Malarial Anaemia Flashcards
how does malaria contribute to anaemia?
Malaria leads to anemia through:
Direct destruction of infected RBCs. - hemolytic anaemia
Suppression of erythropoiesis (suppress EPO) by inflammation or bone marrow dysfunction. - iron-restricted erythropoiesis
Increased hemolysis of uninfected RBCs.
free heme released during hemolysis - contributes to inflammation + oxidative stress
what is a typical treatment for anaemia and why might it cause negative effects if used in malarial anaemia?
EPO therapy
Erythropoietin (EPO) stimulates RBC production
In malaria, EPO therapy could inadvertently increase reticulocytes, which are targeted by Plasmodium vivax, potentially worsening the infection.
what is the mechanisms behind anaemia in bacterial/malarial infections
hepcidin - produced by liver in response to inflammatory cytokines.
HEPCIDIN INHIBITS ferroportin - iron export protein - and degrades it to prevent iron from leaving rbc or being recycled by macros / inhibits iron going into bloodstream
inflammation = more hepcidin = iron sequestered in cells, reduced iron availability in bloodstream = nutritional immunity: limits iron availability to pathogens to reduce their growth/proliferation
this contributes to iron restricted erythropoesis - not enough iron in bloodstream for erythropoiesis
High hepcidin levels suppress iron export, limiting erythropoiesis and worsening anemia.
how does hypoxia contribute to erythropoiesis
hypoxia via sequestration causes low hepcidin levels so ferroportin remains active, and iron is released from host cells for erythropoiesis/RBC production
hypoxia - increase EPO production = more erythropoesisi
idk summary
In malarial/coinfection anemia, the body faces a conflict:
On one hand, it needs to maintain iron levels for erythropoiesis (to produce red blood cells and improve oxygen transport).
On the other hand, it must limit free iron to avoid feeding the pathogen.
pathogen infection/hemolysis - heme release due to parasite burst = inflammation = higher hepcidin levels = lower iron levels in bloodstream = anaemia, not enough iron to make new red bloods
malaria sequestration= hypoxia = lower hepcidin = more iron in blood stream = more RBCs
why do we see anaemia even in uncomplicated malaria cases
iRBCs hemolysis - free heme released
free heme is toxic, causes oxidative damage to uninfected RBC membranes = bystander hemolysis
overwhelms hemopexin system, which usually binds heme to neutralise it. = anaemia and more hemolysis
inflammation upregulates or downregulates erythropoiesis
generally downregulates
what is bystander hemolysis
hemolysis of iRBC = release of free heme
free heme causes oxidative damage to membranes of uninfected RBCS
uninfected RBCs undergo eryptosis - uninflammatory cell death through caspace activation or PS membrane flipping - TIM4+ macros eat
