Acids and Bases

Question 1

how is H+ found and measured in solution?

Answer 1

• Intra- and extra- cellular fluids are complex solutions with multiple solutes existing in various degrees of ionisation
• Free [H+] is very low - mostly complexed with water or other molecules
• [H+] measured mainly using ion-selective electrodes, which generate potential proportional to log [H+]
• Electrodes actually measure ‘activity’ but we assume this = concentration

Question 2

how does pH and H+ relate?

Answer 2

• pH is derived from the use of ion-selective electrode to measure H+
• pH = -log10H+
  
  • Change in H+ by a factor of 2 leads to a change in pH of 0.3
  • Each point on pH scale is equivalent to 10x [H+]
  • So, doubling of H+ from 40-80 = fall in pH from 7.4-7.1

Question 3

where is the most acidic part in our body?

Answer 3

pH 0.78 in gastric acid

Question 4

where is the most alkaline part of our body?

Answer 4

alkaline bile - pH 7.5 to 8

Question 5

what is the normal physiological range for pH?

Answer 5

7.36-7.44

Question 6

why does the regulation of H+ matter?

Answer 6

• At physiological pH, most biosynthetic and metabolic pathways involve precursors that are ionised
  
  • This traps them within cells/organelles
• Deviation of pH hugely impairs cellular and metabolic function
• Proteins e.g. enzymes also influenced by pH (e.g. state of hydrogen bonds maintaining 3D structure)

Question 7

what are some cardiovascular acid base disorders?

Answer 7

BP, cardiac rhythm

Question 8

what are some respiratory acid base disorders?

Answer 8

ventilation, resp rate

Question 9

what are some metabolic acid base disorders?

Answer 9

protein wasting, bone

Question 10

what are some renal acid base disorders?

Answer 10

electrolytes

Question 11

what are some near acid base disorders?

Answer 11

confusion, seizures

Question 12

what threats does the body face to acid base homeostasis?

Answer 12

• Generation of CO2 from aerobic respiration
• Metabolism of food generating acid or alkali
  
  • Metabolism of amino acids creates acid load (e.g. lysine, arginine, methionine, cysteine) or alkali load (glutamate, aspartate)
  • Protein rich ‘Western Diet’ is acid-loaded
• Incomplete respiration (anaerobic)
  
  • Keto-acid, lactic acid
• Loss of alkali in stool or loss of acid in vomiting

Question 13

what are the 3 main components of acid base homeostasis?

Answer 13

• Buffering - near enough instantaneous
• Ventilation - control of CO2 - over minutes
• Renal regulation of HCO3 and H+ secretion and reabsorption - takes longer - hours/days

Question 14

what is the fundemental concept we need to remember in the acid base homestasis?

Answer 14

H+ can be normal in the presence of acid-base disturbance
this will be at the expense of other blood chemistry

Question 15

what is a buffer?

Answer 15

weak acid that partially dissociates in solution
-react poorly with water and are available to react with either H+ or OH-
-concentration of acid/base&raquo_space; [H+]
-this allows consumption of WA/base and avoid big changes in [H+]

Question 16

what is the principle buffering system in the body?

Answer 16

carbon dioxide/carbonic acid/biocarb system
(henderson-Hasselbach equation)
CO2 + H20 <-> HCO3 + H+

Question 17

how does phsyiological buffering occur?

Answer 17

-because C02 is highly diffusible and CO2 is regulated and controlled by respiration, CO2 is held constant
- addition of H+ consumes HCO3 which generates CO2 + H2O - CO2 is then exhaled and there is little free H+
-loss of H+ leads to generating HCO3
-at physiological pH [HCO3-]:[H2CO3]= 20:1, so the system effectively buffer H+
-maintenance of [H+]=maintenence of [HCO3]

Question 18

where can buffering occur?

Answer 18

intracellular fluid or extracellular fluid

Question 19

what other buffering systems do we have?

Answer 19

haemoglobin - buffers CO2 in blood
proteins - important intracellular buffer
bone - long term buffer
PO4- intracellular an urinary buffer

Question 20

what is the difference between volatile and fixed acids?

Answer 20

-CO2 is a volatile acid meaning it can be eliminated by the body as a gas
-CO2 and HCO3 are independently regulated
-dietary acids and acids produced by aerobic resp are fixed but cannot be converted to CO2
-buffering a fixed acid consumes HCO3, but although CO2 will be ventilated, this will be at expense of lowered [HCO3]- to remove H= effectively more HCO3 must be generated
-regulation of [HCO3] is the job of the kidneys, where excretion of H+ and regeneration of HCO3 are linked

Question 21

is CO2 an acid?

Answer 21

• Strictly speaking… no
• Effectively, yes!
• Cannot directly donate H+
  -so given unlimited supply of H29 is effectively an acid

Question 22

how do kidneys regulate acid base balance?

Answer 22

• Reabsorb filtered HCO3
• Secrete ‘fixed’ acid
  
  • Titrate non-HCO3 buffer in urine - primarily PO4
  • Secrete NH4 into urine
• These goals are achieved by using selective permeability of the luminal and baso-lateral cell membranes to match transport of H+ and HCO3 in opposite directions.

Question 23

how much HCO3 is reabsorbed per day?

Answer 23

-filtration of HCO3 = [HCO3] x GFR =>4000mmol/day
-active process largely in proximal tubule with small contribution from TALH and DCT
-inablity to reabsorb filtered HCO3 is a cause of metabolic acidosis

Question 24

what is the normal metabolic generation of CO2?

Answer 24

generatres 12-13,000mmol/day all of which is ventilated

Question 25

what is the general mechanism for reabsorbing HCO3?

Answer 25

-maintaining acid-bade homeostasis requires that (virtually) all filtered HCO3 is reabsorbed -very active process consuming large amount of energy due to active transport -no net loss of H+ or gain of HCO3

Question 26

what is the process of excretion of acid in the body?

Answer 26

-required to eliminate fixed acid 70mmol/day -similar principle but tubular cells generate a new HCo3, which is absorbed, along with a H+ that binds to a base other than HCO3 or is fixed with NH3 -this takes the form of either titration or filtered PO4 or secretion of NH4 into urine -titration of PO4 is dependent on delivery of filtered buffer and is relatively fixed -mehcnaism of NH4 excretion is complex but is able to be up regulated in acidosis -failure to be able to secrete H+ is another cause of acidosis

Question 27

how is the titration of phosphate done?

Answer 27

-PO4 is major non-HCO3 buffer in urine -delivery of PO4 not amenable to much regulation but completeness of titration depends on urine pH -accounts for excretion of 40mmol H+/day

Question 28

how is ammonium excreted?

Answer 28

-regulated by metabolism of glutamine -acidosis stimulates glutamine transport of oxidation -in normal conditions generation of NH4+ accounts for 50-100mmol H+/day but it can be increased -each H+ secreted is matched by the generation of a new HCO3 which is absorbed -excretion of fixed acid has 2 components -excretion of titratable acid (mostly phosphate) -excretion of NH4+

Question 29

what is common between all clinical acid-base disorders?

Answer 29

- In all types of acid-base disorder there is a primary disturbance which tends to make [H+] abnormal - The acute change will be buffered and there will be a compensatory response - so [H+] remains in or close to normal range, but at the expense of abnormal HCO3, or CO2. - In practice, given time the renal compensatory response may be complete, but respiratory compensation may be limited - there is a limit to how hard patients can drive ventilation without tiring, and they can't stop breathing. - 'osis vs aemia' - more patients will be acidotic (abnormal HCO3) than acidaemic (decreased pH)

Question 30

what do we need to know to diagnose acid base disorders?

Answer 30

- iagnosing the acid-base disorder requires knowledge of H+, HCO3, CO2 (blood gases), electrolytes (Na, K, Cl) and a ***clinical history*** - In many cases, the diagnosis will be obvious - e.g. DKA

Question 31

what is respiratory acidosis?

Answer 31

condition where arterial pCO2 rises -increased generation of CO2 -reduced ventilation of CO2 almost always due to reduced ventilation

Question 32

why do we have respiratory acidosis in COPD?

Answer 32

-reduced central sensitivity to hypoxia and hypercapnia -destruction of lung tissue causing ventilation/perfusion mismatch -respiratory muscle fatigue

Question 33

how does the body compensate for acid-base disorders?

Answer 33

- If the cause of the disorder is respiratory, the compensatory response must be metabolic - Acute phase - buffering - Chronic phase - compensation

Question 34

how does the body buffer respiratory acidosis?

Answer 34

CO2 +H2O <-> H2CO3 <-> HCO3 =H+ -addition of CO2 drives reaction to right, generating H+ -the system cannot buffer itself -acute rise in H+ is buffered by protein, esp Hb and phosphate , leaving behind the HCO3, which rises slightly

Question 35

what is the metabolic compensation of respiratory acidosis?

Answer 35

-effect in increased arterial pCO2 is to promote renal retention of HCO3 -increased ammonium excretion

Question 36

why are the kidneys a crucial site for compensation of acid base balance?

Answer 36

they control HCO3 excretion and resorption and H+ excretion

Question 37

what are the causes of metabolic acidosis?

Answer 37

-addition of extra acid generation of organic acid through metabolism lactic acidosis, kept acidosis -ingestion of acid (eg methanol) failure to excrete acidosis -loss of HCO3 in stool or urine primary abnormality is fall in plasma HCO3 -compensatory response is fall in pCO2 due to resp drive