Week 6-7: Lungs Flashcards
3 pathologies of pneumonia
1) aspiration
2) droplet transmission
3) hematogenous spread
What colour is gram positive?
purple
What colour is gram negative?
pink
What sort of shape is a coccobacilli?
Rods and spheres and rod/spheres
Ex: haemophilus influenzae
What do diplococci look like?
cocci in pairs
Ex: moraxella catarrhalis
Most common pathogens in community-acquired pneumonia?
Step pneum
Haemophilus influenzae
Moroxella
Tidal volume
the amount you normally breathe in and out (500 mL)
Inspiratory reserve volume
The amount you can breathe in if you tried really hard (1900 mL additional)
Expiratory reserve volume
The amount you can breathe out if you try really hard (700 mL additional)
Residual volume
the amount left in your lungs that will never be breathed out. 1200 mL
Inspiratory capacity
the total amount you can forcibly breathe in (TV + IRV)
Functional Residual Capacity
Residual Volume + Expiratory reserve volume (the amount left in your lungs if you are just breathing normally)
Vital capacity
Inspiratory reserve volume + Tidal Volume + Expiratory Reserve Volume
Total Lung Capacity
All lung volumes combined (including residual capacity)
Hyperventilation
ventilation exceeds the metabolic demands of the body
Hypoventilation
ventilation is insufficient to meet the demands of the body
Minute Ventilation
the amount of air inhaled or exhales from the lungs per minute.
Product of Tidal Volume x Resp Rate
Alveolar Ventilation
The amount of air reaching the alveolus per minute. This is air that takes part in gas exchange.
Dead Space Ventilation
The volume of air inhaled that does not take part in gas exchange because it remains in the conducting airways or it reaches alveoli that are not perfused or poorly perfused.
Anatomic Dead Space
Total volume of the conducting airways from the mouth/nose down to the level of the terminal bronchioles.
~150 mL on average in humans
Alveolar Dead Space
Volume of air in the alveoli that does not participate in gas exchange (ventilation without perfusion)
Physiologic Dead Space
Sum of anatomic and alveolar dead space
Name the factors that affect diffusive transport of gas from alveolar air to pulmonary capillary blood and discuss how these relate to the diffusing capacity of the lungs
- Membrane thickness
- Membrane surface area
- Pressure difference across the membrane
- Diffusion coefficient of gas
Partial pressures of O2 and CO2 in alveoli
PAO2 = 105 mmHg (compared to 159 in atmospheric air) PACO2 = 40 mmHg (compared to 0.3 in atmospheric air)
Partial pressures of O2 and CO2 in mixed venous blood
PO2 in venous blood = 40 mmHg
PCO2 in venous blood = 45 mmHg
Partial pressures of O2 and CO2 in arterial blood
PaO2 = 100 mmHg PaCO2 = 40 mmHg
Define pnemonia
Pneumonia is a generic term that refers to inflammation of the pulmonary parenchyma. It is often associated with consolidation (solidification) of the lung. Usually infectious etiology.
Predisposing factors for pneumonia
- suppression of cough reflex (anaesthesia, neuromuscular disorders)
- Impaired immunity
- Impaired mucociliary apparatus (smoking, syndrome)
- Impaired alveolar macrophage function (alcohol, smoking)
- Pulmonary edema (cardiac failure)
- General debility (alcoholism, post-op, malnourishment)
Lobar pneumonia
Restricted to lobe; Most common CAP; majority are strep pneum
Broncho pneumonia
- patchy infective consolidation of the lung in a predominantly lobular distribution.
- Common, especially in hospitalized patients; often terminal complication
- Usually bilateral
- Pre-existing bronchitis spreads to cause bronchiolitis and extends to involve adjacent lung parenchyma
Complications of Bacterial Pneumonia:
○ Bacteremia - bacterial dissemination into the blood
○ Lung abscess formation due to destruction of pulmonary parenchyma and suppuration (pus formation)
○ Empyema - extension of inflammation to pleural cavity (pus in pleural cavity –> fibrosis of pleura)
○ Death
Interstitial pneumonia
the issue isn’t in alveolar lumen. Alveolar walls are thickened by infiltration with mononuclear leukocytes in contrast to the intra-alveolar PMN exudate of bacterial pneumonia
Usually viruses, chlamydia, mycoplasma, pneumocystis
Mechanism of cough
A reflex. Stimulant of irritant receptors in airway leads to activation of inspiratory muscles including diaphragm, as well as activation of expiratory muscles and larynx.
Pathogenesis of asthma
- primarily allergen-driven TH2 response (also viruses and pollutants)
- APC presents to T cells, which differentiate to TH2. TH2 cells prime B cells with IL-4, IL-5, IL-12 to produce IgE, which are mounted in mast cells —> inflammation
Airway remodelling in asthma
- mucous plug containing inflammatory and desquamated epithelial cells
- smooth muscle hypertrophy
- thickened basement membrane
- goblet cell metaplasia
- inflam cell infiltration
How does smoking contribute to pathogenesis of COPD?
- smoke (in combination with genetics, infections, and other exposures) leads to two elements of COPD:
1) obliteration of parenchyma, destroying recoil and causing emphysema
2) inflammation of airways, leading to remodelling and thickening and ultimately small airways disease. - final outcomes in reduced expiratory flow, hyperinflation, and reduced gas exchange
Mechanism of action of nicotine in the CNS
Nicotine binds preferentially to nicotine ACh receptors in the CNS - especially the nACh receptor in Central Tegmental Area
- binding of nicotine in nACh receptor in ventral tegmental area results in release of dopamine in nucleus accumbens, which is believed to be linked to reward
First line pharmacotherapy for tobacco dependence
- nicotine replacement therapy
- antidepressant (bupropion)
- nicotine ACh receptor partial agonist (Varenicline)
What is the strongest predictor of all-cause mortality in patients with COPD?
Physical activity
Define hemoptysis
Expectoration of blood
Pathology of asthma
- Smooth muscle contraction around central and peripheral airways
- wall thickening and remodeling
- increased mucous production and airway obstruction
- allergic, IgE mediated,
Pathology of bronchiectasis
- irreversible dilation of the bronchial tree and obliteration of peripheral small airways
- due to repetitive/persistent infection
- wall thickening and remodeling
- damage undermines mucociliary clearance, resulting in occlusion
What is bronchitis?
- chronic inflammation of the bronchi
What is bronchiolitis
- infection of bronchioles, mostly in children
- results in wall thickening and obliteration
Hydrostatic pressure
Pressure exerted by a liquid at equilibrium.
Oncotic pressure
Due to proteins and osmoles in the plasma. Draws fluid into capillaries
Transudate vs exudate
Transudate is non-inflammatory pleural fluid (heart failure, cirrhosis, nephrotic syndrome).
Exudate is inflammatory derived pleural fluid. Could be from infection, malignancy, pulmonary embolism, etc.
How does pulmonary embolism lead to pleural effusion?
Increased R heart pressure leads to increased pulmonary capillary permeability pushing fluid into the pleural space. The fluid may be a transudate (non-inflammatory) or exudate (inflammatory)
Small Cell Carcinoma (prevalence and macroscopic features)
- Lung Carcinoma type
- 15% of lung cancers
- Predominantly central
- highly malignant and often disseminated at time of presentation
Small cell carcinoma (microscopic features)
- cells have small oval hyperchromatic nuclei and scanty cytoplasm
- Tumor cells exhibit neuroendocrine differentiation
What are the implications of subdividing lung cancer into two categories, small cell and non-small cell
Has to do with immunochemistry of the cancers as relevant to therapeutic agents.
Small cell carcinoma is P40 -ve and TTF1 +ve (as is adenocarcinoma)
Large cell carcinoma
- prevalence
- macroscopic features
- microscopic features
- 10% lung cancers
- often peripheral & probably cases of very poorly differentiated adenocarcinoma
- Large polygonal cells with vesicular nuclei and prominent nucleoli. No specific differentiation.
Adenocarcinoma
- prevalence
- subcategories
- macroscopic features
- microscopic features
- 50%+ lung cancers
- Subcategories based on bronchiolo-alveolar carcinoma growth patterns and invasive adenocarcinoma growth patterns
- 2/3 peripheral and 1/3 central lung. Commonest lung cancer in non-smokers. Peripheral tumors cause puckering of pleura
- Usually cells form glands and/or produce mucin
Squamous cell carcinoma
- Prevalence
- Macroscopic features
- microscopic features
- 25% of lung cancers
- Mostly central growth with cavitations. Adjacent epithelium often displays abnormal growth as well.
- Variably resemble squamous epithelium with keratin formation and intercellular bridges
Massive hemoptysis from a vascular bleed is most likely to come from…
Bronchial vessels (95% of the time) over pulmonary vessels (5% of the time). And bronchial artery > vein
A normal Alveolar-arterial (Aa) gradient (PAO2 - PaO2) is associated with hypoxia in which situation?
Decreased alveolar ventilation (VA)
Define empiric therapy
○ Presumptive therapy based on the likelihood of pathogen and type of infection
○ Usually “broad spectrum”
○ Goal to decrease morbidity and mortality
Infections where pathogens cannot be diagnosed
Targeted antibiotic treatment
- narrow-spectrum
- based on susceptibility results
- minimize toxicity to patient and risk of developing resistance
define Bacteriostatic
drugs slow of stop replication so immune system can eliminate bacteria
Bactericidal
drugs that kill bacteria directly
Antibiotic synergy
2 drugs together have high bactericidal activity than either alone (Ex: B-lactam + aminoglycoside)
4 mechanisms of antibiotic resistance
1) efflux pumps - most common
2) B-lactamases - gram -ve
3) Alteration of penicillin-binding protein
4) Alter porin size
How would you treat MRSA
Resistant bacteria.
PO: TMP-SMX | Linezolid | doxycycline +/- clindamycin
IV: Vancomycin, daptomycin, ceftaroline
How would you treat pseudomonas
Resistant bacteria.
PO: ciprofloxacin
IV: Pip-Tazo | Cefepime | Ceftazadime | Merepenem | Imipenem
How would you treat ESBL
ESBL is extended spectrum beta-lactamase. A resistant bacteria.
Treat with carbapenems
What are carbapenems really useful to treat
ESBL
Which antibiotic doesn’t work in the lungs and why is this?
Daptomycin doesn’t work in the lungs because it is inactivated by surfactant.
Which pneumonia bacteria are gram +ve
The S ones
Strep pneumo and staph aureus
