In this learning unit,
we want to discuss the basic principles of the pathophysiology of Ebola virus disease.
Our learning objectives here are to describe the basics but also to discuss very
briefly how the different complications encountered in
Ebola patients are caused by different pathogenic mechanisms.
In a nutshell, here we do see the virus actually and the first line of cells,
which is involved in the propagation of Ebola virus infection.
The virus with its glycoprotein spikes,
docks onto monocytes, macrophages,
dendritic cells on contact with all cells.
Once the contact has been made between the virus from
infectious bodily fluids with
damaged skin or directly with the bloodstream of the patient,
for example, or the bloodstream of the person to be infected,
for example, during a needle stick accident.
So, once the virus has entered this first line cells,
the virus travels within integrates itself into the genome,
into the DNA of the human cells,
the replication process starts and the virus travels within
those cells to virtually all organs of the human being infected.
It spreads to lymph nodes and starts to replicate and
disseminate to other tissues actually.
What we see is
a very strong systemic inflammatory response in people who develop the disease.
Ebola virus infection triggers the secretion of inflammatory mediators.
Lymphocyte apoptosis is induced, tissue damage ensues,
and loss of vascular integrity contributes to multi-organ failure and shock.
The infected cells release variants and soluble shared glycoprotein.
The soluble shared glycoprotein triggers remote targets, promoting cytokine release,
and the resulting amplified inflammation likely contributes,
again, to multi-organ failure and shock of the patient.
Infection of macrophages and dendritic cells leads to the depletion of lymphocytes and
impairment of the host response and an increased susceptibility to secondary infections,
for example, bacterial sepsis is one of the secondary.
Infection or necrosis of hepatocytes causes dysfunction and decreased production of
clotting factors and the haemorrhagic tendency
becomes pronounced that can be internal bleedings,
internal haemorrhages, or external hemorrhages.
But as we said before,
this is only seen in a minority of the patients with severe disease.
Infection or necrosis of
the adrenal cortical cells leads to an impaired synthesis of steroids,
again, contributing to the development of shock.
In conclusion, of course these are only the very basic principles but in conclusion,
we can say, that Ebola generates a systemic inflammatory response,
which can cause multi-organ failure and shock.
In particular lymph nodes, the liver,
and adrenal glands are affected leading to immune suppression and
decreased production of clotting factors and corticosteroids.
As we can see from a rapidly growing list of excellent references,
the last word on the understanding of the pathophysiology
has not been spoken yet but in the future,
we hope that the better understanding of the pathophysiology,
which is naturally growing during large outbreaks like SO1 encountered now,
will also help us in identifying possible adjuvant therapies,
which we're in the current situation not routinely applying it.