1. Acid Base Balance Mike Clark, M.D.
This can be further studied in my A&P 1 PowerPoint file of Chemistry Inorganic.

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

3. Acid-Base Balance Normal pH of body fluids
Blood pH range – 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)

4. A substance that resists a change in pH
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

5. What is a pH Buffer?
A pH buffer resists a change in pH
A pH buffer is chemically comprised of a weak acid in association with its conjugate base

6. Are all the substances above acids?
Strength of Acids
(1) H3A H3A
(2) H3A H2A- + H+
(3) H3A HA H+
(4) H3A A H+
Are all the substances above acids?

7. Are all the substances above acids?
Strength of Acids
(1) H3A H3A
(2) H3A H2A- + H+
(3) H3A HA H+
(4) H3A A H+
Are all the substances above acids?
No, number 1 did not liberate protons, so it is not an acid. An acid is a proton donor; it must liberate the proton(s).
For a better explanation – look in my A&P 1 PowerPoint file at acid base.

8. Chemical Buffer Systems
Three major chemical buffer systems
Bicarbonate buffer system – main extracellular buffer
Two non-bicarbonate buffer systems
Phosphate buffer system
Protein buffer system – most abundant – main intracellular buffer
Any drifts in pH are resisted by the entire chemical buffering system working together in a confluent manner – known as the “isohydric principle”

10. 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.

11. Arterial Blood Gas Report

12. Clinical Signs of Acidosis
Metabolic acidosis- headache, coma, reduced cardiac output, abnormal heart rhythm, lethargy, respiratory distress, hyperventilation, muscle fatigue, osteomalacia, fractures
Respiratory acidosis- combativeness, confusion, hallucinations, transient psychosis, myoclonic jerks, flapping tremor, constricted pupils, reduced tendon reflexes, papilledema, breathlessness, cyanosis, pulmonary hypertension, warm skin, flushed skin, bounding pulse, Cor Pulmonale, Low Blood Pressure, Peripheral Edema, Azotemia, Easily fatigued, Chronic cough, Wheezing, irritability, gait disturbance,

13. Clinical Signs of Alkalosis
Metabolic Alkalosis – headache, stupor, seizures, tetany, weakness, delirium, hypoventilation, hypoxemia, hypokalemia, hypocalcemia, excessive urination, excessive thirst, kidney cysts
Respiratory Alkalosis – confusion, dizziness, fainting, numbness, constriction of brain blood vessels, reduced intracranial pressure, light-headiness, increased deep tendon reflexes, chest pain, paresthesia's in the extremities, laryngeal spasm, muscle cramps,

14. 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 – but is more long lasting

15. Why is the regulation of blood pH so important
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.

16. pH Scale Goes from 0 – 14 with 7 being neutral Below seven is acidic
Greater than 7 is basic (alkaline)

17. 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)

18. Henderson-Hasselbach
pH = pKa + Log [Base] / [Acid]
The equation was derived from the universal pH equation. The equation uses the reaction
H2CO HCO3- + H+
as its basis
Using this reaction the pKa is 6.1
The Base is HCO The Acid is H2CO3

19. 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 the amount of CO2 dissolved in the blood which is governed by 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 ]

20. The ideal arterial pH of the blood should be 7.4
So if 7.4 = 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)

21. [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

22. Normal Arterial Blood Gas Values
pH – 7.35 – 7.45
PaO to 100 mm Hg.
HCO3-  - 22 to 26 mEq/liter
PaCO mm Hg

23. 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

24. 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

25. pH = 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

26. pH = 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 syndrome

27. 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

29. Davenport Curves

30. 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.

31. 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

32. cell of collecting duct
Figure New HCO3– is generated via buffering of secreted H+ by HPO42– (monohydrogen phosphate).
Slide 1 1 3b
CO2 combines with water within the
type A intercalated cell, forming H2CO3.
For each H+ secreted, a HCO3– enters the
peritubular capillary blood via an antiport
carrier in a HCO3–-CI– exchange process. 2
H2CO3 is quickly split, forming
H+ and bicarbonate ion (HCO3–). 4
Secreted H+ combines with HPO42– in
the tubular filtrate, forming H2PO4–. 3a
H+ is secreted into the filtrate by a
H+ ATPase pump. 5
The H2PO4– is excreted in the urine.
Nucleus
Filtrate in
tubule lumen
Peri-
tubular
capillary
H2O + CO2 1
H2CO3
HPO42–
Primary active
transport 2 3a 3b
Secondary
active
transport H+
H+ + HCO3–
HCO3–
(new)
ATPase 4
Simple
diffusion
Cl–
Cl–
Facilitated
diffusion
Cl–
Type A intercalated
cell of collecting duct
Transport
protein
H2PO4– 5
Ion channel
out in urine
Carbonic
anhydrase

33. 1 2b 2a 3 PCT cells metabolize glutamine to For each NH4+ secreted, a
NH4+ and HCO3–. 1
For each NH4+ secreted, a
bicarbonate ion (HCO3–) enters the
peritubular capillary blood via a
symport carrier. 2b
This weak acid NH4+ (ammonium) is
secreted into the filtrate, taking the
place of H+ on a Na+- H+ antiport carrier. 2a 3
The NH4+ is excreted in the urine.
Nucleus
Filtrate in
tubule lumen
Peri-
tubular
capillary
PCT tubule cells
Glutamine
Glutamine
Glutamine
Deamination,
oxidation, and
acidification
(+H+) 1 2a 2b
NH4+
2NH4+
2HCO3–
HCO3–
HCO3–
(new) 3
Na+
Na+
Na+
Na+
NH4+
out in urine
Primary
active
transport
2K+
2K+
ATPase
Secondary
active
transport
3Na+
3Na+
Na+
Simple
diffusion
Tight junction
Transport
protein
Figure 26.14