Physiology II Exam II Acid-Base

there should be pictures here but wordpress won’t let me paste them.

Depending on pH

Depending on pCO2

If CO2 is lost, Bicarb will grab a proton and transform to replace it, even if there are not enough protons
Metabolic acidosisBuffer system: Bicarb sequesters as many protons as it can (to threshold)

However, pCO2 does not change until respiratory system compensates, and only then the equilibrium can move to the right

Respiratory acidosis: shift leftH2CO3 will fall apart to HCO3 and H+

Immediate increase in bicarb seen even though plasma becomes more acidic as well

Key points, the night before the acid-base exam…

–          Change in pCO2 will shift the Ubiquitous Equation to the left or the right, resulting in more or less Bicarb and more or less H+. This is why it is referred to as an acid. I’m pretty sure I wrote this same statement a week ago and then forgot.

–          Sleep is better for yr grades than staying up til 6AM

–          Staying awake until 6AM if you are a nocturnal creature is good for yr happiness though

–          Calculate the equilibrium constant for grades and happiness and get back to me

–          Change in Bicarb or [H+] will not shift the equilibrium, just the pH

–          Once the lungs compensate by adjusting pCO2, THEN the equilibrium will shift and normal pH be restored

–          By this logic, a metabolic disturbance will be corrected more quickly

Bicarb

–          May increase because the system became more alkaline or because [CO2] became elevated

–          May decrease by accepting a proton and transforming to CO2 or by leaving the system as itself

CO2

–          Omnipresent; and everywhere CO2 goes, bicarb and H+ go too, including CNS chemoreceptors

–          The normal ratio is 20 HCO3 to every CO2; so if CO2 increases, HCO3 is going to have a difficult time catching up

Increased CO2 caused by hypoventilation Increased H+ caused by increased CO2 Increased HCO3- caused by increased CO2
Increased H+ caused by decreased HCO3-
Increased H+ caused by increased H+ Decreased HCO3- caused by
Decreased CO2 caused by hyperventilation Decreased H+ caused by decreased CO2 Decreased HCO3 caused by decreased CO2

Key points, the morning after the acid-base exam…

–          That was cheasy and I am ridiculous

–          Good habits: understanding the foundations

–          Bad habits: obsessing over minute points in the foundations

–          For example right now I am about to go off on a tangent but I hereby feedback-inhibit myself

–          The only important buffer in CSF: Bicarb.

–          T CO2 (measured in mM) is relevant because you subtract [HCO3-] to get [CO2]. And then if you like you can divide that by 0.03 to get pCO3.

–          The Bicarb/CO2 ratio is significant because it tells you which changed first. Well first you look to see whether values have increased or decreased (they should always move in the same direction; if not you can dignose the animal with defying physics). Whether they decreased or increased does not tell you whether the disorder is acidic or alkaline; for that you need the ratio.

–          This question made sense in my head during the exam but explaining it is proving difficult because I am terrible at translating my brain. Note to self stop trying to help people.

–          A ratio of 20 Bicarbs:1 CO2 is normal. A ratio greater than that means plasma is alkaline because the equation is Bicarb-heavy. A ratio less than 20 means the plasma is acidic because the equation is leaning towards CO2. You can get the exact pH if you feel like it by putting the values into the Henderson-Hasselbalch equation.

–          Well if the ratio points to acidic and Bicarb and CO2 are decreased, it’s a metabolic acidosis. Because the chart I made says so. But really because if it were a respiratory acidosis, CO2 would have increased and Bicarb would have then increased to try to catch up. So the ratio would still be CO2-heavy (less than 20 and acidic), but the values for CO2 and Bicarb would be greater than normal.

–          If both values had decreased but the equation was Bicarb-heavy, the condition would be respiratory alkalosis. In that case, CO2 would have been lost through excessive ventilation (which by the way can be a result of pain), and Bicarb would just pile up because it’s useless in basic conditions. Some Bicarb would convert to CO2, but as H+ leaves the building it becomes less likely. And by ‘pile up’ I mean it would be unable to convert to CO2, its concentration relative to CO2 is increasing, not that its actual [concentration] in mM is increasing. So CO2 is lost, and the solution in response becomes more alkaline.

–          If CO2 and HCO3- values increase and the equation is Bicarb heavy (alkaline), it’s a metabolic alkalosis. Either excessive H+ was lost or excessive Bicarb was added to the system. The latter only really happens when a practitioner is incompetent and administers too much bicarb. H+ is lost in vomit. I probably will never see this one. Either way, bicarb collides with H+ less often, and so its concentration increases. The medulla oblongata responds to alkaline conditions by decreasing respiration, so CO2 goes up too, but not enough to overcome Bicarb.

–          Back to metabolic acidosis. Either H+ was added in excess or Bicarb was lost (as in diarrhea). Either way, Bicarb collides with H+ more often, and CO2 is formed, but not very much because H2CO3 only falls apart into H2O and CO2 when [CO2] is low. Still not sure of the mechanism for this of than ‘because Le Chatlier says so’ but it does not matter. The respiratory response to increased [H+] (as well as increased [CO2]) is hyperventilation, which leads to CO2 lost. So– with metabolic acidosis, CO2 may increase briefly before it decreases. I hope that was not on the exam.

–          I did not understand most of that before the test. And really I don’t/didn’t need to. I think too much like a scientist/total geek and not enough like a practitioner. Sometimes you need to be able to look at a chart and accept it without understanding it fully. Or maybe eventually I will be able to understand this ish intimately.

alkaline

acidic

Compensation

CO2 elevated

CO2 elevated

Abnormal hypoventilation

Abnormal hyperventilation

CO2 low

CO2 low

Compensation

Either added abnormally or in response to low H+

Bicarb elevated

1˚ (maybe)

Bicarb elevated

Passive; following abnormal hypoventilation

Slight; because of abnormal hyperventilation

Bicarb low

Bicarb low

1˚ (maybe)

Either because of compensatory hyperventilation or because it was lost

–          Well that was question 7

–          Ethylene glycol toxicity: antifreeze is not ‘inherently’ poisonous, but converted to strong acids by liver metabolism, the most deadly of which is oxalate 2-. The most common tx is administration of IV ethanol to get the animal drunk so it doesn’t care. Ethanol is a competative inhibitor of ethylene glycol at the liver enzymes, so its metabolism is slowed… shit. So it continues to be added to plasma but the kidney excretes it so hopefully it is maintained at non-toxic levels until it is gone. Feck. I said that administration of alcohol should reduce plasma [oxalate], and I mean it could, if liver metabolism is slowed to the point that kidney excretion exceeds it. And I mean that’s what you want, if you are treating an unconscious animal. Maybe that was correct. In addition, it should reduce the anion gap—because oxalate 2- etc is uncounted. And if it is removed, the anion gap goes down.

–          ‘The common development of acidemia in animals with diarrhea’… would this not be a bicarb-losing metabolic acidosis, where acidemia develops because there is no buffer? That wasn’t an option. Tissue perfusion is reduced, secondary lactic acidosis. Next.

–          Aldosterone stimulates alpha-intercalated cells. I don’t know how I knew this but I learned it last night. The class notes. Renal compensation for metabolic alkalosis accompanied by dehydration is faulty because Angi and Aldo increase bicarb reabsorption/H+ excretion. Lesson lesson study the class notes.

–          COPD: Chronic Obstructive Pulmonary Disease. Not in the notes. I almost certainly got this wrong because I thought too much. My thinking: horse has poor perfusion. A high V/Q mismatch, if you will. It breathes with difficulty and poor perfusion, leading to CO2 increase. [H+] rises, and the animal increases ventilation in response. Google says that this disease does indeed cause decreased perfusion. Probably CO2 diffuses fine but O2 does not à lactic acidosis à increased ventilation? My common-sense software says the thing would hypoventilate because breathing is difficult, but my brain says nay. We’ll see.

–          God damn this is boring and I’m hungry.

–          Siggard may have fucked this one up for me. ‘Acute hyperventilation’ (ie sudden flight from something scary) + intense skeletal muscle activity à lactic acidosis. Which cells experience NO change in [H+] as a result? Well blood cells are anaerobic-respirating all the time, but that’s not what I was thinking. H+ increases all over the body because homeostasis. I just wrote heterostasis by accident. Wut.

–          Siggard said something like ‘Erythrocytic H+ does not increase in response to respiratory acid/base disorders’ and that’s why we use it to calculate base excess: an indicator of non-respiratory acid/base status.

–          The notes say: The contribution of Hb buffer depends on [Hb] and pK of hemoglobin (differs by species) (the question was not specific).

–          Siggard says: acute respiratory acid base disturbances are characterized by an acute change in pCO2 associated with an acute change in pH but with unchanged ‘ctH+Efc’ (=titratable H+ of the extended extracellular fluid (including erythrocytes). IDK man. There’s no way I’m doing this after every test just because I have somewhere to put it.

–          Gastric dilatation and volvulus: wtf is this. Notes: Absomasal volvulus under Metabolic alkalosis; H+ is seqestered in the lumen of the abomasum. Wiki: A volulus is a bowel obstruction where the loop has completely twisted around its mesenteric attachment. Gastric dilatation: excessive gas causes stomach to distend. Question: Gastric dilatation and volvulus can cause respiratory acidosis. Brain: H+ from the tum is not returned to circulation (with bile I think?) and so plasma [H+] decreases. Respiratory compensation in the form of hypoventilation increases [H+]. Maybe too much.

–          Next question: Gastric dilatation and volvulus can be the cause of metabolic acidosis: I saif false, but if it untwists suddenly or bursts and that built-up H+ is returned to the system all at once…

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compensation mechanisms for normal acid-base disturbances.

Acids produced by normal metabolism are added to the pool and disrupt homeostasis.

‘These are called metabolic acids because they do not arise from CO2’ – does this mean CO2 produced as a result of cellular respiration does not contribute to metabolic acidosis? Does it count as respiratory?

Cells possess buffers that protect them from their own metabolism.The most common intracellular buffer is phosphate. Two reasons: cells have lots of phosphate anyway, as it is primarily used for energy metabolism (ATP, ADP, creatine phosphate). Also, phosphate has a pKa of 6.8, which is closer to the cell’s ideal then bicarb.

Cells also possess membrane transport proteins that regulate the export of protons / base according to pH. A decrease in extracellular pH caused by one cell group will cause others to retain their H+ and increase buffering instead, until normal extracellular pH is restored. In this manner, the H+ ions in a body are dispersed evenly.

 

Respiration compensates for metabolic acids by expiring CO2.

As H+ is increasingly produced, it collides more frequently with bicarb to form carbonic acid. The metabolic acid that is was previously bound to is no longer a threat and is excreted by the kidney, eventually. As CO2 is expelled by the lungs, carbonic acid (catalyzed by carbonic anhydrase) tends to form CO2 (rather than bicarb; where would it put the H+?)  to compensate. In the process, a H+ is removed from the pool.

As a result, the bicarbonate (and indeed total CO2) supply dwindles.

–          Bicarbonate is a counted anion. When it accepts the H+ from a metabolic acid, it becomes neutral and the charge is transferred to the conjugate base of the metabolic acid, an uncounted anion.

–          The excessive loss of Bicarb through this route (buffering), resulting in increased uncounted anions, is reflected in plasma samples as an increased anion gap.

–          Bicarbonate that leaves the body with its charge still attached will be accompanied by the other counted ions, and will not result in an increase in the normal anion gap.

Kidneys compensate for metabolic acids by producing HCO3.

In the process, H+ is removed from the pool.

how plasma becomes alkaline/acidic

water acts as both a weak acid and a weak base. it is more stable as H2O, but one one molecule can act as a nucleophile and take another’s H+. the result is H3O and OH. the H2O molecule is about 550,000,000 x more common than the hydronium ion or hydrogen ion, but the ions are highly reactive and therefore significant.

Hydronium (H3O) is the strongest acid that can exist in (aq) without dissociating. Hydroxide is a super strong base. As quickly as they dissociate, they react with each other to return to H2O form, unless they collide with something else reactive first.

If H3O donates a proton to a species other than OH, it returns to H2O. the [H] has decreased and [OH-] increased; the solution has become more basic.

OH and H3O are not in equilibrium with each other; this was a hard one for me to grasp. they are in equilibrium with H2O, although their formation never puts a dent in [H2O]. as one is lost, the concentration of the other goes up. the product (rather than sum) of their respective concentrations always equals 1e-14 (this being their equilibrium constant). this means that their concentrations increase and reciprocally decrease exponentially, which is still too much for my brain to wrap around.

edit: nope. 1e-14 is water’s ionization constant (=dissociation constant, equilibrium constant since water is a weak acid/base). this means that if ions are removed, add’l water molecules dissociate, and if ions are added, add’l water molecules are formed (unless one exceeds the other…). as a result, (H)(OH)=1e-14, and just because this is a tiny number and you can’t find an online calculator that provides that many significant figures doesn’t mean that the relationship does anything wacky. [H] = 1e-14/[OH]. it’s linear.

If OH acts as a nucleophile and reacts with a molecule other than H3O (such as CO2), the [OH] decreases, [H+] increases, and the solution becomes more acidic.