Acid Base Balance

Presenter : DR B Sharath Chandra Kumar Post Graduate Anaesthesiology

Moderator : DR B Syama Sundara Rao, Prof, MD;DA

History

The concept of acids and bases is relatively new

In the early part of the 20th century, it was known that in

critical illness the CO2 content of the blood decreased.

In 1831, O'Shaughnessy identified loss of “carbonate of soda”

from the blood as a fundamental disturbance in patients dying

of cholera.

We now know that the loss of bicarbonate was related to

hyperventilation and buffering of free hydrogen ions in

dysmetabolic states

1903, the revolutionary theory of Arrhenius

Arrhenius acid is any substance that delivers a hydrogen ion

into the solution. A base is any substance that delivers a

hydroxyl ion into the solution

In 1909, Henderson coined the term acid-base balance

that later was refined by Hasselbalch in 1916

In 1923, Brønsted and Lowry proposed an expanded theory

of acids and bases. They defined acids as proton donors and

bases as proton acceptors. All Arrhenius acids and bases

were also Brønsted-Lowry acids and bases Acid: H+ donor

Base: H+ acceptor

Introduction

H+ has variations in local production & clearance

Deviations from normal range can cause marked alterations

in protein structure & function, enzyme activity, & cellular

functions

H+ produced in large amounts from oxidation of

carbohydrates

H+ concentration regulated to maintain a

pH of 7.35 to 7.45

pH = - log[H+] nmol/L

pH=-log [H+]

Henderson-Hasselbalch equation

pKa = the ionisation exponent of the acid

pH = pKa + log [salt/base] / [acid]

Why [H+], why not Na+

Because H+ conc. are low relative to other cations

At normal pH, H+ conc = 40 nmol/L, where as

Na + conc= 140000000 nmol/L

Osmotic effect of H+ is negligeble when compared to

Na +

a decrease of pH by 0.3= doubling of H+

a increase of pH by 1.0= 10 fold ↓ of H+

What is p in pH

p means –ve logarithmE.g. , pH= -log H+, pKa= -log Ka

Hydrogen ions ( nmol/L ) pH

100 7.0

80 7.1

63 7.2

50 7.3

42 7.38

40 7.4

38 7.42

32 7.5

25 7.6

20 7.7

Production of acids in human body

1. Volatile : As a metabolic byproduct during carbohydrate

metabolism in the form of carbon dioxide. 200ml/min or 288L/day. Acid production 12960 meq/d. the gas is eliminated via lung, there fore called as volatile

2. Nonvolatile : usually during protein degradation

e.g. sulfuric acid,HCl, phosphoric acid Accounts for 70mmol/d Lactic acid is often neglected to calculate as it is further

degraded to CO2 in liver.

Acid base homeostasis Requires both elimination/production of acid or

recovery of base The H+ conc compatible with life can vary 10 fold i.e.

from 16-160 nmol/L (pH 6.8-7.8 )

Regulation of hydrogen ions1.Buffer system a. bicarbonate buffer

b. hemoglobin buffer c. protein buffer d. phosphate buffer

2.Ventilatory response

3.Renal response

1. Buffer systemDefinition :A buffer is defined as a solution or

reagent that resists a change in pH with the addition of either an acid or a base

It is a mixture of a weak acid or weak base and its salts that resists changes in pH when a strong acid or base is added to the solution.

Effectiveness of a buffer depends on ◦ the pK of the buffering system and ◦ the pH of the environment in which it is placed

1a. Carbonic acid- Bicarbonate buffer

Major buffer of metabolic acid/base in the plasma Does not function to buffer respiratory acid. pKa- 6.1 A strong acid like HCl if increases

A strong base like NaOH if increases

If Co2 is added to this system H+ & HCO3- are equally produced

HCl+NaHCO3 -------> NaCl+H2CO3-----NaCl+H2O+CO2

NaOH+H2CO3--- NaHCO3+H2O

CO2+H2O+NaHCO3---- H+ + HCO3- + NaHCO3

The effectiveness of the buffer system is based on - 1) Its present in high concentration (> 20

mmol/L)

2) The lungs can dispose of readily or retain CO2 (as changes in CO2 modify the ventilation rate)

3) The bicarconate (HCO3-) can be readily

disposed of or reclaimed by the kidneys.

1b. Hemoglobin buffer

Predominant non carbonic buffer in ECF. pKa-6.8 Buffers both resp & metabolic acids Buffers CO2 by 2 methods - allows CO2 to combine directly with A.A to form

carbamino compound. Accounts for 15-25% of total CO2 transport

- CO2 is catalyzed in RBC to H+ & HCO3- by carbonic anhydrase enzyme. H+ buffered by Hb to HHb. The free HCO3 diffuses into plasma in exchange to Cl-, known as chloride shift

1c. Protein buffers

Play as buffer due to large total concentration & some have free acid/basic radicals

AA having free acid radicals in the form of COOH can buffer alkali by liberating H+

AA having free base radicals in the form of NH3OH can buffer acid

COOH+OH- ----- COO- + H2O

NH3OH + H+ ----- NH3+ + H2O

1d.Phosphate buffer

Largest inorganic buffer Predominantly intracellular pKa 6.8 For strong acid

For strong base

HCl + Na2HPO4 --- NaH2PO4 =NaCl

NaOH + NaH2PO4 --- Na2HPO4 = H2O

2. Ventilatory response

Limited to CO2 excretion by lung Regulated by medullary centres sensitive primarily to H+

Also serves to compensate metabolic acid-base disturbances

A decrease in HCO3- decreases pH, increases ventilation and vice-versa

3. Renal Response Mainly to recover HCO3- and eliminate H+ Bicarbonate filtered by kidney is 4320 mmol/day HCO3- is absorbed into the interstitium with the help of

carbonic anhydrase Apart from re-absorption HCO3- is generated newly in

the proximal tubules by glutamate metabolism

Methods of assesment of acid-base balance

In vitro tests:1) Hendersen Hasselbach equation2) Alkali reserve3) Standard HCO3- 4) Astrup method5) Buffer base and buffer excess system

In vivo tests: In vivo titration curves are derived from collation of

normal human values of pH PaCO2 and HCO3- in acute and chronic disorders

Clinical sample values are then compared with these values and the deviation from them may be characterized and quantified for both acute and chronic disorders

Stewart Approach

2. Weak Acid “Buffer” Solutions

A TOT = weak ions , mainly albumin & phosphate

3. CO2 content

Carbon Dioxide–Bicarbonate (Boston) Approach acid-base chemistry using acid-base maps and the

mathematical relationship between CO2 tension and serum bicarbonate (or total CO2),

Base Deficit/Excess (Copenhagen) Approach

The standardized base excess (SBE) = 0.9287 [ HCO3- - 24.4 + (pH-7.4) ]

Assessment of A-B balance

Arterial blood Mixed venous blood

range range

pH 7.40 7.35-7.45 pH 7.33-7.43

pCO2 40 mmHg 35 – 45 pCO2 41 – 51

pO2 95 mmHg 80 – 95 pO2 35 – 49

Saturation 95 % 80 – 95 Saturation 70 – 75

BE 2 BE

HCO3- 24 mEq/l 22 - 26 HCO3

- 24 - 28

Acid Base disturbances

Acidosis: pH<7.35 Metabolic and respiratory

Alkalosis: pH>7.45 Metabolic and respiratory

Respiratory Acidosis

Any event (drug or disease) that decreases alveolar ventilation results in an increased concentration of dissolved carbon dioxide in the plasma (increased PaCO2).

By convention, carbonic acid resulting from dissolved carbon dioxide is considered a respiratory acid, and respiratory acidosis is present when the pH is <7.35.

Dissolved CO2 produces equal amounts of H+ and HCO3- but still pH falls because the relative increase in H+ is greater than the relative increase in HCO3-

Respiratory alkalosis

Due to increased ventilation, removing excess CO2 May be due to hypoxia or iatrogenic or psychological Increases pH> 7.45 Hypocalcemia accompanies it, may precipitate tetany

Metabolic Acidosis Any acid other than due to CO2 retention is considered

metabolic Bicarbonate deficit - blood concentrations of bicarb

drop below 22mEq/L Causes:

◦ Loss of bicarbonate through diarrhea or renal dysfunction

◦ Accumulation of acids (lactic acid or ketones) which may occur in DM,starvation,high fever.

◦ Failure of kidneys to excrete H+

Anion gap

sum of anion and cations is always equal sodium and potassium accounts for 95% of cations chloride and bicarbonate accounts for 68% of anions there is difference between measured anion and cation the unmeasured anions constitute the ANION GAP. they are protein anions ,sulphates ,phosphates and organic

acid

AG can be calculated as (Na+ + K+)—(HCO3- + Cl-)

high anion gap acidosis:renal failure,DM normal anion gap acidosis:diarrhea hyperchloremic acidosis

Metabolic alkalosis

Due to excessive vomitings, nasogastric suction, chronic thiazide use, excessive aldosterone

Clinical effects of acid base disorders

CVS: Heart rate: increases as pH decreases from 7.4 to 7.1

due to release of catecholamines from adrenal medulla. In a sympathetically blocked patient the effect of acidemia is bradycardia due to vagal stimulus

Cardiac rhythm: Both atrial and ventricular arrhythmias are more common in acidosis. It may be due to rise in ECF potassium in acidosis

Myocardial contractility: On isolated heart direct depression. In sympathetically active heart contraction increases due to catecholamine increase upto a certain level

Cardiac Output: Mild acidosis increases Cardiac Output but as acidosis increases cardiac output falls

Systemic vascular Effects: With acidosis, Vasodilatation on systemic arteries

except on splanchnic vessels On venous system acidosis causes constriction

Respiratory Effects: With acidosis, minute ventilation increases due to

medullary centre stimulation Airway resistance: Acidosis causes variable response,

whereas alkalosis causes broncho-constriction

Renal effects: Renal vascular resistance increases as the pH falls

Utero-placental effects: Effects fetus directly through placenta and indirectly by

changing placental blood flow CO2 has more effect than H+ or HCO3- Acidosis has same effects on fetal organ function as in

adults Acidosis causes increased uterine blood flow Alkalosis causes a left shift of ODC, causing decreased

O2 delivery to fetus

Neuro-endocrine effects: CBF increases with increase in pCO2 and vice-versa With increase in cerebral CO2 mental changes occur and

lead to coma Hypothermia occurs in respiratory acidosis Acidosis causes increase in catecholamine levels

Electrolyte balance: Acidosis causes increased serum ionized calcium and

vice-versa pH and serum K+ are inversely proportional: 0.1 units of

pH change causes 0.6 mmol/L change in K+

Effect of temperature on pH

As the temperature falls, CO2 becomes more soluble causing PCO2 to fall , H+ to be more buffered by Hb and an increase in pH

1° fall in temp -- 0.015 units rise in pH

pH stat management

Return of pH & pCO2 of hypothermic blood to normal by adding CO2

Advantage : better cerebral circulation Disadvantage : cerebral micro embolus

Uses : surgery for congenital heart disease, during cooling stage, before profound hypothermic circulatory arrest

The degree of ionisation (alpha) of the imidazole groups of intracellular proteins remains constant despite change in temperature.

The pH will be corrected and reported by machine for 37° C

Even though the actual pH is alkaline in hypothermia, the enzyme function will be retained because of alpha of the imidazole groups

Alpha stat

Simple acid-base disturbances can be evaluated using the following strategy:Step 1. Look at the pH (three possibilities):

<7.35—acidosis 7.35-7.45—normal or compensated acidosis >7.45—alkalosis

Step 2. Look for respiratory component (volatile acid = CO2):

PCO2 <35 mm Hg—respiratory alkalosis or compensation for metabolic acidosis (if so, BD * > -5)

PCO2 35-45 mm Hg—normal range PCO2 >45 mm Hg—respiratory acidosis (acute if pH <7.35,

chronic if pH in normal range and BE[†]> +5)

Step 3. Look for a metabolic component (i.e., buffer base utilization):

BD >-5—metabolic acidosis BE -5 to +5—normal range BE >5—alkalosis

Put this information together. Options: 1. Acidosis, CO2 <35 mm Hg, ± BD >-5—acute metabolic

acidosis 2. Normal range pH CO2 <35, BD >-5—acute metabolic

acidosis plus compensation 3. Acidosis, PCO2 >45 mm Hg, normal range BE—acute

respiratory acidosis 4. Normal range pH, PCO2 >45 mm Hg, BE >+5—prolonged

respiratory acidosis 5. Alkalosis, PCO2 >45 mm Hg, BE >+5—metabolic alkalosis

6. Alkalosis, PCO2 <35 mm Hg, BDE normal range—acute respiratory alkalosis

7. If the acid-base picture does not conform to any of these, a mixed picture is present.

A 45-year-old man is admitted after a motor vehicle crash. He is bleeding, and his pulse is thready. Blood pressure is 90/50 mm Hg, heart rate is 120 beats/min, respiratory rate is 36/min, and temperature is 35°C.

A serum chemistry and blood gas are taken. Does he have any acid-base disturbances?

Na+ 144, K+ 4, Cl- 110, total CO2 8, urea 10, creatinine 2, albumin 4, lactate 16, pH 7.28, PCO2 24, HCO3

- 8, BE -16Anion gap = 26Corrected anion gap = 27.25

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