Acid Base Balance

Mike Clark, M.D.

• Acid - proton H+ donor• Base – proton H+ acceptor• Buffer – a chemical that resists a change in pH

Acid-Base Balance

• Normal pH of body fluids– Blood pH range 7.35 – 7.45– Arterial blood is 7.4– Venous blood and interstitial fluid is 7.35– Intracellular fluid is 7.0

• Alkalosis or alkalemia – arterial blood pH rises above 7.45

• Acidosis or acidemia – arterial pH drops below 7.35 (physiological acidosis)

pH BufferA substance that resists a change in pH

• Composition: A weak acid in equilibrium with its conjugate base

Weak Acid Conjugate Base• [H3A] [H2A-] + [H+]

• A weak acid does not completely dissociate -liberate its H+ whereas a strong acid completely or almost completely dissociates

• Add outside acid to buffer it combines with the base H2A- to make more weak acid – add base it combines with the acid H+ to make more weak acid

Chemical Buffer Systems• Three major chemical buffer systems

1. Bicarbonate buffer system – main extracellular buffer

– Two non-bicarbonate buffer systems2. Phosphate buffer system3. Protein buffer system – most abundant – main

intracellular buffer• Any drifts in pH are resisted by the entire

chemical buffering system

What Is the Problem with the wrong pH in the Human Body?

• Improper pH denatures (bends out of shape) proteins.

• When proteins bend too far out of shape they cease to function.

• Functions of Proteins- Contractile, Regulatory, Enzymatic, Structural, Transport, Hormones

• Most important function of all “Enzymes” • Why? They direct the pathway of all

biochemical reactions.

What are the mechanisms in the human body that regulate blood pH?

• Concentration of hydrogen ions is regulated sequentially by:– Chemical buffer systems – act within seconds– The respiratory center in the brain stem – acts

within 1-3 minutes– Renal mechanisms – require hours to days to

effect pH changes

Why is the regulation of blood pH so important? Don’t we have other fluids and tissues to protect also?

• Since blood transports throughout the entire human body (except dead areas like the top of the skin) – it keeps the pH of the other body areas proper – if its pH is proper.

pH Scale

• Goes from 0 – 14 with 7 being neutral

• Below seven is acidic• Greater than 7 is basic (alkaline)

What is pH and how is it determined?• pH – stands for the powers of hydrogen• It is calculated using a mathematical formula

pH = - Log [H+]• This is the universal formula used in all of

chemistry to determine pH• However – the biochemical community uses

another formula derived from the universal pH formula (Henderson-Hesselbach formula)

Henderson-Hasselbach• pH = pKa + Log [Base] / [Acid]• The equation was derived from the universal

pH equation. The equation uses the reactionH2CO3 HCO3

- + H+

as its basis• Using this reaction the pKa is 6.1• The Base is HCO3

- The Acid is H2CO3

•

• In an arterial blood gas – one does get the HCO3

- (bicarbonate) value but not the H2CO3 (carbonic acid value). But the amount of Carbonic acid in the blood depends on Henry’s law – thus the partial pressure of the gas times the solubility coefficient. Thus .03 x PaCO2 is used. The arterial blood gas does give the value of PaCO2.

• pH = pKa (6.1) + Log [HCO3- ] / .03 x [PaCO2 ]

• The ideal arterial pH of the blood should be 7.4

• So if 7.4 = 6.1 + Log [HCO3- ] / .03 x [PaCO2 ]

• The Log of Base of Acid needs to equal to 1.3• The Log of 20 is 1.3 – thus the ratio of base to

acid needs to be 20 (20 more times base than acid)

[Total Acid] = [Volatile Acid] + [Fixed Acid] • The total [H+] (Acid) in the blood is measured when you

calculate pH – it makes no difference where the H+

came from There are two acid types in the body

• Fixed Acids and Volatile Acids• There is only one type of Volatile Acid – Carbonic acid –

created from carbon dioxide mixing with water• All the other Acids in the body are termed “fixed acids”

like lactic acid, hydrochloric acid and others • Homeostasis – if the fixed or volatile acid concentration

goes up because of a problem the acid concentration without the problem should go down to compensate

Normal Arterial Blood Gas Values

• pH – 7.35 – 7.45 • PaO2 - 80 to 100 mm Hg.• HCO3

- - 22 to 26 mEq/liter• PaCO2 - 35-45 mm Hg

When Acid/Base Balance in the Blood Goes Wrong

• Respiratory Acidosis – Lungs caused the acidosis• Metabolic Acidosis – there is blood acidosis, but

the lungs did not cause – something else in the body caused it

• Respiratory Alkalosis – Lungs caused the alkalosis• Metabolic Alkalosis - there is blood alkalosis, but

the lungs did not cause – something else in the body caused it

Respiratory Acidosis and Alkalosis

• Result from failure of the respiratory system to balance pH

• PCO2 is the single most important indicator of respiratory inadequacy

• PCO2 levels– Normal PCO2 fluctuates between 35 and 45 mm Hg– Values above 45 mm Hg signal respiratory acidosis– Values below 35 mm Hg indicate respiratory

alkalosis

pH = 6.1 + Log [HCO3]/PaCO2 x .03Must keep a ratio of 20 to 1 Base to Acid for pH to

be 7.4. • Respiratory AcidosisIf PaCO2 goes up then the ratio drops and the blood

becomes acidic – unless the kidney holds on to more bicarbonate to compensate

• Respiratory AlkalosisIf PaCO2 goes down then the ratio increases and the

blood becomes basic – unless the kidney removes (urinates out) more bicarbonate to compensate

pH = 6.1 + Log [HCO3]/PaCO2 x .03Must keep a ratio of 20 to 1 Base to Acid for pH to be 7.4. • Metabolic AcidosisIf PaCO2 is normal or low and the blood is acidotic then the lungs

are not the problem since they are not causing more carbonic acid to be made – thus the acidosis is due to something else in the body “metabolic” - the lungs maybe blowing off more CO2 than usual to help – thus compensate. Examples Lactic Acidosis or Diabetic Ketoacidosis

• Metabolic AlkalosisIf PaCO2 is normal or elevated and the blood is alkalotic then the

lungs are not the problem since they are not causing less carbonic acid to be made – thus the alkalosis is due to something else in the body “metabolic” - the lungs maybe holding on to more CO2 than usual to help – thus compensate. Example Milk alkali sydrome

Compensatory Actions• Complete compensation – though a metabolic or

respiratory problem – the compensatory mechanism is so good it completely compensates – thus pH stays completely normal (this very, very rarely occurs – for the most part never)

• Partial compensation- though a metabolic or respiratory problem – the compensatory mechanism tries to keep the pH normal – and does to some extent.

• Respiratory Acidosis (completely or partially) compensated by a metabolic alkalosis

• Metabolic Acidosis (completely or partially) compensated by a respiratory alkalosis

• This also occurs for respiratory or metabolic alkalosis

Davenport Curves

pH Problems

• Arrhythmias can result when the pH falls below 7.25, and seizures and vascular collapse can occur when pH rises above 7.55.

PLAY InterActive Physiology ®: Acid/Base Homeostasis, page 34

Reabsorption of Bicarbonate• Carbonic acid

formed in filtrate dissociates to release carbon dioxide and water

• Carbon dioxide then diffuses into tubule cells, where it acts to trigger further hydrogen ion secretion

Figure 26.12

Copyright © 2010 Pearson Education, Inc.

CO2 combines with water within the type A intercalated cell, forming H2CO3.

H2CO3 is quickly split, forming H+ and bicarbonate ion (HCO3

–).

H+ is secreted into the filtrate by a H+ ATPase pump.

For each H+ secreted, a HCO3– enters the

peritubular capillary blood via an antiport carrier in a HCO3

–-CI– exchange process.Secreted H+ combines with HPO4

2– in the tubular filtrate, forming H2PO4

–.The H2PO4

– is excreted in the urine.

Nucleus

Type A intercalatedcell of collecting duct

Filtrate intubule lumen Peri-

tubularcapillary

H+ + HCO3–

Cl–

Cl–

HPO42–

H2PO4–

out in urine

H2O + CO2

H2CO3

H+

Primary active transport

Simple diffusion

Secondary active transport

Facilitated diffusion

Carbonic anhydrase

Transport protein Ion channel

Cl–

HCO3–

(new)ATPase

Figure 26.13 New HCO3– is generated via buffering of secreted H+ by HPO4

2– (monohydrogen phosphate). Slide 1

1

24

53a

3b

1

2

4

5

3a 3b

Figure 26.14

Nucleus

PCT tubule cells

Filtrate intubule lumen

Peri-tubularcapillary

NH4+

out in urine

2NH4+

Na+

Na+ Na+ Na+ Na+

3Na+3Na+

Glutamine GlutamineGlutamine

Tight junction

Deamination,oxidation, and acidification(+H+)

2K+2K+

NH4+ HCO3

–2HCO3– HCO3

–

(new)

ATPase

1 PCT cells metabolize glutamine to NH4

+ and HCO3–.

2a This weak acid NH4+ (ammonium) is

secreted into the filtrate, taking the place of H+ on a Na+- H+ antiport carrier.

2b For each NH4+ secreted, a

bicarbonate ion (HCO3–) enters the

peritubular capillary blood via a symport carrier.3 The NH4

+ is excreted in the urine.

Primary active transport

Simple diffusion

Secondary active transport

Transportprotein

1

2a 2b

3