracell ph - acid almost complete dissoc
form carb - small net increase H= - H= require buffering
Formation carbamino not affect buffering capacity Hb - a/w increase H+ conc
Carriage Co2 - bic & carbamino increase H+ - buffered histidine
Define pH
Negative log H+ conc
effective concentration or activity -
pH glass electrode - respond activity rather than concentrations
pH -Log 10 aH+
AH+ activity hydrogen ion
pKa
Ka - equil dissoc conc for dissoc acid Ha prod H= & acid anion A- {HA<=> H+A-]
pKa neg log to base 1- of dissoc constant
ph equal to pKa - acid is 5-% dissoc
ie equal amount Ha & A
Why is Hb > important carry co2 than plasma protein
- Concentration 150 v 70
- Mol wt alb & hb close - hb treramer each mol con 4N term groups - compare 1 alb
carbamino compound form w/ N terminal - Abil Hb form carbamino compound increased 3.5 times becomes deoxygenated - situation peripheral capillary
Volatile acid
carbon dioxide which can be excreted by the lungs - ketones -> excreted partly lungs - volatiles amount small
Fixed acids
Fixed or metabolic acids - excreted kidneys phosp/sulphuric or metab body - lactic
Carbon dioxide an acid
Not -bronsted lowry a/b system
Molecule Co2 can be converetred to carbonic - co2 repesenting portenial produce equal amount acid
what is a bronsted lowry acid
acid donate hydrogen ion to another sub
donor - conjugate acid - acceptor conjugate base
more comple than arrhenius sytem - acid defined capable H ion aqeuous soltuin
CO2 not acid - doesnt cotain H
Co2 - acidic propertys not H
Lewis - anycompund that was a potential elctor pair acceptor
Bronsted lowry - carbonic acid is the acid & not CO2
a-b discussions co2 - acid when dissolced exhibt acidic proerty
Resp excretion dffierent to renal excertion
Excretion via lung more rapid - amount acid deal lung 20000mmol day large v fix acid load kidney 70mmpol day
Co2 only acid excrete lung
excretion co2 rapid
system high capicty
Respiratory regulation of AB balance
Ventilation - rapidly - cause pH change all compartment co2 cross membranes easily
change ventilation alters paCo2
Change Paco2 alter pH
Change alveolar ventilation inversely related to change in art PCO2:
PaCO2 = K x Co2/Ca
Art partial pressure co2 paco2, vco2 - co2 production, va - alveolar vent k - propor constan
Change alveolar ventilation inversely related to change in art PCO2:
equation
PaCO2 = K x Co2/Ca
Art partial pressure co2 paco2, vco2 - co2 production, va - alveolar vent k - propor constant
Change in arterial pco2 cause change in pH
pH = pKa + log [HCO3] . .03 x pco2
How does the body sense & respond to change in arterial pco2
Central chemo rec
Medulla - sep resp centre
change H+ conc - adjacent brain ecf
Co2 - x bbb - immed change in brain [H+]
Stim resp centre increase ventilation - H+ rises
Systemic metabolic acidosis - not cause immed stim of central chemo - neither H+ nor acid anion can x bbb
equilib of hc03 - slowly - metabolic will eventually csf h change - central stim
Peripheral chemo
aortic carotid body - respond change art po2 pco2 ph
Ventilatory response to increase in art pco2 - 80% central 20% periph
Periph more important - may respond more rapidly to acute changes
Overall ventilatory respond to change in arterial pco2 - rapid & effective under normal circumstances
Ventilation increase - 2l/,in for mmHg rise art pco2
size increase - vary
cartoid sinus is a
carotid body is a
sinus = baroreceptor
Body = chemoreceptor
Carotid body IX - sensitive O2 Co2 & pH
What are the major routes excretion for acid from body
lungs gas
kidney urine
Term used to describe acid exreted in urine
Fixed acid / metabolic
Major processes involved in renal a-b excretion
Reabsorption of bic
Net excretion H and acid anion body
Processes
Secretion of H+ in prox tubule - respons reab 90% filtered bic
Secretion of H+ into distal tubule - H+ mostly buffered by phospahte buffer =- responisble for some bic reabs
Secretion of NH4 into prox & dist
What is the source of H ion secreted into proximal tubule
H+ is produced from hydration of Co2 in reaction catalysed by carbonic anhydrase
present in cytoplasm of prox tub cell & brush boreder of mminal membrane
H+ actively transpiorted into prox tubular lumen
Main function of secretion of H+ into prox tube
Reabs filtered bic - filter bic 4-5000 mmol/day
Calc as product of GFR & plsam HCo3 conc - 180l day x 24mmols
Filtered bic - reacts w/ secreted H+ in presence brush border carbonic anyhdratse - co2 & water co2 lipid solbue - diffuse into prox tubular cell
Filtered bic - elim & replaced by bic produced in cell in reaction which genereation H- secreted into lumen
bic aenter blood stream across BLmembrane
large secretion Hion not lead net exretion H body - net effect prevent acidfiyin effect loss of bic
What is the effect of H ion secretion On Na reabs in prox tubule
Na cross luminal membrane into prox tubule - x2 ways
- Diffusion thru Na channel
- Carried mediated facilitated diffusion thru luminal membrane
cotransport - glucose & AA
countertport against H secretion
Na moves down electrical & concentration gradient to enter cell
Active tport Na out - BL membrane - energy drives reabsorptionNa @ luminal membrane - secondary active transport - water reabsorption here & thru kidney passive in response to osmotic gradient
65% filtered Na load reabs in prox tubule
90% hco3 reab prox tubule
Prox tub tport H a/w 1/4 Na reabs
Exchange H & Na - electoneutrality - net effect section 1 mol H tfre 1 mol Na & 1 mol Hco3 peritubular
Why is proxtimal tubular system for H - ‘High capacity / low gradient sytem’
High capactiy - total daily secretion of H+ 5000 large
low gradient - limitng pH prox tubule 7.0 so max gradient only 60nmole
What is source H ions ecretd into distal
Reaction CO2 & H20 - carbonic anhydrase
Prod H & HCo3
H secreted tubule intercalated cell
Main function of the secretion of H ion into distal
Net acid excretion
High rate secretion H - nearly all converted water - no net excrretion urine from site
Distal tubule - lower rate secretion ~70 - this account nearly all H excreted
Why is distal tubular low capacity high gradient
low gradient cause 70-100 mmmoles day
High grad max h gradient about 3 pH units - high than prox tubuule
What is lowest urinary pH achievable
4.4
What is the gradient hion across the distal tubular cell
pH diff 3 - means max H gradient accross teh tidtal tubule cell
what are the buffers in the distal tubular fluid
Phosphate & ammonium
Where does the ammonia come from
Glutamine & gultamate
Ammonia split from gulatmine - rxn catlyse gyltaminse
Mostly proximal tubule
Ammonia total present as ion Nh4 as pKa very high
Mostl removed LO
if pH low in ditsal tubule - augment trasnfer meddulary interstitum into dital tubular fluid
Mostly produced prox tubule cell
Medullary cycling proccess - removed LOH enter medulla - some renter late prox tubule - some enter medullary collecting duct
Why doesnt ammonium ion contribute to titratable acidity
Ammonium ion charged Nh4 - water soulbe
not lip solube
trapped in tubule lumen
pKa - high - enterile ionised almost
titrating urine pH 7.4 - not release any H from NH4
Contribution - determined only measuring amount ammonium present
Creatine important urine buffer?
Normally no
pK 4.97 - so low urinary pH higher
Diff if pH low - max acidity 4.4 - can 1/4 titratable acidity
dKa beta hydorxybutyrate 0 excreted large amount in acid urine - large part titratable
Total amount fixed acids per day = renal excretion
Body produce 1-1.5 `mosm / kg/ day 70-100 of fixxed acids require renal excretion
normal circmstances - acid involed mostly phos & suplhate
Lactate is higher 1500 metabolised or converted back to gluc and not excreted
What is hyperncapnia
arterial pCo2 >44mhg =5.8kPa
Why does it cause physiological effects
- Co2 crosses lipid barriers - ease obtains rapid entry all cell
- Rapidly reacts with water - intracellular acidosis
- Intracellular acidosis - adverse effects on enz/metab
- buffering minimise change pH
Due to hypoventilation normally - typically a/w hypoxia - exerts effects
cns effects of Hypercapnia
Co2 cross membrane - intracellular acidosis
Affects all cell - nervous cvs 8 resp predom clinically
Cerebra;
- Increased CBF
- Increased ICP
- Potent stimulation of ventilation
- . Sympathetic stim
- central depress very high >100mmHg
- A/w hypoxia - also effects
for ever 1 rise in mmHg - CBF increase 4% -
MV increase 1-3l.min
Stim - correction
if its a compensatory to met alk - cent depressed
inadeq alveolar vent - most causes
CVs hyperncapnia
Indirect effets
- Sympathetic stimulation]
- Coexistent hypoxia
- Underlying illness medication
Direct 1. Increased BF 2.general peripheral vdiln 3. depression myocardium 4. Increased arrytyhmia
CVs effects - balance by direct and inderect
warm flushedsweaty tachy w/ boundy pulse
Adverse effects of hyponcapnia
Ref range art pco236-44
pH 7.36-7.44 = [H+] - 44-36
Adverse effects of hypocapnia
- Shift oxyhb dissoc curve left
- increase iaffinity - impair delivery - Decrease Serum - acute alk - small decrease
- Decrease CO -
myo contract decrease slightly w/ acute alk - Decr CBF (desired neuro_
Decrease 4% mmHg - decrease art pCo2 - down to 15 - Resp depression
Intraop hypocapnia - obligatory hypoventilatiion @ end-
Implication for CBF end of procedure
Hypoventilation - allow pco2 - rise - increase cbf - exceed preop
Continued hypocania - decrease cbf dimin time
Circ d/t ISF pH rather than Pco2 - 6-8h hypocap - bic almost requil bbb increase brain ISF conc -
restore isf pH normal - cbf normal
Rise art Pco2 - increase CBF hgiher than normal
ICP increase - exacreb depression of ventiolaion - opoiod
Main causes of hypoxaemia end of anaesthetic
- Hypocapnia - resp depression
central depressin agents
resp centre depress - narctic
diffusion hypoxia
Redduced FRC d/t aneaes
upper airway obstruction
resp musle weak - inadeq reversal
bronchospasm - aspiration
- lung collapse
Low inspired pO2 hypovent shunt v/q diffusion
Diffsuion hypoxia - outpouring insol NO into at end reduced alvoelar po2
interpreation of abg
Full interp - patient history
speculation
Acidosis - w/ acidaemia - low bic low
Alveolar gas equation
PaO2 = PiO2 - PaCo2/R
How could metabolic disorder quatnified
Use of base excess
comparing actual & expected PCo2
How much vic decrease normal - most excell buffer bic - fall hco3 = equivalent amount acid hidden
Altered bic
1 compensatory change pco2 - cause change measure bic
2 if pre exist met acidosis - measured bic metraolic acidosis can be higher than 24
uncomplicated metabolic acidosis - measure value plasma bic - simple approach
Is it a simple / mixed acid base disorder
expected PCO2 formula
Mixed - 2/+ disorders
Resp disorder on top?
Determ ventilatory compensation appropriate
- if compensation maximal - expected pco2
exp pco2 = 1.5 x bic + 8
mmHg
actual pco2 - same - suggest max compenation no respiratory compenent
Resp compensation can take 12h
Combo met acidosis - dka+lactic
Further Invx metabolic acidosis
Urine test - glucose / ketons
blood gucose
Urea & creat
Na * Cl - anion gap
lactate
Common causes of HAGMA
Lactic acidosis
ketoacidosis
Renal failure
Toxins
Normal anion gap acidosis
Loss of HCo3 from ec Chlroide excess addisons/acetozolamide Gi Extra
Infusion 1N HCL
1n HCL central line - load 100mmols of H+
Sufficent met acidosis
Defence against change
buffering
compensation
correction
Buffering
Rapid process - titration body acid ecf buffer - bic
biv 24 ecf vol 19 - pool 450
acid load 100 titral bic buffer to 18.7
assume all vuffer aecf - by bic
Compensation
met acidos - periperhal chemo = Inc ventilation
hypocapnia - phys compesn response - cant take 24h reach max
Comepnsation not return ph complete normal
Expected pco2 = 1.5 X[HCO3] + 8
Pco2 is arterial pco2 and bic mmol abg
Correction
Kidney excrete excess Acid anion Cl- equilvaent reabosprtion of bic & excretion acid - normal AB status restored - slower
Other physiological effects acid infusion
right shift o2 dissoc - o2 unload
aAG - unchgen acidos hypercholaemic
Met acids - not x bbb - brain non signaif - perph chemo for resp
Hyper H -K exhchange across membrane - urine K loss increased
Hypcapn - intracell alkaosis - depress cell activityy
why is rep compesation 12h
Perpheral chemo - hypercent
Result decrease H around central chemo as Co2 can diffsue
Central - medaited injuib limit rise vent
bic equilivrates slowly across bbb & H increase & removed central inhibition
Causes of normal anion gap acidosis
Hyperchloraemic
GIT acute severe diarrhyo admin acid salt obstruct ileal conduit ureteroenterostomy drain panc / biliary secretion
RTA
carbonic anhyudrase inhib
isterstil renal
recov DKA
Infusion of 8.4% sodium bic
what is its osmoliaty
2 osm/kg 2000 mOsm kg
7x plsama osmalilty
8.4NaHCO3 - one molar solution
each molecule dissoc into two particles - in soltuion so osmolality is double the molality
Effects infusing 8.4% sodium bic
Hypertonic
alkanising
Na restrict distrib of admin solution
hypertonic nautre - draw water out cells until ecf icf equal- increase ecf volume greater than vol admin
ECF Na conc - increase dep amount of solution admin
water drawn will minimise increase
Na bic - occasionaly recommend actue hypo
ECF [HCo3] incrase - exog admin base 0 met alk
K move intracell ecf K decrease
Basis rx hyperkalameia
Normally - plasma bic>27 - hco3 rapdiyl exccrete urine - actue met alkalosis - rapidly correct unless additioanl factor maintais
ADH levels increase 0if tonicty 1-2 rise
sense hypotahlamic osmorectpor
incrase blood bol - 10
5 - low pressure barorcep inhib adh rel - net result balance on effects
Increase blood vol d/t infusion fall in pslam oncotic pressure & h2o reabs in prox tubule decrease slihgly d/t glom tub imbal - small percent decrease in proc tubule - large increase urine flow
