Acids and Bases Flashcards

1
Q

how is H+ found and measured in solution?

A
  • 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
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2
Q

how does pH and H+ relate?

A
  • 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
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3
Q

where is the most acidic part in our body?

A

pH 0.78 in gastric acid

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4
Q

where is the most alkaline part of our body?

A

alkaline bile - pH 7.5 to 8

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5
Q

what is the normal physiological range for pH?

A

7.36-7.44

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6
Q

why does the regulation of H+ matter?

A
  • 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)
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7
Q

what are some cardiovascular acid base disorders?

A

BP, cardiac rhythm

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8
Q

what are some respiratory acid base disorders?

A

ventilation, resp rate

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9
Q

what are some metabolic acid base disorders?

A

protein wasting, bone

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10
Q

what are some renal acid base disorders?

A

electrolytes

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11
Q

what are some near acid base disorders?

A

confusion, seizures

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12
Q

what threats does the body face to acid base homeostasis?

A
  • 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
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13
Q

what are the 3 main components of acid base homeostasis?

A
  • Buffering - near enough instantaneous
  • Ventilation - control of CO2 - over minutes
  • Renal regulation of HCO3 and H+ secretion and reabsorption - takes longer - hours/days
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14
Q

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

A

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

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15
Q

what is a buffer?

A

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+]

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16
Q

what is the principle buffering system in the body?

A

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

17
Q

how does phsyiological buffering occur?

A

-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]

18
Q

where can buffering occur?

A

intracellular fluid or extracellular fluid

19
Q

what other buffering systems do we have?

A

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

20
Q

what is the difference between volatile and fixed acids?

A

-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

21
Q

is CO2 an acid?

A
  • Strictly speaking… no
  • Effectively, yes!
  • Cannot directly donate H+
    -so given unlimited supply of H29 is effectively an acid
22
Q

how do kidneys regulate acid base balance?

A
  • 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.
23
Q

how much HCO3 is reabsorbed per day?

A

-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

24
Q

what is the normal metabolic generation of CO2?

A

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

25
Q

what is the general mechanism for reabsorbing HCO3?

A

-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

26
Q

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

A

-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

27
Q

how is the titration of phosphate done?

A

-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

28
Q

how is ammonium excreted?

A

-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+

29
Q

what is common between all clinical acid-base disorders?

A
  • 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)
30
Q

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

A
  • 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
31
Q

what is respiratory acidosis?

A

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

32
Q

why do we have respiratory acidosis in COPD?

A

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

33
Q

how does the body compensate for acid-base disorders?

A
  • If the cause of the disorder is respiratory, the compensatory response must be metabolic
    • Acute phase - buffering
    • Chronic phase - compensation
34
Q

how does the body buffer respiratory acidosis?

A

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

35
Q

what is the metabolic compensation of respiratory acidosis?

A

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

36
Q

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

A

they control HCO3 excretion and resorption and H+ excretion

37
Q

what are the causes of metabolic acidosis?

A

-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