pulmonary 2 Flashcards
What is the flow of events in COPD?
Lungs encounter a decrease in PAO2 -> chronic pulmonary vasoconstriction -> chronic pulmonary HTN -> cor pulmonale & subsequent right ventricular failure (JVD, edema, hepatomegaly)
What is the equation for pulmonary vascular resistance?
PVR = [P(pulmonary artery) - P(left atrium)] / CO
What do P(pulmonary artery), P(left atrium), and CO represent?
P(pulmonary artery) = pressure in the pulmonary artery; P(left atrium) = pulmonary wedge pressure; CO = cardiac output
What is the equation for resistance in a vessel?
R = (8?l) / (?r^4)
What do ?, l, and r represent in the resistance equation?
? = viscosity of blood; l = vessel length; r = vessel radius
What is the normal amount of hemoglobin in the blood?
15 g/dL
What level of hemoglobin denotes cyanosis?
When deoxygenated Hb > 5 g/dL
How much O2 can be bound by 1 gram of normal Hb?
1.34 mL O2
What is the formula for O2 delivery to tissues?
O2 delivery to tissues = CO x O2 content of blood
What is the alveolar gas equation?
PAO2 = PIO2 - (PaCO2/R)
What do PAO2, PIO2, PaCO2, and R represent in the alveolar gas equation?
PAO2 = alveolar PO2 (mmHg); PIO2 = PO2 in inspired air (mmHg); PaCO2 = arterial PCO2 (mmHg); R = respiratory quotient = CO2 produced per O2 consumed
How can you normally approximate the alveolar gas equation?
PAO2 = 150 - (PaCO2 / .8)
What is the A-a gradient?
PAO2 - PaO2 = 10 to 15 mmHg
When does an increased A-a gradient occur?
Hypoxemia
What are the potential causes of increased A-a gradient?
Shunting; V/Q mismatch; fibrosis (impairs diffusion through an increase in barrier thickness)
If hypoxemia exists but the A-a gradient is normal, what may be the causes?
High altitude; hypoventilation (i.e. opioid use)
If hypoxemia exists and the A-a gradient is increased, what may be the causes?
V/Q mismatch; diffusion limitation (i.e. fibrosis); right-to-left shunt
If hypoxia exists, what might be the causes?
Decreased cardiac output; hypoxemia; anemia; carbon monoxide poisoning
If ischemia exists in the lung, what might be the causes?
Impede arterial flow; reduced venous drainage
What is the ideal ventilation & perfusion ratio for adequate gas exchange?
1
What is the V/Q mismatch at the apex of the lung?
3 (wasted ventilation) due to a decrease in perfusion; part of the physiologic dead space
What is the V/Q mismatch at the base of the lung?
.6 (wasted perfusion) due to too much blood (this is called shunting as there is venous blood leaving the lung without O2)
What area of the lung do organisms that thrive in high O2 prefer?
Apex
Example: TB
What is the V/Q during exercise?
Exercise increases the CO, there is vasodilation of apical capillaries causing an increase in perfusion -> V/Q = 1
Where are both ventilation and perfusion the greatest?
Base of the lung due to gravity pulling more blood to the base
If V/Q approaches 0, what is the cause?
Airway obstruction (shunt)
NOTE: Giving 100% oxygen will NOT improve PO2 due to nothing getting to the alveoli anyway
If V/Q approaches infinity, what is the cause?
Blood flow obstruction (physiologic dead space)
NOTE: Assuming <100% dead space, 100% oxygen WILL improve PO2
What zone of the lung has PA > Pa > Pv?
Zone 1 (apex)
What zone of the lung has Pa > PA > Pv?
Zone 2
What zone of the lung has Pa > Pv > PA?
Zone 3
Compare V & Q at the base of the lung to the apex.
Both V & Q are increased at the base of the lung due to gravity, however perfusion increases way more!
What are the three forms of transported carbon dioxide?
Bicarbonate (HCO3- - 90%); carbaminohemoglobin or HbCO2 (5%); dissolved CO2 (5%)
Where does CO2 bind hemoglobin?
N-terminus of globin, NOT heme
NOTE: Carbon monoxide binds the heme group
What form of hemoglobin does CO2 binding favor?
Taut (O2 unloaded)
What is the Haldane effect?
Oxygenation of Hb –> H+ dissociates from Hb –> equilibrium shifted to CO2 formation –> CO2 is released from RBCs
IN LUNGS
What is the Bohr effect?
Increased H+ (CO2) from tissue metabolism –> curve shifted right (favors ‘T’ form of Hb) –> O2 unloaded
IN TISSUES
How is the majority of blood CO2 carried?
As bicarbonate
What channel is necessary in the RBC membrane for release of CO2 (as HCO3-) from the RBC?
Cl- / HCO3- antiporter
What enzyme is required in the RBC for CO2 to be converted to HCO3-?
Carbonic anhydrase
What is the acute body response to being in high altitude?
Decrease in Po2 -> decrease in PaO2 -> increase in ventilation -> decrease in PaCO2 (due to breathing more you blow off more CO2) -> respiratory alkalosis -> altitude sickness
What is the chronic ventilation response to high altitude?
Increased ventilation
How does erythropoietin change in response to high altitude?
Increased erythropoietin –> increased hematocrit AKA 40->65 & hemoglobin AKA 15->20 (chronic hypoxia!)
How does 2,3-BPG change in response to high altitude?
Increased 2,3-BPG –> binds to hemoglobin –> curve shifts right –> O2 unloading favored –> hemoglobin releases more O2
What cellular changes are seen in response to high altitude?
Increased mitochondria
How does renal excretion of bicarbonate change in response to high altitude?
Respiratory alkalosis –> increased renal excretion of bicarbonate –> metabolic compensation
What is the result of chronic hypoxic pulmonary vasoconstriction?
Pulmonary HTN & RVH
How does the respiratory system respond to exercise?
Increased CO2 production from muscles –> increased venous CO2 content; increased O2 consumption –> decreased venous O2 content; increased ventilation rate to meet O2 demand; V/Q ratio from apex to base becomes more uniform, approaches 1; increased cardiac output –> increased pulmonary blood flow; lactic acidosis –> decreased pH during strenuous exercise
NOTE: No change in PaO2 and PaCO2
What is Rhinosinusitis?
Obstruction of sinus drainage into the nasal cavity -> inflammation & pain over affected area (typically maxillary sinuses, which drain into the middle meatus, in adults)
What is the most common acute cause of Rhinosinusitis?
Viral URI; may be superimposed bacterial infection (i.e. S. pneumoniae, H. influenzae, M. catarrhalis)
What is an Epistaxis?
Nosebleed
Where does Epistaxis most commonly occur?
Anterior segment of nostril (Kiesselbach plexus)
Where do life-threatening Epistaxis hemorrhages occur?
Posterior segment (i.e. sphenopalatine artery, a branch of the maxillary artery)
What is the most common type of head & neck cancer?
Squamous cell carcinoma
What are the risk factors for head & neck cancer?
Tobacco; alcohol; HPV-16 (oropharyngeal); EBV (nasopharyngeal)
What is the most common, normally fatal, congenital pulmonary anomaly?
Diaphragmatic hernia
What is a DVT?
Blood clot within a deep vein (i.e. femoral, popliteal, iliofemoral) -> swelling, redness warmth & pain
What is Virchow’s triad, and what is its significance?
TRIAD (‘SHE gets a lot of clots’) 1) stasis (i.e. post-op, long drive/flight) 2) hypercoagulability (i.e. defect in coagulation cascade proteins, such as factor V Leiden) 3) endothelial damage (i.e. exposed collagen triggers clotting cascade
SIGNIFICANCE: predisposition to DVT
What is the most common cause of hypercoagulability?
Factor V Leiden (most common defect in coagulation cascade proteins)
What is the complication of DVT?
Pulmonary embolus
What physical examination provocative test is most indicative of DVT?
Homan’s sign = dorsiflexion of foot –> calf pain
What is used for prevention and acute management of DVT?
Heparin
What is used for chronic prevention of DVT recurrence?
Warfarin, rivaroxaban
What clinical test is used to RULE OUT DVT?
D-Dimer lab test (high sensitivity, low specificity)
What clinical test is used to RULE IN DVT?
Imaging test (Ultrasound)
What is the effect to the body of getting a PE?
PE causes hypo perfusion of affected lung parenchyma, which leads to a redistribution of pulmonary blood flow & a V/Q mismatch. The resulting hypoxemia stimulates hyperventilation & acute respiratory alkalosis. ABG shows an increase in pH & a decrease in PaCO2, along with a decrease in PaO2
What are the symptoms of a PE?
Sudden-onset dyspnea, chest pain, tachypnea & tachycardia
What happens with a large or saddle embolus of the pulmonary artery?
May cause sudden death
What do lines of Zahn in a pulmonary embolus indicate?
That the thrombi is pre-mortem
NOTE: Lines of Zahn are interdigitating areas of pink (platelets and fibrin) and red (RBCs) found only in thrombi formed before death
From where do the majority of pulmonary emboli arise?
Deep leg veins
What are the types of pulmonary emboli?
Fat; Air; Thrombus; Bacteria; Amniotic fluid; Tumor
–an embolus moves like a FAT BAT–
What is the best imaging test of choice for a pulmonary embolism?
CT pulmonary angiography (look for filling defects)
Describe obstructive lung diseases.
Obstruction of air flow resulting in air trapping in lungs. **Extended expiratory phase; can’t get rid of air in lungs!
In obstructive lung diseases, how do RV, FRC, TLC, FEV1, FVC, FEV1/FVC ratio, and V/Q change?
RV increased; FRC increased; TLC increased; FEV1 greatly decreased; FVC decreased; FEV1/FVC decreased; V/Q mismatch
What is FEV1?
Air expired in 1 second
What is FVC?
Total air expired in a forced breath
Why does the FVC decrease in obstructive lung disease?
Volume of air that can be forcefully expired decreases
Why is TLC increased in obstructive lung disease?
Air trapping
Why does diffusion decrease in obstructive lung diseases?
Decrease in surface area
At what percentage is the FEV1 considered ‘very severe’?
<30%
At what percentage is the FEV1 so severe that dyspnea at rest will be seen?
<25%
NOTE: There will also be increased PCO2
How much of the lung capacity may be lost before onset of dyspnea?
3/4
How is COPD defined?
Chronic lung disease with obstructive physiology
**(usually, chronic bronchitis + emphysema)
What are the diagnostic criteria for chronic bronchitis?
Productive cough for >3 months per year (not necessarily consecutive) for > 2 years, especially in a smoker
What is the pathogenesis of chronic bronchitis?
Hypertrophy of mucus-secreting glands in bronchi –> Reid index > 50% (thickness of mucosal gland layer to thickness of wall between epithelium & cartilage) –> decreased air flow
**More than 1/2 of bronchial wall is compromised of mucus-secreting glands
What is the formula for the Reid Index?
Mucosal glands layer / (mucosal gland layer & epithelium)
**Cartilage is NOT included
Is chronic bronchitis caused by smoking?
Yes
Of what is a Reid index of <40% indicative?
Normal bronchi
Of what is a Reid index of >50% indicative?
Chronic bronchitis
What happens to the dLCO in chronic bronchitis?
Normal
What happens to the RV & TLC in chronic bronchitis?
RV increases; TLC does not increase as much as emphysema
What are the findings in chronic bronchitis?
-Productive cough due to mucus production; ‘flare ups’; increased risk of infection and cor pulmonale; wheezing, crackles, cyanosis, early-onset hypoxemia due to shunting, mucus plugs trap carbon dioxide (hypercapnia), secondary polycythemia
What are the chronic complications of chronic bronchitis?
Pulmonary HTN, cor pulmonale
What is a trick name for chronic bronchitis patients?
‘Blue bloaters’
What is the effect of bronchodilators in chronic bronchitis?
Some response, but will not return patient to normal
How is chronic bronchitis treated?
Bronchodilators; glucocorticoids; broad-spectrum antibiotics; O2
In emphysema, what changes will be seen in RV, FRC, TLC, and diffusion?
RV increased; FRC increased; TLC increased; diffusion decreased (i.e. decreased dLCO)
Describe the overall criteria for emphysema.
Enlargement of air spaces; decrease elastic recoil; increased compliance; decrease diffusing capacity for CO from destruction of alveolar walls
Is emphysema caused by smoking?
Yes
What is a trick name for emphysema?
‘Pink puffers’
What is the cause of centriacinar emphysema and its location?
Smoking (upper lobes); destruction of central portion of acini
‘Smoke rises to the UPPER LOBES’
What is the cause of panacinar emphysema and its location?
Alpha-1 antitrypsin (A1AT) deficiency (lower lobes); destruction of entire acini
What is A1AT, and what is its function?
Alpha1-antitrypsin, inherited in an autosomal co-dominant pattern
What is the cause of centriacinar emphysema? Location?
Smoking (upper lobes); destruction of central portion of acini.
What is the cause of panacinar emphysema? Location?
Alpha-1 antitrypsin (A1AT) deficiency (lower lobes); destruction of entire acini.
What is A1AT, and what is its function?
Alpha1-antitrypsin, inherited in an autosomal co-dominant pattern; neutralizes proteases (i.e. elastase) in the lower lobes.
What is the result of A1AT deficiency?
Misfolding of protein –> (1) lack of antiprotease –> air sacs vulnerable to protease mediated damage –> panacinar emphysema; (2) accumulation of mutant A1AT in endoplasmic reticulum of hepatocytes –> liver damage.
Describe the pathway once the A1AT deficiency goes into effect.
Increased elastase activity -> loss of elastic fibers -> increase lung compliance.
What will a biopsy of the liver in A1AT deficiency emphysema reveal?
Note the pink, PAS-positive globules in hepatocytes.
Where in the lung is panacinar emphysema most severe?
Lower lobe.
Where in the lung is centracinar emphysema most severe?
Upper lobes.
What is the normal allele in A1AT deficiency?
PiM; two copies are usually expressed (PiMM).
What is the most common clinically relevant mutation in A1AT deficiency?
PiZ.
What heterozygotes in A1AT deficiency are usually asymptomatic? What greatly increases this individual’s risk for emphysema?
PiMZ; smoking.
Which homozygotes are at significant risk for panacinar emphysema and cirrhosis?
PiZZ.
What are the clinical features of emphysema?
- Dyspnea and cough with minimal sputum, hyperventilation, wheezing.
- Prolonged expiration with pursed lips (‘pink puffer’; this increases airway pressure and prevents airway collapse during respiration).
- Weight loss.
- Barrel-shaped chest.
- CXR shows increased AP diameter, flattened diaphragm, increased lung field lucency.
What are the late complications of emphysema?
Destruction of capillaries in the alveolar sac –> hypoxemia; cor pulmonale.
Describe asthma.
Bronchial hyper-responsiveness that causes REVERSIBLE bronchoconstriction.
What happens to the smooth muscle during asthma?
Hypertrophy (b/c muscles are working harder).
Key findings in asthmatic patients?
Curschmann spirals (shed epithelium forms whorled mucus plugs); Charcot-Leyden crystals (eosinophilic, hexagonal, double-pointed, needle-like crystals formed from breakdown of eosinophils in sputum).
What are the triggers of asthma?
Viral URIs; allergens; stress.
What type of hypersensitivity reaction is asthma?
Type I.
Clinical diagnosis of asthma?
Supported by spirometry & methacholine.
What are the clinical features of asthma?
Cough; wheezing; tachypnea; SOB; hypoxemia; decreased inspiratory/expiratory ratio; pulsus paradoxus (drop in SBP > 10 mmHg during inspiration).
What is a finding on CXR during asthma?
Peribronchial cuffing.
I say ‘Curschmann’s spirals,’ you say…?
Asthma.
I say ‘Charcot-Leyden crystals in sputum,’ you say…?
Note the numerous eosinophils also; asthma.
How will the FEV1, RV, FRC, and resistance change in asthma?
FEV1 decreased; RV increased; FRC increased; resistance increased.
What is bronchiectasis?
Permanent dilatation of bronchioles and bronchi; loss of airway tone –> air trapping.
What is the pathogenesis of bronchiectasis?
Chronic necrotizing infection/inflammation of bronchi –> damage to airway cells –> permanently dilated airways, purulent sputum, recurrent infections, hemoptysis & digital clubbing.
What are the possible causes of bronchiectasis?
Poor ciliary function: cystic fibrosis, Kartagener syndrome, smoking; obstruction: tumor or foreign body; infectious: necrotizing infection (H. influenza, P. aeruginosa), allergic bronchopulmonary aspergillosis.
What is Kartagener syndrome?
Inherited defect of the dynein arm –> no ciliary movement –> sinusitis, bronchitis, infertility, situs inversus.
Which individuals are most prone to allergic bronchopulmonary aspergillosis?
Asthmatics, cystic fibrosis patients (hypersensitivity reaction to Aspergillus –> chronic inflammatory damage).
What are the clinical features of bronchiectasis?
Cough, dyspnea; purulent, foul-smelling sputum; recurrent infections; hemoptysis.
What are the complications of bronchiectasis?
Hypoxemia with cor pulmonale; secondary amyloidosis (AA).
How do you treat COPD?
STOP SMOKING; vaccinate against influenza, Streptococcus pneumonia; treat acute purulent bronchitis with bronchodilators (beta adrenergic, anticholinergic); inhaled steroids for partial response; regular exercise; oxygen tank in chronic hypoxemia.
What are the obstructive lung diseases?
COPD; chronic bronchitis; emphysema; asthma; bronchiectasis.
What is the basic criteria for restrictive lung diseases?
Restricted lung expansion causes a decrease in lung volumes; can’t fill lung very well; decreased diffusion d/t thickened tissue.
What are the restrictive lung diseases (interstitial lung diseases; inside lung)?
ARDS, neonatal RDS (hyaline membrane disease); pneumoconioses (Coal Workers’ pneumoconiosis, silicosis, berylliosis, asbestosis, anthracosis); sarcoidosis; idiopathic pulmonary fibrosis; Goodpasture’s syndrome; Wegener’s (granulomatosis with polyangiitis); pulmonary Langerhans cell histiocytosis (eosinophilic granuloma); hypersensitivity pneumonitis; drug toxicity (bleomycin, busulfan, amiodarone, methotrexate).
What are the restrictive lung diseases (poor breathing mechanics; outside lung)?
Poor muscular effort (polio, myasthenia gravis, Guillain-Barre); poor structural apparatus (scoliosis, morbid obesity).
How are TLC, FEV1, FVC, and the FEV1:FVC ratio changed in restrictive lung diseases?
TLC decreased; FEV1 decreased; FVC decreased; FEV1/FVC ratio normal or increased (>80%).
Why does the TLC decrease in restricted lung disease?
Restricted lung expansion –> decreased lung volumes –> decreased TLC.
What issues of poor muscular effort may result in poor breathing mechanics sufficient enough to cause restrictive lung disease?
Polio; myasthenia gravis.
What issues of poor structural apparatus may result in poor breathing mechanics sufficient enough to cause restrictive lung disease?
Scoliosis; morbid obesity.
If restrictive lung disease is due to poor breathing mechanics, what labs will be seen?
Extrapulmonary; peripheral hypoventilation; normal A-a gradient.
If restrictive lung disease is due to interstitial lung diseases (the most common causes), what labs will be seen?
Pulmonary; lowered diffusing capacity; increased A-a gradient.
