The Acid-Base Balance And Disorders:

Study Objectives:

· To define pH, pK, PaCO2, acids, bases, buffers, buffer bases (titratable base), actual bicarbonate and non-carbonic buffers, the extended extracellular fluid volume (ECV extended with red cells), and the base excess of the extended ECV.

· To describe the daily acid-base balance, titratable acidity and the net excretion of acid in the urine, the base excess of the blood and extended ECV, and the buffers of the intracellular fluid volume.

· To calculate the third variable of the Henderson-Hasselbalch equation from two measured variables.

· To draw the acid-base charts (ie, a double logarithmic plot of the Henderson-Hasselbalch equation).

· To explain the acid-base chart, metabolic processes involved in the regulation of pH, tubular H+-secretion, and renal bicarbonate reabsorption. To describe intracellular buffers and pH, transport of H+ across the cell membrane. To describe four acute disorders of the acid-base status (primary respiratory and metabolic acidosis and alkalosis) and their chronic counterparts with therapeutic suggestions.

· To use the acid-base variables in problem solving and diagnosis of acid-base disorders.

Principles

· The mass action equation. Blood plasma is an open system where gasses are in equilibrium both with the alveolar air in the lungs and with the extracellular fluid volume (ECV). ECV and all red cells work as a buffer unit called extended ECV. Bicarbonate -carbonic acid is the strongest buffer and haemoglobin is the strongest non-carbonic buffer. The pH of arterial blood plasma is a function of PaCO2 and of the concentration of titratable buffer bases in the extended ECV (Box 17-1). The concentration of titratable base (Base Excess, BE) is measurable, and BE remains zero during acute changes of PaCO2.

· The disorders of the acid-base balance are described by the following two interrelated chemical reactions:

CO2 + H2O Û* H2CO3 Û H+ + HCO3- and

[ Acid form] « H+ + [ Non-carbonic buffers-]

Non-carbonic buffers - or non-bicarbonate buffers - refer to all other relevant buffers than the carbonic acid-bicarbonate buffer system. The enzyme carbo-anhydrase is shown with an asterisk: *.

Definitions

· Acid (HB) is defined as a compound that can release a hydrogen ion or proton (H+), whereas a base (B-) can bind H+.

· Acidosis (acidaemia) is defined as a disorder with accumulation of acids in the extended ECV. The pH measured in the arterial blood is less than 7.35.

· Alkalosis (alkalaemia) is defined as a condition with accumulation of bases in the extended ECV. The pH of the arterial blood is larger than 7.45.

· Actual bicarbonate concentration is the concentration calculated from PaCO2 and pH measurements in the arterial blood sample. The value can be calculated with Eq. 17-6 or read from an acid-base chart with a bicarbonate axis (slope -1 in Fig. 17-3).

· The acid-base buffer capacity of a system is defined as the amount of strong acid or base added to one litre (l) of the system (ie, mmol per l or mM) in order to change the pH one unit.

· A buffer is a corresponding acid-base pair, which acts as a pH-stabiliser.

· Buffer base (BB) refers to the total concentration of all carbonic buffer anions plus the non-carbonic anions.

· Carbonic acid refers to carbon dioxide.

· Carbonic buffers refer to the carbonic acid-bicarbonate buffer system.

· Glomerular filtration is due to a hydrostatic/colloid osmotic pressure gradient - the Starling forces

· The acid-base buffer capacity of the extended ECV is normally 61 mM per pH unit as an average (Box 17-1).

· Non-carbonic buffers (non-bicarbonate buffers) refer to all other buffers than the carbonic acid-bicarbonate buffer system in the extended ECV (Box 17-1).

· The Base Excess (BE) of the extracellular fluid (extended ECV) is calculated as the concentration difference of buffer bases in the actual sample and in the same sample following titration with strong acid or base and equilibration to standard conditions (pH 7.4, PaCO2 5.3 kPa or 40 mmHg). The difference is given in mmol of strong acid or base, which must be added to 1 l of the sample. The base excess remains normal (zero) in acute respiratory acid-base disorders

· Extended extracellular fluid volume (extended ECV) is the extracellular fluid volume (ECV) plus the erythrocyte volume. A useful model of the extended ECV is an arterial blood sample diluted three folds with its own plasma (ie, 2+1). Extended ECV behave as a functional buffer unit. As a model extended ECV is considered to be all red cells distributed evenly in the extracellular fluid volume. The extended ECV of a healthy standard person covers approximately 20% of body weight. The principal buffers of the extended ECV in a healthy person are shown below (Box 17-1). Extended ECV serves as an early distribution volume in acid-base disorders.

· Intracellular fluid volume (ICV minus red cells) comprises approximately 40% of the body volume. The principal buffers of ICV are proteins, phosphate and bicarbonate. The transport across cell membranes take hours to equilibrate and the intracellular buffer effect is involved in the delayed distribution. The intracellular buffer effect is larger in disorders with negative base excess (acidosis with pH approaching pK for the best buffers) than with positive base excess. OH- has a molecular weight 17 times larger than that of H+, so H+ diffuses faster through the cell membrane, since the diffusion rate depends on the hydrated ionic radius

· pH is defined as the negative logarithm to the proton concentration. In this Chapter the pH is measured with glass electrodes in the arterial blood sample, and used in the extended ECV

· pK is equal to pH, when the concentration of acid and of base is the same.

· Partial pressure of carbon dioxide in the arterial blood sample (PaCO2) is measured with glass electrodes, and PaCO2 refers to the extended ECV in this Chapter.

· Metabolic acidosis is acidosis with negative Base Excess. - Negative Base Excess means that the numeric difference between the measured buffer base (BB) and the normal buffer base (NBB) is negative.

· Metabolic alkalosis is alkalosis with positive Base Excess. - Positive Base Excess means that the numeric difference between the measured buffer base (BB) and the normal buffer base (NBB) is positive

· Metabolic acid-base disorders are caused by changes of the titratable base of the extended ECV (Base Excess is positive or negative).

· Nephron - the functional renal unit. Each nephron consists of a glomerulus, a proximal convoluted tubule, a Henle loop and a distal tubule ending in a collecting duct with several other nephrons.

· Respiratory acid-base disorders are caused by alterations of PaCO2, without any change of the amount of titratable base in the extended ECV (BE is zero).

· Respiratory acidosis is an acidosis with a PaCO2 above 6.4 kPa or 48 mmHg at rest

· Respiratory alkalosis is an alkalosis with a PaCO2 below 4.4 kPa or 33 mmHg at rest.

· Titratable phosphate acidity in the daily urine is the amount of base (mmol) needed to titrate an acidic urine (phosphoric acid) back to the pH of plasma and glomerular filtrate (pH = 7.4 and PCO2 of 5.3 kPa).

· Tubular reabsorption is the movement of water and solute from the tubular lumen to the tubule cells and to the peritubular capillary network

· Tubular secretion represents the net addition of solute to the tubular lumen.

Essentials

This paragraph deals with 1. Proton concentration & pH, 2. Buffer capacity and the bicarbonate buffer , 3. Buffer capacities, 4. From the H-H-equation to the acid-base chart, 5. Extended ECV & Base excess, 6. Metabolic acid-base production, 7. Renal acid-base control, 8. Intracellular buffers.

1. Proton concentration and pH

Normally, the [H+] of arterial plasma of humans at rest is maintained by the lungs and kidneys within the range of 40 ± 5 nM, corresponding to a pH of 7.36-7.44. The [H+] of the arterial plasma is also maintained during strenuous conditions and diseases: 16-160 nM or pH 6.8-7.8 (Fig. 17-1). Proton concentrations in nM differ by a factor 10-6 from the normal standard-[Na+], which is around 140 mM.

A pH of 6.8-6.9 is not sustainable for long, and the patient is dying in a state of coma. In contrast, a healthy athlete can survive a pH of 6.85 following supramaximal exercise with headache as the only consequence.

A pH approaching 7.8 implies dissociation of all buffer proteins in order to produce H+ (Eq. 17-7), and negative albumin charges capture Ca2+, so the extracellular Ca2+ falls and the patient dies in tetanic cramps including laryngeal spasms (Fig. 17-1). Tetanic cramps are spontaneous prolonged or continuous muscular contractions (for explanation see later)

Fig. 17-1: Relationship between pH and the proton concentration

2. Buffer capacity and the bicarbonate buffer

The acid-base buffer capacity of a system is defined as the amount (mmol) of strong acid or base added to one litre (l) of the system (ie, mmol per l or mM) in order to change the pH one unit

The importance of the CO2/bicarbonate buffer is easily realised when comparing the addition of one mmol of strong acid to one litre of a closed and an open system with 24 mM bicarbonate each (pH 7.4; PCO2 5.3 kPa).

Fig. 17-2: The CO2/bicarbonate buffer working in a closed and an open system.

In the closed system, the base concentration is reduced by 1 mM to 23, and the acid concentration is increased by one mM, because the reaction is shifted towards formation of CO2 causing a high PCO2 (Fig. 17-2). Accordingly, the acid concentration is now: ([0.225 × 5.3] + 1) = 0.225 × newPCO2. Thus the newPCO2 is 2.19/0.225 or 9.73 kPa. The pH of the closed system is changed to 7.02 (Fig. 17-2). The buffer capacity is 1/(7.4 - 7.02) = 2.6 mM per pH unit, which is negligible.

In an open system such as the body, the ventilation simply eliminates excess carbon dioxide and the PCO2 is kept constant: 5.3 kPa or 40 mmHg. The chemoreceptors are bathed in extracellular fluid. Any rise in the PCO2 of the extracellular fluid is sensed by the chemoreceptors and releases a proportionate rise in ventilation. Thus, the new pH is 7.38 (Fig. 17-2). The buffer capacity is at least: 1/(7.4 - 7.38) = 50 mM per pH unit, which is an essential capacity (see Box 17-1)

3. Buffer capacities

The buffer capacity of a system is already defined as the amount of strong acid or base added to one litre (l) of the system in order to change the pH one unit

The most important buffer system for the regulation of [H+] in extended ECV is the carbonic acid (CO2)/bicarbonate system (82%), although its pK is 6.1 and not so close to ideal as for the primary/secondary phosphate system (Box 17-1).

The CO2/bicarbonate buffer is distributed in the extended ECV (up to 15 l of CO2 is bound as bicarbonate). Its buffer capacity is high, since PaCO2 is rapidly maintained normal by respiration, and the kidneys control bicarbonate excretion.

Box 17-1: Principal buffer concentrations and their contribution to the buffer capacity of the extended ECV in a healthy person.


Net-anion Concentration (mM, mean)
Buffer capacity (mM per pH unit)

Bicarbonate
24 (67%)
50 (82%) at constant PaCO2

Non-carbonic buffers
12 (33%)
11 (18%)

Haemoglobin
7
9

Plasma Protein
4
2

Phosphate
1
0.4

Total
36 (100%)
61 (100%)


Of the non-carbonic buffer bases (18%), the haemoglobin has the dominating buffer value with 9 mM per pH unit in the extended ECV, leaving only about 2 mM per pH unit for proteins (essentially albumin) and phosphate (Box 17-1).

Chapter17