Pulm Flashcards
Collapsing pressure
Collapsing pressure = 2 * surface tension / radius
Alveoli have increased tendency to collapse on expiration as radius decreases (Law of Laplace)
Surfactant
Secreted by type II pneumocytes
Complex mix of lecithins, lecithin to spinhingomyelin ratio greater than 2 indicates fetal lung maturity
Club (clara) cells
Nonciliated, low-columnar/cuboidal with secretory granules
Secretes component of surfactant, degrade toxins, and act as reserve cells
Respiratory tree
Large airway warms, humidifies, and filters air, ends at bronchi
Cartilage and goblet cells extend to end of bronchi
Pseudostratified ciliated columnar cells extend to beginning of bronchioles, then transition to cuboidal cells
Airway smooth muscles extend to end of terminal bronchioles
Simple squamous cells from end of terminal bronchioles all the way to alveoli
Methemoglobin
Oxidized form of Hb (Fe3+) that does not bind O2 as readily, but has increased affinity for cyanide
Nitrates cause poisoning by oxidizing Fe
Methemoglobinemia may present w/ cyanosis and chocolate-colored blood
Methemoglobinemia can be treated w/ methylene blue
- To treat cyanide poisoning:
1. Use nitrate to created methemoglobin, which binds nitrate
2. Add thiosulfate to bind cyanide and excrete cyanide renally
Carboxyhemoglobin
Form of Hb bound to CO in place of O2
CO has 200x greater affinity than O2 for Hb
Cause decrease in oxygen binding capacity leading to decreased O2 delivery and unloading in tissue
Oxygen-hemoglobin dissociation curve
Sigmoidal shape due to positive cooperativity of Hb (increased O2 binding leads to greater affinity for O2)
Myoglobin is monomeric and thus does not show cooperativity
When curve shifts to right (H+, CO2, altitude, temperature), decreased O2 binding affinity leading to greater O2 unloading into tissue
Fetal Hb has higher binding affinity for O2 and thus curve shift to left
V/Q mismatch
Apex of lung: V/Q = 3 (wasted ventilation)
Base of lung: V/Q = 0.6 (wasted perfusion)
Ventilation and perfusion are both greater at the base of the lung, but increase in perfusion is much greater than increase in ventilation at bottom of lung
With exercise, vasodilation of apical capillaries, resulting in V/Q that approaches 1
V/Q = 0, airway obstruction (shunt), does not improve w/ 100% O2 V/Q = infinity, blood flow obstruction (physiologic dead space), improves w/ 100% O2 as additional capillaries/alveoli can open up to compensate for obstructed blood flow assuming dead space < 100%
Haldane effect
In lung, oxygenation of Hb promotes dissociated of H+ from Hb, shifting equilibrium toward CO2 production and release by combining w/ existing HCO3
(H+ + HCO3 –> H2CO3 –> H20 + CO2)
Increased oxygenation also shifts dissociation curve to the left, leading to release of CO2 from RBC
Haladane (hoard oxygen)
Bohr effect
In peripheral tissue, increased CO2 from tissue metabolism shifts equilibrium to production of HCO3 and H+ (CO2+H2O –> H2CO3 –> H+ + HCO3
H+ binds to Hb, leading to a rightward shift of dissociation curve, and increased O2 release into tissue
CO2 transport
3 forms:
HCO3: 90%
Carbaminohemoglobin: 5% HbCO2
Dissolved in plasma: 5%
Response to high altitude
Decreased atm O2 leading to decreased PaO2 –> increased ventilation –> decreased PaCO2
Decreased PaO2 –> increased erythropoietin –> increased hematocrit and Hb
Decreased PaO2 –> increased 2,3BPG –> increased O2 release in tissue
Decreased PaO2 –> increased renal excretion of HCO3 to compensate for decreased PaCO2 (respiratory alkalosis)
Response to exercise
No change in PaO2 and PaCO2
Increased CO2 production and O2 consumption
Increased ventilation to meet O2 demand, apex/bottom V/Q becomes more uniform
Increased pulmonary blood flow due to increased cardiac output
Increase in venous CO2 content and decrease in venous O2 content
Asbestosis
Associated w/ shipbuilding, roofing, and plumbing
“Ivory white” calcified pleural plaques
Affects lower lobes
Increased incidence of bronchogenic carcinoma and mesothelioma
Silicosis
Associated w/ foundries, sandblasting, and mines
Macrophages respond to silica and release fibrogenic factors, leading to fibrosis
Affect upper lobes
Silica may disrupt phagolysosomes and impair macrophages, increasing susceptibility to TB
Increased incidence of bronchogenic carcinoma
Neonatal respiratory distress syndrome
Surfactant deficiency leading to alveolar collapse
Lectin sphingomyelin ratio less than 1.5 predict ant
Treatment: maternal steroids before birth
Acute respiratory distress syndrome
Can be caused by trauma, sepsis, shock, gastric aspiration, uremia, acute pancreatitis, or amniotic fluid embolism
Diffuse alveolar damage leading to increased alveolar capillary permeability and protein rich leakage
Initial damage due to release of neutrophilic substances toxic to alveolar wall, activation of coagulation cascade, and oxygen derived free radicals
Xray shows near complete opacification of lungs w/ obscured cardiomediastinal silhouette
Staining shows frothy alveolar fluid and thickened intra-alveolar hyaline membrane
Adenocarcinoma of lung
Peripheral
Most common lung cancer in nonsmokers
Activated mutations including k-ras, EGFR, and ALK
Associated w/ clubbing of fingers
Squamous cell carcinoma of lung
Central
Hilar mass arising from bronchus
Associated w/ cavitation, cigarettes, and hypercalcemia (PTHrP)
Seen w/ keratin pearls
Small cell carcinoma
Central
Undifferentiated –> very aggressive
May produce ACTH, ADH, or antibodies against presynatic Ca2+ channels (Lambert-Eaton)
Seen w/ Kulchisky cells: small dark blue neuroendocrine cells
Inoperable, treat w/ chemo
Large cell carcinoma
Peripheral
Highly anapestic tumor, poor prognosis
Seen w/ pleomorphic giant cells
Remove surgically
Bronchial carcinoid tumor
Excellent prognosis, rare metastasis
Symptoms usually due to mass effect, sometimes carcinoid syndrome
Mesothelioma of lung
Malignancy of the pleura associated w/ asbestosis
Results in hemorrhagic pleural effusions and pleural thickening
Psammoma bodies seen on histology
Diphenhydramine, chlorpheniramine
1st generation H1 blockers
Treat allergy, motion sickness, and insomnia
Leads to severe sedation and anti-muscarinic effects
Loratidine, cetirizine
2nd generation H1 blockers
Treat allergy
Far less sedation than 1st gen because of decreased CNS penetration
Guaifenesin
Expectorant
Thins respiratory secretions, but does not suppress cough reflex
N-acetylcyesteine
Mucolytic
Can loosen mucous plug in CF patients by breaking down disulfide bonds in mucus
Also antidote for acetaminophen overdose
Dextromethophan
Antitussive agent (antagonizes NMDA glutamate receptors)
Codeine analog with mild opioid effect when used in excess (naloxone can be given for overdose)
Pseudoephedrine, phenylephrine
Sympathomimetic alpha agonist nonprescription nasal decongestants
Reduce nasal congestion, open obstructed eustachian tubes
Can cause hypertension and anxiety
Theophylline
Methylxanthines: cause bronchodilation by inhibiting phosphodiesterase and increasing cAMP levels
Narrow therapeutic index
Ipratropium
Muscarinic antagonist: competitively block muscarinic receptors and preventing bronchoconstriction
Used for COPD as well as asthma
Montelukast
Block leukotriene receptors
Especially good for aspirin induced asthma
Omalizumab
Monoclonal anti-IgE antibody, binding mostly unbound serum IgE
Used in allergic ashtma resistant to steroids and long acting beta2 agonists
Methacholine
Muscarinic receptor agonist, leading to bronchoconstrition and bronchospasm
Used in bronchial provocation challenge to help diagnose asthma
Bosentan
Used to treat arterial hypertension
Competitively antagonizes endothelin-1 receptors and decreases pulmonary vascular resistance
