Acid/Base in body Flashcards

1
Q

pH

A
  • log10[pH]
  • pH is the logarithmic translation of Hydrogen concentration
  • Acidity Is really how many free H ions you have
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2
Q

Normal Physiological pH of blood

A
  • 7.4
  • range is 7.35 to 7.45
  • blood pH above or below this range indicates pathological changes
  • If the blood pH ranges outside of 6.8 to 7.8 the animaml CANNOT SURVIVE
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3
Q

pKa

A
  • Dissociation Constant for an acid- a quantitative measure of the strength of that acid
  • Ka = [H+][A-]/[HA]
  • large Ka= strong acid
  • small Ka= weak acid (little is dissociated)
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4
Q

Henderson-Hasselbach equation

A

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

or pH=pKa+log([salt]/[acid])

pKa=pH-log([A-]/[HA])

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5
Q

In a healthy anima, blood pH may be affected by…

A
  • Inconsistent amounts of acid or alkali in the diet
  • Large and inconsistent amounts of acid/base produced from normal metabolism (even more so in disease)
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6
Q

Acid Base Balance

A
  • is the process of regulating H+ to normal and consists of 2 processes
    1. Matching the excretion of acids and bases to their input (ultimately yhe goal, but can be difficult to fix)
  • Buffer systems (HCO3-) to minimise changes temporarily
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7
Q

Buffers

A
  • Buffer is a compound that can accept or donate [H+] to minimise changes in pH more effectively than an equal volume of water
  • A buffer solution consists of a weak acid and its conjugate salt
  • When a strong acid is added to the buffer solution, the dissociated H+ are donated to the salt of the weak acid and he pH is minimised
  • binds up the free H+ ions
  • If you add a strong acid to a buffer solution, all those H ions that should be there are binded up (mitigated) by the salt
  • H2CO3 –> H+ + HCO3-
  • conjugate base: BICARBONATE
  • Think about net effect: add acid, lots of free H ions, by conjugating with bicarbonate, will make a bunch of WEAK ACID CONJUGATES (H2CO3)
  • yes there is more acid, but an acid that the body is ok dealing with. Not free H ions
  • We are shifting equation to the left, don’t want to use all the bicarbonate (buffer) in the system though, body has ways to protect from this
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8
Q

Titration (buffer) curve

A
  • Where buffer is most effective pH = pKa. Buffer is most efficient if its pKa is about 1 or less off of the pH. Think about blood
  • Small change in pH IS your buffer acting on the solution and it therefore changing into an acid and keeping the pH low
  • Think of a “pot” where you keep adding base
  • small change in pH is your buffer working and keeping the pH from varying too much
  • These are sigmoidal curves that are almost linear in the midrange
  • The change in pH is smallest for a given amount of added acid or base
  • Greatest buffer capacity (pH=pKa)
  • Buffering is MOST EFFICIENT with the pH (of solution)=pKa(of buffer) +/- 1-2pH units
  • Blood pH is 7.4 so you want buffers that have pKa’s close to that
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9
Q

Buffering Systems: Extracellular fluid buffers

A
  • Bicarbonate (pKa 6.1)
  • Exists in equilibrium with CO2
  • Not as close to blood pH as one would suggest
  • most important buffer in the body
  • high amount of [HCO3-] in the body. Useful because there is so much
  • The HCO3-/H2CO3 pair functions as an open system
  • H2O and CO2 can become bicarbonate! Reactions are catalysed by the enzyme carbonic anhydrase (CA) in both directions
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10
Q

Body Buffers: Intracellular fluid buffers

A
  • Proteins (haemaglobin, albumin) : pKa various
  • Phosphates (ATP, ADP, 2,3-DPG) : pKa 6.8
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11
Q

Why is bicarbonate such a good buffer?

A
  • Compare the amount of this buffer system to that of phosphate –> it is effective because there is just so much of it
  • If we didn’t have a means of replacing the bicarbonate then we would be in trouble, it is great as a buffer because it wont run out!!
  • also a means of getting excess acid out of the body
  • have another means by which we can make this buffer
  • can rid of CO2 by breathing out, connects this buffer system to the outside world–> can get rid of free H+ ions this way as well
  • body is so reliant on this buffer system that it even has enzymes to catalyze this reaction. Body has a lot of this and needs processes to happen efficiently
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12
Q

CO2 and acid base buffering

A
  • We control CO2 by breathing, can control acid/base a s a result as well
  • can breathe faster or slower
  • CO2 is removed by alveolar ventilation in the lungs
  • Keeps the [CO2] relatively constant rather than being depleted (PaCO2=40 mmHg)
  • Any rise or fall in CO2 resulting from the loss/addition of H+
  • Sensed by the respiratory centres of the brainstem
  • Rate of ventilation altered to restore the concentration
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13
Q

Proteins as buffers

A
  • Their buffering ability is a result of their dissociable side groups
  • Imidazole group of histidine residues (pKa 6.4-7.0)
  • Also, aa terminal groups (pKa 7.4-7.9)
  • H sticks to side roots of the plasma proteins so they therefore act as buffers in the body as well
  • Haemoglobin is responsible for over 80% of the non-bicarbonte buffering capacity of whole blood
  • Plasma proteins (albumin>globulins) contribute 20%
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14
Q

Buffering action of Hb

A
  1. In the tissues, CO2 produced from metabolism diffuses into RBC’s
  2. RBC’s contain the enzyme carbonic anhydrase which rapidly combines CO2 and H2O to make H2CO3
  3. H2CO3 then dissociates into H+ and HCO3-
  4. The HCO3- is secreted into the plasma in exchange for a Cl-, and thus helps to buffer the acidifying effect of the CO2
  5. The H+ reacts with HbO2 forming HbH and releasing the O2. This buffers the change in pH and allows the delivery of O2 to the tissues
  • H+ is now bound to Hb in a good way, releasing oxygen (helpful process!) In the leg muscle you have buffered the acid but also have had an oxygen production so you can keep exercising
    6. When the RBC’s reach the lungs, the O2 tension is high. this pushes the reaction in the opposite direction, forming HbO2 and releasing the H+. The first two reactions are then also reversed, forming Co2 and H2O, which are then excreted via the lungs, thus removing the H+ from the body. Bohr Effect
  • Think about when you exercise, going to have a lot of CO2 in the blood, want to get that out and buffer it (metabolism)
  • In lungs, the high amount of O2 present will knock the H+ off of HbH again and then you will breathe out the acidic components (H+)
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15
Q

Compensation and Correction by the body for acid/base disturbances

A
  • Control of the partial pressure of CO2 in the body by alterations in the rate of alveolar ventilation
  • Control of the plasma bicarbonate concentration by changes in renal H+ excretion
  • Compensation- somewhat making do in the middle. To aid until medication works. Ex. Use lung to make pH a bit better (using opposite system to aid in pH problem but it is not the underlying issue). Other system trying to help without fixing the overall problem.
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16
Q

Acidaemia

A
  • blood pH below normal range (less than 7.35)
  • TOO ACIDIC
17
Q

Alkalaemia

A

Blood pH above normal range (more than 7.45)

TOO ALKALOTIC

18
Q

Acidaemia or Alkalaemia may be caused by…

A
  • 4 possible issues that can cause acid base disturbances
  • “osis” is the process that has caused the acid base disturbance
  • Changes may be a result of changes in the:
  1. respiratory system
    - respiratory acidosis or respiratory alkalosis
  2. Metabolic System
    - metabolic acidosis or metabolic alkalosis
19
Q

Respiratory Acid Base Disorders

A
  • due to a change in the arterial CO2 tension which is regulated by alveolar ventilation
  • CO2 is an acid due to its ability to combine with water and form carbonic acid
  • An increase in CO2 in plasma–> respiratory acidosis: due to hypoventilation (moving air in and out of lung at lower rate and more CO2 staying in the body)
  • A decrease in CO2 –> respiratory alkalosis: due to hyperventilation
20
Q

Control of Alveolar Ventilation

A
  • Neural controller: respiratory centres of the brainstem. Act to alter respiratory rate and depth
  • Respiratory Motor Output: muscles of breathing (intercostal muscles, diaphragm, upper airway muscles, others)
  • Sensors: peripheral (carotid and aortic bodies) and central (CNS) chemoreceptors - detect changes in CO2 and pH
  • Body’s checks and balances
  • Disease at any 3 parts of this pathway could lead to an acid base disturbance
21
Q

Regulation of Blood pH by the Kidney

A
  • Kidney has two major roles in acid base balance
  • Excretion of acid (or alkali) produced from metabolism
  • Replacement or maitenance of the ‘alkali reserve’
  • alkali reserve is the the blood pool of HCO3- and must be maintained
  • Regulation of blood pH by respiration leads to loss of one HCO3- for each H+ excretion
  • This is done by 3 mechanisms:
  • Re-absorption of bicarbonate
  • Excretion of acid urine
  • Excretion of ammonia
22
Q

Re-absorption of Bicarbonate

A
  • In a normal animal, all the HCO3- in the blood freely filters through glomerulus, and would be excreted in urine if it were not re-absorbed –> would cause severe acidaemia
  • First mech which occurs in proximal tubules is designed to re-absorb all this HCO3- to maintain the alkali reserve
  • Diagram on slide
  • Goal is just to get bicarb back in the blood!

Also result in sodium as well

  • Net result is the excretion of acid (as H2O) and the reabsorption of all the HCO3-
  • Is so efficient that all the HCO3 which passes into the glomerular filtrate has been re-absorbed by the time it reaches the distal tubules
  • This mech does not result in the acidification of urine
  • In the distal tubules a second mech functions to excrete acid urine
23
Q

Excretion of Acid Urine

A
  • similar to the re-absorption of HCO3- except that HPO42- which passes from the blood into the glomerular filtrate is used to accept the H+ which leaves the tubule
  • Diagram on slide
  • Make urine more acidic in the distal tubule
  • net result of this is the excretion of acid
  • This mech causes the urine to become acid, as H2PO4- is an acid salt
  • Can’t be used to excrete any more acid once the urine pH reaches 4.5 (H+ gradient between the cell and lumen becomes to great to be maintained)
  • If more acid needs to be excreted, a third mechanism to excrete ammonia operating in the distal tubules is used
24
Q

Excretion of Ammonia

A
  • In this mech, ammonia generated from metabolism is used to excrete acid
  • Similar mech, but the NH3 produced from the metabolism in tubular cell is able to diffuse into the lumen. It accepts the H+ that was exchanged for Na+ forming NH4+
  • NH4+ cannot pass back into the cell as it is now charged and is excreted in the urine together with an anion from the glomerular filtrate
  • The HCO3- in the tubular cell then passes into the blood together with an Na+
  • Net result is the excretion of acid (as NH4+)
  • This mechanism does not: cause urine to become acid, involve any loss of Na+
  • Particularly important during periods of prolonged acidosis
25
Q

Base Excess (BE)

A
  • Defined as the amount of acid or base that must be added to a sample of oxygenated whole blood to restore the pH to 7.4 at 37C and at a PCO2 of 40mmHg
  • Normal range -4 to +4 mEq/L (very little)
  • Better marker of metabolic contribution to acid base than HCO3 as independent of CO2
  • -more reliable in the presence of CO2 abnormalities
  • Decreased BE (base deficit): more negative, metabolic acidosis
  • Increased BE (base excess): more positive, metabolic alkalosis
26
Q

Approach to acid base analysis

A
  1. Evaluate the pH
    - acidaemia or alkalaemia?
  2. Evaluate respiratory component (PCO2)
    - respiratory acidosis (high PCO2)
    - respiratory alkalosis (low PCO2)
  3. Evaluate the metabolic component (HCO3 or BE)
    - low HCO3, negative BE: metabolic acidosis
    - high HCO3, positive BE: metabolic alkalosis
  4. Define the primary process (respiratory or metabolic)
    - which process is causing a change in the same direction as the pH change?
  5. Is there compensation present as expected?
27
Q

Compensatory Responses

A
  • lungs compensate for metabolic disorders very quickly (minutes) where as kidneys compnesate for respiratory disorders slower (4-5 days)
  • Won’t really see compensation in acute disorder as there isn’t enough time
  • If you do see compensation, likely chronic as there has been adequate time for compensation
  • Overcompensation does not occur! Compensation will only return the pH closer to normal but it will remain on the side of the original disturbance
28
Q
A