Acid Base Balance

Question 1

Define homeostasis

Answer 1

The state of equilibrium in the body with respect to various functions (biochemical, physiologic, etc) and chemical compositions of the fluids and tissues.

Question 2

Normal Blood H+ concentration

Answer 2

35 - 45 nmol/l

Question 3

Concentrations of H+_____ or are generally incompatible with life______

Answer 3

Below 20 nmol/l
above 120 nmol/l

Question 4

The definition of pH is :

Answer 4

pH = -log [H+ ]

Question 5

The pH homeostasis is regulated by_______

Answer 5

the acid/base concentration in the ECF

Question 6

The pH homeostasis is regulated by_______

Answer 6

the acid/base concentration in the ECF

Question 7

The main sources of H+ in the body include

Answer 7

1. Normal body metabolic processes (aerobic/anaerobic metabolism, oxidative processes)
   2. Diet, e.g. …
   3. Drugs, e.g. aspirin, PCM(paracetamol)

Question 8

The acid/base balance regulation is a function of which systems

Answer 8

RESPIRATORY AND RENAL SYSTEMS

Question 9

The main ways of excreting H+

Answer 9

1. Buffering
2. Respiratory system - hyperventilation
3. Renal system - secretion of H+, reclamation of HCO3-, etc

Question 10

Sources of hydrogen ions via metabolic processes

Answer 10

1. Oxidation of proteins, nucleic acids and phospholipids produces phosphoric and sulphuric acids.
2. Incomplete (anaerobic) metabolism of fat and carbohydrates produces organic acids such as lactic, acetoacetic and β-hydroxybutyric acids. In solution these dissociate to yield hydrogen ions.
3. Complete (aerobic) metabolism of fat and carbohydrates produces CO2. In solution, CO2 forms a weak acid (carbonic acid) which also has the potential to affect [H+] and pH, via dissociation.

Question 11

What processes in the body remove the bulk of H+ produced?

Answer 11

Normal metabolic processes such as gluconeogenesis and oxidation of ketones remove the bulk of the hydrogen ions produced

Question 12

Excess production of 50 - 100 mmoles of hydrogen ions per day are removed via

Answer 12

1. Buffers
2. Lungs: CO2 is volatile, and under normal circumstances is transported to the lungs in the blood and is rapidly excreted by the lungs. Only if respiratory function is impaired do problems occur.
3. Kidneys: Excess H+ produced are excreted by the kidneys

Question 13

Define an acid

Answer 13

Acid: An acid is a compound which dissociates in an aqueous solution to produce H+, e.g.

H CO ↔ H+ + HCO - 233
H PO -↔H+ +HPO42- 24

Acids dissociate in water to varying degrees, depending on their strength.

Question 14

Define a base

Answer 14

Base: A base is a substance that is capable of accepting hydrogen ion, e.g.

HCO - + H+ ↔ H CO 32- + 2 3-
HPO4 + H ↔ H2PO4
Bases dissociate in water to varying degrees, depending on their strength.

Question 15

Define strong and weak acids with examples

Answer 15

The strength of an acid is defined by its tendency to dissociate, thereby producing free hydrogen ions

A strong acid dissociates completely even in acidic solutions
e.g., H SO → H+ + HSO - 244

A weak acid only dissociates partially in acidic solutions, reaching a state of equilibrium between the acid HA and its conjugate base A- e.g.,
H2PO ↔ H+ + H PO - 34 24
H CO ↔ H+ + HCO - 233
NH + ↔ H+ + NH 43

Question 16

How can the strength of an acid be measured by it’s dissociation constant?

Answer 16

For a strong acid, K is large (> 1) and pK is small (< 0)

For a weak acid, K is small (<10-3) and pK is large (>3)

Question 17

what are the conjugate pairs of the following:
H2PO4-
H2CO3/
HHb/
NH4+

Answer 17

H2PO4- /HPO42-
H2CO3/HCO3-
HHb/Hb-
NH4+/NH3

Question 18

Define a buffer

Answer 18

A compound/substance that limits the change in H+ concentration (and so pH) when H+ are added or removed from the solution.

A mixture of a weak acid and a salt of it’s conjugate base that resists a change in pH when a strong acid or base is added to the solution.

Question 19

What is the Henderson-Hasselbalch equation

Answer 19

It expresses the relationship between pH and a buffer pair. In aqueous solution, the pH is determined by the concentration ratio of the acid to its conjugate base.

Question 19

What are acidemia and alkalemia?

Answer 19

Acidemia – arterial pH < 7.35
Alkalemia – arterial pH > 7.45

Question 20

What are acidosis and alkalosis?

Answer 20

Acidosis – pathological states that lead to acidemia
Alkalosis - pathological states that lead to alkalemia

Question 21

Define Respiratory component

Answer 21

The term defines the PCO2 level as this parameter is ultimately controlled by respiration. A high PCO2 (>45 mmHg) is a respiratory acidosis and a low PCO2 (<33 mmol/L), a respiratory alkalosis.

Question 21

Define Metabolic component

Answer 21

This describes the plasma bicarbonate concentration. Metabolic acidosis is defined by a low plasma [HCO3-] (e.g., <23 mmol/L) and metabolic alkalosis, by a high plasma [HCO3-] (>33 mmol/L).

Question 22

pH vakues for acidosis and alkalosis

Answer 22

Below pH 7.35 —– ACIDOSIS / Below 6.9 — DEATH

Above pH 7.45 —– ALKALOSIS /Above 7.8 — DEATH

Question 23

What is the Plasma anion gap?

Answer 23

In plasma, as in any other fluid compartment in the body, the number of electrical charges on the cations equals the number of charges on the anions, i.e., electrical neutrality is maintained. However, the routine biochemistry laboratory generally only measures the sodium, potassium, chloride, and bicarbonate ions and, by convention, the difference between the sum of the measured cation concentrations (Na+ + K+) and the sum of the measured anion concentrations (CI- + HCO3−) is called the anion gap

Question 24

Why anion gap?

Answer 24

The anion gap (the unmeasured anions) is constituted by the charges of the plasma proteins and amino acids, and the organic acid anions (acetoacetate, β-hydroxybutyrate, etc). The protein concentration remains relatively constant, but the concentrations of other unmeasured anions can vary considerably in disease.

Question 25

normal value of anion gap

Answer 25

15–20 mmol/L

Question 26

Usefulness of anion gap

Answer 26

Its usefulness lies in the fact that metabolic acidosis can be classified as either a high anion gap metabolic acidosis or a normal anion gap metabolic acidosi

Question 27

Benefit of urinary gap

Answer 27

urinary anion gap can also be measured and is useful in the diagnosis of renal tubular acidosis.

Question 28

Types of BUFFER SYSTEMS

Answer 28

(a) Bicarbonate buffer
(b) Haemoglobin buffer
(c) Phosphate buffer
(d) Ammonia buffer

Question 29

5 ways the Renal System balances pH

Answer 29

1. Na+-H+ exchange leading to H+ secretion
2. Bicarbonate reclamation (reabsorption of filtered HCO3-)
3. Bicarbonate regeneration
4. Excretion of H+ as H2PO4-
5. Renal production of NH3 & excretion of ammonium ion

Question 30

pK values of buffer systems

Answer 30

Bicarbonate system: H2CO3/HCO3- (pK = 6.1)

Protein system: protein+/protein- (pK = ??)

Haemoglobin system: HHb/Hb- (pK = 7.3)

Phosphate system: H2PO4-/HPO42- (pK = 6.8)

Ammonia system: NH4+/NH3 (pK = 9.8)

Question 31

What is the most important, most effective buffer pair and why?

Answer 31

The bicarbonate system is the most important & effective buffer in the body because:
● it accounts for 60-75% of blood buffering capacity (present at higher concentrations than other buffers, with the exception of Hb),
● the lungs can readily dispose of or retain CO2,
● H+ secretion by the kidney depends on it,
● the renal tubules can increase or decrease the rate of reclamation of bicarbonate from the glomerular filtrate,
● it is necessary for efficient buffering by Hb, which provides most of the rest of the blood buffering capacity.

Question 32

How do simple buffers lose their effectiveness

Answer 32

Simple buffer systems, including proteins and Hb, lose their effectiveness when the association of H+ with the base reaches equilibrium with the weak acid.

Question 33

What limits the effectiveness of the bicarbonate buffer system?

Answer 33

The only thing which thus limits the effectiveness of the bicarbonate buffer system is the availability of HCO3-. Should the HCO3- concentration drop too much, buffering would cease. Under physiological circumstances however, this is prevented by the fact that the body both conserves existing HCO3- (reclamation), and in the process of excreting H+ also regenerates new HCO3-.

Question 33

Why does the bicarbonate buffer system not lose it’s effectiveness (explain the open buffering system)

Answer 33

In the bicarbonate buffer system, however, the weak acid carbonic acid can dissociate into H2O and CO2. This process is normally extremely slow, but is accelerated by the enzyme carbonic anhydrase (CA) which is present in the RBC and kidneys. The CO2 which is formed is volatile, and is continually removed by the lungs. This “open” buffering system means that equilibrium is never reached, and continual buffering of H+ is achieved at the expense of continually consuming HCO3-.

Question 33

Role of lungs/haemoglobin - transport of CO2 and buffering (Respiratory System) - AEROBIC METABOLISM

Answer 33

CO2 from complete (aerobic) metabolism of fat and carbohydrates, diffuses out of cells into the ECF. In the ECF a small amount combines with water to form carbonic acid, thereby increasing the [H+] and decreasing the pH of the ECF.

Question 33

Role of lungs/haemoglobin - transport of CO2 and buffering (Respiratory System) - IN RBC

Answer 33

In red blood cells (RBC) metabolism is anaerobic and no CO2 is formed. CO2 therefore diffuses into RBC down a concentration gradient. In the RBC the majority of the CO2 combines with water to form carbonic acid, due to the presence of C.A. The carbonic acid dissociates to form H+ and HCO3-, and the H+ are bound by the Hb. Deoxygenated Hb binds H+ more strongly than oxygenated Hb, and in fact the binding of H+ to Hb facilitates the release of oxygen (the Bohr effect). The overall effect of this process is that CO2 is converted to HCO3- in red blood cells. The HCO3- diffuses out of the RBC along a concentration gradient, to be replaced by chloride ions (the chloride shift).

Question 34

The difference between the mechanisms for HCO3- reabsorption and generation

Answer 34

The mechanisms for HCO3- reabsorption and generation are very similar and easily confused, the difference is in net H+ excretion.

Question 34

Role of lungs/haemoglobin - transport of CO2 and buffering (Respiratory System - LUNGS

Answer 34

In the lungs, the reverse occurs, because of the low partial pressure of CO2 in the alveoli: HCO3- diffuses into the red cells, combines with H+ released when Hb binds oxygen, and is converted into CO2, which diffuses into the alveoli to be excreted. The role of Hb is therefore to transport O2 and by converting CO2 to bicarbonate, to minimise changes in the HCO3- /CO2 ratio between venous and arterial blood, which helps to minimise pH changes.

Question 35

Role of the kidney in handling bicarbonate and hydrogen: Reclamation

Answer 35

The glomerular filtrate contains the same concentration of HCO3- as the plasma. The luminal surface of the renal tubular cells is impermeable to HCO3- , and direct reabsorption can thus not occur.

Within the renal tubular cells, CO2 combines with water to form carbonic acid, due to the presence of C.A. The carbonic acid dissociates to form H+ and HCO3-. The H+ are secreted into the tubular lumen in exchange for Na+, while the HCO3- pass across the basal border of the cells into the interstitial fluid together with the Na+.

In the tubular lumen the H+ combine with the filtered HCO3- , form carbonic acid and then CO2 and water, some of which filters back into the renal tubular cell.

The net effect of this process is that filtered HCO3- is reabsorbed, but although there is H+ secretion, there is no net H+ excretion. This process takes place as long as filtered HCO3- is present in the tubular lumen, which is essentially in the proximal renal tubule.

Question 36

Role of the kidney in handling bicarbonate & hydrogen: Excretion of H+ & regeneration of HCO3-

Answer 36

After filtered HCO3- is fully reabsorbed, H+ secretion into the tubular lumen causes a net excretion of H+. This process uses the same mechanism as described above, but requires the presence of urinary buffers, otherwise the H+ gradient created would prevent further H+ secretion. The main urinary buffer is phosphate, which is present predominantly as HPO42-. This combines with secreted H+ to form H2PO4.
Another important urinary buffer is ammonia, produced by deamination of glutamine in renal tubular cells. The enzyme responsible, glutaminase, is induced by chronic acidosis, and there is thus an unlimited supply of NH3. The NH3 can diffuse across the renal tubular membrane, but NH4+ cannot. This process takes place as long as there is no more filtered HCO3- present in the tubular lumen.