Malaria Pathophysiology

Summary

This video explains the pathophysiology of malaria, detailing the life cycle of the Plasmodium parasite, from mosquito transmission to infection of the human liver and red blood cells. The video covers how infected red blood cells lead to the release of pro-inflammatory cytokines, triggering symptoms such as fever, chills, and anemia. It explores how these immune responses contribute to complications like cerebral malaria, acute respiratory distress, and kidney issues. The activation of immune pathways, including toll-like receptors and NF-kB, amplifies inflammation, further contributing to the clinical manifestations of the disease.

Takeaways

• 😀 Malaria is caused by the *Plasmodium* species, transmitted through the bite of an infected *Anopheles* mosquito.
• 😀 The parasite enters the human bloodstream as sporozoites, which travel to the liver to replicate in hepatocytes.
• 😀 In some cases, *Plasmodium vivax* and *Plasmodium ovale* can form dormant hypnozoites in the liver, which can reactivate later.
• 😀 The asexual blood cycle in malaria involves merozoites infecting red blood cells, leading to fever, chills, and other symptoms.
• 😀 Some merozoites differentiate into gametocytes, which are ingested by another mosquito to continue the parasite's lifecycle.
• 😀 Malaria’s symptoms are largely due to the immune response, where macrophages and monocytes release pro-inflammatory cytokines.
• 😀 The spleen helps remove infected red blood cells, but also contributes to anemia and releases cytokines like TNF-alpha and interleukin 1B.
• 😀 Infected red blood cells adhere to endothelial cells in blood vessels, triggering clot formation, inflammation, and potential organ damage.
• 😀 Organ-specific complications from malaria include cerebral malaria (brain), acute respiratory distress (lungs), placental malaria (pregnancy), and kidney damage.
• 😀 The immune system detects the parasite through pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), triggering cytokine release and inflammation.

Q & A

What is the role of Anopheles mosquitoes in the life cycle of the Plasmodium parasite?

Anopheles mosquitoes are responsible for transmitting the Plasmodium parasite to humans. When a female mosquito bites a human, it injects sporozoites, the infective form of the parasite, into the human's bloodstream, starting the infection process.

How do sporozoites infect the human body after being injected by the mosquito?

After being injected into the human bloodstream, sporozoites travel to the liver, where they infect liver cells (hepatocytes) and replicate to form merozoites. These merozoites are then released into the bloodstream to infect red blood cells.

What is the significance of hypnozoites in malaria infection?

Hypnozoites are a dormant form of the Plasmodium vivax or Plasmodium ovale parasites that can remain in the liver for up to 1-2 years without replicating. When activated, they re-enter the cycle of replication, causing a relapse of malaria.

What happens when merozoites enter red blood cells?

Merozoites infect red blood cells and undergo further stages of development, including the ring stage, trophozoite, and schizont stages. These stages involve the parasite feeding on hemoglobin and replicating within the red blood cells, leading to their rupture and the release of new merozoites.

How does the immune system respond to the presence of malaria parasites in red blood cells?

The spleen plays a key role in detecting and removing infected red blood cells through macrophages. These macrophages also release pro-inflammatory cytokines such as TNF-alpha and interleukin-1B, which cause the symptoms associated with malaria, including fever and chills.

What are the clinical manifestations caused by the release of pro-inflammatory cytokines in malaria?

The release of pro-inflammatory cytokines leads to symptoms such as fever, chills, sweating, headache, low blood pressure, and excessive perspiration. These cytokines also impair erythropoiesis, contributing to anemia in malaria patients.

How does the expression of adhesion molecules by endothelial cells contribute to the pathology of malaria?

Infected red blood cells can adhere to endothelial cells in various organs, such as the brain, lungs, placenta, and kidneys, due to the increased expression of adhesion molecules like CD36 and ICAM-1. This can cause vessel obstruction, inflammation, and contribute to conditions like cerebral malaria and placental malaria.

What is cerebral malaria, and how is it related to the obstruction of blood vessels in the brain?

Cerebral malaria is a severe form of malaria that occurs when infected red blood cells block blood vessels in the brain. This leads to tissue inflammation, impaired blood flow, and can result in fatal outcomes due to the lack of oxygen and nutrients.

How does the inflammatory response in the lungs and placenta contribute to malaria-related complications?

In the lungs, vessel obstruction and inflammation can lead to acute respiratory distress. In the placenta, it can cause placental malaria, which is dangerous for both the mother and the fetus. Both conditions can be fatal if untreated.

What are the roles of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) in triggering inflammation in malaria?

PAMPs, such as genetic material from the parasite or GPI (glycosylphosphatidylinositol), and DAMPs, such as heme, are recognized by toll-like receptors on immune cells. This recognition activates inflammatory pathways, leading to the release of pro-inflammatory cytokines and the symptoms of malaria, such as fever and rigor.