basics of diseases Flashcards
types of upper respiratory tract infections
1) common cold - viral rhinitis
2) sinusitis
3) pharyngitis
4) acute laryngitis
URTI - common cold - viral rhinitis
- affect nasal passages
- SS: sore throat, congestion, runny nose, sneezing, cough,
- AA: rhinovirus (most common), influenza virus, coronavirus, respiratory syncytial virus (RSV)
- rhinovirus: host immune response not drug induced tissue damage
URTI - sinusitis
- sinus cavities
- symptoms: congestion, facial pain & pressure, headache, runny nose
- AA: streptococcus pneumoniae
- pathogenesis
1) obstruction of sinus ostia
2) dysfunction of muco-ciliary action (infection when cannot clear mucous properly)
3) alteration in mucous secretion (infiltration of immune cell & protein -> increase lipophilicity -> impair ciliary function)
URTI - pharyngitis
- affect pharynx
- SS: sore throat, congestion, pharyngeal inflammation
- AA: adenovirus & rhinovirus (most common), streptococcus pyogenes, Group A Streptococcus (GAP) (Associated with acute rheumatoid fever)
- inflammatory mediators: bradykinin, prostaglandin
URTI - acute laryngitis
- larynx
- SS: hoarse voice with decrease phonation & voice projection
- AA: major virus & several bacteria
- local inflammation due to trigger -> influx of WBC to site of infection -> enhance vocal cord oedema
types of LRTI diseases
1) bronchitis
2) bronchiolitis
3) pneumonia
LRTI - bronchitis
- bronchitis
- SS: acute cough wo signs of pneumonia
- AA: viral (most likely), bacteria (less likely)
- pathogenesis: direct cytopathology + host immune response -> inflammation of large and medium sized airways
LRTI - bronchiolitis
- bronchioles
- SS: wheezing, tachypnoea (increased respiratory rate), nasal flaring (more common in young children & infants)
- AA: RSV (most common)
- inflammation of small airways: airway obstruction, air trapping, hyperinflation of lungs, atelectasis
LRTI - pneumonia
- alveoli & alveolar sacs
- SS: fever, cough, dyspnea, sputum production, tachypnoea, systemic when severe (chest pain, fatigue, sweats, headache, nausea, abdominal pain, diarrhea)
- AA (community acquired pneumonia (CAP)): streptococcus pneumoniae, mycoplasma pneumonia, community respiratory virus
- defect in host immune defense (smoke/alochol)
- pneumonia (inflammation & infection) vs pneumonitis (infection only)
aetiology of rhinovirus infection - general
loss in tight junctions between cells -> opportunity for opportunistic infection & increase cytokine/growth factor penetration
aetiology of rhinovirus infection - infection process
1) virus bind to viral receptors on epithelial cells (ICAM1, LDL-R, CDHR-3)
2) receptor mediated endocytosis
3) uncoating & genome release -> mRNA transcription
4) transcription by RNA polymerase
- error prone -> viral mutation
5) replication
6) assembly of viral core structure
7) leave cell via lytic (cell death) or non-lyric mechanisms
aetiology of rhinovirus infection - response to infection
1) TLR3/7/8 recognise rhinovirus associated proteins
2) activate NFK beta
3) increase release of inflammatory cytokines
4) activation & recruitment of immune cells
aetiology of rhinovirus infection - immune response to infection
1) innate immunity
- recruitment of WBC (neutrophil, eosinophil)
- increase release of cytokine, chemokine, inflammatory markers
- increase viral clearance & activation of adaptive immune system (humoral, cellular)
2) humoral immunity
- activate B cells: produce serologic specific antibodies to rhinovirus antigenic type
- block ligand attachment, opsonisation of cells for presentation to phagocytic cell, initiating NK cell mediated cytotoxicity
3) cellular immunity
- activate T cells to
. CD 4+ T cells: produce IFN-gamma & facilitate humoral immunity
. CD8+ T cells: kill virus infected cells
influenza aetiology
. infiltration process
1) viral entry: receptor mediated endocytosis
2) release of viral genome
3) translation, transcription, replication
4) assembly, budding, leave host, further infection
. viral surface proteins
- neuraminidase (NA): cleave sialic acid receptor to leave host cell
- haemagglutinin (HA): viral entry
types of mutation in virus
1) antigenic shift
- drastic change after genetic reassortment
- coinfection: mixing of genetic material
2) antigenic drift
- gradual accumulation of mutations
- why is mutations relevant?
. antigenic shift: changes viral subtype, need to come up with seasonal vaccines
. vaccines: life-attenuated/inactivated/RNA
aetiology of pneumonia
- hospital vs community acquired pneumonia
- causative agents:
1) bacterial: streptococcus pneumoniae, staphylococcus aureus, haemophilus influenzae
2) viral: RSV (kids), Influenza A (adults)
3) others: mycoplasma pneumoniae
pathophysiology of pneumonia
1) respiratory epithelium
- MCC
- mucin, antimicrobial
- chemotactic peptides (recruit other immune cells)
- phagocytosis
- intracellular killing
2) alveolar macrophage
- pro-inflammatory & chemotactic mediators (IL-1, TNF-alpha cause fever)
- phagocytosis
- intracellular killing
- apoptosis
3) neutrophils
- pro-inflammatory & chemotactic mediators
- phagocytosis
- intracellular killing
- neutrophil extracellular traps (NETs)
- recruit other effector cells
4) platelet
- pro-inflammatory & chemotactic mediators
- interact with leukocytes
- increase NETs
histopathology of pneumonia
- when host pulmonary defenses has defects
- stages of pneumonia
1) early stage: congested, leaky capillaries - mild intra-alveolar oedema
- congestion in capillaries cuz recruitment of immune cells to site of infection
2) day 3-7: red hepatisation - accumulation of neutrophils, RBC, fibrin in alveolar spaces
- hepatisation: tissue harden
3) day 4-7: grey hepatisation - subsequent, gradual disintegration of RBC & neutrophils
4) resolution - break down & clearance of RBC, macrophages, fibroblasts
- gradual
- cleared in sputum produced & productive cough
how does pneumonia affect breathing
- pneumonia -> inflamed & thickened alveolar wall with mucous & inflammatory cells -> lower diffusion across barrier -> shunt perfusion (constrict capillaries, shunt blood to other capillaries) -> lower ventilation/perfusion ratio (<0.8)
- lower ventilation + constriction = hypoxia = tachypnoea
TB
- SS: cough, fever, night sweat, weight loss
- AA: mycobacterium tuberculosis
- types
1) latent: asymptomatic, non-transmissible - bacteria affect cell, migrate to T cell for priming but does not escape granuloma
2) active: transmissible if re-enter respiratory tract - increase bacteria load until escape granuloma
