Acid - Base Regulation

Acid - Base Regulation - Lecture 31

Acid - Base metabolism
generation of H⁺
Buffers - bicarbonate
Kidney's role
state of acid-base balance
exam

Hydrogen ion regulation - important because metabolic reactions are sensitive to hydrogen ion concentration pH - 7.4

6.8 if too much H⁺ - CNS depression

8.0 not enough - CNS overexcitabilty

therefore regulate H⁺ concentration - kidney most important

Acid - Base Balance

acid - compound that releases hydrogen ions (proton donor) - pH < 7.0

base - compound that combines with hydrogen ions (proton acceptor) - pH > 7.0

buffers - chemical that prevent large changes in H⁺

Generation of H⁺

1) Ingestion - consume little directly but consume food that produces H⁺.

A. from protein breakdown

proteins with phosphorous à H₂PO₄- (phosphoric acid) à H⁺ + HPO₄^2- proteins with sulfur à H₂SO₄ (sulfuric acid) à 2H⁺ + SO₄-

note fruits and vegetables produce bases that neutralize the acids

B. Fatty acids, lactic acid

ketone bodies (ketone acid) produced during fatty acid metabolism which results during glucose sparing

C. CO₂ :

CO₂ + water à H₂CO₃ (carbonic acid) à H⁺ + HCO₃-(bicarbonate)

lungs buffer this by expiration of CO₂

if disease or too much CO₂ à increased H⁺ à kidneys eliminate

normal concentration = 0.000,04 mmol/l pH = 7.4

pH = - log [conc.] = - log 0.000,000,04 (moles/l)

1) Buffers - control amount of H+ - pH

a. Bicarbonate - CO₂ - primary extracellular
b. Proteins - primary intracellular
c. Phosphates - primarily urinary - also some intracellular
d. Hemoglobin - in RBCs

Buffer- + H⁺ ó H . buffer (this does not influence pH -- only free H⁺)

the amount of H⁺ determines the direction of the reaction

Bicarbonate (primary buffer)

HCO₃- + H⁺ à H₂CO₃ à water + CO₂ (controlled by lungs)
this is a reversible reaction - the enzyme carbonic anhydrase controls reaction in both directions

Audio - Lecture -

HCO₃- is controlled by kidneys and is normally 24.0 meq/l

Henderson - Hasselbalch - describes relationship between acid and base

pH = pK + log [base]/[acid]

very important in Pharmacology and Biochemistry

pK = pH + log [protonated]/[nonprotonated]

the pK is the pH at which you have 50% base and 50% acid

for bicarbonate buffer system the pK = 6.1

pH = 6.1 + log [HCO₃-/CO₂] normally 20:1, therefore pH = 7.4

log 20/1 = 1.3

conc. of blood HCO₃- is normally quite high - and is closely regulated by kidney

conc. of blood CO₂ is regulated by the lungs

If add a lot of H⁺ to blood, expect CO₂ in blood to increase -- this does not occur

in fact, CO₂ decreases

WHY?

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this pushes reaction even faster to the right.

HCO₃- (in blood) + H⁺ à H2CO₃ à water + CO₂

if CO₂ is decreased, even faster to right

if lower H⁺ - just the opposite

Renal regulation of H⁺ - i.e. removal from body

American diet - consume protein - 40-80 mmol of H⁺/day

total extracellular fluid = 14 L ---- 80 mmol/14 L = 6 mmol/L

original 0.00004 mmol/L

the extra H⁺/day will increase amount to 6.00004 mmol/L or a pH = 2.2; log 0.00600004 moles = pH = 2.2

Audio - Lecture -

must eliminate H+ from body - can not tolerate a pH of 2.2

almost all H⁺ enters tubules via secretion - H⁺ is not filtered at Bowman's capsule because little free H⁺ in the plasma

increase H⁺ -- increase urinary secretion and thus excretion

must have buffers in urine

-HCO₃- filtered and reabsorbed

-HPO₄(^2-) phosphate anion -- filtered not reabsorbed

-NH₃ ammonia -- formed in cells lining tubule from amino acids - deamination

(after 1-2 days of increased H+)

HPO₄(2-) + H⁺ à H₂PO₄- (phosphoric acid)

NH₃ + H⁺ à NH₄⁺ (ammonium) - this cannot be reabsorbed (water soluble)

Secretion of H⁺ - takes place in proximal tubule and collecting tubule, some distal tubule

Bicarbonate Reabsorption and H⁺ secretion - whenever filtered HCO₃^- is present

New Bicarbonate and H+ secretion

after all HCO₃- has been reabsorbed then

Audio - Lecture -

States of Acid - Base imbalance

A. Resp. Acidosis ---- increase pCO₂ -- decrease pH -- hypoventilation, this may be due to drugs, Resp. disease

1. eliminate CO₂ -- increase ventilation through central chem.
2. kidney -- increase reabsorption. HCO₃^3- and increase secretion H⁺

B. Resp. alkalosis - CO₂ is blown off -- increase pH -- fever, anxiety, drugs, hyperventilation

1. decrease ventilation - central chem.
2. decrease HCO₃- reabsorption - and decrease H⁺ secretion

Audio - Lecture -

C. Metabolic acidosis - excess H⁺ , not CO₂ - actually decreased CO₂

1. heavy exercise -- lactic acid
a. increase ventilation - blow off CO₂ - peripheral chem. sense increased H⁺
b. kidneys increase reabsorb of HCO₃ - ----- increase secrete H⁺
2. diabetes mellitus or fasting - break down fatty acids (ketone acids); cannot store glycogen - no insulin
a. increase ventilation - peripheral chemo. sense increased H⁺
b. stimulate kid. increase reabsorb HCO_3- increase secrete H⁺

D. Metabolic alkalosis - increase pH - increased CO₂ - vomiting , loss of H⁺ (HCl from stomach or drugs)

a. decrease ventilation - increase CO₂ - peripheral sense decreased H⁺
b. decrease HCO₃- reabsorption and decrease H⁺ secretion

How to determine acid-base balance?

1) First - measure arterial blood pH - normal 7.4

2) Second - measure arterial pCO₂ - normal 40 mm Hg

does pCO₂ explain the pH - if so, the problem is respiratory

Examples

a. pH = 7.55 alkalosis (1) pCO₂ = 32 mm Hg (2) this is low and thus causes the alkalosis

patient - respiratory alkalosis

blow off too much CO₂

b. pH = 7.34 acidosis pCO₂ = 28 (less than normal, therefore not respiratory)

metabolic acidosis with respiratory compensation

respiration opposite of cause - diabetes - production of ketones

c. pH = 7.34 acidosis pCO₂ = 53 this is the cause

respiratory acidosis

REVIEW QUESTIONS

A 35 year-old female was admitted to the hospital. The following blood values were obtained: pH=7.49 and pCO₂=55 mm Hg. The patient's acid base status can be evaluated as
1. more tests are necessary for diagnosis of this patient
A person that overdoses on drugs and enters a coma will have a pH of _____ and a pCO₂ of _____mm Hg.
1. 7.33, 51
2. 7.36, 35
3. 7.48, 51
4. 7.5, 32
5. 7.4, 38
A weak acid with a pKa of 6.0 is found in a base to acid ratio of 10.0. The pH of the solution is:
1. 6.0
2. 7.0
3. 8.0
4. 5.0
5. 4.0
Which of the following is incorrect about H⁺?
1. Very little H⁺ is filtered in the glomerular capillaries.
2. Addition of H⁺ to the blood increase CO₂ in the blood.
3. Secretion of H⁺ takes place primarily in the proximal tubule and collecting tubule.
4. Secretion of H⁺ requires ATP.
5. During secretion of H⁺ and production of new bicarbonate, H⁺ in the urine is buffered by NH₃ or HPO₄^2-.

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