Download Acid Base Balance (2)

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 Buffer
A 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 systems
2. Phosphate buffer system
3. 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 reaction
H2CO3
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 .03
Must keep a ratio of 20 to 1 Base to Acid for pH to
be 7.4.
• Respiratory Acidosis
If PaCO2 goes up then the ratio drops and the blood
becomes acidic – unless the kidney holds on to
more bicarbonate to compensate
• Respiratory Alkalosis
If 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 .03
Must keep a ratio of 20 to 1 Base to Acid for pH to be 7.4.
• Metabolic Acidosis
If 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 Alkalosis
If 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
venport 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.
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
PLAY
InterActive Physiology ®:
Acid/Base Homeostasis, page 34
Figure 26.12
Figure 26.13 New HCO3– is generated via buffering of secreted H+ by HPO42– (monohydrogen phosphate).
Slide 1
3b For each H+ secreted, a HCO3– enters the
1 CO2 combines with water within the
peritubular capillary blood via an antiport
carrier in a HCO3–-CI– exchange process.
type A intercalated cell, forming H2CO3.
2 H2CO3 is quickly split, forming
H+ and bicarbonate ion (HCO3–).
4 Secreted H+ combines with HPO42– in
H+ ATPase pump.
5 The H2PO4– is excreted in the urine.
the tubular filtrate, forming H2PO4–.
3a H+ is secreted into the filtrate by a
Nucleus
Filtrate in
tubule lumen
Peritubular
capillary
H2O + CO2
1
H2CO3
HPO42–
2
3a
H+ + HCO3–
H+
4
H2PO4–
3b
HCO3–
(new)
ATPase
Cl–
Type A intercalated
cell of collecting duct
5
out in urine
Copyright © 2010 Pearson Education, Inc.
Cl–
Cl–
Primary active
transport
Secondary
active
transport
Simple
diffusion
Facilitated
diffusion
Transport
protein
Ion channel
Carbonic
anhydrase
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 NH + is excreted in the urine.
4
Nucleus
Filtrate in
tubule lumen
Peritubular
capillary
PCT tubule cells
Glutamine
Glutamine
Deamination,
1 oxidation, and
acidification
(+H+)
2a
NH4+
3
Na+
Glutamine
2b
2NH4+ 2HCO3–
HCO3–
Na+
Na+
Na+
NH4+
out in urine
2K+
HCO3–
(new)
2K+
ATPase
3Na+
Tight junction
3Na+
Na+
Primary
active
transport
Secondary
active
transport
Simple
diffusion
Transport
protein
Figure 26.14