Viral Respiratory Tract Infections Flashcards
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List upper respiratory tract infections
Upper resp tract
Common cold / Coryza ;Covid-19 Influenza / Flu Acute tonsillitis Acute pharyngitis ( Sore Throat ) Acute otitis media Acute sinusitis
Nasal cavity
Oral cavity
Pharynx
Larynx
Coryza/ Common cold causitive agents
Adults & Children - Rhinovirus ,
Coronavirus ( COVID -19 ) ,
R.S.V.- ( Respiratory Syncytial Virus ).
Clinical features of Coryza/ common cold
Surfactant - explain term
Type 1 pneumocyte function
SARS-CoV-2 Pathogenesis
Fatigue Feeling cold Nose burning , Obstruction , Running of nose Sneezing Fever
Increased surface tension increases cohesion within the alveoli, pulling the alveoli closed.
The alveolar cells produce a specialized liquid, surfactant, that decreases the surface tension in the airways reducing the amount of energy required to expand the lungs.
Gas exchange
Pathogenesis
Virus attaches to Type 2 pneumocytes (f’n to produce surfactants) in alveoli
Virus spike protein (S spike) binds to ACE2 on membrane
Virus enters cell and releases +sense ssRNA
Virus uses ribosomes to convert mRNA to proteins via translation
RNA dependent RNA polymerase makes more mRNA
Polyproteins formed which are then cleaved by proteinases to form essential viral protein components
(cleaves the precursor viral polyprotein to produce functional proteins and enzymes)
Virus copies exit cell
– Type 2 pneumocyte becomes damaged and releases IFN-gamma which stimulates macrophages to respond (DAMPs released from within cell)
– Macrophage secretes :
IL-1, IL-6, TNF-alpha
– These cytokines travel to capillary and act as inflammatory mediators
(Inflammatory mediators = vasodilation + increased capillary permeability)
– Fluid leaks to outside alveoli and compresses alveoli
(Water has high surface tension b/c of H+ bonding btw H2O
Surfactant lines alveoli to prevent collapse due to high surface tension
Fluid moves into alveoli and drowns out surfactant thereby increasing the surface tension inside alveoli)
– Alveoli collapse + fluid surrounding alveoli impairing gas exchange = Hypoxemia (low O2)
This can lead to Acute respiratory distress syndrome (ARDS) (rapid onset of widespread inflammation in the lungs)
– Neutrophils come to area and destroy pathogen via ROS (e.g. proteases) which causes cell damage (type 1 and 2 pneumocyte) as well = less surfactant production + alveoli collapse
– Alveoli will contain cell debris of type 1 and 2, macrophages, neutrophils, fluid = lung consolidation
( occurs when the air that usually fills the small airways in your lungs is replaced with something else )
– Gas exchange process altered = hypoxemia
Productive cough (from consolidation)
– IL-1, IL-6, TNF-alpha travel to brain if in high amts and go to hypothalmus causing fever
– Low partial pressure of O2 stimulates chemoreceptors which causes SNS to be stimulated which causes increased heart rate
chemoreceptor detects changes such as > in blood levels of CO2 (hypercapnia) or < in O2 (hypoxia), and transmits info to CNS which engages body responses to restore homeostasis.
– Inflammation can spread through entire circulatory system causing increased capillary permeability and fluid leakage into surrounding tissues = low blood volume
– Vasodilation occurs = Lowered total peripheral resistance
(resistance of the arteries to blood flow. As the arteries constrict, the resistance increases and as they dilate, resistance decreases)
– Low blood volume + low peripheral resistance = low bp
– Low bp leads to low perfusion i.e. less blood moving to organs = multi system organ failure
Syndrome - define
group of symptoms which consistently occur together
COV-19 caused by
severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2 )
COV-19 spread via
Via respiratory droplets ( coughing , sneezing ) during face-to-face exposure or by surface contamination.
Most common symptoms of Cov-19
fever ,
cough ,
shortness of breath - (weakness , fatigue , nausea vomiting , diarrhea)
Lab ID - COV-19
PCR / RT-PCR testing of nasopharyngeal swab
Treatment - COV-19
Supportive care . Recent trials – dexamethasone decreases mortality , supplemental oxygen / ventilator .
COV-19 prevention methods
Face masks , N95 respirators , Physical social distancing , Hand washing / sanitizer , Travel restrictions , Isolation of patients , Quarantine of exposed people , Avoiding personal contact with pts. , PPE – healthcare workers
Causative organisms for (influenza) flu in order of prevalence
Influenza virus 80 %
Parainfluenza 2-9 %
Adenovirus 4 %
Features of (influenza) flu
Causes Epidemics and Pandemics
Highly contagious - viral infection.
Myxoviruses are divided into two families
1 ) Orthomyxoviridae e.g. Influenza viruses ;
2 ) Paramyxoviridae e.g. Parainfluenza virus and ( Mumps virus , Measles virus , Respiratory syncytial virus ).
Flu (Influenza) features
Common cold symptoms - because of HA binding to mucin receptors on RBC + epithelial cells of resp tract
Sudden onset after 12 - 24 hrs incubation
General weakness & fatigue
Feeling cold , shivering , temp.- Up to 39-40 C
No sore throat or No running nose
Severe back , muscle and joint pain
Influenza viruses are a member of Orthomyxoviridae
Spherical,
80 – 120 nm,
Helical nucleocapsid symmetry and surrounded by an lipoprotein - envelope.
Nucleic acid – negative sense single stranded RNA.
Structural proteins:
- PB1, PB2, PA - RNA transcription and replication
- NP - nucleoprotein (gives rise to nucleocapsid with helical symmetry)
- Matrix proteins: M1 - shell, M2 - ion channel
- Hemagglutinin (HA) and Neuraminidase (helps virus to pass through cell layer) - glycoproteins inserted in lipid envelope
- Non-structural proteins NS1 - interferon antagonist + inhibits pre mRNA splicing ; NS2 - export of molecules across the nucleus
Transmission - influenza
– cough , sneeze, contacts , fomites
Target cells to enter
–alveolar cells
Influenza multiplies locally where?
–respiratory epithelial cells
Influenza spreads to where?
–lower respiratory tract
Incubation period - influenza
18-72 hrs
Symptoms - influenza
chills , headache ,dry cough ,fever ,anorexia.
Specimen - influenza
Nasophyryngeal swab , kept at 4 C
Isolation of virus
In embryonated eggs and primary monkey kidney cell lines
Growth is detected by hemadsorption , hemagglutination test .
Molecular methods
Real time RT PCR : detects viral RNA
Antibody detection
ELISA
Treatment of Influenza
Neuraminidase inhibitor ( Zanamivir , Oseltamivir –[ Tamiflu ] for influenza A and B and also for H1N1- 2009 flu , H5N1 avian flu ) MoA- Blocks NA from allowing escape of virus from host cell to infect other cells so virus components stick to cell surface.
Matrix protein M2 inhibitor ( Amantadine and Rimantadine – for influenza A infection )
Neuraminidase inhibitor - MoA
Block the function of viral neuraminidases of the influenza virus, by preventing its reproduction by budding from the host cell.
Matrix protein M2 inhibitor - MoA
During viral entry, the intake of a proton via an M2 protein induces unfolding of the HA protein such that the fusion peptide is activated.
Thus Matrix protein M2 inhibitor blocks viral entry
(Amantidine - very successful in influenza A)
Prevention - influenza
Strict hand hygiene , isolation , use mask , remain at home and Vaccination prophylaxis .
EBV is mostly asymptomatic (T/F)
The manifestation of symptoms in EBV is referred to as ?
EBV- [Epstein –Barr virus] - Kissing Disease signs and symptoms
True
Infectious mononucleosis
Fever, Headache, Pharyngitis, Cervical lymphadenopathy, exaggerated fatigue
Splenomegaly - Stores many B cells so infected B cells will go there and CD8 T cells will follow to destroy infected cells causing swelling of spleen
Another name for Infectious Mononucleosis
Glandular Fever
Prevalence for Infectious mononucleosis
Among adolescents & Young adult
Clinically useful Laboratory tests : For - Epstein-Barr Virus
Heterophilie antibody : ( Paul - Bunnel Test - sheep RBCs)
Monospot test –modified heterophile agglutination test –hourse RBCs
IgM antibody to Viral Capsid Antigen ( VCA )
Atypical Lymphocyte ( Abnormal )
Heterophile antibody test
Heterophil antibodies have the ability to agglutinate red blood cells of different animal species.
The Paul-Bunnell test uses sheep erythrocytes; the Monospot test, horse red cells.
Monospot test
Monospot test - form of the heterophile antibody test, is a rapid test for Epstein–Barr virus (EBV).
- It is an improvement on the Paul–Bunnell test
IgM antibody to viral capsid antigen (VCA)
Presence of VCA IgM antibodies indicates recent primary infection with Epstein-Barr virus (EBV).
The presence of VCA IgG antibodies indicates infection sometime in the past.
Atypical lymphocytes
EBV affects which cells?
EBV pathogenesis
Normal lymphocyte - Small nucleus + little cytoplasm
Atypical lymphocytes - Bigger nucleus + more cytoplasm
- Reactive CD8 T cells killing infected
B cells
A few atypical lymphocytes are probably of little clinical significance.
A large number of atypical lymphocytes are often found in viral infections like mononucleosis (many B cells need to be killed), cytomegalovirus infections and hepatitis B.
Epithelial cells, B cells, T cells
- Transmission via saliva
- Virus infects epithelial cells of mouth then replicates and goes to oral pharynx (back of throat)
- Virus moves to lymphoid tissues of oral pharynx i.e. tonsils where B cells and T cells are and infects them
- B cells spread through lymph to other lymphoid tissues and infect those B cells
- Infection is eventually controlled with antibodies binding free floating virus + CTLs killing infected B cells
Molecular methods for EBV
– Detects EBV DNA by PCR .
Transmission - EBV
transmitted through salivary contact
EBV is a member of?
Herpesviridae
Treatment of EBV
Supportive such as analgesics used in infectious mononucleosis . Acyclovir is antiviral drug used in treatment .
Prevention of EBV
Patient isolation
Sore throat/ Pharyngitis - causative organisms
Pharyngitis vs Tonsillitis
- Epstein-Barr virus
- Adenovirus
- Influenza A , B
- Respi .syncytial virus
- Parainfluenzae
Both cause inflammation.
If tonsils are affected - tonsillitis.
If the throat is affected - pharyngitis.
Signs and symptoms of pharyngitis/tonsillitis
Sore throat Fever > 38 C Difficulty in swallowing Enlargement of tonsils Congested tonsils and pharynx Headache , fatigue Muscle pain
Tonsillar hyperemia / exudates
Soft palate petechia
Absence of nose drip
Enlarged tonsillar lymph nodes
Middle Respiratory Tract Infections
Epiglotitis Laryngitis Croup Tracheatitis Bronchitis Bronchiolitis
Contributing factors to middle respiratory tract infections
Smoking , previous lung damage , atmospheric pollution & cold damp weather
