Acid Base Balance (2)

• 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

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