58: Buffers; Normal pH homeostasis

Question 1

Acids

Answer 1

compounds that can donate a hydrogen ion (H+) to a solution/ accepts electrons

Question 2

Bases

Answer 2

compounds that accept hydrogen

ions/ donates electrons

Question 3

Strong acids

Answer 3

dissociate completely in solution

Question 4

weak acids

Answer 4

dissociate to a limited extent

Question 5

pH

Answer 5

negative log of [H+]

Question 6

Plasma pH

Answer 6

7.4

[H+] = 35-45nmol/L

Question 7

Buffers

Answer 7

weak acid and
its conjugate base

resist a change in pH, on addition of small quantities of acid
(H+) or base (OH-)

reversibly bind to H+

Question 8

When pH=pK then….

Answer 8

[weak acid] =[conjugate base]

maximum buffering capacity

Question 9

When is buffer usually effective?

Answer 9

at a pH, pKa +/- 1

ex: pKa = 4.8
buffer at pH 3.8-5.8

Question 10

What does the buffering capacity depend on?

Answer 10

pKa (dissociation constant)

conc. of the buffer
- >higher buffer, higher buffering capacity

Question 11

Henderson-Hasselbalch equation

Answer 11

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

Question 12

Most drugs are?

Answer 12

Weak acids or weak bases

Question 13

How are drugs absorbed?

Answer 13

in their uncharged
forms (permeant forms), as they can cross
membranes

Question 14

(Weak) Acidic drugs

Answer 14

present in the uncharged
state in the stomach

better excreted in alkaline urine

Question 15

(Weak) Basic drugs

Answer 15

better absorbed in
the intestine

better excreted in
acidic urine

Question 16

Aspirin

Answer 16

is present in the
uncharged form (–COOH) at the pH of the stomach (pH 1-2), and can be absorbed in stomach

Question 17

Morphine

Answer 17

weak base

charged at pH of stomach

uncharged form at the
intestinal pH (8) where its mainly absorbed since pKa ~7.9

Question 18

What do you have to do to accelerate excretion of a drug?

Answer 18

Prevent its reabsorption from the tubule by adjusting urine pH to ionize the drug

Question 19

Volatile acid

Answer 19

Carbondioxide (CO2)

major metabolic acid (22,000 mmol/day)

Question 20

Nonvolatile acids

Answer 20

(40-80 mmol/day)

Inorganic: Phosphoric (metabolized phospholipids) and Sulfuric Acids (metabolized sulfur containing amino acids)

Organic: ketone bodies and lactic acid

Question 21

Body buffers

Answer 21

first line of defense

plasma pH 7.4, intracellular 7.1

Question 22

What are the major buffer systems in the body?

Answer 22

Bicarbonate-carbonic acid buffer (ECF)

Hemoglobin (RBC) – due to histidine
residues

Phosphate buffer (ICF)

Proteins (ICF and plasma) - due to histidine residues

Question 23

bicarbonate buffer system

Answer 23

CO2 + H2O H2CO3 –> H+ + HCO3-

weak acid (H2CO3) and conjugate base (HCO3-)

pKa = 6.1

Question 24

Ratio of [Base]/[Acid] in plasma?

Answer 24

at pH 7.4 bicarbonate buffer system is 20:1

Question 25

How to determine acid base status?

Answer 25

use of blood gas analyzers that estimate the blood pH, PCO2 | and HCO3-

Question 26

Which system regulates bicarbonate levels?

Answer 26

Renal System

Question 27

Which system regulates PCO2 levels?

Answer 27

Respiratory System

Question 28

Transport of CO2 | from tissues to lungs

Answer 28

1. O2 dissociates from Hb --> deoxyHb and O2 enters tissue 2. CO2 diffuses from tissues into blood 3. CO2 --> H2CO3 by carbonic anhydrase 4. Carbonic acid (weak acid) dissociation (H+ & HCO3-) 5. H+ ions buffered by Hb histidine residues

Question 29

CO2 in the lungs

Answer 29

1. O2 from alveoli to RBC, binds to Hb--> OxyHb. 2. H+ are released from Hb histidine residues 3. HCO3- + H+ --> H2CO3 4. H2CO3 --> CO2 by carbonic anhydrase 5. CO2 diffuses into alveoli and lost by expiration

Question 30

Hemoglobin

Answer 30

functions as a buffer, and accepts H+ formed by CO2 during the transport of CO2 from the tissues

Question 31

Carbonic Anydrase

Answer 31

Rich in RBC

Question 32

Respiratory | acidosis

Answer 32

Accumulation of CO2 b/c of disorders that decrease the rate of ventilation

Question 33

Respiratory alkalosis

Answer 33

Washout of CO2 b/c of disorders that increase the rate of ventilation

Question 34

Metabolic acidosis

Answer 34

blood pH falls causing HYPERventilation increased washout of CO2, lowering PCO2

Question 35

Metabolic alkalosis

Answer 35

blood pH rises causing HYPOventilation increased retention of CO2, increasing PCO2

Question 36

Compensatory response

Answer 36

Respiratory system regulates PCO2 (acid) component of bicarbonate buffer

Question 37

Role of kidney

Answer 37

regulate plasma [HCO3-] by filtration at glomerulus Filtered HCO3- reabsorbed ( urine pH 5.8) secrete H+ accepted by urinary buffers (phosphate and ammonia) HCO3- can also be ‘newly’ formed in the renal tubules to replenish HCO3- lost by buffering nonvolatile acids

Question 38

What happens to HCO3- in the kidney?

Answer 38

All the filtered HCO3- is reabsorbed (No HCO3- in urine)

Question 39

Reabsorption of filtered bicarbonate

Answer 39

For every H+ into tubular lumen, a HCO3- (bicarbonate) gained by the blood process regulated by reducing

Question 40

What has to happen if HCO3- needs to be excreted?

Answer 40

Reduce the secretion of protons from tubular cel into tubular lumen

Question 41

Formation of NEW bicarbonate (Phosphate Buffer)

Answer 41

H+ secreted into tubular lumen and buffered by filtered HPO4^2- forming H2PO4- which is excreted NEW bicarbonate gained by blood

Question 42

Acetazolamide

Answer 42

Carbonic Anhydrase inhibitor

Question 43

Formation of NEW bicarbonate (Ammonia) ** better system

Answer 43

ammonia forming in tubular unlimited and is stimulated during prolonged acidosis H+ secreted into tubular lumen and buffered by NH3 forming NH4+ which is excreted as NH4Cl Glutamine metabolized into NH3 in tubular cell NEW bicarbonate gained by blood to increase blood HCO3- levels