Acid base physiology Flashcards
why is pH homeostasis important?
Change in [H+] will effect ionisation state of proteins and can cause denaturing - enzymes, receptors, structural proteins = disruption to cellular functions. including O2 carrying capacity of Hb
disruption to membrane potentials - positive charge will effect the balance inside and out and hence can cause excitability or reduce this. this can alter myocardial contractility and neuronal transmission
H+ ions also cause vasodilation in most vascular beds and vasoconstriction in pulmonary vasculature.
H+ **exchanges with K+ **and causes hyperkalaemia too. which has its only problems in causing arrhythmias and increasing neuronal excitability
define pH
pH is the negative logarithm for hydrogen ion concentration.
pH = -log [H+]
it is used to allow easier interpretation of acidity as H conc is in nanomoles.
since the relationship is logarithmic it is not linear and a 1 fold change in pH is equivalent to 10 fold change in H+
for example a pH of 7 = 10^-7 M
and pH of 8 = 10^-8 M
state the henderson hasselbach equation…
how is anion gap calculated?
anion gap = [Na + K] - [Cl +HCO3]
what is pKa
the pH at which 50% of ions are in dissociated form and 50% are undissociated.
it is the negative log of Ka , which is the dissociation constant ([H][A]/[HA])
pKa = - log [Ka]
it is the measure of an acids strength.
the larger Ka the more dissociated, take the negative logs mean the smaller the pKA, the more dissociated, stronger the acid.
what is the normal pH
7.35 to 7.45
equivalent to 34nM to 46nM
what is normal values for bicarb and CO2?
bicarb = 22 to 26 mM
CO2 = 4-6kpa (5.3kpa)
what is the pKA of different buffer systems?
bicarb = 6.1
phosphate = 6.8
Hb buffer = 7.8
plasma proteins = 7.4
define an acid
by Brownsted lowry definition
this is a proton donor
a molecule that dissociates to form conjugate base and H+ ions
a strong acid fully dissociates
a weak acid partially dissociates
define a base
by Brownsted lowry definition
this is a proton acceptor
a molecule that associates with a H+ to become ionised
(an alkali is a base that produces OH- ions)
define a buffer
A solution that can resist pH changes by reacting with H+ ions or releasing H+
usually consists of weak acid and its conjugate base
as pH / H+ conc chnages it will shift reaction in one direction to buffer the chnages.
what is standard bicarbonate?
plasma conc of bicarb when pCO2 is corrected to 5.3kpa , at 37 degrees and when Hb is fully saturated
it represents the bicarb that there would be once CO2 deviations are eliminated. Gives a cleaner picture of metabolic acid-base disturbances without resp influence
what is meant by the base excess / deficit?
the amount of base required to restore 1 litre of blood to normal pH (7.4) at CO2 of 5.3kpa and body temp of 37 degrees.
marker of severity of metabolic acidosis
if negative e.g. -3 then 3mmol/l of base required to reach pH of 7.4
normal BE = -2 to +2
what does the pKa tell you about when acids and bases ionise?
acids ionise ABOVE their pKA
bases ionise BELOW their pKA
what is the difference between acidosis and acidaemia ?
acidosis = an underlying process that causes acidaemia
acidaemia = blood pH of less than 7.35
can be acidotic without acidaemia
describe how a buffer solution works
slightly wrong in diagram - should say if H+ fall more acid disocciates.
this is know as Le Chatelliers principle = equilibrium shifts in order to minimise change.
derive the henderson hasselbach equation
- write out the equilirbium
- state K1 = K2 at equilibrium i.e the rates of forward and back
- Ka is the dissociation constant i.e. how much of the forward product exists at equilirbium / how shifted to the right
- Ka = [H+][A-} / [HA}
- hence the bigger Ka, the more dissociated, the stronger the acid
- Rearrange this and take logs off both sides
should end up with
pH = pKA + log [A]/[HA]
proove using HH equation that when the pKA is equal to pH the dissociation is 50%
pH = pKa + log [A]/[HA]
pH-pKa = log [A]/[HA]
when they are equal..
0= log [A]/[HA]
10^0 = 1 = [A]/[HA]
hence ratio is 1 so top and bottom are equal
what is a buffer titration curve?
tells you at which pH ranges a buffer is most effective.
pH on y axis
% of acid/base added to buffer on x axis
can read across y axis at what pH the buffer gets exhausted.
what are the characteristics of an ideal buffer?
An ideal buffer system in the blood is one ..
1. present in high enough quantities to work effectively - the more present the buffering capacity
2. pKa is close to physiological pH such that it works optimally around deviations to norm.
3. open system - can be removed at one end/ added at one end. e.g. CO2 removed, HCO3 added to maintain the buffer even when used up.
what is the isohydric principle?
all buffer systems within body are connected by common component = H+
hence if one buffer system shifts to adjust pH it will have an effect on other buffer systems.
they all exist in equilibrium with one another
outline the mechanism for maintaining pH homeostasis
immediate buffering
* buffer systems act within seconds
* main extracellular one is bicarbonate but also phosphate and plasma proteins (carboxyl groups)
* Phosphate is the main intracellular buffer system but again there are proteins including haemaglobin
compensation
* respiratory compensation occurs within minutes
* increased CO2 triggers chemoreceptors in brain to increase MV
correction
* renal correction occurs within next few days
* H+ secretion and HCO3 reabsorption to help maintain pH and restore buffers
* also correction of the issue e.g. cori cycle to remove lactate or treatment of sepsis etc.
how does haemaglobin work as a buffer?
histidine residues on haemaglobin can bind H+.
major intracellular buffer in RBCs
closed buffer system
38 histidine per Hb
its buffering capacity changes depending on if oxygenated or deoxygenated. e.g. oxygenated Hb has pKa of 6.6. hence more dissociated (less bound to H+) whereas deoxyHb has pkA of 8.2 so more bound
part of haldane efect.
explain how the bicarbonate buffer system works..
H20 + CO2 reaction catalysed by carbonic anhydrase which is present in RBC. HCO3 leaves RBC in exchange for chloride
open at both ends - CO2 removed, HCO3 added.
rate of HCO3 reabsorption by kidney depends on H+ secretion which is higher at lower pH.
why is the bicarbonate buffer an effective buffer system?
abdundant
although pKa 6.1 and not close to physiological pH, this is compensated for by it being an open system.
buffers in both directions.
describe the phosphate buffer system..
H3PO4 <–> H2PO4 - +H+ <–> HPO4 2- + H+
main intracellular buffer - more abundant here.
small role as ECF buffer in renal tubules.
how do the kidneys handle acid?
PCT, DCT and collecting duct are main regions for acid/base handling
1. HCO3 reabsorption
2. H+ secretion
3. production of ammonium to act as a buffer
HCO3/ H+
* H+ secreted by primary and secondary AT
HCO3 is freely filtered at glomerulus and then reabsorbed at PCT
* The more acidic the blood, the easier to secrete H+ into lumen and hence reabsorb HCO3
* in DCT and collecting duct similar mechanism occurs however H+ exchanged for K+ instead of Na.
the H+ secreted is buffered by ammonia
* ammonium ions are produced by PCT cells by deamination of glutamate to glutamic acid and oxoglutarate (a-ketoglutarate)
* oxoglutarate reacts with H+ and forms glucose which is reabsrobed by blood (gluconeogenesis)
* NH3 enters tubules and buffers H+ to aid further secretion of H+ into tubules.
* oxoglutarate also indirectly produces HCO3 for reabsorption
how do urinary buffers contribute to acid /base homeostasis?
there are a number of urinary buffers - ammonia and phosphate are the main ones.
- ammonium ions are produced by PCT cells by deamination of glutamate to glutamic acid and oxoglutarate (a-ketoglutarate)
- oxoglutarate reacts with H+ and forms glucose which is reabsrobed by blood (gluconeogenesis)
- NH3 enters tubules and buffers H+ to aid further secretion of H+ into tubules.
- oxoglutarate also indirectly produces HCO3 for reabsorption
how does the liver contribute to pH homeostasis ?
urea cycle - NH3 produced from deamination of aa is combined with CO2 to produce urea normally
in times of acidosis, there is less of this reaction and liver instead produces glutamine to be handled by kidneys to produce more NH3 for buffering and H+ secretion
also produces plasma proteins for buffering
Cori cycle - removes lactate
define anion gap
difference between measures cations and measured anions in serum
should be 8 to 16mM
if raised suggests there are unmeasured anions in the system e.g. lactic acid, albumin, ketones
explain what happens when there are unmeasured anions.
e.g. lactic acid present
H+ from this will react with HCO3 and reduce HCO3
hence anion gap will increase because less HCO3
(the lactate + isnt accounted for in the equation )
can you give examples of raised anion gap?
alcohol
lactic acid
salicyclates
ketones
methanol
uraemia
when is a low anion gap possible?
loss of albumin
hyperchloraemic acidosis
therefore hypoalbuminaemia may make anion gap inaccurate e.g. lactic acidosis to raise anion gap but low albumin lowers it and then appears normal.
what are the causes of acidosis with normal anion gap?
loss of HCO3 , compensated for by increase in Cl
e.g. if CL increases, HCO3 drops -
seen in diarrhoea and HCO3 loss
hyperchloraemic acidosis
renal tubular acidosis
how does renal failure cause acidosis?
failure to secrete H+
failure to reabsorb HCO3
accumulation of organic acids - kidneys arent excreting these as well e.g. lactic acid, ketones
loss of other anions e.g chloride
renal failure may increases anion gap as organic acids e.g. lactate accumulate. may get a hypochloraemia to compensate.
define respiratory acidosis and expalin its causes
respiratory acidosis is a result of increase in partial pressure of CO2 due to respiratory dysfunction
PaCO2 > 6kpa
may or may not get renal compensation
caused by
* rebreathing CO2
* increased production of CO2 - sepsis, MH, laparoscopic surgery
* poor excretion - hypoventilation
define metabolic acidosis
reduction in HCO3 and hence a negative base excess
HCO3 less than 22mM
may or may not have respiratory compensaiton
what are the causes of respiratory alkalosis?
rise in pH due to lowering of CO2
due to hyperventilation - pain, anxiety, iatrogenic, respiratory distress e.g. asthma , altitude
define metabolic alkalosis
a rise in pH due to metabolic component e.g bicarb of more than 26mM
may be caused by loss of acid e.g vomitting, diuretics
what are the different types of lactic acidosis ?
cohen and woods classification
type A = inadequate O2 delivery and anerobic respiration
type B = adequate but cant use e.g. cyanide, inborn errors of metabolism
how does sepsis cause lactic acidosis
sepsis is a severe immunological reaction to infection or cell injury.
the presence of PAMPs and DAMPs activates immunological processes which become out of hand and uncontrolled.
huge surge in inflammatory mediators and cells.
results in more DAMPs and more inflammation etc
systemic vasodilatory response from histamines etc - hypotension and poor organ perfusion –> anaerobic respiration –> lactate
micro clots develop –> ischameia and again lactic acidosis
above = type A lactic acicosis
cells also become sick - mitochondrial dysfunction and cant use O2 = type B lactic acisosis
how does pH measurement differ in hypothermia?
dissociation of acids reduces with temperature.
if blood from hypothermic patient is taken and warmed to measure pH, they will appear acidotic when actually they arent.
also more CO2 dissolved at lower temp, when heated, this will increase partial pressure CO2 - hence lower pH
the blood gas analyser needs to adjust this for body temp of patietn.
how is pH measured?
qualative method - litmus paper
quantatative method - pH electrode
estimation - siggard anderson nonogram
how does litmus paper work?
made of different dyes which change colour depending on pH
universal indicator paper consists of a collection of dyes hence can turn different colours depending on conc of H ions.
explain how a pH electrode works?
2 half cells
reference electrode = silver/silver chloride + KCl solution. AgCl + e- –> Cl- + Ag
measuring electrode = silver / silver chloride electrode + 0.1M HCl buffer solution. pH sensitive glass in contact with blood. pH sensitive glass is negativley charged on both sides(silica) , H+ ions bind and need to be equal on both sides, causes HCL to dissolciate and Cl free to react with Ag. produces AgCl + e- .
kept at a constant temp
potential difference betwen 2 half cells is measured.
how is the pH electrode maintained?
constant temp - 37 degrees
maintainance of membrane and pH sensitive glass - proteins deposit with time and needs removing
2 point calibration at pH of blood and at pH of buffer solutoon
what is the siggard anderson nonogram?
a graphical representation of pCO2 and pH and HCO3
helps to derive one if others are known
can be used to derive base deficit and therefore helps in diagnosis of metabolic acidosis.
using bicarbonate buffer demonstrate the proportions of HCO3 and CO2 when pH is 7.1
pH = pKa +log [HCO3]/ 0.225 xPaCO3
7.1-6.1 = 1
hence 10x more HCO3 than [CO2]
what is normal CO2 value in mmHg?
40mmHg
conversion for partial pressure of CO2 to amount dissolved
mmHg = x0.03
kPa = x 0.225
tell me about carbonic anhydrase
enzyme catalysing CO2+H20 –> H2CO3
found in RBC, PCT of kidneys, aqueous humour of eye and parietal cells
involved in CO2 transport, acid base homeostasis, stomach acid production
Pneumonic for normal anion gap acidosis?
CAG
chloride
addisons
GI - diarhoea, pancreatitis
