58: Buffers; Normal pH homeostasis Flashcards
Acids
compounds that can donate a hydrogen ion (H+) to a solution/ accepts electrons
Bases
compounds that accept hydrogen
ions/ donates electrons
Strong acids
dissociate completely in solution
weak acids
dissociate to a limited extent
pH
negative log of [H+]
Plasma pH
7.4
[H+] = 35-45nmol/L
Buffers
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+
When pH=pK then….
[weak acid] =[conjugate base]
maximum buffering capacity
When is buffer usually effective?
at a pH, pKa +/- 1
ex: pKa = 4.8
buffer at pH 3.8-5.8
What does the buffering capacity depend on?
pKa (dissociation constant)
conc. of the buffer
- >higher buffer, higher buffering capacity
Henderson-Hasselbalch equation
pH = pKa + log [A-]/[HA]
Most drugs are?
Weak acids or weak bases
How are drugs absorbed?
in their uncharged
forms (permeant forms), as they can cross
membranes
(Weak) Acidic drugs
present in the uncharged
state in the stomach
better excreted in alkaline urine
(Weak) Basic drugs
better absorbed in
the intestine
better excreted in
acidic urine
Aspirin
is present in the uncharged form (–COOH) at the pH of the stomach (pH 1-2), and can be absorbed in stomach
Morphine
weak base
charged at pH of stomach
uncharged form at the intestinal pH (8) where its mainly absorbed since pKa ~7.9
What do you have to do to accelerate excretion of a drug?
Prevent its reabsorption from the tubule by adjusting urine pH to ionize the drug
Volatile acid
Carbondioxide (CO2)
major metabolic acid (22,000 mmol/day)
Nonvolatile acids
(40-80 mmol/day)
Inorganic: Phosphoric (metabolized phospholipids) and Sulfuric Acids (metabolized sulfur containing amino acids)
Organic: ketone bodies and lactic acid
Body buffers
first line of defense
plasma pH 7.4, intracellular 7.1
What are the major buffer systems in the body?
Bicarbonate-carbonic acid buffer (ECF)
Hemoglobin (RBC) – due to histidine
residues
Phosphate buffer (ICF)
Proteins (ICF and plasma) - due to histidine residues
bicarbonate buffer system
CO2 + H2O H2CO3 –> H+ + HCO3-
weak acid (H2CO3) and conjugate base (HCO3-)
pKa = 6.1
Ratio of [Base]/[Acid] in plasma?
at pH 7.4 bicarbonate buffer system is 20:1
How to determine acid base status?
use of blood gas analyzers that estimate the blood pH, PCO2
and HCO3-
Which system regulates bicarbonate levels?
Renal System
Which system regulates PCO2 levels?
Respiratory System
Transport of CO2
from tissues to lungs
- O2 dissociates
from Hb –> deoxyHb and O2 enters tissue - CO2 diffuses from
tissues into blood - CO2 –> H2CO3 by carbonic anhydrase
- Carbonic acid (weak
acid) dissociation (H+ & HCO3-) - H+ ions buffered by Hb histidine residues
CO2 in the lungs
- O2 from alveoli to RBC, binds to Hb–> OxyHb.
- H+ are released from Hb histidine residues
- HCO3- + H+ –> H2CO3
- H2CO3 –> CO2 by carbonic
anhydrase - CO2 diffuses into
alveoli and lost by
expiration
Hemoglobin
functions as a buffer, and accepts H+ formed by CO2 during the transport of CO2 from the tissues
Carbonic Anydrase
Rich in RBC
Respiratory
acidosis
Accumulation of CO2 b/c of disorders that decrease the rate of ventilation
Respiratory alkalosis
Washout of CO2 b/c of disorders that increase the rate of ventilation
Metabolic acidosis
blood pH falls causing HYPERventilation
increased washout of CO2, lowering PCO2
Metabolic alkalosis
blood pH rises causing HYPOventilation
increased retention of CO2, increasing PCO2
Compensatory response
Respiratory system regulates PCO2 (acid) component of bicarbonate buffer
Role of kidney
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
What happens to HCO3- in the kidney?
All the filtered HCO3- is reabsorbed (No HCO3- in urine)
Reabsorption of filtered bicarbonate
For every H+ into tubular lumen, a HCO3- (bicarbonate) gained by the blood
process regulated by reducing
What has to happen if HCO3- needs to be excreted?
Reduce the secretion of protons from tubular cel into tubular lumen
Formation of NEW bicarbonate (Phosphate Buffer)
H+ secreted into tubular lumen and buffered by filtered HPO4^2- forming H2PO4- which is excreted
NEW bicarbonate gained by blood
Acetazolamide
Carbonic Anhydrase inhibitor
Formation of NEW bicarbonate (Ammonia) ** better system
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