Cardio - Respiratory Infections + Immunity Flashcards
What are the signs and symptoms of upper tract infection?
→ Cough → sneezing → Runny + stuffy nose → Sore throat → Headache
What are the signs + symptoms of lower tract infections?
→ Productive cough w phlegm → Muscle aches → Wheezing → Breathlessness → Fever Fatigue
What are the signs and symptoms of pneumonia?
→ Chest pain
→ Blue tinting of lips
→ Severe fatigue
→ High fever
What are the demographic and lifestyle risk factors for pneumonia?
→ Age <2 years and >65 years
→ Cigarette smoking
→ Excess alcohol consumption
What are social risk factors for pneumonia?
→ Contact with children aged <15 years
→ Poverty
→ Overcrowding
What are medical history risk factors for pneumonia?
→ COPD → Asthma → Heart disease → Liver disease → Diabetes Mellitus → HIV → Malignancy → Hyposplenism → Complement or Ig deficiencies → Risks factors for aspiration → Previous pneumonia
What are medication risk factors for pneumonia?
→ Inhaled corticosteroids
→ Immunosuppressants
→ Proton pump inhibitors
What are specific risk factors for certain pathogens for pneumonia?
→ geographical variations
→ Animal contact
→ Healthcare contacts
What are the bacterial causative agents of respiratory infections?
→ Streptococcus pneumoniae
→ Myxoplasma pneumoniae
→ Haemophilus Influenza
→ Mycobacterium TB
What are the viral causative agents of resp infections?
→ Influenza A or B virus → Respiratory Syncytial Virus → Human metapneumovirus → Human rhinovirus → Coronaviruses
What are the 2 main ways of acquiring pneumonia?
→ Community acquired
→ Hospital acquired
What agents are the main bacterial causes of community acquired pneumonia?
→ streptococcus pneumoniae (40%-50%) → myxoplasma pneumoniae → staphylococcus aureus → chlamydia pneumoniae → haemophilus influenzae
What 6 agents are the main causes of hospital acquired pneumonia?
→ Staphylococcus aureus → Pseudomonas aeruginosa → Klebsiella species → E.coli → Acinetobacter spp. → Enterobacter spp.
What can community acquired pneumonia be further split into?
→ Typical
→ Atypical
What agents causes typical community acquired pneumonia? (Hint : SMH)
→ Streptococcus pneumoniae
→ Haemophilus influenzae
→ Moraxella catarrhalis
What agents cause atypical community acquired pneumonia? (hint : MCL)
→ Mycoplasma pneumoniae
→ Chlamydia pneumoniae
→ Legionella pneumophilia
What is the the most common method of hospital acquired pneumonia?
→ Ventilator associated pneumonia
What is pneumonia?
Inflammation and swelling of alveoli
What are the main mechanisms of damage of bacterial pneumonia?
→ Lung injury
→ Bacteremia
→ Systemic inflammation
→ Can all lead to organ injury or dysfunction
How is potential bacterial pneumonia graded?
CRB-65 or CURB-65 scoring (1 point per item)
→ Confusion
→ Urea = 7 mmol/L (only added in hospital)
→ Respiratory Rate > 30 breaths/min
→ Blood Pressure < 90 systolic / 60 diastolic
→ 65 or older
What are the supportive therapies for pneumonia?
→ Oxygen (for hypoxia) → Fluids (for dehydration) → Analgesia (for pain) → Nebulised saline (may help expectoration = coughing up sputum) → Chest physiotherapist?
What are the antibiotics classes mainly given for resp tract infections?
→ penicillins
→ macrolides
How does penicillin work?
→Beta lactams that bind proteins in the bacterial cell wall to prevent transpeptidation
How do macrolides work?
Bind to bacterial ribosome to prevent protein synthesis
What is treatment is given for a CAP patient with a CURB-65 score of 0?
Amoxicillin or clarithromycin / doxycycline if penicillin allergic
What is treatment is given for CAP and a CURB-65 score = 1 or 2 ?
Amoxicillin + Clarithromycin (or doxycycline)
What is given for a patient with CAP and a CURB-65 score of 3-5?
Benzyl penicillin IV + clarithromycin. PO (or teicoplanin + clarithromycin)
What is given for a patient with a HAP and a CURB-65 score of 0-2?
Not severe
Doxycycline PO
What is given to a patient with HAP and a CURB-65 score of 3-5?
Severe so give tazocin (piperacillin-tazobactam) IV +/- gentamicin IV
What is present in our oropharynx?
→ Strep viridans → Coagulase neg. Staph → Veronella → Fusiforms → Treponena spp. → Beta-haem → Strep (Haemophilus spp. Staph. Aureus Strep. Pneumoniae)
What is present in our nose?
→ Coagulase neg. Staph → Haemophilus spp. → Staph. aureus → Strep. Viridans (Strep. Pneumoniae)
What is our human microbiome?
the microbial cells that populate our body at every barrier surface
What is our microbiota?
Ecological communities of microbes found inside multicellular organisms
What is commensal?
→ Microbes that live in a “symbiotic” relationship with their host
→ Providing vital nutrients to the host in the presence of a suitable ecological niche
What is an opportunistic pathogen? What is a pathobiont?
→ microbe that takes advantage of a change in conditions (often immuno-suppression)
→ microbe that is normally commensal, but if found in the wrong environment (e.g. anatomical site) can cause pathology.
How do viral infections result in disease?
→ mediator release
→ cellular inflammation
→ local immune memory
→ damage to epithelium: which results in loss of cilia, bacterial growth, poor barrier to antigen, loss of chemoreceptors
How do viruses result in severe disease?
→ Highly pathogenic strains
→ Absence of prior immunity
→ Predisposing illness/conditions
What determines where a virus infects the respiratory tract?
Depends on what cell it binds to?
they like to bind to upper tract if they have existed in humans for a prolonged time
What is the first line of defence in the respiratory tract?
Respiratory Epithelium
What features of epithelium are useful as the first line of defence against resp epithelium?
→ Tight junctions – prevents systemic infection
→ Mucous lining and cilial clearance – prevents attachment, clears particulates
→ Antimicrobials – recognise, neutralize and/or degrade microbes and their products
→ Pathogen recognition receptors – recognise pathogens either outside or inside a cell.
→ Interferon pathways – activated by viral infection. Promotes upregulation of anti-viral proteins and apoptosis.
What are serotypes?
pathogens which cannot be recognized by serum (really antibodies) that recognize another virus – implications for protective immunity
What is anti-body mediated immunity?
→ Humoral immunity
→ Adaptive, so dependent on prior
exposure
→ B cells activated to differentiate into antibody secreting plasma
cells
→ Different antibody classes provide different biochemical properties and functions
What antibodies are common in the upper tract? What features make it so?
IgA :
→ High frequency of IgA-plasma cells
→ ECs express poly IgA receptor, allowing export of IgA to the mucosal surface
→ Homodimer is extremely stable in protease rich environment
What antibodies are common in the lower resp tract? What features make it so?
IgG:
→ Thin-walled alveolar space allows transfer of plasma IgGs into the alveolar space
How is does our immunity hold up against influenza?
No re-infection by the same strain
Do we have vaccinations for influenza?
Imperfect vaccines:
• Vaccine-induced immunity rapidly wanes
• Mainly homotypic immunity
• Annual vaccination required
How does our immunity hold up against RSV?
recurrent re-infection with similar strains
Do we have vaccines for RSV?
No vaccine
• Poor immunogenicity
• Vaccine-enhanced disease
• Very active research field
How does our immunity hold up against COVID-19?
no prior immunity
Do we have vaccines for COVID-19?
Newly licensed vaccine
• Waning immunity
• Potential for re-infection
• Unclear what vaccination regime will be required
What effect does RSV bronchiolitis have on infants?
- Leading cause of infant hospitalization in the developed world
- 50% of children infected in year 1 of life, all children by year 3.
- 1% develop severe bronchiolitis.
- Can repeatedly infect children.
What are the risk factors for infants for RSV?
- Premature birth
* Congenital heart and lung disease
List UR tract infections, LR tract infections and pneumonia in order of most frequent to least.
→ Upper Resp TI
→ Lower Respiratory
→ Pneumonia
List UR tract infections, LR tract infections and pneumonia in order of most severe to least.
→ Pneumonia
→ Lower Resp
→ Upper Resp
What is the breakdown of viral + bacterial causes of lower respiratory tract infection mortality in 28-365 days old?
Out of 20.1% : → Rhinovirus = 6.7% → Hib = 4.4% → Pneumonia = 3.4% → Influenza = 2.8% → Other = 2.8%
What is the breakdown of viral + bacterial causes of lower respiratory tract infection mortality in 2-5 year olds?
Out of 12.4% : → Pneumonia = 3.4% → Other = 3% → Hib = 2.7% → Influenza = 1.8% → RSV = 1.6%
Wha tare the symptoms of RSV bronchitis in an infant?
→ nasal flaring → chest wall retractions → hypoxemia → cyanosis → croupy cough → expiratory wheezing + prolonged expiration → rales + rhonci → tachypnea with apneic episodes
How does RSV affect adults?
→ Repeated colds.
→ Transmitters.
→ Very rarely severe
How does RSV affect young children?
→ infantile bronchiolitis
→ casually related to wheeze
→ older siblings are transmitters usually
What are the supportive therapies available for COVID?
• Oxygen (for hypoxia) • Fluids (for dehydration) • Analgesia (for pain) • Nebulised saline (may help expectoration) • Chest physiotherapy?
What are the vaccination options for COVID?
- Major surface antigen – spike protein
- Viral vector (e.g. adenovirus vaccine e.g. Oxford/AZ)
- mRNA vaccines (e.g. BioNtech/Pfizer)
What anti-inflammatory treatments are used for COVID?
- Dexamethasone (steroids)
- Tocilizumab (Anti-IL6R) or
Sarilumab (anti-IL6)
What anti-virals are used to treat COVID?
- Remdesivir – broad spectrum antiviral – blocks RNA- dependent RNA polymerase activity
- Paxlovid – antiviral protease inhibitor
- Casirivimab and imdevimab - monoclonal neutralising
antibodies for SARS-CoV-2
How do respect infections interplay with chronic lung disease?
• Viral bronchiolitis is associated with the development of asthma
• Rhinoviruses are the most common cause of asthma and COPD
exacerbations
• High likelihood of secondary bacterial pneumonia after viral
infection
• 55% of rhinovirus-infected COPD patients also have bacterial infections
