Malaria Case Sep 24 Flashcards
Describe the life cycle of plasmodium vivax.
- A mosquito carrier will have the plasmodium sporozoites in its saliva
- Mosquito bites a human and injects the sporozoites under the skin
- Sporozoite enter circculation and travel to the liver where they infect hepatocytes.
- They undergo asexual reproduction within the hepatocytes and form merozoites.
- The merozoites lyse the hepatocytes and aainst enter circulation
- The merozoites infect red blood cells where they again undergo aseuxal reproduction - schizontony
- After reproduction, the RBCs will lyse, releasing the mature trophozoites into the blood to be taken up by another biting moquito and transferred to a new host
Under normal conditions, why do RBCs not lyse?
Under normal conditions, RBC ion channels are VERY tightly regulated. THe only major ion movement is Cl-, which needs to happen so the RBCs can exchange Cl- for bicarb in the lungs to manage blood pH.
RBCs also have aquaporins to make sure the RBC size does not differ to any great extent
What does the malaria parasite do to cause eventual RBC lysis? Why doesn’t it want to lyse the cell right away?
The malaria parasite hijacks the ion channels of the RBC. First this is to allow nutrients to enter the RBC (after they’ve eaten the heme), but later on it’s to lyse the cell.
They dpn’t want to lyse right away because they need to reproduce first
What is the normal RPM of a red blood cell and what channel is mainly responsible for that? How can we tell?
The RPM is about -10 mV
THe main channel responsible for this is the Cl- channel
We know this because the RPM is very close to the Erev of Cl- for RBCs - -8 mV
What are the reversal potentials for Na+, K+, and Cl- in the RBCs?
Na+ = 83 mV
K+ = -85 mV
Cl- = -8 mV
Given that Na+’s Erev is 83 mV, what direction will Na+ want to flow under normal RBC conditions?
What would need to happen to the RPM in order for Na+ to flow the opposite direction?
At the normal conditions of RPM = -10 mV, Na+ will want to enter the cell due to the concentration gradient
For Na+ to want to leave the cell, the RPM would have to increase beyond 83 mV
Given the Erev of -85 mV, what direction will K+ want to flow under normal conditions in an RBC?
What would need to happen for the K+ to flow in the other direction?
At the normal conditions of RPM = -10 mV, K+ will want to flow out of the cell due to its concentration gradient
In order for K+ to reverse and flow into the cell, the RPM would have to decrease to below -85 mV
Given the Erev of -8 mV, in what direction will Cl- want to flow under normal RBC conditions?
What would need to happen for Cl- to flow th eother way?
At an RPM of -10 mV, Cl- will want to flow out slightly due to it’s electric gradient.
It doesn’t takae much to change that in this case, because the RPM would only have to increase past -8 mV in order for the Cl- to flow in down its concentration gradient
What happens to ion flow during a malaria infection?
The parasite hijacks the ion channels with K+ opening first, then NA+
- K+ channels open and K+ rushes out of the cell (based on the concentration gradient)
- The efflux of K+ serves to hyperpolarize the membrane
- In response to live, Cl- also leaves the cell down it’s electrical gradient
- Na+ channels open after this and Na+ will rush into the cell
- This results in a depolarization of the membrane,
- Once the depolarization goes above -8 mV, Cl- will also rush into the cell
- Water will follow by osmosis and the RBC will lyse
What are the main transporters/channels that are active in an RBC under normal conditions?
What channels does the parasite use during infection?
The main transporters under normal conditions are the Cl-/HCO3- exchanger, the aquaporins, the Na+/K+ ATPase. Pretty much NO cation channels, but plenty of anion channels.
During infection, the parasite relies on large, poorly selective anion channels in the membrane. They use them for bring in nutrients and expel waste. Because these are anion channels, K+ will leave the cell first, followed by an influx of Na+
