Pneumonia Flashcards
is community acquired pneumonia normally bacterial or viral and what is the pathophysiology behind it?
often bacterial infection which follows an upper respiraotry tract infection
bacterial invasion of the lung parenchyma causes the alveoli to fill with inflammatory exudate causing consolidation of the pulmonary tissue
what are some predisposing factors for CAP
- age: 65 years
- co-morbidities: HIV infection, diabetes mellitus, chronic kidney disease, malnutrition, recent iral respiraory infection
- other respiratory conditions: CF, bronchiectasis, COP, obstructing lesion
- iatrogenic: immunosuppressant therapy
list some common bacteria which cause CAP and some of their virulence factors
- Streptococcus pneumonae: virulence factors - contain polysaccaride capsule, lack catalase, IgA protease, autolysis, pilli that mediate adherence to eopithelium, gram positive, lancet shaped diplococci, neutrophils, penicillin
- Haemophilus influenxae: encapsulated or unencapsualted (95%), virulence factors- pili, factor that disorganised ciliary beating, protease that degrades IgA, capsule, gram negative
- Moraxella - increasing cause
- Staphylococcus aureus: secodnary following viral respiraotry illness, associated with high incidence of complications (lung abscess, empyema)
- Klebseilla Pneumoniae: gram negative, affects delibiated and malnourished esp alcoholics, thick gelatinous sputum due to abundant viscid capsular polysaccharide
- Pseudomonas aeruginosa: nosocomial infections
- Leginella Pneumophilia: rapid diagnosis via antigens in urine or positive fluorescent antibody test
list some organisms that cause community acquired pneumonia and some that cause hospital acquired pneumonia
CAP: streptococcus pneumoniae, H influenzae, moraxella catarrhalis, staph aureus, legionalle pneuophilia
Atypical CAP: mycoplasma pneumoniae, chlamydia, coxiella burnetti, viruses (RSV, parainfluenza, influenza A and B)
Nosocomial pneumonia: gram negative rods belonging to enterobacteriaeceae (klebsiella, serratia marcescens, E coli) and pseudomonas spp, staph aureus
Aspiration pneumonia: anaerobic oral flow (bacteriocides, prevotella, fusobacterium), aerobic bacteria (strep pneumoniae, staph aureus)
list some organisms that cause pneumonia in an immunocompromised host
Pneumonia in an immunocompromised host: CMV, pneumocystic carinii, mycobacterium avium, invasive candidiasis, invasive aspergillosis
what is the mechanism of action of a penicillin
target the penicillin binding proteins (PBO) in bacterial wall including transpeptidases. this results in irreversible inactivation of transpeptidase via blocking cross-linking peptide chains attached to peptidoglycan backbone - bacteriocidal to growing cells (autolysis) and bacteriostatic to entire populations
include: benzylpenicillin, amoxicillin, phenoxymethylpenicillin, flucolaxicillin
what is the mechanism of action of cephalosporins
bacteriocidal drugs containing a beta lactam that inhibit bacterial wall synthesis similar to penicillins - generations (I-V) are defined on spectrum of activity, with later generations having expended activity against gram negative bacteria (but decreasing against gram positive)
list: cefadroxil, cefuroxime and ceftriaxone)
what is the mechanism of action of glycopeptides
bacteriocidal drugs that inhibit peptidoglycan synthesis with possible effects on RNS synthesis
list: vancomycin
what is the mechanism of action of carbapenems
binds to penicillin binding proteins, preventing bacterial wall synthesis.
able to circumvent beta-lactamases by binding with high affinity and acylating the enzyme, rendering it inactive - broadest antibacterial spectrum compared with other beta-lactam drugs
list: ertapenem, imipenem
what is the mechanism of action of monobactams
bind to penicilling binding proteins, inhibiting synthesis of bacterial cell wall, thereby blocking peptidogylcan crosslinking
list: aztreonam
what is the mechanism of action of metronidazole
bactericidal drugs that is metabolised to an intermediate that inhibits bacterial DNA synthesis and degrades existing DNA. it is selective as it is intermediate is not produced in mammalian cells - should not be given to pregnant women
list: tinidazole
what is the mechanism of action of quinolones
DNA gyrase inhibitors
inhibit bacterial nucleic acids - affect DNA replications and packaging
bactericidal drugs that inhibit prokaryotic DNA gyrase, preventing packaging DNA into supercoils that is essential for DNA replication and repair - cannot give quinolones with theophylline this will prevent toxicity
List: nalidix acid, ciprofloxacin
what is the mechanism of action of Rifampicin
Rifampicin
affect transcription
bactericidal drug that inhibits DNA dependent RNA polymerase
what is the mechanism of action of macrolides and lincosamides
bacteriostatic/bacteriocidal drugs that reversibly bind to the 50S subunit of the bacterial ribosome, preventin translocation movement of ribosome alone mRNA
list: erythromycin, clarithromycin, azithromycin
list (lincosamide): clindamycin
what is the mechanism of action of aminoglycosides
MOA: bacteriocidal drug that bind irreversibly to the 30S portion of the bacterial ribosome. this inhibits the translation of mRNA to protein and causes more frequent misreading of the prokaryotic genetic code
list: gentamycin, streptomycin, netilimycin, amikacin
what is the mechanism of action of tetracyclines
MOA: bacteriostatic drugs that work by selective uptake into bacterial cells due to bactive bacterial transport system not possessed by mamalian cells - binds reversibly to the 30S subunit of the bacterial ribosome, interfering with the attachment of tRNA to the mRNA ribosome complex
list: tetracyclin, minocycline, doxycycline
what is the mechanism of folic acid inhibitors
Trimethroprim
Sulphonamids
MOA
- folate is an essential co-factor in the sunthesis of purines and DNA. bacteria unlike mammals synthesie their own folic acid from para-aminobenzoic acid. this pathway can be inihibited at two points - sulfonamides (inhibit dihydrofolate synthetase) and trimethoprim (inhibits dihydrofolate reductase)
- both drugs are bacteriostatic. sulfonamides are used for simple UTIs whereas trimethoprim and co-trimoxizole are used for UTIs and respiratory tract infection
list the broad categories of how antibiotics work
- DNA gyrase
- DNA-dpt RNA polymerase
- 50S inhibitors
- 30S inhibitors
- tRNA inhibitors
CM structure disruption
inhibit folic acid metabolism
inhibit cell wall synthesis
list the normal defenses of the lung
physical defenses
- humidification
- filtering of large particles (by nose hairs)
- turbulent air flow - particles are removed in the nostrils and nasopharynx by adhering to mucosa
- mucociliary escalator - betwene the nose and terminal bronchioles - mucus coating is secreted by goblet cells in epithelium - traps small particles in inspired air and ciliated epithelium beats continually towards the pharynx and removes particles
- particle expulsion - sensory nerves receive irritating signals and respond - gag, cough, sneezing reflex
- barrier function
respiratory tract secretions
- mucus (secreted by goblet cells) contains acidic and neutral polysaccharides
- alveolar lining fluid contains surfactant, phospholipids, neutral lipids, IgG, IgE, ansd IgA
innate immunity
- pulmonary alveolar macrophages - phagocytose particles and are removed by the mucociliary escalator
- cytokines - alpha-1-antitrypsin, interferons
- complement
- granulocytes
- nautral killer cells
Adaptive immunity
- B cells/plasma cells
- T cells
what is the role of IgA
a benign immunoglobulin that binds to mucus and optimises viscocity, neutralises foreign antigens, does not active the complement cascade, may also block IgG induced complement activation (hence anti-inflammatory) and can induce apthogen killing when required
impairment of host defense mechanisms
- loss/suppression of cough reflex –> coma, general anaesthetics, pain, neuromuscular disease, endotracheal tube and drugs
- injury to mucociliary blanket/escalator - smoke, viral, alcohol
- descrease in macrophage function - alcohol, anorexia, oxygen toxicity and phagocyte killing defect
- impairment of immune system
- unusual virulent microbes
what are some common virulence factors for respiratory pathogens
establishment (staying in) - polysaccharide capsule (inhibit phagocytosis and adhere to surfaces), fimbrae (allow attachment), adhesins (glycolipids/lipoproteins allows adherence to tissue), virions
defeating the host defenses
passive defenses - capsule (protects against phagocytosis) and cell walls (defends against host defenses)
active defesnes - enzymes - leukocidins (destroy WBC), hemolysins (membrane damaging toxins that disrupt PM of host cells and cause cells to lyse), coagulase (cause fibrin clots to form the blood of the host), kinsase (breakdown dibrin and dissolve clots), hyaluronidase/collagenase AND penetrating inside host cell - invasion and cadherin (pathogen able to use host cell cadherin to move from cell to cell without exposing itself to the host’s immune defenses
Damaging the host
direct damage -
indirect damage - exotoxins, endotoxins, immune system
what is lobar pneumonia
- acute bacterial infection resulting in fibrinosuppruative consolidation of a larger portion of a lobe or an entire lobe. may spread through pores of Kohn (Alveolar connections)
- common in health young adults and has an acute onset
- pathogens involved: pneumococci (90%), Klebsiella, staph, strep, H influenzae, proteus and pseudomonas
what are the complications of lobar pneumonia
- pleural effusion empyema organisation of exudate (calcification) abscess formation bacteraemia, endocarditis, meningitis, arthritis
what are the stages of the inflammatory responses (pathology)
congestion (1-2 days) - lung is heavy, boggy and red - characterised by vascular engorgment, intra-alveolar fluid with few neutrophils, numerous bacteria and vascular congestion, clinically fine crackles and watery sputum
red hepatitisation (2-4 days) - characterised by massive confluent exudation with red cells (congestion), neurophils and fibrin filling with alveolar spaces, on examination - appears distinctly red, firm and airlness with a live like consistency (hence the term hepatitisation), vlinically - bronchial breathing and rusty sputum
gray hepatitisation (4-8 days) - disintegration of red cells and persistence of a fibrinosuppurative exudate give the gross appearance of a grayish brown, dry surface - clinically moist bronchi
resolution (8 days) - consolidation within the alveolar spaces undergoes progressive enzymatic digestion to produce granular, semifluid debris that is resorbed, ingested by macrophages, coughed up or organised by fibroblasts growing into it
what is bronchopneumonia?
inflammation of conducting airways (Terminal bronchioles)
often the cause of death in the eldery in conjunction with a debilitating illness
what pathogens are involved with bronchopneumonia
strep, staph, pneumococci, H influenzae, pseudomonas, cloiforms, candida, aspergiullus
what is the pathology behind bronchopneumonia
- patchy consolidation of acute suppurative inflammation. may occur in one lobe but is more often multilobar and frequently beilateral and basal because of the tendency of secretions to gravitate into the lower lobes
- well developed lesions are usually 3-4 cm in diameter, slightly elevated, drug, granular, gray red to yellow and poorly delineated at their margins
- necrosis centrally, tends to be more destructive than lobar pneumonia
histologically: reaction usually elicits a suppuratives, neutrophil-rich exudate that fills the bronchi, bronchioles and adjacent alveolar spaces
what are some complications of bronchopneumonia
abscess formation
empyema
suppruative pericarditis
emtastatic abscesses
what is the clinical course of bronchopneumonia
major symptoms for CAP, abrupt onset of high fever, shaking, chills, productive cough of mucopurulent sputum, haemoptysis, pleuritic pain and pleural friction rub
clinical picture is dramatically modifiable by the administration of antibiotics. treated patients may be relatively afebrile with few clinical signs in 48-72 hours after the initiation of antibiotics
what is atypical (interstitial) pneumonia?
a combination of atypical presentation and atypical organisms, usually, CAP
clinically defined based on the presence of extrapulmonary manigestations
transmitted via droplet spread (inhalation) in children and young adults and generally is insidious onset gfollowing UTRI
what is the clinical presentation of atypical (interstitial) pneumonia
moderate sputum production no eviedence of consolidation moderate elevation of WCC lack of alveolar exudate CXR: more impressive than expected with lower lung fields, bilateral and perihilar
what is the pathology of atypical (interstitial) pneumonia
predominant in the interstitial nature of the inflammatory reaction, virtually localised within the walls of the alveoli. alveolar septa are widened and edematous and usually have a mononuclear inflammatory infiltrate of lymphocytes, histiocytes and occasionally plasma cells (neutrophils may be present acutely)
alveoli may be free from exudate but many patients may hav eintra-aveolar proteinaceous material (cellular exudate) and a characteristically pink hyaline member lining the alveolar walls. these changes reflext alveolar similar (similar to ARDS). Eradication of infection is followed by reconstruction of normal lung architecture
what is the clinical course of atypical (interstitial) pneumonia
- clinical course extremely varies and even patients with well established pneumonnias may have few localisation symptoms
- cough may be absent and the major manigestations may consist only of fever, headaches, muscle aches and pains in legs
- oedema and exudation are both strategically located to cause mismatching of ventilation and blood flow and thus evoke symptoms out of proportion to the scanty physical findings
discuss the principles of choosing empirical antibiotic therapy
empirical antibiotic therapy is employed on the basis of choosing an antibiotic that will treat the most probable organism based on the patients clinical signs, history and radiological investigations
it is employed as it is important to begin therapy early to avoid the patients deteriorating
recognise the importance of microbiological diagnosis in management
microbiological diagnosis is important to the narrow the antibiotic treatment
Microbiology Indication Narrowest spectrum possible Doseage needs to be adequate to achieve MIC Minimise duration of treatment Ensure monotherapy where possible
explain the pathophysiology of acute respiratory failure in severe pneumonia
respiratory failure is inadequate gas exchange by the respiraotry system, with the result that levels of arterial oxygen, carbon dioxide or both cannot be maintained within their normal ranges
during an infection such as pneumonia the acut einflammatory response will result in an increas ein cytokine production –> vasodilation of pulmonary arterioles –> increased blood flow to fight infection –> poorly ventilated areas receive a large blood flow –> V/Q mismatch –> blood in corresponding pulmonary venules low in oxygen
in healthy lung - vasodilation of arterioles in well-ventilated areas increases gas transport. poorly ventilated lung areas result in vasoconstriction, decrese blood flow to the aras
what are some types of respiratory distress
- hypoxaemia
- hypercapnoea
what is the treatment of respiratory failure
specific, treat the underlying cause/diserase process
general supportive management:- correct hypoxaemia (oxygen therapy), deal with hypercapnoea (HIV), nutrition, prevent DVT, monitor patient
explain type 1 respiratory failure
failure of lung parenchyma/perfusion
hypoxia without hypercapnia (CO2 must be normal or low) that is caused by V/Q mismatch
classification: PaO2 low (>55-60mmHg) and PaCO2 normal or low ((
explain type 2 respiratory failure
failure of pump/ventilation
hypoxia with hypercapnea and is caused by inadequate alveolar ventilation
classification: PaO2 decreases (55-60mmHg), PaCO2 increase (>50mmHg)
caused by conditions that build up CO2 but cannot get rid of it. these include: increased airway resistance (eg COPD, pulmonary disease and asthma), reduced breathing effort (eg drug effects, obesity, brainstem lesion), decreased area of lung available for gas exchange (eg chronic bronchitis), neuromuscular conditions (Eg GBS), deformed, rigid or flail chest
clinical symptoms of CAP
- acute onset with a cough, purulent sputum, breathless, fever, together with physical and radiologicla signs/changes showing lung consolidation
clinical features of CAP
cough breathlessness fever chest pain extrapulmonary features: haemolysis, thrombocytopenia, myalgia, arthalgia and malaise, myocarditis, pericarditis, headache, skin rashes
how to interpret and CXR
airway bones/soft tissue cardiac diaphragm equal volume fine detail gastric bubble hilum/hardware
clinical methods of obtaining samples for microbiological investigations
throat swap nasopharyngeal swab sputum blood nasal swap pleural fluid aspirate percutaneous transtracheal aspiration
what is the criteria for refusal for treatment
- valid refusal of treatment requires the satisfaction of the same conditions as consent to treatment
decisions must be - voluntary (not under duress)
- informed (patient has received sufficient information to make the decision)
- made by a competent person, who is someone who can - comprehend and retain info, understand nature and effects of decisions, elevate information and predicted consequences in relation to one’s situation, goals and values; offer reasons for one’s decisions (justification); communicate one’s decision to others; ability to follow through with decision
- for specific procedure
what are some values in medical ethics
- autonomy
- beneficience
- non-maleficence
- justice
what are some risk factors for pneumonia
- age over 50 years
- alcoholism
- asthma
- COPD
- dementia
- heart failure
- immunosuppression
- indigenous background
- location - eg tropical settings
- insitituationalisation
- seizure disorders
- smoking
- stroke
what are the virulence factors of strep pneumoniae
capsule
pili
IgA protease
what are the microbiological causes of community acquired pneumonia
lobar: strep pneumoniae, Klebsiella, burkholderia mallei (meiliodisis) tropical issue
bronchopneumonia: strep, H influenzae, S aureus, moraxella catterhalis
atypical/interstitial: moraxella cattarhalis
aspiration: enterococci (E coli, serratoa), klebsiella
what are the microbiological causes of nosocomial pneumonia
aspiration as above
polymicrobial
paseudomonas, S aureus
differ as they are harder to treat and bugs have increased exo and endotoxins
what are the microbiological causes of immuno compromised pneumonia
candida
fungal eg pneumocysitis jiemii
CMV
all of the above
how can you prevent (or try to prevent) pneumonia
vaccination
dont smoke
compliance
pneumococcal vaccination –> part of routine
