07. acid base disorders

Acid base balanceAcid base balanceAcid base balanceAcid base balance

Suchitra Ranjit MDSuchitra Ranjit MDPediatric Intensivist,Pediatric Intensivist,

Apollo Hospitals, ChennaiApollo Hospitals, Chennai

For past 100 yrs, acid base has occupied a special corner of clinical medicine

Physicians generally agree that acid base is important, but struggle o understand the science, pathology and application

Also need to be aware of “traditional” vs modern physical-chemical approach

Why knowledge of blood gases are important…“Long periods of boredom punctuated by moments of utter panic.”

Understanding acid-base physiology:

from Henderson-Hasselbalch to Stewart….

Earliest concepts developed in the beginning of 20th century

Arrhernius, then Henderson followed by Hasselbalch, Bronsted Lowry

Acid (HA) is a proton donor, donates H+

Base ( A-) is a proton acceptor, accepts H+

•The acidity of the solution is thus a measure of the hydrogen ion activity

•The normal concentration of H+ is in nanomole range (nmol/L)

• 1 nmol/L = 10 -6 milliequivalents/L

•Serum sodium concentration is 3 million times H+ concentration

•Becoz such figures and units may be confusing, H+ concentration expressed as pH units

•pH = negative log10 of hydrogen ion concentration in nmol/l

•The p refers to the German word ‘potenz’ (power) so pH means 'power of hydrogen'.

pH = -log10[H+]

Relationship between pH and [H+]

pH[H+](nanomoles/l)

6.8 158

6.9 125

7.0 100

7.1 79

7.2 63

7.3 50

7.4 40

7.5 31

7.6 25

7.7 20

7.8 15

A doubling or a halving of [H+] means a

change in pH by 0.3 either up or down.

Acid production in the body

Volatile acids during oxidative metabolism

• Can leave solution and enter the atmosphere (e.g. carbonic acid)

•CO2 production: 12,500 mEq of H+ equivalents/day

•Excreted by lungs

Non volatile (fixed) acids produced by daily catabolic load•Acids that do not leave solution (e.g. sulfuric and phosphoric acids) until eliminated by the kidney.

Organic acids Participants in or by-products of aerobic metabolism

(eg, lactic acid)

Normal range of pH : 7.35- 7.45

Why maintain pH in such a narrow range ?

Plasma pH

• Plasma pH is maintained by homeostasis in the range 7.35 – 7.45

• pH has a widespread effect on cell function- most cell enzymes work best at physiological

pH• An abnormal pH can result in disturbances in a wide

range of body systems

• Alteration outside these boundaries affects all body systems but mainly nervous &

cardiovascular (coma, cardiac failure, and circulatory collapse)

pH balance regulated by:

1. Chemical buffer system (acts immediately)

1. Respiratory centre in brain stem (1-3 minutes)

2. Renal mechanisms (hours / days)

Weak vs strong acids.. Which are better buffers?

• An acid is “strong” if it dissociates its H+ easily • ie, corresponding base has low affinity for it• ie, dissociation constant is high (pK low)

•“Weak” acids only partially dissociate

• Corresponding base has high affinity for it

•Acid and base pairs are present in equimolar proportions in solution

Acid pair can efficiently buffer (resist) changes in pH after addition of base

Base pair can efficiently buffer (resist) changes in pH after addition of acid

Weak vs strong acids.. Which are better buffers?

•Weak acids: Acid and base pairs are present in equimolar proportions in solution

•Most effective as buffer when pka of solution closest to physiological pH

Physiological buffering systems

Two general categories

1.Bicarbonate/carbonic acid ( HCO3/H2CO3) buffering system ( ECF and within RBC)

2.Non bicarbonate buffers ( Hb, oxyHb, organic and inorganic phosphates, plasma proteins)

Buffers cannot eliminate H+ from the body , but temper sudden changes in pH and buy time until problem corrected or a new balance is reached

• pH = pKa + log [HCO3-]/[H2CO3]

• pH = pKa + log [HCO3-]/0.03 x PCO2

• pH = 6.1 + log [HCO3-]/0.03 x PCO2

• 7.4 = 6.1 + log 20/1• 7.4 = 6.1 + 1.3• The solubility constant of CO2 is 0.03

• The pKa of carbonic acid is 6.1

• Plasma pH equals 7.4 when buffer ratio is 20/1

• Plasma pH may be affected by a change in either the

bicarbonate concentration or the PCO2

• The [HCO3-] and PCO2 values determine plasma pH

Henderson-Hasselbalch equationExpresses the relationship of the HCO3/H2CO3

buffering system to pH

• pH = pKa + log [HCO3-]/[H2CO3]

• pH = pKa + log [HCO3-]/0.03 x PCO2

• pH = 6.1 + log [HCO3-]/0.03 x PCO2

• Disadvantages of HH

• Better quantification of resp component than metabolic

• No quantification of non carbonic acids

Henderson-Hasselbalch equationExpresses the relationship of the HCO3/H2CO3

buffering system to pH

Bicarbonate buffer system• Mixture of:

- carbonic acid (H2CO3) and

- sodium bicarbonate (NaHCO3)Tremendously efficient becoz of rapid interconversion to volatile CO2

• When pH of solution rises (becomes more alkaline), the carbonic acid dissociates releasing more H+ which reduces pH

• When pH of a solution drops (becomes more acidic), the bicarbonate combines with extra H+ mopping them up which ensures that pH rises.


1. Chemical buffer system (act immediately)



Respiratory system regulation of pH

• Eliminates CO2 from blood whilst replenishing stores of O2

• CO2 generated by cellular respiration.

• Enters RBC and converted to bicarbonate for transport in plasma to lungs

CO2 + H2O H2CO3 H+ + HCO3-

Carbonic anhydrase

Carbonic acid

Bicarbonate ion


1. Chemical buffer system (act immediately)



Renal Mechanisms• Kidneys alter/replenish H+ by

altering plasma [HCO3-]

[H+] plasma (alkalosis) kidneys excrete lots of HCO3

-

[H+] plasma (acidosis) kidneys produce new HCO3

-

In acid-base balance, the kidney is responsible for 2 major activities:

1. Re-absorption of filtered bicarbonate: 4,000 to 5,000 mmol/day

2. Excretion of the fixed acids (acid anion and associated H+): about 1 mmol/kg/day.

Both these processes involve secretion of H+ into the lumen by the renal tubule

•Losing a bicarbonate ion is the same as gaining a hydrogen ion;

•reabsorbing a bicarbonate ion is the same as losing a hydrogen ion

The contributions of the proximal tubules to acid-base balance are:

•firstly, reabsorption of bicarbonate which is filtered at the glomerulus

•secondly, the production of ammonium

Daily filtered bicarbonate equals the product of the daily glomerular filtration rate (180 l/day) and the

plasma bicarbonate concentration (24 mmol/l). This is 180 x 24 = 4320 mmols/day (or usually quoted as

between 4000 to 5000 mmols/day). About 85 to 90% of the filtered bicarbonate is

reabsorbed in the proximal tubule and the rest is reabsorbed by the distal tubule and collecting ducts

Reabsorption of bicarbonate back into the plasma

Bicarbonate Handling… cont.

• BUT secreted H+ is not excreted

• Combines with HCO3- in lumen to form CO2

and H2O

• Therefore, filtered HCO3- disappears, but

you have some HCO3- production inside the

cell from CO2 and H2O

• Gains equal losses so we achieve balance• Except during alkalosis, the kidneys

reabsorb all filtered HCO3-, preventing loss

of HCO3- in the urine

Addition of New HCO3- to

Plasma• What if you use up all filtered HCO3

- in the lumen, and you still have free, excess H+?– Recombine H+ with another buffer e.g.

HPO42-

– Excreted as H2PO42-

– Gives net gain of HCO3- by plasma

• But you can also generate new HCO3- to

increase the pH of the plasma• However, it would be unusual to do this

because you have lots of filtered HCO3- to use

up first (25 x amount of non-HCO3- buffers)

Addition of bicarbonate back into the plasma by secretion of H+

Another way of making HCO3-…..

• Renal production and secretion of ammonium (NH4+)

• Urinary H+ excretion = renal addition of new HCO3- to

plasma

Renal responses to acidosis

• H+ ions secreted to reabsorb all filtered HCO3-

• Even more H+ secreted, contributing new HCO3- to

plasma as these H+ ions are excreted bound to non-HCO3

- urinary buffers such as HPO42-

• Tubular glutamine metabolism and ammonium excretion are enhanced to make more HCO3

- (TAKES TIME!!!)

• NET RESULT: More new HCO3- into blood,

increasing plasma [HCO3-]. This compensates for

the acidosis. Urine is highly acidic (lowest pH is 4.4)

The response to alkalosis

Traditional versus modern

views of blood gas analysis

Traditional view

When we first study acid-base balance, it is too easy believe that the concentrations of the hydrogen and bicarbonate ions, [H+] and [HCO3-], are at the heart of the problem - are dominant forces.

We do, after all, discuss them, measure them, andtreat them:

Whatever an acid or a base does, must be due to the pH, i.e., the concentration of H+.

In addition [HCO3-] must surely determine the metabolic state.

Disadvantages of the traditional view in the critically ill

Failed to take into account contributions of albumin in calculation of anion gap/SBE

Unsatisfactory explanations for changes in pH with fluid (saline) administration

Stewart (1981): physical chemical approach

• Concept of electrolytes as critical factors in acid/base balance

• Balance of SID is maintained by the dissociation and reassociation of water

Stewart's Independent Variables:

There are three variables which are amenable to change in-vivo:

1.partial pressure of carbon dioxide (PCO2),

2. total weak non-volatile acids [ATOT],

3.net Strong Ion Difference [SID].

The influence of these three variables can be predicted through six simultaneous equations

Stewart's Dependent Variables:

Stewart listed a total of six ion concentrations as dependent: [H+], [OH-], [HCO3-], [CO3--2], [HA], [A-] (weak acids and ions).

In-vivo and clinically, therefore, these are not subject to independent alteration.

Their concentrations are governed by concentrations of other ions and molecules.

Na+Na+

K+K+

Ca++, Mg++Ca++, Mg++

Cl-Cl-

XA-XA-

HCO3-HCO3

-

Albx-Albx-

Piy-Piy-

SID eff

Strongcations

Stronganions

SID apparent =

Strong cations

+

Strong anions

Na+Na+

K+K+

Ca++, Mg++Ca++, Mg++

Cl-Cl-

XA-XA-

HCO3-HCO3

-

Albx-Albx-

Piy-Piy-

Strongcations

Stronganions

SID eff

Strong ion gapSID apparent =

Strong cations

+

Strong anions

SID

effective

[SID]:The Strong Ion Difference is the difference between the sums of concentrations of the strong cations and strong ions:

[SID] = [Na+] + [K+] + [Ca2+] + [MG2+] - [CL-] – [Other Strong Anions].

[ATOT]:[ATOT] is the total plasma concentration of

the weak non-volatile acids, inorganic phosphate, serum proteins, and albumin:

[ATOT] = [PiTOT] + [PrTOT] + albumin.

Total CO2:

Predominantly pCO2, also H2CO3, carbonates

The effects of changes on PCO2 are well understood and produce the expected alterations in [H+]:CO2 + H2O <—> H2CO3 <—> HCO3- + H+

Metabolic (Non-Respiratory):

Metabolic disturbances, obviously, cannot be viewed as a consequence of bicarbonate concentration because bicarbonate is merely a dependent variable.

The two possible sources of metabolic disturbances are either [SID] or [ATOT].

With normal protein levels, [SID] is about 40mEq/L

Any departure from this normal value is roughly equivalent to the standard base excess (SBE), i.e., if the measured [SID] were 45 mEq/L, the BE would be about 5 mEq/L, and a measured [SID] of 32 mEq/L would approximate to a BE = -8 mEq/L.

Changing [SID]:[SID] can be changed by two principal methods:1) Concentration:•Dehydration or over-hydration alters the concentration of the strong ions and therefore increases, or decreases, any difference. •The body's normal state is on the alkaline side of neutral. •Therefore, dehydration concentrates the alkalinity (contraction alkalosis) and increases [SID]; •Overhydration dilutes this alkaline state towards neutral (dilutional acidosis) and decreases [SID].

2) Strong Ion Changes:If the sodium concentration is normal, alterations in the concentration of other strong ions will affect [SID]:

2) Strong Ion Changes:If the sodium concentration is normal, alterations in the concentration of other strong ions will affect [SID]:a. Inorganic Acids:The only strong ion capable of sufficient change is chloride, Cl- (potassium, calcium and magnesium donot change significantly). An increased Cl- concentration causes an acidosis and a decreased [SID] causes alkalosis.Because the chloride ions are measured, the anion gap will be normal.b. Organic Acids:By contrast, if the body accumulates one of the organic acids, e.g., lactate, formate, keto-acids, then themetabolic acidosis is characterized by a normal chloride concentration and an abnormal anion gap because of the presence of the "unmeasured" organic acid.

Changing [ATOT]:The non-volatile weak acids comprise inorganic phosphate, albumin and other plasma proteins. Making the greatest contribution to acid-base balance are the proteins, particularly albumin, which behave collectively as a weak acid.

Hypoproteinemia, therefore, causes a base excess and vice versa.

Phosphate levels are normally so low that a significant fall is impossible. However, in renal failure, high phosphate levels contribute to the acidemia.

Pros and Cons:

1) Understanding:Stewart's greatest contribution may be his focus on the importance of the factors controlling pH. [H+], [OH-] and [HCO3-] are merely dependent variable.

This emphasis on the importance of the underlyingcauses rightly diminishes the importance of the bicarbonate ion.

2) Shortcomings :A major shortcoming lies in calculating a value for [SID] which depends upon accurate measurements of several variables.

An acceptable level of error in the underlying measurements becomes less acceptable after subtraction.

This is partly because the errors are summed and partly because any error now appears proportionately large against the resulting small value.

3) Standard Base Excess Accuracy:Standard base excess has been well validated both for accuracy and for clinical relevance through manyyears of familiarity and clinical correlation.

Albumin correction:AG corrected=AG OBSERVED+ 2.5 (4.2-observed

albumin)

Clinical application facilitated by determination of 4 variables

1. The SBE from blood gas analysis

2. The SBE effect from NaCl: ( Na- Chl-38)

3. The BE effect of albumin: 2.5(4.2-obs albumin)

4. The BE effect of unmeasured anions (UMA)

Which Model to Use?• Ultimately personal preference!

– All models are simply a means of explaining observed physical findings

– All models have inbuilt assumptions and limitations … to varying degrees

• IF you choose to rely upon a more simple model, this is reasonable, providing:– The model ‘works’ for the majority of clinical

scenarios– You are aware of the limitations of the model– You are aware of the existence of more

accurate models, when they exist.

SIDS and effects of fluid administrationCritical Care 2005, 9:204-211

Stewart's quantitative physical chemical approach enables us to understand the acid–base properties of intravenous fluids. Lowering and raising plasma SID while clamping ATOT cause metabolic acidosis and alkalosis, respectively.

Fluid infusion causes acid–base effects by forcing extracellular SID and ATOT toward the SID and ATOT of the administered fluid.

Thus, fluids with vastly differing pH can have the same acid–base effects.

The stimulus is strongest when large volumes are administered, as in correction of hypovolaemia, acute normovolaemic haemodilution, and cardiopulmonary bypass.

Saline, SID and Stewarts

Henderson-Hasselbalch theory

Stewart’s approach

Conclusion:For most acid-base disturbances, and for the foreseeable future, the traditional approach to acid-base balance seems certain to prevail.

For the clinician, the three variables of greatest us are the pH, PCO2,and standard base excess (SBE).

What might change this?

The answer would have to be published cases where clinical management has been critically improved by using Stewart's approach.

Such cases would have to be accumulated, evaluated, and approved before any major switch to his approach seems warranted.

Useful Websites• Mainly Traditional + History +

Terms– http://www.acid-base.com/

• Traditional & Stewart– http://www.qldanaesthesia.com/

AcidBaseBook/ABindex.htm

• Stewart Approach– http://www.anaesthetist.com/icu/elec/ionz/St

ewart.htm http://www.AcidBase.org

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