This document provides an overview of the biochemical and physiological dysfunctions that commonly occur during viral haemorrhagic fever caused by the Ebola virus. It discusses how Ebola virus primarily targets immune cells like macrophages and dendritic cells, triggering lymphocyte apoptosis and immune system dysfunction. This allows the virus to spread and infect multiple organs like the liver, where damage to hepatocytes leads to impaired biochemical functions and disruption of homeostasis. Specific issues addressed include liver dysfunction impacting blood pressure regulation, coagulation, and glucose levels, as well as adrenal damage interfering with electrolyte balance. The multi-organ impacts ultimately result in conditions like disseminated intravascular coagulation and shock that characterize late-stage Ebola haem
Few of the latest research findings on the novel corona virus 2019 (SARS-CoV-2) have been compiled. The basic biology of corona virus, its life cycle and its evolutionary relationship with corona viruses derived from other animals (including bats and pangolin corona viruses) has been depicted highlighting it’s inter species transmission. One of the key pathogenicity and transmissibility determinants (i.e. a furin-like S1/S2 cleavage site in the S protein) unique to SARS-CoV-2 might be responsible for its distinct mechanism to promote its entry into host cells. The last slide leaves the readers with basic research questions pertaining to the genetic divergence and evolution of coronaviruses in bats, its pathogenesis and mechanism of disease transmittance. In these times of crisis due to the outbreak of novel corona virus 2019 in Wuhan and subsequently leading to a pandemic, it is important to understand the basic biology of corona virus and the latest research findings related to its cross species transmission and key pathogenicity determinant that allows the novel corona virus a distinct mechanism to gain entry into the host cells. The structural biology approach to study the interaction of SARS-CoV-2 spike protein with receptor binding domain of angiotensin-converting enzyme-2 (ACE2) is underway and it is hoped that these findings will help in the design of new vaccines candidates targeting SARS-CoV-2 spike protein.
Medcrave - MERS coronavirus - current statusMedCrave
CDC: Centers for Disease Control; MERS-CoV: Middle
East Respiratory Syndrome Coronavirus; RT-PCR: Reverse
Transcriptase Polymerase Chain Reaction; VLP: Virus Like
Particles.
Recently, a new virus started to infect certain individuals in the Middle-East. It was soon identified as a previously unknown coronavirus that caused severe respiratory disease with a high rate of mortality. This virus, MERS-CoV, is still closely watched by health authorities as it has the potential to evolve and cause a major epidemic.
Few of the latest research findings on the novel corona virus 2019 (SARS-CoV-2) have been compiled. The basic biology of corona virus, its life cycle and its evolutionary relationship with corona viruses derived from other animals (including bats and pangolin corona viruses) has been depicted highlighting it’s inter species transmission. One of the key pathogenicity and transmissibility determinants (i.e. a furin-like S1/S2 cleavage site in the S protein) unique to SARS-CoV-2 might be responsible for its distinct mechanism to promote its entry into host cells. The last slide leaves the readers with basic research questions pertaining to the genetic divergence and evolution of coronaviruses in bats, its pathogenesis and mechanism of disease transmittance. In these times of crisis due to the outbreak of novel corona virus 2019 in Wuhan and subsequently leading to a pandemic, it is important to understand the basic biology of corona virus and the latest research findings related to its cross species transmission and key pathogenicity determinant that allows the novel corona virus a distinct mechanism to gain entry into the host cells. The structural biology approach to study the interaction of SARS-CoV-2 spike protein with receptor binding domain of angiotensin-converting enzyme-2 (ACE2) is underway and it is hoped that these findings will help in the design of new vaccines candidates targeting SARS-CoV-2 spike protein.
Medcrave - MERS coronavirus - current statusMedCrave
CDC: Centers for Disease Control; MERS-CoV: Middle
East Respiratory Syndrome Coronavirus; RT-PCR: Reverse
Transcriptase Polymerase Chain Reaction; VLP: Virus Like
Particles.
Recently, a new virus started to infect certain individuals in the Middle-East. It was soon identified as a previously unknown coronavirus that caused severe respiratory disease with a high rate of mortality. This virus, MERS-CoV, is still closely watched by health authorities as it has the potential to evolve and cause a major epidemic.
There are nearly 100 viruses of the herpes group that infect many different animal species.
Official name of herpesviruses that commonly infect human is Humans herpesvirus (HHV)
herpes simplex virus types 1 (HHV 1)
Herpes simplex virus type 2 (HHV 2)
Varicella-zoster virus (HHV 3)
Epstein-Barr virus, (HHV 4)
Cytomegalovirus (HHV 5)
Human herpesvirus 6 (HHV 6)
Human herpesvirus 7 (HHV 7)
Human herpesvirus 8 (HHV 8) (Kaposi's sarcoma-associated herpesvirus).
Herpes B virus of monkeys can also infect humans
hELMINTHS#corona virus#Aspergillosis#BUGANDO#CUHAS#CUHAS#CUHAS
Analysis in to the Epidemiology and Pathophysiology of Respiratory Syncytial ...Pırıl Erel
Respiratory Syncytial Virus (RSV) places the heaviest clinical burden on paediatric wards in the UK and the US. It is in fact, a global issue with 3.4 million hospitalisations and approximately 66,000 deaths worldwide per annum (Bush et al., 2007) (Lambert et al., 2014). RSV is the leading cause, especially during the winter months, of severe respiratory infections in infants resulting in a rise in hospital admissions where 0.5-1% of infected babies die from respiratory failure. It is also a significant respiratory concern in the elderly population. (Agoti et al., 2014)
RSV has shown to have a willful ability to enter the host resulting in illness both by viral mechanisms and proteins encoded by RSV, dysregulating the synthesis of systemic immune response of the host. Alongside the infiltration of RSV, the heath status and genotype of the host will be a key factor in predetermining disease susceptibility and severity.
It is important to understand RSV has been implicated with further acute and chronic illnesses therefore by considering the epidemiology and pathophysiology of RSV treatment may be implicated during early stages which can influence possible outcomes in the future.
I used this for my class presentation for diseases but the professors said that it isn't scientific. I guess I should have stuck with the boring black & white format.
Running Head PATHOPHYSIOLOGY 1PATHOPHYSIOLOGY5.docxglendar3
Running Head: PATHOPHYSIOLOGY 1
PATHOPHYSIOLOGY 5
Pathophysiology
Student name
School
Instructor
Date
Rheumatoid Arthritis (RA) is a joint inflammatory disorder that can, at times, extend the effects to other body organs like lungs and blood vessels; The condition complicates the body's immune system with the advancement of the symptoms( explain types of symptoms) and citation needed(>>>>>>>>) Patients suffering from RA are prune to severe conditions that may arise as the condition matures. patients have distinct symptoms expressed outwardly based on the level and stage of the inflammatory disorder, some of which are similar to those expressed by the patients in the case study. The condition is not hereditary or family born but thought to result from genetic risk factors such as…… (citation needed) The patient in the case study was aware that increased inflammatory could result in the highlighted symptoms and thus presented them to identify whether they were emanating from the condition or any other source of infection.
Identify the genes that may be associated with the development of the disease.
A variety of gene pairs are associated with the RA condition as significant risk factors. The causative genes to the condition are suspended in the immune system function ( citation). Change in human Leukocyte antigen genes (HLA) in the significant contributor to Rheumatoid Arthritis ( citation needed). The genes, RLA-DRB1, are highly associated with triggering the Rheumatoid Arthritis condition. It is associated with the production f body proteins. The HLA proteins assist the immune system in distinguishing immune proteins and those proteins produced by body invaders like viruses (Soo P, n.d). Variation in other genes has a little impact on the condition ( citation needed).
Explain the process of immunosuppression and the effect it has on body systems.
Immunosuppression is a process that subdues the human immune system to individuals undergoing organ transplants or those with autoimmune conditions like Rheumatoid Arthritis(>>>>>>>>). The process involves administering drugs to ensure that the immune system does not repel the organs being transplanted (McCance & Huether, 2019). The physicians must first carry an examination of different body organs them makes a prescription to the patient. After the examination, a strict medical plan or therapy session is created, which patients should stickily follow. During the process, the doctor monitors the patients effectively on a close observation. Immunosuppression has different side effects in the body, some of which arise due to the drugs ( citation needed). The effects include; decrease in bony density, a decrease in muscle functioning, effect on the operation of muscle fiber, which reduces muscle protein production and cases of hyperglycemia and severe diabetes. The effects get controlled through regular exercise. This paragraph should lead to the 4th or next paragraph this p
Invasiv.
Running Head PATHOPHYSIOLOGY 1PATHOPHYSIOLOGY5.docxtodd581
Running Head: PATHOPHYSIOLOGY 1
PATHOPHYSIOLOGY 5
Pathophysiology
Student name
School
Instructor
Date
Rheumatoid Arthritis (RA) is a joint inflammatory disorder that can, at times, extend the effects to other body organs like lungs and blood vessels; The condition complicates the body's immune system with the advancement of the symptoms( explain types of symptoms) and citation needed(>>>>>>>>) Patients suffering from RA are prune to severe conditions that may arise as the condition matures. patients have distinct symptoms expressed outwardly based on the level and stage of the inflammatory disorder, some of which are similar to those expressed by the patients in the case study. The condition is not hereditary or family born but thought to result from genetic risk factors such as…… (citation needed) The patient in the case study was aware that increased inflammatory could result in the highlighted symptoms and thus presented them to identify whether they were emanating from the condition or any other source of infection.
Identify the genes that may be associated with the development of the disease.
A variety of gene pairs are associated with the RA condition as significant risk factors. The causative genes to the condition are suspended in the immune system function ( citation). Change in human Leukocyte antigen genes (HLA) in the significant contributor to Rheumatoid Arthritis ( citation needed). The genes, RLA-DRB1, are highly associated with triggering the Rheumatoid Arthritis condition. It is associated with the production f body proteins. The HLA proteins assist the immune system in distinguishing immune proteins and those proteins produced by body invaders like viruses (Soo P, n.d). Variation in other genes has a little impact on the condition ( citation needed).
Explain the process of immunosuppression and the effect it has on body systems.
Immunosuppression is a process that subdues the human immune system to individuals undergoing organ transplants or those with autoimmune conditions like Rheumatoid Arthritis(>>>>>>>>). The process involves administering drugs to ensure that the immune system does not repel the organs being transplanted (McCance & Huether, 2019). The physicians must first carry an examination of different body organs them makes a prescription to the patient. After the examination, a strict medical plan or therapy session is created, which patients should stickily follow. During the process, the doctor monitors the patients effectively on a close observation. Immunosuppression has different side effects in the body, some of which arise due to the drugs ( citation needed). The effects include; decrease in bony density, a decrease in muscle functioning, effect on the operation of muscle fiber, which reduces muscle protein production and cases of hyperglycemia and severe diabetes. The effects get controlled through regular exercise. This paragraph should lead to the 4th or next paragraph this p
Invasiv.
12Toxoplasmosis and Effects on Abortion, And Fetal A.docxrobert345678
12
Toxoplasmosis and Effects on Abortion, And Fetal Abnormalities
Toxoplasmosis and Effects on Abortion, And Fetal Abnormalities
Abstract
The placenta is an immune-privileged organ that may tolerate antigen exposure without eliciting a strong inflammatory response that could result in an abortion. After that, the pregnancy can progress normally. Th1 answers, characterized by interferon-, are essential for suppressing intracellular infections. Therefore, the maternal immune system finds a catch-22 when intracellular parasites invade the placenta. The pro-inflammatory response required to eradicate the virus carries the danger of causing an abortion. Toxoplasma is a potent parasite that causes lifetime infections and is a leading cause of abortions in people and animals. This paper speculates that the pregnancy outcome may be affected by the Toxoplasma strain and the effectors of the parasite, both of which can modify the signaling pathways of the host cell.
Introduction
Fetuses infected with the protozoan parasite Toxoplasma gondii can develop a disorder known as toxoplasmosis, sometimes called congenital toxoplasmosis. This disease is transmitted from mother to child in the womb. A miscarriage or a stillbirth might happen as a result. A child with this illness may also have significant and progressively deteriorating difficulties in their vision, hearing, motor skills, cognitive ability, and other areas of development. The parasite Toxoplasma gondii is blamed for many pregnancies ending in miscarriage (Arranz-Solís et al., 2021). Most abortions happen in the first trimester of pregnancy or during the early stages of acute sickness. This research aimed to determine if women who had an abortion were more likely to be infected with toxoplasmosis.
To make matters worse, the toxoplasmosis-causing Toxoplasma gondii is an obligate intracellular pathogen that infects nearly every animal species with a thermoregulatory system. Transferring Toxoplasma from one host to another requires the development of tissue cysts that are infectious when ingested. This means the parasite is incentivized to ensure that the host organism lives during the infection. The parasite does this by stimulating an immune response powerful enough to limit parasite reproduction. Toxoplasma, on the other hand, uses a unique set of effectors to evade the immune response and ensure that the parasite population does not decrease to zero.
Results
Type II strains are the most common cause of infection in both animal and human hosts. However, all four clonal lineages of Toxoplasma may be found throughout Europe and North America. It has been established, however, that the bulk of the South American isolates identified is genetically distinct from the strains seen in North America and Europe. Certain sorts of isolates have been labeled as atypical strains. Birth abnormalities apart, type II strains are the most common in Europe and North America, where the great majority of .
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3. Viral Haemorrhagic Fever.
An insight into the biochemical and physiological
dysfunctions which are commonly associated.
4. Viral Haemorrhagicfever(VHFs) isaname givenreferringtoa groupof illnessesthatare causedby
several familiesof viruses,thistermisusedtodescribe asevere multisystemsyndromeinwhich
manyorgans withinthe bodyare effected.There are four maintaxonomicfamilies of viruseswhich
may cause a viral haemorrhagicfever,these are representedinfigure1.
As youcan see,dependingonthe responsibleVirusthe severity,withregardstofatalityrate,varies
fromup to 90% to lowerthan1%. The reasonfor thisrequiresanunderstandingof the different
challengesthateachvirusintroducestothe humanbodyonce an infectionhasoccurred.Depending
on the causative virus,the symptomsandclinical features thatoccurwithinthe bodyvary.The
severityof the altercationstothe body’snormal biochemistryandphysiology generally correlatesto
the virus’sfatalityrate.Due tothe highfatalityrate Iwill focusonthe Ebola virus;the causative virus
of EbolaHaemorrhagicFever(EHF),andthe challengesthe humanbodyispresentedwithupon and
duringan infection.
It isnecessarytonote that there are 5 speciesof Ebolavirus;Zaire,Bundibugyo,Sudan,Restonand
Taï Forest.Dependingonthe speciesthe symptomsmayvary,soto avoidconfusionthisreportwill
concernthe general biochemical andphysiological dysfunctionsthatmayoccur.EHF maylast forup
to 21 days,afterthe 4-10 dayincubationperiod,amultitude of biochemical andphysiological
altercationscanoccur duringthistime period(see figure2),howeverdetrimental effectspost-
infectionhave been reportedbyFormenty(1999) tolast up to 3 months.
Virus Family;(ViruseswithinFamily) Fatality rate
Filoviridae;(Ebolaand Marburg
viruses)
Ebola:50% to 90%,
Marburg: 23% to 70%
Arenaviridae;(NewWorld
haemorrhagic feverand Lassa fever)
New worldhaemorrhagicfever:15% to 30%,
Lassa fever:>1%
Bunyaviridae;(Rift Valleyfever,
Crimean-Congofever)
RiftValleyfever:14% to 17%
Crimean-Congofever:10% to 40%
Flaviviridae;(yellowfever,Omsk
haemorrhagic fever,Kyasanur Forest
disease)
Yellow fever:>50%
Omskhaemorrhagicfever:0.5% to 3%
KyasanurForestdisease:3% to10%
General Clinical features associated with (EHF).
Clinical Features Laboratory findingsdue toEHF
vomiting,headache,prostration, fatigue
(< 1 week)
Chestpain, Diarrhoea, Acute onsetof
fever,cough, pharyngitis
Maculopapar rash
Haemorrhagic manifestation
Pancreatitis,hepatitis,conjunctival
inflammation
CNS dysfunction
Shock with DIC and organ failure ( < 7
days after symptoms begin)
Sequelae:oculardisease,hearingloss,
pericarditis,arthralgia
Leukopenia
Leukocytosis
Thrombocytopenia
Elevatedliverenzymes
Elevatedamylase
Lab featuresof DIC
FIGURE 1. Represents virusesresponsible for causing viralhaemorrhagicfever with corresponding fatality rate. (S.F. Dept Public
health,2008).
FIGURE 2. Table displaying the general Clinical featuresand Laboratory findingsassociatedwith an EBOV infection (S.F. DeptPublic
health,2008)
5. Accordingto Lee & Sapphire (2009), Symptomsof EHF generally begintooccur withina4-10 day
incubationperiod,howeverinfatal cases,deathcanoccur as earlyas 6-9 daysafter onsetasa result
of uncontrolledviral replicationandmultiple organfailure.Tounderstandhow some of the
symptomswithintable 2become apparentwithinthe humanbody,itisnecessarytounderstandthe
initial stagesof EHF.Many studieshave beenconductedtodetermine the initialtargetcell of the
Ebolavirus (EBOV),andaccordingto Ströheret al (2001) morphological studiesonpost-mortem
material suggeststhatthe primarytargetfor viral replicationare;dendriticcellsandmacrophages
viaCD4 and CD8 receptors.These cellsare thenthoughttocirculate viathe lymphaticsystemto
regional lymphnodeswhere viral replicationcancontinue,andthe targetcell-associatedvirionsare
able to spread.HoweverEBOV isable toeffectothercellsindirectly,the virusdoesthisbyusing
infectedcellsalmostlikeabiochemical weapon,tocause dysfunctiontocellswhichdon’tappearto
be adequate hosts.
Lymphocytesare notdirectlyinfected byEBOV however,
studiesindicate thatlymphocyte apoptosisisaprominent
feature of infection(Bradfute etal,2010). It istherefore
hypothesisedthatfactorssecreted orexpressedbytarget
cellsare responsiblefortriggeringthe cell deathwithin
lymphocytes.Evidencesupportingthishypothesiscanbe
derivedfromastudyconductedbyGeisbertetal (2003),
data obtainedfromthisstudysuggestthatdendriticcells
and macrophagesincrease the expressionof tumour
necrosisfactor-α (TNFα) (see figure 3),aswell as
apoptosis-inducingligandandFastranscriptduringanEHF
infection.Thisdataissupportedbyseveral otherreports
statingsimilarresults (Formentyetal,1999), and mayhelp
to explainwhyLeukopeniatypicallyoccursduringthe
earlystagesof EHF. Asa resultof this the innate immune
response maybecome dysfunctional, leavingthe hostwith
little time toadaptivelyrespondtothe infection. Although
damage focuseswithin the lymphaticsysteminitially,itisalsostatedby Geisbertel al (2003a) that
whenEBOV entersthe blood system,the virus exhibitstissuetropismforthe;liver,adrenal gland
and spleen.
The Liverappearsto be an importanttargetof EBOV,data obtainedbyGeisbertetal (2003) suggests
that Kupffercellsare anadequate hostcell thus;viral replicationcontinueswithinthe Liver.Initial
infectionof the liveroccurswithinthe earlystagesof the infectioncausingdamage directlyto
hepatocytesandothercellsfoundwithinthe liver. Reportshave shownthatenzymes; Aspartate
aminotransferase,andAlanine aminotransferaseare bothelevated(see figure 4).Thissupports that
the viruscausesdamage to livertissue eitherdirectlyviareplicationorasa resultof a biochemical
imbalance due tofactorsreleaseduponcell lysis.
As a resultof the damage it maybe difficultforthe livertocontinue itsfunctionbothbiochemically
and physiologically,the liverplaysvitalroleswithinawide range of systemswithinthe body,
therefore progressiveliverdysfunctioncanbe catastrophictothe body’snormal homeostatic
procedures(see figure5).
FIGURE 3. Displaysthe increase ofTumour NecrosisFactor
during an EHF in Cynomolgusmacaques, data obtained by
Geisbert etal, (2003a).
6. POSSIBLE BIOCHEMICAL DYSFUNCTION
ASSOCIATED WITH LIVER DAMAGE; WITH
RELEVANCE TO EHF.
EFFECTS ON BODY DUE TO DYSFUNCTION.
- Inadequate secretionof precursor
molecule angiotensinogen.
- As the precursorto hormone
Angiotensin,inadequate amountsof
angiotensinogenmayinhibitthe
vasoconstrictionprocessthus
preventingvasoconstriction;aprocess
crucial for raisingbloodpressure and
slowingdown haemorrhage/acute
bloodloss.Thismayplaya role inthe
amplificationof the haemorrhagic
feature associatedwiththisinfection.
- Inadequate secretion,viathe liver,of
glycoproteinhormone;
thrombopoietin.
- Responsible forstimulating
Megakaryocytopoiesis,aninadequate
amountof thrombopoietinmayleadto
a reducedplateletproductionthus
directlyeffectingthrombusformation;
causingthrombocytopeniaandmassive
altercationstothe clottingcascade.
- Inabilitytosecrete/synthesizesufficient
quantitiesof glycogen
- Insufficientquantitiesof Glycogenmay
cause the bodyto entera
hypoglycaemicstate.Thisdysfunction
wouldrenderthe liveruselessan
unresponsive withinthe feedback
systemsimplementedforbloodglucose
homeostasis.
- Disruptiontothe livernormal
metabolicpathways
- Inabilityforthe livertocarry outits
normal metabolicfunctionsismassively
detrimental tothe body,asa resultof
such dysfunctionsmanysystemswithin
the bodywouldbe effected.In
particularthe Central NervousSystem
wouldnotreceive sufficient nutrients
to supportfunctionthuscausingCNS
dysfunction.
FIGURE 4. Biochemical valuesduring EHF; noteelevated ASTandALT. ALT-Alanine aminotransferase, AST-Aspartate
aminotransferase in comparisonto referencestandard. Data obtained by Formentyet al,(1999)
FIGURE 5. Showsexamplesof biochemical dysfunctionsthat may be causedby liver damage;an organ thatis largely damaged
during EHF.
7. In relationtothe liver,ithasbeenreportedthatnumerousorgansare manifestedwithEBOV during
EHF, for example Geisbertetal (2003) constructeda graph,showninfigure 6, whichrepresentssuch
activity.
In relationtothe liver,the adrenal glandappearstobe directlyaffectedbyEHF,data obtainedby
Geisbertetal,(2003a) indicatesthaton day 4 of an infectionEBOV wasdetectedinadrenal cortical
cellswithinthe zonafasciculate andzonareticularis. EBOV wasalsodetectedwithinstromacellsin
the adrenal cortex and withinfibrocytesinthe adrenal capsule,thisthenfurtherdevelopedinto
multifocal congestionof the adrenal cortex andmultifocal degradationof the adrenal cortical cells
(Geisbertetal,2003a). It isknowthat the adrenal cortex playsanimportantrole withinthe renin-
angiotensin-aldosterone systemwhichregulatesbloodpressure,figure7representsthisfeedback
system.
FIGURE 6. Showsmean infectivity of6 Cynomolgusmacaques; note themulti-organ involvement. LN-LymphNode. (Geisbertet al,
2003a)
FIGURE 7. A)Shows negativefeedback system involving kidneys and adrenalglands implementedfor controlofBlood pressure
homeostasis and thecontrol ofbloodelectrolytelevels. B)Adrenalcortex biochemicalinvolvement inthesynthesis ofhormones
Aldosteroneand Corticosterone. Image fromRossier (2010).
8. Adrenocortical necrosis,asaresultof EHF, has beenreportedinhumansbyFormentyetal, (1999),
and innon-humanprimatesby Geisbertetal, (2003a),thus renderingthe organunresponsive within
the negative feedbacksystemrepresentedinfigure 7a.Asa result of such dysfunctionthe adrenal
glandis be unable tosynthesizesufficientaldosterone,this preventsthe kidneyfromregulatingNa+
and K+
and, as a resultof this,ultimatelychronicbloodvolume;andthusbloodpressure (Boothetal,
2002). It is reportedbyFeldman(2011) that impairedsecretionof aldosterone leadstohypotension
and Na+
losswithhypovolaemia,therefore impairmentof adrenocortical functioncouldhave an
importantrole inthe shockthat typicallyoccursinlaterstagesof EHF. There are manyother
dysfunctionsthatoccurwithinthe body,the coagulationcascade alsoseemstobe largelyeffected
duringEHF.
A prominentmanifestationof EHFis disseminatedintravascularcoagulation(DIC),thisisthe
formationof microthrombi via activationof the clottingcascade.These microthrombi mayrestrict
bloodsupplytherefore maybe acontributingfactorto the multiple organdysfunctioncharacteristic
of EHF. Infact pathological dataobtainedbyGando(1999) suggeststhatfibrindepositionisafactor
that contributestomultipleorganfailure.Howeverbefore acute DICcanbecome apparentthere
mustbe sufficientstimulustooverwhelmthe natural anticoagulationprocesses (Feldmann&
Geisbert,2011). Anticoagulationfactors whichare mainlysynthesizedprimarilywithinthe liver
Parenchymal cells,whichhave mostlikelyalreadybeendamaged atthispointdue to viral assault,
act to inhibitthe formationof microthrombi,howeverif the rate at whichthese factorsare
consumedexceedsrate of synthesis;levelsof
inhibitorswithinplasmawill decline (Feldmann&
Geisbert,2011). For example Geisbertetal
(2003a) reportedthatactivatedProteinC,an
importantsubstance whichpreventsthrombus
formation,concentrationdropssignificantly
duringEHF (see figure 8);thisgoesto show that
the virusis able toovercome the body’snatural
anticoagulationsystems.
DuringDIC, the extrinsiccoagulationpathway,
whichisTissue Factor (TF) dependent,isthe
dominantroute forthrombinproductionand
thusfibrindeposition(Geisbertetal,2003b). The
factor that inducesDICwithinEHFismost likelyan
increase of TF,the majorinitiatorof the
coagulopathywitnessedwithinEHF,howeverin
orderto explainhowthisoccurswe
needtobeginwiththe initial targetof
EBOV;monocytes/macrophages.Data
obtainedby Geisbertetal,(2003b)
suggeststhatthe expressionof TFwas
onlyobserved in
monocytes/macrophagesthatshow
evidence of EBOV replication,thus
suggestingthatexpressionof TFmay
be directlyincreasedbyEBOV infection
(Geisbertetal,2003b).
FIGURE 8. ShowsconcentrationsofProtein C during EHF,
note the concentrationonly returns to 60% when
compared to pre-infectionconcentration.Data obtained
by Geisbert et al, (2003b).
FIGURE 9. Representsthe increase ofTF during EHF. Indirectfluorescent
antibodyanalysis was performedfor TF from peripheral blood mononuclear
cells ofanEBOV-infected rhesus macaqueat day 2 (B) andatday5 (C)
(Geisbertetal, 2003b).
9. As youcan see infigure 9, the concentrationof TF withinthe bloodincreasesduringthe progression
of an infection,thisishypothesizedby Geisbertetal (2003b) to be an importantfactorinthe
diagnosisof DICwithinEHF.DIC resultsinwidespreadactivationof the clottingcascade andthusthe
formationof multiplefibrinthrombi withinsmall vesselsthroughoutthe body.
As a resultof this,bloodflowisrestrictedthroughoutthe bodyandorgansreceive inadequate blood
supply,thisthenleadstoand/orhemorrhagicshock,whichappearstobe a lot like septicshock,
multiple organfailureandfinallydeathof the host(Geisbertetal,2003a); all featureswhichare
reportedby S.F.DeptPublichealth(2008) infigure 2.
Aroundday4-5, afterincubation,of EHF it may become clearwhetherthe hostismore likelyto
survive the infection, productionof antibodies,orwhetherthe infectionwillbe fatal, progressionto
hypercytokinemia,referredtoasthe “cytokine storm”;possiblythe final eventof EHF. It is
necessarytonote that thismay notoccur inall casesand dysfunctionswhichprecede thisstage may
be a significantfactorinthe deathof the host.Like manyof the symptomsassociatedwithEbola,
theymostlyall originate fromdysfunctionscausedtothe primarytargetcells. AccordingtoPérezet
al (2014), macrophage cellsare mainlyresponsibleforthe increasedsecretionof anti andpro-
inflammatorycytokinesduringEHF,thisreportalsoindicatesthatEBOV glycoprotein(GP) are the
likelyroute usedforactivationof the cytokinecascade viamacrophages,thisisshowninfigure 10.
As youcan see,endothelialcellsappeartobe affecteddue tothe release of cytokineswhichare
activatedandsecreteddue toEBOV GP. It has beenreportedbyWahl-Jensenetal (2005) that EBOV
causesa deregulatedinflammatorycytokine response,whichisresponsible inthe decreased
endothelial cellbarrierfunctionassociatedwiththisinfection.
FIGURE 10; Role ofshed GP during EHF. It is reported further by Pérez et al (2014) that EBOV GP aresecretedfrom infected cells, as
well as replicated virions, theseGP then bind tofurther cells using TLR-4,wherethey then activate thecells ability tosecrete various
cytokines. Image fromPérez et al(2014).
10. In fact studieshave shedfurtherlightonthisarea, Geisbertetal (2003c) emphasizedthe
involvementof TumorNecrosisFactor-α (TNFα) withinthe lossof vascularintegrity.TNFα isnow
consideredtobe the majorcytokine responsiblefor increasedpermeabilityof vasculartissue,and
data acquiredby Geisbertetal (2003c) supportsthis. InrelationtothisEBOV GP is able toinfect
endothelial cellsdirectly,thisproducescytopathiceffectsanddirectdamage tothe cellsbarrier,via
viral replication.Thisaccompaniedbythe cytokine effectsonendothelial cells leadstothe lossof
vascularintegrity,andasa resultlarge quantitiesof small breaksoccurthroughoutthe circulatory
systemamplifying;andfurtherreducing
bloodpressure.Incontrastto this
pressures,due tofluidleakage,within
organ cavitiesmayincrease,causing
excessivestresstoorganswhich,atthis
stage,may alreadybe dysfunctional,
causingfurtherdamage andamplifying
physiological damage. Inadditionto
thisit hasbeenreportedby Geisbertet
al (2003c) that withinendothelialcells,
small molecularweightproteinAlbumin
showsa significantdecreaseinvalue
whenthe cell become infected (see
figure 11),causinga vastnet decrease of
Albuminthroughoutthe body.Since itis
knowthat thisproteinhasa major function
inthe control of colloidosmoticpressure,anexcessive reducedamountwouldreduceplasma
osmoticpressure,thisdysfunctioncouldthenresultinedema. Furtherswellingtothe bodycould
induce furtherCNSdysfunctionandpossiblyleadtopermanentphysiological dysfunctionof organs
such as the brain(Geisbertetal,2003c).
It isalso thoughtthatduringthe late stagesof EHF, Nitricoxide (NO) levels begintoelevate(see
figure 12), possiblyasa response tothe heavyvirusloador may resultfromcytokine-induced
overexpressionof inducibleNOsynthase inphagocyticcellsthroughoutthe body(Sanchezetal.
(2004). Anincrease of NOwithinthe bloodcancause some seriousphysiological dysfunctions, for
example Sanchezetal (2004) reportedthatfatal
cases,whichexhibithighNOconcentrations,are
associatedwithcardiacstressandheart failure.It
alsosuggestedthatelevatedNOmaycontribute
to the hypotensioncharacteristicof EHF,as well
as the possibilityof thisfactorformingtoxic
molecule whichmayfurtherstressthe host.
To summarize EHFis capable of causing a wide
range of biochemical dysfunctions toahost, which
resultsina wide range of physiological
dysfunctionswithinthe humanbody;andnon-
humanprimates(Geisbertetal,2003a). Examples
withinthisreportare accompaniedwithmanyother
dysfunctionsthatoccurduringEHF.
Figure 12; Shows acomparisonoffatal and non-
fatal NOlevels in peripheral blood ofEbola-S
virus-infected
Patients. (Sanchezet al, 2004)
Figure 11; Showstotal serum protein and albumin valuespost-
infection in Cynomolgus monkeys. Note the decreaseofprotein
Albumin. Data obtainedfrom Geisbert etal, (2003c).
11. The initial attackappearsto be on monocyteswithinthe immune system, the virusisable to
transcribe andsynthesize variousfactorsandproteinswhichallow ittorecruitfurthercellsforviral
replication.Inthisprocessbiochemical imbalancesare created,causingothercells,suchas
lymphocytes, tobecome effected. Transportation,viathe lymphaticsystem,tothe spleenisthe
likelyroute usedtoenterthe vascularsystem, where the virus isthenable toaffectorganssuchas
the adrenal glandand the liverwhere necrosisoccurscausinglarge amountsof
physiological/biochemical dysfunction(Feldmanetal,2011). Asa resultof thisfurtherorganssuch
as the kidneysmaybecome effectedindirectlybyevenfurtherbiochemicalimbalancesdue to
necrosiswithinotherorgans.Forexamplethe kidneysinabilitytoregulate K+
andNa+
due
insufficientAldosterone synthesiswithinthe zonaglomerulosaof the adrenal gland,subsequently
causinghypotensionNa+
loss. InfactGeisbertetal,(2003a) foundthat almostall organsare effected
eitherdirectlyorin-directly,thishighlightsthe level of dysfunction,bothphysiological and
biochemical,whichoccursduringEHF.DIC alsooccurs whichresults ininadequate bloodsuppliesto
mostorgans throughoutthe body,resultinginmultiple organfailure andeventuallydeath.With
little treatmentavailable,therapiesonlyappearto rehydrate patientsinahope that theirimmune
systemwill produce antibodies.
If the hostsurvivesduring the multiple organfailureassociatedwithEHFthenthe infectionmay
progression intoitspreliminaryphase,which presentsamassive cytopathicattackon numerouscells
throughoutthe body.Thisiscombinedwithabodywide activationof masscytokine secretion,
causingconsiderate fluidlossanduncontrollablebleeding;deathmostlikelyfollowsthisphase.
Althoughactivationof the cytokine cascade isanimmune responsewhichusuallyoccursduring an
infectioncausedbyanewor particularlyharmful pathogen;italsoinflictsalarge amountof damage
to the host. In the unlikelysituationthatthe hostsurvivesthensubsequent conditionssuchas
deafnessandhairlosshave beenreportedbyFormenty etal,(1999).
So to trulyconclude;it’snotthe virusthat killsthe host,it’sthe hostsownbiochemical functionsand
immune responseswhichare hijackedduringEHFthat are the mostlikelycause of death.
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