Trophozoite
After invading the erythrocyte, the parasite loses its specific invasion organelles (apical complex and surface coat) and de-differentiates into a round trophozoite located within a parasitophorous vacuole in the red blood cell cytoplasm. The young trophozoite (or "ring" stage, because of its morphology on stained blood films) grows substantially before undergoing schizogonic division.
During asexual development the parasite increases in size to ~50% of the uninfected erythrocyte volume: the infected erythrocyte volume remains relatively constant. Haemoglobin content gradually decreases but its concentration remains constant until the early trophozoite stage when it decreases by 25%. It then remains constant again until just prior to rupture. During early sexual development the gametocyte has a similar morphology to a trophozoite but subsequently undergoes a dramatic shape change.
The parasite's presence within the erythrocyte induces changes in the properties of the host cell. Relative membrane deformability is less than 10% of uninfected erythrocytes. This change may contribute to the capillary occlusions that occurs in this disease. The deformability of the membrane is also dependent on the temperature and decreases with increased temperature. Deformability is reduced by a factor of 3-4 between 37 and 41 degrees Celsius. The fever that is commonly found in malaria may also contribute via this mechanism to capillary occlusion. The stiffness of the erythrocyte membrane increases as the parasite matures. The overall effect of these chances are to transform the erythrocyte from its normal biconcave shape into a parachute like structure. This change is apparent at high pressure rather than at low. Transition occurs at flow rates of ~65 microns per second. The mechanism of these changes are not known but changes in ATP consumption or alterations to the erythrocytes' spectrin framework may be important.
Within the red blood cell, the parasite metabolism depends greatly on the digestion of hemoglobin. A set of enzymes known as plasmepsins which are aspartic acid proteases are used to degrade hemoglobin. The parasite digests 70-80% of the erythrocyte's haemoglobin but utilizes only ~15% in de novo protein synthesis. Intraerythrocytic Plasmodium falciparum utilizes only a fraction of the amino acids derived from the digestion of host cell cytosol for the biosynthesis of its proteins. The excess amino acids are exported from the infected erythrocyte by new transport pathways created by the parasite. The reason proposed for this apparently excessive digestion of haemoglobin is the colloid-osmotic hypothesis which suggests that the digestion of haemoglobin increases the osmotic pressure within the infected erythrocyte leading to its premature rupture and subsequent death of the parasite. To avoid this fate much of the haemoglobin is digested and exported from the erythrocyte. This hypothesis has been experimentally confirmed.
Infected erythrocytes are often sequestered in various human tissues or organs, such as the heart, liver and brain. This is caused by parasite derived cell surface proteins being present on the red blood cell membrane and it is these proteins that bind to receptors on human cells. Sequestration in the brain causes cerebral malaria, a very severe form of the disease, which increases the victim's likelihood of death.
The parasite can also alter the morphology of the red blood cell causing knobs on the erythrocyte membrane.
Erythrocyte invasion and growth leads to activation of several distinct anion channels and a non-selective Ca2+-permeable cation channel. The non-selective cation channel's activation allows entry of Ca2+ and Na+. Absence of the channels is incompatible with pathogen survival. Although the mechanism of activation of these channels is not know it is presumed to be due to oxidation stree generated by the parasite because similar or identical channels are activated by oxidation of non-infected erythrocytes. Ca2+ entry stimulates an intraerythrocytic scramblase that facilitates bi-directional phospholipid migration across the bilayer. This results in an alternation of the cell membrane's phosphatidylserine asymmetry. Exposure of phosphatidylserine at the outer surface of the cell membrane is followed by binding to phosphatidylserine receptors on macrophages and the subsequent phagocytosis of the affected erythrocyte. It appears that the parasite because of its growth requirements is in a race to complete its life cycle before the infected erythrocyte is phagocytosed.
Read more about this topic: Plasmodium Falciparum Biology, Erythrocytic Stage