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Flashcards in Pulmonology Deck (43):
1

Conducting zone

Do not participate in gas exchange: warm, humidify, filter air; "anatomic dead space"

Large airways:
- Nose
- Pharynx
- Trachea
- Bronchi (cartilage, goblet cells to end)

Small airways:
- Bronchioles
- Terminal bronchioles (pseudostratified ciliated columnar cells and smooth muscle to end)

2

Respiratory zone

Gas exchange; NO cilia
Parenchyma:
- Respiratory bronchioles: cuboidal cells
- Alveolar ducts: simple squamous cells up to alveoli
- Alveoli: Type I, Type II pneumocytes, Clara cells, alveolar macrophages

3

Type II pneumocytes

1. Pulmonary surfactant production
Surfactant= dipalmitoylphophatidylcholine
- Begins at week 26
- Mature at week 35: indicated by lecithin-to-sphingomyelin ratio > 2.0 in amniotic fluid
- Glucocorticoids enhance surfactant production in premature babies
- Clara cells= secrete component of surfactant (also degrade toxins, act as reserve cells)

2. Precursors to Type I pneumocytes (Type I= 97% of alveolar cells)

4

Inspiratory muscles

Quiet breathing= diaphragm

Exercise inspiration= External intercostals, scalene, sternocleidomastoids

5

Expiratory muscles

Quiet breathing= passive

Exercise expiration= Abdominals, Obliques, Internal intercostals

6

Determination of physiologic dead space

Vd/ Vt = (PaCO2-PeCO2)/PaCO2

dead space/tidal volume = (arterial PCO2- expired PCO2)/arterial PCO2

Tidal volume= 500 mL
Total lung capacity ~ 6 L, residual volume= ~1.2 L
* Dead space= conducting airways (think increased in snorkel breathing)

7

Lung compliance

Change in lung volume for given change in pressure:
- Decreased in pulmonary fibrosis, pneumonia, pulmonary edema
- Increased in Emphysema, normal aging, alpha-1-antitrypsin deficiency

8

Hemoglobin forms

4 polypeptide subunits (2 alpha, 2 beta):

Taut form= low affinity for O2
- increases in Cl-, H+, CO2, 2,3-BPG, temperature--> taut form (dump O2 in tissue)
- Shifts O2-hemoglobin curve to Right

Relaxed form= high affinity for O2 (300x higher)
- Seen in a decrease in any factor (temp, [H+])

Fetal hemoglobin= 2 alpha, 2 gamma subunits:
- Lower affinity for 2,3-BPG--> higher O2 affinity (doesn't unload as easily)
- Left-shifted Oxygen-hemoglobin dissociation curve

9

Methemoglobin

Oxidized hemoglobin (Fe+3) vs normal Fe+2
- Nitrites oxidize iron
- Has increased affinity for cyanide
- Treat methemoglobinemia with methylene blue

Cyanide poisoning:
1. Nitrites administered (form methemoglobin)---> bind cyanide; allow cytochrome oxidase to function
2. Use thiosyulfate to bind cyanide in methemoglobin--> thiocyanate--> renal excretion
3. Convert Methemoglobin back to hemoglobin using methylene blue

Symptoms of Cyanide poisoning: mitochondrial ETC inhibitor
- tachypnea, tachycardia, H/A, cutaneous flushing
- N/V, confusion, weakness

10

Carboxyhemoglobin

Carbon Monoxide (CO) binds hemoglobin with 200 x affinity as O2
- Decreases O2 binding capacity--> shifts curve to Left--> decreases O2 unloading in tissue

PO2= normal
- Decreased % saturation, blood O2 content

Tx: 100% O2

11

Pulmonary circulation: Perfusion and Diffusion

Normal:
- Lungs are perfusion limited
- Gas equilibrates early along length of capillary
- Diffusion only increases if blood flow increases

Disease:
- Lungs are diffusion limited: emphysema (decreased area for diffusion), fibrosis (increased thickness of alveolar walls
- Gas does not equilibrate by the time it reaches the end of the capillary
- In exercise, blood moves faster through capillaries (can't get as much O2)--> therefore rate of respiration increased

** Blood flow (ml/min) ALWAYS= blood flow through systemic circulation

12

Pulmonary HTN

Normal pulmonary artery pressure= 10-14 mmHg
- Pulmonary HTN= 25+ mmHg or >35 mmHG during exercise

** Endothelial cell dysfunction

Pulmonary HTN--> arteriosclerosis, medial hypertrophy, intimal fibrosis of pulmonary arteries--> respiratory distress--> cyanosis (deoxygenated Hb > 5g/dL), R ventricular hypertrophy--> death (decompensated cor pulmonale)

Primary= inactivating mutation in BMPR2 gene (normally inhibits vascular smooth m. proliferation)

Severe respiratory distress--> cyanosis, RVH--> death from decompensated cor pulmonale

13

Causes of Secondary pulmonary HTN

- COPD: hypoxic vasoconstriction--> medial hypertrophy
- Mitral stenosis (increased resistance--> increased pressure)
- Recurrent thromboemboli (decreased cross-sectional area of pulmonary vascular bed)
- Autoimmune disease (inflammation (Sclerosis= T-cells--> TGF-beta)--> intimal fibrosis (collagen, ECM proteins)--> medial hypertrophy)
- Left-Right shunt (increased shear stress--> endothelial injury)
- Sleep apnea/high altitude (hypoxic vasoconstriction--> medial hypertrophy)
- Drugs: diet drugs (fenfluramine, dexfenfluramine, phentamine)

Severe respiratory distress--> cyanosis, RVH--> death from decompensated cor pulmonale

14

Pulmonary vascular resistance

PVR= P(pulm artery)- P(left atrium= wedge pressure)/ CO

Resistance= (P(pulm artery)- P (wedge pressure))/ Q (flow)

Resistance= [8 x (viscosity of blood=n) x length]/ (pi x r^4)

15

Alveolar gas equation

PAO2= PIO2 - PaCO2/R

PAO2= alveolar PO2
PIO2= PO2 of inspired air (generally 150mmHg)
PaCO2= arterial PCO2
R= respiratory quotient (CO2 produced/O2 consumed) ~ 0.8

A-a gradient= PAO2-PaO2= 10-15 mmHg
- Increased in hypoxemia due to shunting, V/Q mismatch, fibrosis (ventilating fine, but blood can't get to oxygen!)

16

V/Q mismatch

Apex: V/Q=3 (wasted ventilation)
- TB thrives here

Base: V/Q= 0.6 (wasted perfusion
- V and Q are greater at base

Exercise: Vasodilation--> V/Q approaches 1

V/Q= 0: airway obstruction (O2 won't help)

V/Q= infinity: blood flow obstruction (pulmonary embolism)--> improves with 100% O2 administration

17

CO2 transport

Three forms:
1. Bicarb= 90%
2. Carbaminohemoglobin (HbCO2)= 5%
- CO2 bound to N-terminus, binding favors taut form of hemoglobin
3. Dissolved CO2= 5%

Haldane effect: de-oxygenated blood has increased ability to carry CO2 (vice-versa)

RBC contents:
1. Carbonic anhydrase (converts CO2 to bicarb)
2. Cl-/HCO3- pump:
- RBC is impermeable to H+, but can exchange bicarb (containing H+) for Cl-
- Venous blood therefore has lower Cl- as the increased CO2 in tissue is converted into bicarb (CO2 + H+)--> exchanged out of RBC for Cl- influx

18

Types of restrictive lung disease

Restricted lung expansion--> decreased lung volumes (decreased FVC and TLC)
- Pulmonary function tests: FEV1/FVC ratio > 80%

1. Poor breaching mechanism: extrapulmonary, peripheral hypoventilation, normal A-a gradient:
- Muscular: polio, myasthenia gravis
- Structural: scoliosis, morbid obesity

2. Interstitial lung disease: pulmonary, lowered diffusion capacity, increased A-a gradient:
- ARDS
- Neonatal RDS (hyaline membrane disease)
- Pneumoconioses (anthracosis, silicosis, asbestosis)
- Sarcoidosis (bilateral hilar adenopathy, noncaseating granulomas; increased ACE and calcium)
- Idiopathic (collagen deposition)
- Goodpasture's
- Granulomatosis with polyangiitis (Wegener's)
- Langerhans cell histiocytosis (eosinophilic granuloma)
- Hypersensitivity pneumonitis
- Drug toxicity (bleomycin, busulfan, amiodarone, methotrexate)

19

Neonatal Respiratory distress syndrome (RDS)

Surfactant deficiency--> increased surface tension--> alveolar collapse
- lecithin:sphingomyelin ratio < 1.5 (should be > 2) in amniotic fluid (administer maternal steroids to improve ratio before birth)
- Low O2 tension--> risk of PDA
- Supplemental O2--> retinopathy of prematurity, bronchopulmonary dysplasia (therefore administer artificial surfactant)

Risk factors:
- Prematurity
- maternal diabetes (elevated fetal insulin)
- c-section (decreased fetal glucocorticoid release)

20

Acute respiratory distress syndrome

ARDS

Caused by:
- Trauma
- Sepsis, shock
- Gastric aspiration
- Uremia
- Acute pancreatitis
- Amniotic fluid embolism

Path:
- Diffuse alveolar damage--> alveolar capillary permeability increases--> protein-rich leakage into alveoli
- Formation of intra-alveolar hyaline membrane (T2 proliferation--> fibrosis)
- Damage due to neutrophilic substances toxic to alveolar wall, coagulation cascade, O2-derived free radicals

Findings:
- Decreased lung compliance
- Increased work of breaching
- Enhanced V/Q mismatch with no change in PCWP
- PaO2/FIO2 < 200

21

Sleep apnea

Cessation of breathing > 10 seconds during sleep--> disrupted sleep--> daytime somnolence

Central sleep apnea= absent respiratory effeort

Obstructive= no effort against airway obstruction
- Obesity, snoring, systemic/pulmonary HTN, arrhythmias, possible sudden death

Tx: CPAP, weight loss, surgery
** Hypoxia==> increased EPO--> erythropoiesis

22

Lung cancer complications

SPHERE:
- Superior vena cava syndrome
- Pancoast tumor
- Horner's syndrome
- Endocrine (paraneoplastic)
- Recurrent laryngeal sx (hoarseness)
- Effusions (pleural/pericardial)

* Leading cause of cancer death
- Most common cause= mets from breast, colon, prostate, bladder
- Metastasizes to: adrenals, brain, bone (pathologic fracture), liver (jaundice, hepatomegaly)

23

Pancoast tumor

Carcinoma that occurs in apex of lung (superior sulcus):
- Affect cervical sympathetic plexus--> Horner's syndrome (ipsilateral ptosis, miosis, anhidrosis)
- Can invade brachial plexus--> weakness and paresthesias of arm
- Recurrent laryngeal nerve involvement--> hoarseness

24

Superior Vena Cava (SVC) syndrome

Obstruction of SVC--> impaired drainage from head ("facial plethora"), neck obstruction (Jugular venous distention= JVD), upper extremity edema
- Caused by malignancy and thrombosis of indwelling catheters
- Medical emergency
- Can raise ICP if severe--> H/A, dizziness, increased risk of aneurysm/rupture of cranial aa

25

Bronchopneumonia

Inflammatory infiltrates from bronchioles to adjacent alveoli
- Patchy distribution (1+ lobes involved)

26

Air-fluid level on CXR

Lung abscess caused by:
- Bronchial obstruction (cancer)
- Aspiration (alcohlics, epileptics)
See air-fluid level due to S. aureus, anaerobes (Bacteroides, fusobacterium, peptostreptococcus) forming abscess--> gas

27

Chylothorax

Thoracic duct injury from trauma or malignancy
- Milk appearing fluid (pleural effusion)
- contains increased TGs

28

Albuterol

Beta-2 agonist
MOA:
- Upregulates adenylyl cyclase--> increased cAMP--> bronchodilation

Workhorse drug for asthma (short-acting)

- First choice quick relief for asthma
- As needed ~every 4 hours
- Higher doses used in acute attack

29

Salmeterol, formoterol

Beta-2 agonist
MOA:
- Upregulates adenylyl cyclase--> increased cAMP--> bronchodilation

Long-acting asthma drug- beta-2 agonist
- Every 12 hours
- Theoretical concerns of tachyphylaxis; NOT for immediate relief
- Should not be administered without inhaled steroids

AEs: Tremor, arrhythmia
- hypokalemia: CV disease with diuretic use= highest risk--> potential arrhythmia (COPD population)

30

Theophylline

MOA:
Methylxanthine
- Inhibits cyclic nucleotide phosphodiesterase enzymes
--> increased cAMP and cGMP,
--> bronchodilation
* Competitive inhibitor of adenosine receptor, which may mediate bronchospasm

*Efficacy probably due more to antiinflammatory and bronchoprotective effects than bronchodilatory effects

Side effects: Caffeine derivative:
- within therapeutic index: nervousness, insomnia, dyspepsia
- Dose-dependent toxicity: nausea, emesis, tachyarrhythmias, seizures
** P450 metabolism

Notes:
Third line agent in asthma
Minor role in management of COPD
Requires therapeutic monitoring
BUT…Inexpensive and oral (3rd world use)

31

Ipratropium

Anticholinergic (competitive block of muscarinic receptors)
- Prevents bronchoconstriction
- Effect depends on vagal tone

Use:
- Asthma
- COPD (tiotropium= long acting, M1 and M3 selective)

32

Beclomethasone, fluticasone

MOA: inhaled steroids
- Inhibit synthesis of all cytokines
- Inactivate NF-kappaB (TF that induces TNF-alpha production)

First line for chronic asthma
- Use in ALL except mildest disease
- No immediate bronchorelaxation

Side effects mild and dose related:
- HPA suppression--minimal
- Cataracts--posterior subcapsular
- Growth velocity in children: Titrate dose to control of disease
- Bone mineral density: significant decrease only at higher doses
- Fractures: no increased risk, but poor data
- Pneumonia—mild risk in COPD patients

Local side effects:
- Dysphonia, thrush: independent of type of steroid
- Strategies to avoid: rinse mouth, spacer device

Treatment side effects typically better than severe disease in children

33

Montelukast, Zafirlukast

Leukotriene receptor antagonist (modifiers): reduces inflammation in chronic asthma, bronchitis
- Very safe
- Good for aspirin-induced asthma

- Add-on controller agent in asthma
- Pediatrics: oral, steroid sparing
- Treats allergic rhinitis
- Heterogenous response
- NO ROLE in COPD

Side effects:
- Churg-Strauss vasculitis (associated with severe asthma, responds to corticosteroids)

34

Zileuton

Leukotriene synthesis inhibitor: 5-lipoxygenase pathway inhibitor (arachidonic acid--> leukotriene blocked)
- BID sustained release
- LFT monitoring needed
- Also blocks LTB4
- Limited use

35

Omalizumab

Recombinant humanized anti-IgE antibody
MOA: Binds circulating IgE, but does not activate cell bound IgE
- Allergic asthma resistant to inhaled steroids, long-acting beta-2 agonists

36

N-acetylcysteine

Mucolytic
MOA: reduces intramolecular disulfide bridges in mucus glycoproteins--> loosen sputum

- Loosen mucous plugs in CF patients
- Antidote for acetaminophen overdose

37

Bosentan

Treatment for pulmonary HTN

MOA: Antagonism of endothelin-1 receptors (A and B)
- Causes Vasodilatation, Antiproliferative

Stabilizes smooth muscle proliferation
Teratogenic, alters metabolism of contraceptives

38

Dextromethorphan

Antitussive (antagonizes NMDA glutamate receptors)
- Synthetic codeine analog
- Mild opioid effects when used in excess (abuse potential)- overdose tx= Naloxone

39

Pseudoephedrine, phenylephrine

MOA:
- Sympathomimetic alpha-agonist
- Nasal decongestant
- Constricts blood vessels in sinus passages

Use:
- Reduce hyperemia, edema, nasal congestion
- Open obstructed eustachian tubes
- Stimulant

Tox:
- Hypertension
- CNS stimulation/anxiety
- BPH: issues with voiding

40

Methacholine

Muscarinic receptor agonist
- Used in asthma challenge testing

41

Non-small cell lung cancer marker

Fusion gene between EML4 (echinoderm microtubule associated-like protein 4) and ALK (anaplastic lymphoma kinase)
--> constitutive tyrosine kinase activity

Mutation seen in young non-smokers with lung adenocarcinoma
- No accompanying EGFR or k-ras mutations

42

Diaphragm structures

"I ate 10 eggs at 12"
IVC= T8
Esophagus (vagus trunks)= T10
Aorta, azygous, thoracic duct= T12

43

Oxygen content of blood

O2 binding capacity= 20.1 mL O2/dL

1g hemoglobin binds 1.34 ml O2
- Normal Hb= 15
- Cyanosis= deoxygenated Hb > 5g/dL

** remember, O2 saturation and PO2 are normal in anemia while the O2 CONTENT is low