Acid Base Balance Flashcards
What is an acid/base?
Activity of hydrogen ions (H+):
Acids donate H+ e.g. HCl
HCl —> H+ + Cl-
Bases accept H+ e.g. NH3
NH3 + H2O —> NH4+ + OH-
Strong acids readily give up H+, strong bases readily accept H+
Conjugate acid:
species formed by the reception of a proton by a base
Ammonium ion, NH4+ (ammonia is the base)
Conjugate base:
species formed by the removal of a proton from an acid
Hydrogen carbonate ion, HCO3- (carbonic acid is the acid)
What is pH?
pH of a solution is defined as the negative logarithm of the hydrogen ion activity
pH = -log10[H+]
pH of blood is 7.4, which = 0.00000004 mol/L (40 nmol/L) of H+ ions circulating the body
Blood [H+] > 45 nmol/L acidaemic (acidosis is not the same)
Blood [H+] < 35 nmol/L alkalaemic (alkalosis is not the same)
What is the difference between acidosis and acidaemia?
Acidaemia – denotes pH < 7.35
Acidosis – process by which disturbance occurs (can have an acidosis but not an acidaemia, as the body can compensate)
What is the difference between alkalosis and alkalaemia?
Alkalaemia – denotes pH >7.45
Alkalosis – process by which disturbance occurs
What is pka?
pKa represents the negative logarithm of the ionisation constant of an acid (Ka)
pKa is the pH at which a buffer exists in equal proportions with its acid and conjugate base
Acids have pKa values < 7.0
Bases have pKa values > 7.0
PH = pKa when 50% of the species is ionised
Ideally want pka and ph to be within 1 unit of each other in a biological buffer
How does tissue Respiration / Oxidative Phosphorylation produce H+?
The production of chemical energy (in the form of high-energy phosphate bonds in ATP) from glucose.
CO2 + H2O H2CO3 H+ + HCO3
Basis of bicarbonate buffer system - most important biological buffer
How does incomplete metabolism of glucose: glycolysis and lactate metabolism produce H+?
Incomplete metabolism of glucose: glycolysis and lactate metabolism.
- An intermediary, anaerobic process that results in hydrogen ion
formation
C6H1206 —> 2 CH3CHOHCOO- + 2H+
Glucose Lactate
Takes place particularly in skeletal muscle and erythrocytes:
- Results in ~1.3 moles of H+/ day in a 70 kg male at rest
- Major route of disposal is by gluconeogenesis in liver and kidney
- At times of strenuous exercise, lactate is completely oxidised to CO2
and H2O
- If so if someone has a heart attack they will get a build up of
lactate
What is the Cori cycle?
Muscle = glucose undergoes glycolysis Liver = gluconeogenesis produces glucose
What is the purpose of the acid-base balance in real life?
Natural defence mechanism for the body; it prevents permanent damage during extreme exertion by slowing the key systems needed to maintain muscle contraction
Once the body slows down, oxygen becomes available and lactate reverts back to pyruvate, allowing continued aerobic metabolism
How does incomplete metabolism of triglycerides (ketogenesis) produce H+?
The liberation of free fatty acids (FFA) from triglycerides in adipose tissue results in the generation of H+
The further metabolism of FFAs to ketones in the liver (ketogenesis) also results in H+ production e.g.
CH3(CH2)14COO- + 6 O2
|
Palmitate |
| 2 CH3COCH2COO- + 2 CH3CHOHCH2COO- + 2 H2O + 3 H+
Acetoacetate 2- Hydroxybutyrate
What is ketoacidosis?
Diabetic ketoacidocis:
Insulin keeps the concentration of hydrogen ions in check in a healthy individual. In diseases such as type one diabetes where there is a complete lack of insulin, a person cant supress glycolysis so they liberate fatty acids as an energy source. Good but this also produces hydrogen ions that are then unregulated.
Alcoholic ketoacidosis:
Alcohol’s own metabolism has issues due to its intermediate metabolism. The process forms acetaldehyde then acetate, which can impair the processes of glycolysis and gluconeogenesis. They alter the conversion of NAD to NADH, necessary for conversion of energy, which therefore in effect renders the person hypoglycaemic. With chronic alcoholism their glycogen stores are low so you don’t have the substrate produce glucose and push through glycolysis and gluconeogenesis. Instead you rely more on the ketoogenesis pathway, where H ions are liberated. Also in situations of stress and dehydration you produce counter regulatory hormones such as catecholamines cause insulin resistance, so any insulin that was there has been rendered useless anyway. You also produce less insulin because you are relying on a fat storage rather than carbohydrates.
How does metabolism of NEUTRAL amino acids (ureagenesis) produce H+?
Process GENERATES hydrogen ions
CH3CHNH3 + COO- + O2 —> CH3COCOO- + 2 NH4+
Alanine Pyruvate
2 CH3COCOO- + 2 H+ —> 6 CO2 + 4 H2O
Pyruvate
CO2 + 2 NH4+ —> CO(NH2)2 + H2O + 2 H+
Urea (Net H production)
How does metabolism of SULPHUROUS amino acids (ureagenesis) produce H+?
Process GENERATES hydrogen ions
2CH3S(CH2)CH(NH3+)COO- + 15O2
Methionine |
|
CO(NH2)2 + 9CO2 + 7H2O + 4H+ + 2SO4-
Urea
Large net increase in H+
How does the metabolism of ACIDIC amino acids (ureagenesis) produce H+?
A process that actually CONSUMES hydrogen ions
2COO-CH(NH3+)CH2COO- + 6O2 + 2H+
Aspartate |
|
CO(NH2)2 + 7CO2 + 5H2O
Urea
H+ ions are consumed not generated!
What is le châtelier’s principle?
A buffering system will react to any change imposed upon it, in an
equal and opposite direction.
What are some biological buffers?
Blood
- Bicarbonate
- Haemoglobin
- Plasma proteins
Bone (Generally not a buffer, but in chronic kidney disease the Ca and K in bone can act as a buffer, may lead to chronic bone disease though)
Urine
- Phosphate
- (Ammonium - Not a real buffer, just a process that consumes H+)
Why do we need buffers?
Daily excretion of hydrogen ions by the kidneys is 40-80mmol/day
Intermediary metabolism accounts for H+ turnover of 2500-3000mmol/day (i.e. Pumped across mitochondrial membranes in the electron transport chain, but these are housed so don’t affect acid base balance)
To compensate for disturbances in the above - to account for if things go wrong!
What is the Henderson-Hasselbach equation?
Explains how acids and bases contribute to pH
Ph = pka + log [base/acid]
pKa + log [Salt]
[Acid]
pH = 6.1 + log( [HCO3-] )
0.025* x pCO2
In physiology, the [acid] is carbonic acid. We do not actually measure carbonic acid but its concentration bears a linear relation to the amount of dissolved carbon dioxide (bicarbonate)
What is the Harber-Weiss equation?
[H+] = k [pCO2]
————
[HCO3]
K – embraces dissociation constants and solubility coefficient of carbon dioxide
K – 180 when H+ in nmol/L, HCO3 in mmol/L and pCO2 kPa
What is the bicarbonate buffer equation?
CO2 + H2O = H2CO3 = H+ + HCO3
This equation is CENTRAL to acid-base balance. From it you can see:
- When dissolved in blood, CO2 becomes an acid
- The more carbon dioxide added to blood, the more carbonic acid
(H2CO3) is produced, which readily dissociates to release H+
- Blood pH depends, not on absolute amounts of CO2 or HCO3-, but the
RATIO of the two = 20:1 HCO3:CO2
- The body will compensate to maintain this
How do renal processes reduce H+?
Formation of H+ in renal tubular cells is accompanied by stoichiometric generation of bicarbonate so excretion of H+ results in regeneration of bicarbonate
Restores and maintains buffering capacity - can take 24 to 48 hours to fix if disturbed, may have to give bicarbonate (run the risk of becoming alkalaemic)
Excess H+ are excreted in the urine and, because the body is a net producer of acid, the urine is usually acidic. To achieve this, the body must:
- Reabsorb bicarbonate filtered at the glomerulus (Renal tubule acidosis
type 1 - inability to reabsorb bicarbonate - RTA-1)
- Excrete H+, usually against a steep concentration gradient (Renal tubule acidosis type 2 - inability to excrete H ions - RTA-2)
Glomerular filtrate contains bicarbonate at the same concentration as the plasma (18-24mmol/L)
Urine is virtually bicarbonate-free (the kidney is not 100% efficient at reabsorption)
How is urine acidification achieved?
Achieved by active secretion of H+ by the intercalated cells of the distal tubular cells and proximal collecting duct cells
- Minimal urine pH that can be achieved (4.5 or ~38 µmol/L)
- Insufficient to remove daily H+ production, which is measured in
mmol - Significant acid excretion is achieved by H+ being buffered by
phosphate, titrating HPO42- and H2PO4- -kidney damage means
people can’t excrete phosphate so they are susceptible to acid base
disturbances
How is bicarbonate reabsorbed?
85-90% reabsorbed in PCT
10-15% reabsorbed in DCT/CD
4000-5000mmol/day filtered by the kidney
Getting rid of H+ ions from the Renal system regenerates and increases the ability to reabsorb bicarbonate. This helps us up and down regulate processes associated with an imbalance of acid and helps the kidney = Renal compensation. Though can take 24-36 hours, so isn’t an instant fix. When patients are really compromised they will be given IV bicarbonate, similarly if they are in cardiac arrest to reset the pH balance. However, must be careful with the amount given as you run the risk of making the patient alkalaemic.
90% bicarbonate reabsorption occurs in proximal convoluted tubule and the remaining 10% occurs in the distal convoluted tubule. Bicarbonate is delivered to the tubular part of the kidney where it combines with hydrogen ions, these are pumped back through the membrane by a transporter molecule combines to form carbonic acid which is impermeable to the tubule. Carbonic anhydrase reacts with carbonic acid to form CO2 and water. The CO2 is freely diffusible accross the membrane towards the inside of the membrane, where it reacts with water to reform carbonic acid under a reaction with carbonic anhydrase. The carbonic acid can then dissociate to bicarbonate, which is reabsorbed into circulation and the H ions are pumped out.
What is the phosphate buffering system?
This is the main buffering system that we see in the urine. When pH is close to pKa it is a good buffering pair - here it is within one unit (6.8 is close to 7.4 - physiologically optimum).
However each species isn’t present in high concentrations in our system, to really be an effective system. But they are present in very high concs in the renal filtrate, so good here!
Once CO2 and water reproduce carbonic acid, H ions are driven accross the membrane into the lumen where they combine with monohydrogen phosphate to give dehydrogen phosphate which can be excreted in the urine.
Monohydrogen (HPO42-) and dihydrogen phosphate (H2PO4-) form a buffer pair with a pKa of 6.8
While this buffer system seems favourable, plasma concentrations of these anions are too low
Renal filtrate, they are present in higher concentrations and are an important buffer in urine
