Acid base theory Flashcards
pH =
pKa + Log 10 (A-/HA)
Base acid base equation
HA + H20 –> A- + H30+
Arrhenius definition of an acid
acid produces H+ ions in solution
Arrhenius definition of a base
contributes hydroxide ions to the solution
Arrhenius acid reaction equation
- HA → H+ + A-
Problems with Arrhenius definition of acid base (3)
◦ Hydrogen ions isolated is not really seen, instead H20 has such an affinity that it forms H30+
◦ Solvent must play a role - does not account for anything other than water
◦ Salts dissociate into non neutral solutions
Bronstead Lowry thoery of acid base works well for?
- Suited to discussions of acqueous solutions and protic acids
Why is the Bronstead Lowry definition an improvement on Arrhenius?
- Improved from Arrhenius definition as dissociation was no longer mandatory
◦ Thus, the acid HA actually contains a “conjugate base”, i.e. the A- which holds the proton in the absence of a solvent.
Bronstead Lowry acid definition
- Acid can donate a hydrogen ion to another substance
◦ Then other substance is the acceptor and the conjugate base
◦ The donator is the conjugate acid
Bronstead Lowry base definition
- Base is a chemical species having an available pair of electrons capable of forming a covalent bond with a hydrogen ion
Problems with bronstead lowry theory of acid base
- Problems
◦ No definition of neutrality
◦ Still focused on protons - does not explain CO2 or SO2
◦ Favours polar solvents
Lewis theory of acid base
- Acid - any compound that is a potential electron pair acceptor / forms covalent bond with electron pair
- Base - vacant orbital of some other species
Types of acid - voltaile and fixed mean what?
- Volatile acid
◦ Carbon dioxide can be excreted by the lungs - Fixed acid
◦ Non volatile acids, excreted by the kidneys (phosphoric and sulphuric) or metabolsied (lactate)
‣ Lactate 1500mmols made per daybut metabolised back to glucose by the liver
What does pH mean
pH is the negative logarithm (base 10) of the hydrogen ion activity in a solution
pH = -log (10) aH+
◦ aH is the activity of hydrogen ions - activity more important than concentration
◦ pH of the glass electrode responses to activity rather than concentration
* 40 nmol/L of H+ ions at a pH of 7.4.
What is Ka
- Equilibrium constant for the dissociation of an acid HA to produce H+ and acid anion A-
pKa
- The negative logarithm to the base 10 of the equlibrium dissociation constant
- At a pH equal to pKa the acid is 50% dissociated - equal amounts of A- and HA
pH calculation based on acid base concentrations
pH = pKa + Log (A-)/HA
pH of CO2 calculated by?
pH = pKa + Log A-/HA
pH = 6.1 + log (HCO3)/0.03 x pCO2
0.03 being the solubility constant
How is ventilation related to CO2?
Alveolar ventilation = VCO2/PaCO2 x k
- VA = alveolar ventilation
- VCO2 = CO2 production
- PaCO2 = partial pressure of CO2 (arterial)
- K is the proportionality constant
So * Exclusively deals in CO2 excretion
◦ PaCO2 regulated by ventilation which alters pH
◦ VA is inversely related to PaCO2 as can be seen in the equation below
How does the body respond to alterations in acid base in ventilation?
Detectors
* Peripheral chemoreceptors - aortic and carotid bodies responding to PO2, CO2 and pH
◦ Note carotid SINUS a baroreceptor, carotid BODY a chemoreceptor
* Central chemoreceptors - medulla responding to ECF CO2 levels
◦ Metabolic acidosis does not acutely cause central response however over 12-24 hours there is an equilibration fo HCO3
Response
* Ventilatory response to an increase in arterial pCO2 is 80% mediated by central response, 20% from peripehral
* Peripheral important for rapid changes however
* Ventilation increases 2L/min for every 1mmHg rise in arterial pCO2 from normal
Renal response to acid
- Non volatile/fixed acids/metabolic acids are all the same and 70mmol per day (1-1.5mmol/kg/day) excreted by the kidney
- 2 major aspects
◦ Reabsorption of filtered bicarbonate 4000-5000mmol/day
‣ 85-90% in proximal tubule through secretion of H+ –> also responisble for 1/4 of reabsorbed Na in the PCT’
* High capacity H+ secretion but low gradient because limiting pH in PCT is 7 so maximal H+ gradient is only 60 nmol/L (0.4pH units)
‣ Secretion of H+ in distal tubule buffered by phosphate
* Also from carbonic anhydrase in intercalated cells
* Net excretion of acid rather than reabsorption of bicarbonate only
* 70-100mmol per day excreted here
* Low capacity but high gradient as can work against H+ gradient of 3pH units down to 4.4
◦ Net excretion of H_ and acid anions
‣ Secretion of NH4 into PCT and distal tubule
What happens if you infuse 100mls of HCl via a central line
Acid load of 100mmols of H+
Buffering
* Rapid physicochemical titration of acid by extracellular buffers primarily –> HCO3 in ECF is 24mmol/L over 19L providing a bicarbonate pool of 450mmols
* Acid load of 100mmol –> reduces bicarbonate load
◦ (450 - 100 / 450) x 24 –> new bicarbonate concentration 18.7mmol/L
Compensation
* Metabolic acidosis triggers peripheral chemoreceptors to prompt increased ventilation as a response to compensate
* Expected pCO2 = 1.5 x HCO3 +8 (+/- 2)
* This returns the pH towards normal and takes 12- 24 hours to reach maximal response. pH does not return to completely normal.
◦ Peripheral chemoreceptors induce hyperventilation depressing pCO2
◦ ECF pH in brain paradoxically increases despite intravascular acidosis resulting in centrally mediated inhibition of respiratory centre
◦ Slow equilibration over 12-24 hours removes this central inhibition
Correction
* Kidney will excrete excess acid anion (Cl-) with equivalent reabsorption of bicarbonate and excretion of acid
Physiological effects of infusion
* Oxygen dissociation curve shifts to the right increasing oxygen unloading in peripheral tissues, with minimal effect on pulmonary oxygen loading
* Anion gap unchanged and acidosis tends towards hyperchloraemic metabolic acidosis
* Metabolic acids do not cross BBB
* Hyperkalaemia due to H+/K+ exchange across cell membranes
◦ This is seen more in non anion gap metabolic acidosis
* Hypocapnoea can cause intracelllular acidosis having a depressant effect on cellular activity
Define stewarts strong ion theory of acid base
- Acid base system utilising a mathematical approach factoring in several variables that control H+ in the body
What are the independent variables in Stewarts strong ion theory
Strong ion difference
ATOT
PaCO2
What is the strong ion difference referring to in Stewarts theory of acid base
◦ Strong ion difference = difference between concentration of strong cations and anions
‣ Apparent SID = SIDa = (Na+ + K+ + Ca2+ + Mg2+) – (Cl– + L-lactate + urate)
Explain dehydration and overhydration effect on acid base using Stewarts theory of acid base
‣ Due to excess or deficit of water -
* Excess water ↓ SID, ↓ [Na+]
* Dehydration ↑ SID, ↑ [Na+]
(1) Concentration change
* dehydration: concentrates the alkalinity and increases SID
* overhydration: dilutes the alkaline state (dilutional acidosis) and decreases SID
How do changes in strong ions effect acid base
‣ Due to excess or deficit of strong ions - dissociate completely at body pH
* Strong cations - Na/K/Mg/Ca
* Strong anions Cl/SO42-
* SID
* Chloride excess/ deficit ↓ SID, ↑ [Cl-] ↑ SID, ↓ [Cl-]
* Unidentified anion excess ↓ SID, ↑ [XA-]
(2) Strong Ion changes
* Decreased Na+: decreased SID and acidosis
* Increased Na+: increased SID and alkalosis
* Increased Cl-: decreased SID and acidosis (NAGMA; occurs with normal saline as the relative increase in Cl- exceeds that of Na+)
* increased in organic acids with pKa < 4 (lactate, formate, ketoacids): decreased SID and acidosis (HAGMA))
What is the SID in normal human plasma
SID is 42 mEq/L due to unmeasured anions
What does an increase in the strong ion difference cause?
Alkalosis - increased unmeasured anions
What does a decrease in the SID lead to
Acidosis
What are organic acids? When do they factor in to acid base significantly in Stewarts theory>
Increased in organic acids with pKa < 4 (lactate, formate, ketoacids): decreased SID and acidosis (HAGMA))
What is ATOT in stewarts strong ion theory
◦ A (TOT) - total weak acid concentration
‣ Excess or deficit of inorganic phosphate or albumin
‣ [ATOT] = [PiTOT] + [PrTOT] + albumin.
What are the dependent variables in acid base according to Stewart
thus a change in independent variables causes a change in pH and HCO3 i.e. acidosis or alkalosis
◦ pH - H+
◦ HCO3
◦ OH-
◦ HA and A- wean acids and weak anions
What key laws are followed in Stewarts strong ion theory
◦ Maintenance of electrical neutrality
◦ Dissociation equilibria of weak electrolytes
◦ Conservation of mass
Advantages and disadvantages of Stewarts strong ion theory
- Advantages
◦ Quantitative mathematical explanation of acid base
‣ Physical chemistry applied to traditional acid base
◦ Accounts for multiple factors controlling pH
‣ Low importance of just HCO3 which is a dependent variable
◦ Accessible and logical - Disadvantages
◦ Complex - produces confusion
◦ Vs standard base excess
‣ Strong ion difference only reflects plasma whereas SBE reflects the whole body
‣ SID - Fails to incorporate buffering contirbution of Hb
◦ Numerous variables each with a small margin of error to be measured therefore high potential for measurement error
◦ Lack of clinical correlation to demonstrate benefit
How much volatile acid is produced per day?
13-20mol/day
3/4 converted to carbonic acid
How much fixed acid is produced per day? What is a fixed acid?
Include lactate, sulphate, phosphate, and ketones
Body produces and eliminates 10mmol.kg-1.day-1
40-80mmol/day
Comes from protein metabolism primarily - methionine (sulphuric acid) , lysine/arginine and histidine to HCl. Phosphoric acid from phsoproteins.
How low can urinary pH get?
Urinary pH can fall as low as ~4.4, before the active transport of H+ is inhibited
Derive normal p[H from the Henderson Hasselbach equation
pH=pKa+log ([HCO−3]/[CO2])
=6.1+log 24/1.2
=7.4
Ammonia reaction and pKa? Is it a titratable acid/buffer?
The NH3+H+⇔NH4
reaction has a pKa of 9.2 meaning:
Ammonia cannot act as an effective urinary buffer
Ammonia is not a titratable acid, as it will not release H+ ions as urinary pH increases
This means filtered ammonia does not contribute to the lower limit of urinary pH (4.4), which is why it is so important in the renal correction of severe metabolic acidosis.
How does phosphate buffer in the urine?
Secreted H+ may also combine with a filtered buffer (e.g. PO43-). These H+ ions are not reabsorbed. About 36mmol of H+ is eliminated with filtered PO43- each day, with each PO43- binding two H+ ions.
How many hydrogen ions are in circulation at baseline
40nmol/L
20-160nmol/L gives a range of pH6.8-7.7
H+ =
As per henderson Hasslebach
= K [HA]/[A-]
where K = k1/k2
HA -(k1 forward, k2 backward)-> H+ + A-
What is pKa
pKa is the negative logarithm of the dissociation constant of the substance and the pH at which 50% is dissociated
Lower pKa is a stronger acid than a substance with a higher pKa
How is pH related to H+ concentration?
pH = log 10 [1/H+]
pH = -log 10 (H+)
H+ = 10 ^ -pH
Body response to acid load should be structured as
- Buffer
- Compensation
- Excretion
How does ventilation change for a pH change of 0.1
2 fold
How does the respiratory system as a compensatory mechanism compare in potency to buffers
2x more potent
what is the maximum fixed acid excretion per day by the kdiney
300mmol per day
How much bicarbonate is filtered by the kidney per day
4320 mmol/day
What percentage of bciarbonate reabsorption occurs in the proximal tubule
80%
How would you descirbe the H+ excretion mechanisms in the PCT? lowest pH acheiveable
high capacity, low gradient
Lowest pH 7
Where else is HCO3 reabsorbedother than the PCT
TALH + DCT in intercalated cells
How much of H+ secretion are the intercalated cells responsible for? Are they important? Capacity of this system? What increases secretion?
5%
Very important, as they are important for maximal acidifcation by 900 fold, and reduce urine pH to 4.5
High gradient low capacity
Secretion is controlled by aldosterone
What urinary buffers are there?
Phosphate –> HPO4 binds to H+ changing to H2PO4
Creatinine
Beta hydroxybutyrate
Sulphates
Titratable acidiity is bdinign of hdyrogen ions to buffers in urine and equl to the amount of the alkali required to bring the pH back to 7.4. Most of this happens in PCT
How powerful is the phsophate urinary buffer system
40mmol of acid excretion
Availability of phosphate cannot be icnreased to help acid secretion hwoever
How important is ammonium in the kidney
75% of metabolic acids proudced in the body 50mmol/day excreted as ammonium ion after glutamine is deaminated in the proximal tubule, TA LOH to form 2 NH+ ions, alpha ketoglutarate which is further converted to 2x HCO3 ions
produces NEW bicarbonate
300mmol per day is the maximal capacity fo this system
What clinical effects does acidosis have
Cardiovascular
- Reduced inotropy - inhibtis slow inward calcium current and diminishes release of calcium from sarcoplasmic reticulum (respriatory has a greater effect than metabolic). Somewhat opposed by catecholamine release until pH <7.22 then negative inotropy predominates
- Increased cataceholamine release –> tachycardia
- Increased arrhtyhmias
- Vasodilation fo the skin, skeeltal muscles, uterus and heart (indirect constriction if pH >7.2 due to catecholamines at systemic, renal and splanchnic sites)
Respiratory
- Pulmonary vasoconstriction
- Minute volume increase - in respiratory acidosis for every mmHg rise in PCO2 there is 2-3L/min rise in ventilation . Resp acidosis hyperventilation more rapid (BBB crossed) - hyperventilation peaks at 100mmHg
- Hypercapnoea bronchodilation
- Increased oxygen delivery to the tissues
Electrolyte
- H+ ions compete with negatively charged binding sites on albumin displacing calcium
- Increased ECF K by 0.5mmol/L for every 0.1pH drop
CNS - impaired consciousness
GIT - reduced motility and vasoconstriction
What effect does alkalosis have
Cardiac
- Increased coronary and systemic vascular resistance
Respiratory
- Left shift of oxyhaemoglobin dissociation curve impairing oxygen delivery ot he tissues
Reduced ionised calcium
CNS - epilepsy
Define acid base according to the Bronstead Lowry definition
Acid – Substance that donates a proton or hydrogen ion to another in solution
Base – Substance that accepts protons or hydrogen ions from another in solution
Arrhenius definition of acid base
Acid – Substance that dissociates in H2O to produce H+
Base – Substance that dissociates in H2O to produce OH-
Lewis definition of acid base
Acid – Substance that can accept an electron pair
o Base – Substance that can donate an electron pair
What is pH
The negative base 10 logarithm of H+ activity
An indirect measure of H+ activity
PH = - log (10) [H+ activity)
How is pH related to hydrogen ion activity
Inversely in non linear fashion due to the Log 10 scale
How many mmol/L of hydrogen ions are at pH 7.4? How does this change from 7.36 - 7.44
40nmol/L
36 - 44nmol/L
Is neutral pH temperature dependent?
The temperature where H+ = OH-
Yes
PH of neutral water increases in pH for drops in temperature
Describe what Ka actually is
How is pKa related to Ka
What is the Henderson Hasselbach equation
Show the derivation of the Henderson Hasselbach equation
Net acid excretion equation
NAE = NH4+ + Titratable acids - HCO3
What role does filtered H+ play in acid base balance
Minimal
Note: Filtered H+ at the glomerulus accounts for a very small % of excreted H+ → 36 nM x 180 L/day = 6.48 umol of excreted H+ per day
NH4+ excretion per day can range from? At baseline accounts for?
0-160mmol per day of acid excretion
Baseline 40mmol/day which is 40/70 of the fixed acid excretion (the rest being Titratable acids - or filtered buffers)
WHere is bicarbonate reabsorbed
85% PCT - high capacity and low gradient system - urine pH only 7
15% thick ascending loop of henle - low capacity and high gradient system —>urine pH down to 4.4
Outline how phosphate acts in the kidney
Mainly phosphate buffer system → H+ combines 1°ly with
HPO42- to form H2PO4- (as urine acidity ~ 4.5 → close to HPO42-
buffer pKa of 6.8)
What is Titratable acidity? What are its main determinants?
Aside: “Titratable acidity”
- Measured by the amount of alkali (as NaOH) that must be added to
urine to return its pH to 7.4 (which is the pH of glomerular filtrate) - Accounts for only a FRACTION of the H+ secreted by the kidneys:
o Accounts mainly for the H+ that are bound to “filtered buffers”
(phosphate and organic buffer systems) and excreted in urine
o Does not account for HCO3- buffer system → because H2CO3
is converted and reabsorbed as CO2 and H2O → thus alters
urine pH minimally
o Ammonia buffer system contributes little to “titratable acidity”
→ because of high pKa of buffer system (9.1) (Ie. urine only
titrated up to a pH of 7.4 and not any further)
What happens to Ammonium after it is secreted into the tubular lumen?
Thick ascending limb of LOH 80% reabsorbed generating increased gradient in medullary intersitium
In medullary collecting duct NH3 diffuses fromthe intersitium into cells of the collecting duct then to tubular fluids
H+ secretion by Na/H antiporter combines with tubular NH3 to form NH4+ which becomes ion trapped
What is the pKa of ammonium
9.2
How is H+ secretion unregulated
- (1) Raised PaCO2
- (2) High EC [H+] → Stimulates glutamine production
- (3) K+ and Cl- depletion → ↑ renal HCO3- reabsorption
- (4) Inhibition of CA → H+ secretion is inhibited
- (5) Aldosterone (and cortisol) → Upregulates H+ and H+/K+
ATPases - (6) ECF volume depletion → ↑ renal HCO3- reabsorption - (7) ↓ GFR → ↓ filtration of HCO3-
What is minimum urinary pH? What are the rate limiting steps to acid secretion?
Only a small amount of H+ can be excreted in its free form → because active
transport of H+ secretion is inhibited at high urinary [H+] → thus lowest urinary
pH achieved is 4.4 o As a result, H+ secretion and excretion in urine is dependent on binding to
“urinary buffers” → (i) HCO3- buffer (pKa 6.1), (ii) HPO42- buffer (pKa 6.8), and
(iii) NH3 buffer (pKa 9.1) o In the absence these urinary buffer systems → urine pH of 4.4 would be reached
very rapidly and any further H+ secretion would cease
What effect does acidosis have on the heart
- Negative inotropes - decreases slow inward Ca current and decreased Ca release from SR. <7.2 catecholamine response to acidosis is overcome and becomes more noticeably negatively ionotropic
- Increases SNS activity offsets negative inotropy briefly, increased arrhythmias, increased SVR, renal and splanchnic vasoconstriction
- Cardiac arrhythmias - decreased IC K increases resting membrane potentials
- Vascular effect - increased SVR in renal and splanchnic (SNS), directvasodialtion in skin, skeletal muscle and heart, pulmonary vasoconstriction
What effect does alkalosis have on the heart
Increased coronary vasoconstriction
Increased SVR
What effect does acidosis have on the respiratory system
Increased minute ventilation
Bronchodilator’s (hypercapnoea effect)
Right shift of oxyhaemoglobin curve
Acidosis vs CNS
Impaired LOC
Increased cerebral blood flow
Increased ICP
Effect of acidosis on GIT
SNS mediated splanchnic vasoconstriction and decreased GIT motility
