4.7. Basic terms of acid-base balance. Buffer systems of the body. Parameters of acid-base balance.

Question 1

I. Basic terms of acid-base balance
1. What is the role of Acid-base balance?

Answer 1

Acid-base balance maintains a normal proton concentration in body fluids
=> This is achieved by utilization of buffers

Question 2

I. Basic terms of acid-base balance
2. What are definitions of acid and base?

Answer 2

• Acid: any chemical that can donate H+
• Base: any chemical that can accept H+

Question 3

I. Basic terms of acid-base balance
2A. What are volatile acids?

Answer 3

Volatile acids are defined as those acids which can be converted into a gaseous form and can thus be eliminated by the lungs.
=> Volatile acid in the body is mainly CO2.
-> In the reaction with carbonic anhydrase, CO2 is combined with H2O to make H2CO3 and eventually HCO3- + H+.

Question 4

I. Basic terms of acid-base balance
2B. What are non-volatile acids?

Answer 4

A nonvolatile (fixed) acid is an acid produced in the body from sources other than CO2 and is not excreted by the lungs.
-> These acids are usually produced from amino acids with sulphur (makes sulphuric acid) and phospholipids (phosphoric acid).
-> As mentioned, they cannot be expired in the lungs, so they have to be buffered in the body and excreted in urine.
-> Overproduction of these acids can cause acidosis. (ex: lactic acid, formic acid, etc.)

Question 5

I. Basic terms of acid-base balance
3. What is a Normal H+ conc.?

Answer 5

= 40 nEq/L, pH = 7.4

Question 6

I. Basic terms of acid-base balance
4. What is the normal range of arterial pH?

Answer 6

o Normal range of arterial pH = 7.4 (less: acidemia, more: alkalemia)

Question 7

I. Basic terms of acid-base balance
5. What is the Cytosol of a typical cell pH?

Answer 7

7.2

Question 8

I. Basic terms of acid-base balance
6. What is the definition of pH?

Answer 8

pH – negative logarithm of hydrogen ion concentration (-log [H+])

Question 9

I. Basic terms of acid-base balance
6A. What is the role of pH?

Answer 9

H+ affects biologically important molecules:
- Enzymes, receptors, ion channels, transporters, structural proteins
- If a protein gets protonated (HPr ⇌ H+ + Pr-), the ion concentrations will become very different
=> [K+] and [Ca2+] will especially be independent on PH

Question 10

I. Basic terms of acid-base balance
7A. What is a buffer?

Answer 10

• A solution which resists changes in pH when a small amount of acids/bases are added to it

Question 11

I. Basic terms of acid-base balance
7B. How is a buffer made?

Answer 11

Made of a mixture of a weak acid and its conjugated base OR a weak base and its conjugated acid (a strong acid/base would release the proton, and would not work in the physiological range)
=> Buffers should work close to the physiological range (to maintain blood pH = 7,35 to 7,45)

Question 12

I. Basic terms of acid-base balance
7C. What is the optimal working range of buffer?

Answer 12

Buffers should work close to the physiological range (to maintain blood pH = 7,35 to 7,45)

Question 13

I. Basic terms of acid-base balance
7D. Examples of buffers

Answer 13

• HCO3-/H2CO3 buffer is the most important buffer in the body ([HCO3-]= 23-25mM/L)
• Phosphate buffers are important in the urinary tract
• Proteins are important buffers. In the blood, the key ones are the albumin and hemoglobin

Question 14

I. Basic terms of acid-base balance
7E. How can proteins work as buffers?

Answer 14

Proteins are important buffers. In the blood, the key ones are the albumin and hemoglobin
- Hemoglobin is not only for O2-transport, but also for CO2-transport
- In the Bohr effect: HHb ⇌ Hb + H+ (pH dependency of proton)

Question 15

I. Basic terms of acid-base balance
7F. How can buffer limit pH-changes?

Answer 15

1. If pH low: subject binding
2. If pH high: subject releasing

Question 16

I. Basic terms of acid-base balance
7G. What does pK-value mean?

Answer 16

The pK-value is where the buffering capacity is the greatest

Question 17

I. Basic terms of acid-base balance
7H. What are the characteristics of Open/closed system of buffer?

Answer 17

1. Open system: a system where we can quickly alter the buffers (CO2-buffer = HCO3-/H2CO3)
   => this system is open, because with our respiration we can very quickly change its levels (in minutes)
2. Closed system: a system where we cannot quickly alter the buffer (H2PO4-/HPO42-, HPr/Pr-)

Question 18

I. Basic terms of acid-base balance
7I. Give an Example of buffer mechanism

Answer 18

• H2SO4 is a strong acid and dissociates completely, a lot of protons around
• The buffer, Na+ and HCO3-, will get to work and HCO3- will bind to a proton to give H2CO3 and then CO2
• We will exhale this CO2, this way we have used some of our HCO3- to buffer the protons
• BUT: normal range of protons (nmol – scale) and normal range of bicarbonates (mmol – scale)
  +) If we lose HCO3-, we will still have enough buffering capacity

=> Buffers can limit the real change in the proton concentration, therefore the pH will not change quickly

Question 19

I. Basic terms of acid-base balance
7J. Explain Henderson-Hasselbalch equation

Answer 19

• Used to calculate pH of a buffer solution based on the concentration of acid and its conjugated base, as well as the pK
• On a titration curve of an acid (weak), the pK would be at 50%
• pH is equal to pK when the concentration of acid and conjugated base is equal (log = 0 in that case)

Question 20

II. Buffers of various body fluids
1. What are the 4 locations that you can find buffer systems in the body?

Answer 20

1. Intracellular fluid
2. Extracellular fluid: plasma and interstitial fluid
3. CSF
4. Urinary tract

Question 21

II. Buffers of various body fluids
2. What are the 3 buffer systems you can find in Intracellular fluid?

Answer 21

1. protonated / deprotonated proteins => hemoglobin (RBC)
2. CO2/HCO3-
3. Organic and inorganic phosphate (less important)

Question 22

II. Buffers of various body fluids - ICF buffer systems
2A. How does protonated / deprotonated proteins work as a buffer systems?

Answer 22

• Hemoglobin can reversibly bind either H+ (binds to itself) or O2 (via Fe of heme group); when one is bound, the other is released.
• As blood flows through the systemic capillaries, oxyhemoglobin releases O2 to the tissues and is converted to deoxyhemoglobin. At the same time CO2 is added to systemic capillary blood from the tissues.
• This CO2 diffuses into RBCs and combines with H2O to form H2CO3, which dissociates into H+ and HCO3-.
• Deoxygenated hemoglobin binds to H+ and HCO3- moves out of RBC in exchange for Cl-. (Cl- shift)
• In capillaries of lungs, where O2 level is high, the process mentioned above is reversed, O2 binds to
  hemoglobin and H+ gets released to eventually releases CO2.

Question 23

II. Buffers of various body fluids - ICF buffer systems
2B. How does CO2/HCO3- work as a buffer systems?

Answer 23

• The most important buffer in the body, because it allows quick adaption to change in the pH due to its buffering capacity, as well as the ability for respiratory compensation
• Acidemia triggers hyperventilation via carotid body chemoreceptors, and this response allows the expiration of more CO2, thus allowing the blood pH to back up 
  => Other buffers cannot do this and thus are less effective buffers

Question 24

II. Buffers of various body fluids - Extracellular fluid: consists of plasma and interstitium

3A. What are the 3 buffer systems you can find in plasma of ECF?

Answer 24

1. CO2/HCO3-
   - CO2/HCO3- in plasma, hemoglobin in RBC
2. Protonated / deprotonated proteins -> plasma proteins
3. Inorganic phosphates (less important)

Question 25

II. Buffers of various body fluids - Extracellular fluid: consists of plasma and interstitium 3B1. How do Protonated / deprotonated proteins -> plasma proteins work as a buffer system in plasma of ECF?

Answer 25

- Plasma proteins can also buffer hydrogens with a relationship that exists between Ca2+ and H+-concentration. - These negatively charged plasma proteins are usually bound to Ca2+, but in acidic conditions. - The Ca2+ is replaced with H+, thus increasing the free [Ca2+]. - In alkaline conditions, more Ca2+ becomes bound to the plasma proteins and hypokalemia occurs

Question 26

II. Buffers of various body fluids - Extracellular fluid: consists of plasma and interstitium 3C. What are the 2 buffer systems you can find in Interstitium of ECF?

Answer 26

Interstitium (less protein here = CO2/HCO3- buffer more important) 1. CO2/HCO3- 2. Protonated / deprotonated proteins -> interstitial proteins (less important)

Question 27

II. Buffers of various body fluids - Extracellular fluid: consists of plasma and interstitium 3C1. How does CO2/HCO3- work as a buffer system in interstitial fluid?

Answer 27

- Since CO2/HCO3- is important everywhere, and if the CO2-related buffer system is not working properly or/and if there is no blood perfusion => will not be an ‘’open- system’’ any longer - We wont be able to exhale the CO2 that is produced in the local tissue, if there is no proper perfusion, and CO2 is unable to get to the lung to be exhaled

Question 28

II. Buffers of various body fluids - CSF. 4. Name a buffer system you can find in CSF. Explain its mechanism.

Answer 28

1. CO2/HCO3- - The CSF is very ‘’protein-free’’, therefore there are not many buffer systems, only CO2/HCO3- - Sensed by central chemoreceptors (CCR) -> If CO2 changes -> quick pH-change in the CSF -> sensed by CCR -> drive our respiration

Question 29

II. Buffers of various body fluids - Urinary tract 5. Name 2 buffer systems in urinary tract

Answer 29

1. Inorganic phosphate, creatinine, uric acid 2. NH4+ for ‘’proton trapping’’ (not actually a buffer)

Question 30

II. Buffers of various body fluids - Urinary tract 5A. How do inorganic phosphate, creatinine, uric acid work as a buffer system in the urinary tract?

Answer 30

Phosphate buffers: phosphate is an effective buffer in the kidney, because its pKa is 6,8 (allows more H+ to be buffered before the pH gets too low), but due to the lower concentration, it can only do so much

Question 31

II. Buffers of various body fluids - Urinary tract 5B. How does NH4+ work as a buffer system in the urinary tract?

Answer 31

2. NH4+ for ‘’proton trapping’’ (not actually a buffer) - If it is binding a proton, it is not releasing it any more - A proton trap – important because we want to get rid of them

Question 32

III/ What is the mechanism of Henderson-Hasselbach equation in a buffer system,?

Answer 32

- 1st step (H2O + CO2 ↔ H2CO3) is the rate limiting step -> catalyzed by carbonic anhydrase - Equation is used to quantify how changes in CO2 and HCO3- affect pH - pK’ is the (negative logarithm) of the overall dissociation constant for the HCO3- buffer - the amount of CO2 is determined from the partial pressure of CO2 and its solubility (α) +) α is the solubility factor: describing the solubility of gas in H2O (mM/mmHg) => what is good with the HCO3- - buffer, is that it has a high concentration and also it is an ‘’open-system’’ => respiration can quickly alter it

Question 33

IV. Parameters of acid-base balance 1. What is the value for pH?

Answer 33

7.35 - 7.45

Question 34

IV. Parameters of acid-base balance 2. What is the value for PaCO2?

Answer 34

38 - 42 mmHg

Question 35

IV. Parameters of acid-base balance 3. What are definition and value for standard HCO3 concentration ?

Answer 35

- Standardize it to the situation when pO2 is 40 mmHg - Value: 23 - 25 mol/L

Question 36

IV. Parameters of acid-base balance 4. What are definition and value for actual HCO3- concentration ?

Answer 36

- Actual value that you measure in blood (increasing pCO2 -> increasing HCO3-) - Value: 23 - 25 mmol/L

Question 37

IV. Parameters of acid-base balance 5. What are definition and value for BUFFER BASE?

Answer 37

1. Def: capacity of how many H+ can be buffered in blood 2. Value: 44 - 49 mEq/L

Question 38

IV. Parameters of acid-base balance 6. What are definition and value for BASE EXCESS?

Answer 38

1. Definition: Base Excess is the difference from normal value 2. Value: ± 2.5 mEq/L