Acid – Base Physiology

Question 1

Acid – Base Physiology

Answer 1

• The maintenance of a consistently normal H+ ion concentration in body fluids is critical to survival. Even small variations result cellular compromise and death
• Maintenance of this constant state in the face of changing H+ concentrations has three components:
  1. Buffers of body fluids, both intracellular/extracellular
  2. Respiratory mechanics (C02)
  3. Renal mechanism- excretion of H+, reabsorption and production of HCO3-
• pH is used to describe H+ concentration
  o pH = - log [H+]
   Log curve: small change in pH = very large change in H+ concentration
   Since it is a - log, the lower the pH, the higher the H+ concentration, and vice versa

Question 2

Forms of Acid

Answer 2

• It is helpful to think of acids in humans as existing as one of two basic forms:
  o “Volatile acids”: (H+ + HCO3- —- H2CO3 — C02 + H20); levels may be varied by changes in pulmonary ventilation.
  o “Fixed acids”:
  
  • Sulfuric and phosphoric acids are produced by metabolism of proteins and phospholipids
    -Lactic acid is produced in normal and abnormal states (strenuous exercise, hypoxia)
    -Beta-hydroxybuteric acid and acetoacid are produced in fat metabolism (diabetes mellitus)
    -Ingested acids – vinegar, aspirin (salicylic acid), etc.

Question 3

Buffers

Answer 3

o Buffers are a variety of chemicals and proteins that can absorb free H+ or donate a H+, so that pH changes only minimally, within limits, with addition or removal of H+ from cells, ECF, or blood

o Buffering capacity is critical to survival, otherwise we would see wild changes in tissue pH, both locally (muscle, gut) and systemically with normal activities –ex. Exercise, H+ production in stomach, vinegar on our salad etc.

Question 4

The Equilibrium Constant – K

Answer 4

The Equilibrium Constant is the point at which, for a given acid or base, equilibrium is reached between the dissociated form ([H+] & [A-]) and the associated form ([HA])

K = ([H+]+ [A-])/[HA]

Question 5

The Equilibrium Constant – K

Answer 5

o As an example, for hydrochloric acid (HCL):
This is a strong acid, with most of it in the dissociated form. K for HCL will be a huge number
K = [H+] /[HCl]

o Instead of dealing with huge numbers, scientists convert it to a log function - pK. The pK is the –log of K. For HCL, the K is huge and the pK is small (- log)

Question 6

The Equilibrium Constant – K

Answer 6

We can use this information to calculate the pH of a buffered solution by employing the Henderson – Hasselbalch equation:

pH = pK + log [A-]/[HA]

At equal concentration of [A] and [HA], pH = pK

Question 7

The Equilibrium Constant – K

Answer 7

If you plot a curve of the pH of a solution containing a buffer, while adding acid or base (pH vs. addition of acid or addition of base), you will generate a curve sigmoidal in shape; in the linear portion of the curve only small changes in pH occur with substantial additions / subtractions of H+ vs. the flatter tail portions

Question 8

ECF Buffers

Answer 8

1) Bicarbonate (HCO3-) is the most important extracellular buffer
o pK = 6.1
o Normal serum level is 18 -28 mEq/L
o This buffer, along with carbonic anhydrase, provides a system for a very rapid adjustment of EFC pH by breathing
- Removal of CO2, removes H+, increasing pH
- Retention of CO2 adds H+, lowering pH

Question 9

ECF Buffers

Answer 9

2) Inorganic phosphate 2nd buffer
o PK = 6.8
o Less important than HCO3- because of the large amounts of HCO3- normally present, and because of the ability to rapidly remove CO2

Question 10

ECF Buffers

Answer 10

3) Plasma proteins act as buffer by trading Ca++ for H+

Question 11

ECF Buffers : Pathophysiology

Answer 11

o Alkalemia or alkalosis –less H+ in blood, serum, & ECF – as H+ is pulled off proteins, free Ca++ occupies those available sites on protein, decreasing the available free Ca++. Rapidly occurring depressed levels of free CA++ causes carpal pedal spasm
o Acidemia or Acidosis– excess H+ in blood, serum, & ECF – H+ binds to plasma proteins, increasing free Ca++

Question 12

ICF Buffers

Answer 12

o Organic phosphates – ATP, ADP, AMP, 2-3DPG

o Proteins – hemoglobin, and particularly deoxyhemoglobin

Question 13

Renal Mechanisms in Acid-Base Balance

Answer 13

Slow compensation by:

1. Reabsorption of filtered HCO3- in the proximal tubule increases HCO3- stores (Chronically increased PCO2 levels, as in individuals with severe COPD, is in part, the result of increased reabsorption of HCO3-, resulting in increased serum levels)
2. Excretion of fixed acids.
3. Synthesis of HCO3- – for each H+ excreted, one new HCO3- is synthesized
4. Excretion of H+ as NH4+

Question 14

Pulmonary Mechanisms in Acid-Base Balance

Answer 14

Rapid compensation:

o Maintains pH by varying the minute ventilation which changes PCO2 levels and therefore pH

Question 15

Pathophysiology: Acid-Base Disorders

Answer 15

o Acidemia / Acidosis – disorders resulting in increased [H+] which results in a pH less than 7.35. This may occur because of a relative increase in H+ or a decrease in buffering capacity (HC03-)
o Alkalemia /Alkalosis – disorders resulting in decreased [H+] resulting in pH greater than 7.45. Most commonly results from a decreased H+ concentration secondary to increased minute ventilation

Question 16

Pathophysiology: Acid-Base Disorders

Answer 16

o Metabolic acid-base disturbances: Typically the result of increased fixed acids; occasionally by decreased HCO3- levels

• Increased production of non volatile acids
• Decreased acid excretion by kidney
• Decreased synthesis of HCO3- by the kidney
• “Loss of alkali” (HCO3-) usually GI, occasionally renal

Question 17

Pathophysiology: Acid-Base Disorders

Answer 17

o Respiratory acid-base disturbances: Disturbances of PCO2 levels as the result of:

• Respiratory failure / inadequate minute ventilation resulting in “respiratory acidosis”
• Alkalosis caused by
• Hypoxia, stimulating the respiratory center, increasing minute ventilation
• Anxiety, sepsis, pregnancy, etc.

Question 18

An Approach to Simple Acid Base Disorders

Answer 18

o Easiest to use Arterial Blood Gases (ABG’s) to diagnosis and differentiate acid base disorders
- Identify abnormalities of pH, PCO2, and bicarbonate
• pH identifies the disorder as acidemic or alkalemic
• Abnormalities of PCO2 levels identifies a respiratory component to the pathophysiology
• Abnormalities of HCO3- levels identifies a metabolic component to the pathophysiology

Question 19

An Approach to Simple Acid Base Disorders:

Answer 19

For each change in PC02 of 10 mm, pH will change by approximately 0.08 in the opposite direction

Question 20

Compensation Mechanisms for Acid-Bases Abnormalities

Answer 20

o As pH varies from normal levels, the body will attempt to adapt to bring pH into normal ranges (homeostasis)
o Two primary mechanisms used to maintain normal pH:
1. Respiratory Compensation – PCO2 can be rapidly changed to influence pH
2. Renal compensation – HCO3- levels and acid excretion can be altered to return pH toward normal

Question 21

Some Causes of Acid-Base Disorders - Respiratory Acidosis: caused by a relative Hypoventilation

Answer 21

o CNS problems,
- Narcotics, ETOH, barbiturates, tumor, stroke, quadriplegia, head injury etc.
o Pulmonary disease states – minute ventilation may or may not be normal; diffusion of gases and respiratory mechanic may be fouled up
- COPD, Emphysema, Asthma, etc.
- Pneumonia, CHF, etc.
- Airway obstruction, pneumothorax etc.
oNeuromuscular disease states
- Tetanus, botulism, curare, organophosphate poisoning
- Etc.

Question 22

Some Causes of Acid-Base Disorders - Respiratory Alkalosis caused by hyperventilation.

Answer 22

Conditions that are associated with respiratory alkalosis include:

• Anxiety
• Hypoxia
• Pregnancy (high estrogen state)
• High altitude (resulting from relative hypoxia)
• Sepsis
• As a physiologic attempt to counter a metabolic acidosis; ex. Aspirin overdose (metabolic acidosis) may cause a “compensatory” respiratory alkalosis in the body’s attempt raise pH into the normal range. This may result in a partial or complete compensation of a metabolic acidosis (“mixed acid-base disorder” because both pulmonary and renal mechanisms are involved – this case would illustrates a “metabolic acidosis with a respiratory compensation”)

Question 23

Some Causes of Acid-Base Disorders - Metabolic Acidosis

Answer 23

o Overproduction of Acid
i. Diabetic keto-acidosis
ii. Lactic Acidosis
o Decreased excretion of [H+] – Renal failure
o Loss of HCO3- ex. GI losses, renal losses

Question 24

Some Causes of Acid-Base Disorders - Metabolic Alkalosis

Answer 24

o Vomiting

o Excretion of body acids rapidly

Question 25

Anion Gap: A Measure of Unmeasured Anions

Answer 25

The Anion Gap is used to refine the differential diagnosis of metabolic acidosis (Useful in differentiating the different causes (classes?) of metabolic acidosis.). As an example, in a patient with metabolic acidosis, you may want to determine if the underlying cause to too much fixed acid or not enough bicarbonate.

• Requires only simple blood tests

Question 26

Anion Gap: A Measure of Unmeasured Anions

Answer 26

It is a measure of cation (+) concentration vs. anion (-) concentration. The principle of electrical neutrality results in organisms having equal concentration of cations and anions. The anion gap represents unmeasured anions, mostly the negative charges on plasma proteins
Normal range for anion gap – 12 + or – 4 mEq/l. (Because of improved testing, some authorities feeling 7 +/- 4 is more accurate)

Question 27

Anion Gap: A Measure of Unmeasured Anions

Answer 27

Anion gap:
Anion gap =  [Na+] – ([HCO3-] + [Cl-]
	Normal range 8 –16 mEq/L
	Ex. A Patient’s labs reveals:
•	Na+ = 140,
•	Cl- = 105
•	 HCO3-  =24
 Anion Gap = 140 – (24 +105)
                           = 140 – 129
                           = 11 mEq/L

Question 28

Anion Gap: A Measure of Unmeasured Anions

Answer 28

o In an acidotic patient, if the anion gap is increased – the patient has an “extra acid” present in their system that you are not measuring (examples: ketoacidosis in a diabetic, lactic acidosis, aspirin, methanol)

o If the anion gap is normal – the patient has lost HCO3- (GI or renal losses are most common –diarrhea, pancreatic fistulae). Because of the principle of electrical neutrality, HCO3- losses are replace by increasing Cl- levels (Hyperchloremic metabolic acidosis)

o A low anion gap is often the result of hypoalbuminemia