Mannitol toxicity

[chillaxbro]

Accoridng to Uworld (q 688) one toxicity is that it causes pulmonary edema - it draws too much fluid into vasculature -> higher hydrostatic pressure -> pulmonary edema. Okay I can believe that

It also says mannitol drawing water out of cells will also pull potassium out causing hyperkalemia and metabolic acidosis.

Questions:
Why does mannitol pulling water out also cause K+ to come out? Is it just because there is less water in the cell so K+ comes out to keep the normal K+ amt in a cell?
Why does that cause metabolic acidosis? Wouldn't K+ coming out will cause H+ to go into a cell and thus cause alkalosis?

Thanks

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[chillaxbro]

Dont want to start another thread so here comes another question (unrelated)

1785 - Aplastic anemia -

Absence of splenomegaly is important for diagnosis in aplastic anemia. Why is that?
Is it because big spleen = extramedullary hematopoesis (eg due to leukemia killing the bone marrow)and therefore it is not aplastic anemia since there is hematopoesis occurring?
Or does big spleen = increased killing of blood cells and thus is not aplastic anemia? I can't see how this could cause PANcytopenia tho

What would be the cause of pancytopenia with a big spleen?

 

[Chilladosis]

for your first part, i think your right man:

just saw this on uptodate:
The rise in the plasma potassium concentration following hypertonic mannitol is due to the movement of potassium out of the cells into the extracellular fluid via two mechanisms: (1) the rise in cell potassium concentration induced by water loss favors passive potassium exit through potassium channels in the cell membrane; and (2) the frictional forces between solvent (water) and solute can result in potassium being carried out through the water pores in the cell membrane (a process that is called solvent drag).

so for the hyperkalemia - acidosis part
i assume losing blood volume, activates RAAS and aldoesterone levels go up. i think because of the HIGH levels of potassium that are present (and will be continuous elevated due to the mannitol), aldosterone can continually secrete K+ in exchange for Na+. (never needing to exchange H+ for Na+ because there is persistent hyperkalemia? thus H+, levels increase thereafter? --> metabolic acidosis


...just speculating on that part - since usually like in hyper aldosteronism you get hypernatremia, hypokalemia (K+ to urine for Na+ exchange), and subsequent metabolic alkalosis (H+ to the urine for Na+ exchange once K+ levels fall)...so the levels of K+ can influence levels of H+ in the blood.

 

[chillaxbro]

for your first part, i think your right man:

just saw this on uptodate:
The rise in the plasma potassium concentration following hypertonic mannitol is due to the movement of potassium out of the cells into the extracellular fluid via two mechanisms: (1) the rise in cell potassium concentration induced by water loss favors passive potassium exit through potassium channels in the cell membrane; and (2) the frictional forces between solvent (water) and solute can result in potassium being carried out through the water pores in the cell membrane (a process that is called solvent drag).

so for the hyperkalemia - acidosis part
i assume losing blood volume, activates RAAS and aldoesterone levels go up. i think because of the HIGH levels of potassium that are present (and will be continuous elevated due to the mannitol), aldosterone can continually secrete K+ in exchange for Na+. (never needing to exchange H+ for Na+ because there is persistent hyperkalemia? thus H+, levels increase thereafter? --> metabolic acidosis


...just speculating on that part - since usually like in hyper aldosteronism you get hypernatremia, hypokalemia (K+ to urine for Na+ exchange), and subsequent metabolic alkalosis (H+ to the urine for Na+ exchange once K+ levels fall)...so the levels of K+ can influence levels of H+ in the blood.

Hmm manitol makes you pee more so if anything RAAS will go down due to increased RPF/GFR. That would explain the increased H+. Not sure if that's the reason tho since no mention of RAAS at all in the uworld explantion. All it says is that it's due to water coming out of the cells from the manitol

 

[Chilladosis]

maybe it has to do something with loss of Na+ via decreased RAAS leading to retained H+? thanks for clarifying that part.

 

[TheBDP]

Hyperkalemia can also bring about acidosis on its own. By driving the H/K ATPase pump, more protons are pumped into the ECF in exchange for K.

 

[chillaxbro]

Anyone know anything about aplastic anemia?

 

[worldbeater]

Absence of splenomegaly is important for diagnosis in aplastic anemia. Why is that?
Is it because big spleen = extramedullary hematopoesis (eg due to leukemia killing the bone marrow)and therefore it is not aplastic anemia since there is hematopoesis occurring?

Yeah exactly, in aplastic anemia usually your marrow is full of fat (World describes it as hypodense, clear cells with a pic), so you can't generate your normal RBC levels. Your spleen will compensate, hence the enlargement. Other causes of destruction of marrow are Parvovirus B19 (DNA virus, non-enveloped, single stranded), and some specific drugs: AZT, Benzene, Chloramphenicol, Vinblastine ("blasts bone marrow").

This can be seen more in babies in utero, the spleen and long bones will be generating RBCs like crazy to compensate at specific months (don't remember the exact time markers).

What would be the cause of pancytopenia with a big spleen?

I actually never thought of this, I knew that if the bone marrow is destroyed, the spleen would compensate in terms of generation of RBCs. Technically, all the causes above will would present with pancytopenia (decrease in all values), because your RBCs, WBCs and platelets are generated in the marrow. I am not sure how the WBCs and platelets are regenerated, I'll have to look closer at World next time I hit those type of questions.

 

[Cytarabine]

Dont want to start another thread so here comes another question (unrelated)

1785 - Aplastic anemia -

Absence of splenomegaly is important for diagnosis in aplastic anemia. Why is that?
Is it because big spleen = extramedullary hematopoesis (eg due to leukemia killing the bone marrow)and therefore it is not aplastic anemia since there is hematopoesis occurring?
Or does big spleen = increased killing of blood cells and thus is not aplastic anemia? I can't see how this could cause PANcytopenia tho

What would be the cause of pancytopenia with a big spleen?

lymphoma

 

[chillaxbro]

lymphoma

Basically because of extramedullary hematopoesis right?

I read a different definition of aplastic anemia (basically is hematopoetic stem cells CD34+ aren't working) which makes everything a lot clearer. That would explain why absent splenomegaly has to be a criteria for AA. Thanks

 

[Cytarabine]

Basically because of extramedullary hematopoesis right?

I read a different definition of aplastic anemia (basically is hematopoetic stem cells CD34+ aren't working) which makes everything a lot clearer. That would explain why absent splenomegaly has to be a criteria for AA. Thanks

eh, I don't think I'd call it extramedullary hematopoesis when it's a neoplastic process. When I think of extramedullary hematopoiesis, I think of physiologic causes. I think it's a nomenclature thing, but I could be wrong there, far from a heme expert, and I'm distant from basic sciences at this point. But yea, in aplastic anemia, there's a failure in production (I believe you're correct, the defect is at the level of the stem cell), and there's thus no reason for there to be splenic enlargement. In general, pancytopenia + splenomegaly in my mind is malignancy until proven otherwise