Week 6 (Obstruction, Restriction and Respiratory Failure) Flashcards

Question

Extrapulmonary

Answer 1

**Obesity** **Pregnancy** **Ascites**: HCC with massive malignant ascites can push up against diaphragm and prevent it from being able to move

Answer 2

Diffuse parenchymal lung disease (**DPLD**) has **decreased DLCO/VA** (lung that is there is not able to exchange gas well; whereas in every other case the lung parenchyma that still exists is working well) in addition to decreased TLC (whereas others don't have any change in DLCO/VA) DLCO is overall ability of respiratory system to exchange gas (low even if have one normal lung and one lung was removed) **DLCO/VA** is ability of respiratory system to exchange gas **corrected** for alveolar volume present (so normal if just one functionally normal lung)

Answer 3

**Normal A-a PO2** but **increased PaCO2**: brain (**drug OD**, bulbar poliomyelitis, central alveolar **hypoventilation**), spinal cord (**polio**, Guillain-Barre, trauma, amyotrophic lateral sclerosis), neuromuscular (myasthenia gravis, **muscular** **dystrophy**, tetanus/botulinum toxin), thorax and pleura (massive obesity, **kyphoscoliosis**, flail chest, tension pneumothorax), upper airways (**tracheal** **obstruction**) **High A-a PO2** but **normal/low PaCO2**: lower airways (**COPD**, asthma, bronchiolitis), parenchymal and vascular (**pulmonary** **edema** (cardiac and ARDS), **pneumonia**, **interstitial lung disease**, **pulmonary embolism**)

Answer 4

**High FiO2** (fraction of inspired O2) **Overhydration** **Over-expansion of alveoli**

Answer 5

Movement of volume of air into and out of the lungs **Minute ventilation** (Ve): volume of air in and out during one minute (Vt x bpm) Definition of ventilation that reflects gas exchange is useful and this is **alveolar ventilation**: Va = Vt - Vd (dead space ventilation) Va = (VCO2 x 863)/PACO2

Answer 6

**Inversely** proportional If **alveolar** ventilation is cut in **half**, **PACO2** will **double** (stop breathing as much and CO2 builds up in your alveoli)

Answer 7

**Acute**: new onset failure to ventilate (PaCO2 \>50), **acidotic** pH, no time for renal compensation by retention of bicarb **Chronic**: long standing failure to ventilate (PaCO2 \>50), but have **renal compensation** through bicarb retention so minimal acidosis/**normal pH**

Answer 8

**Metabolic** control system: **resp** **center** stimulated directly by **CO2** (peripheral chemoreceptors) or indirectly by CO2 (**central** chemoreceptors respond to H+ in CSF, but that comes from PCO2) or **hypoxia** (**peripheral** chemoreceptors are the only ones that sense PO2) to produce **neurological** **impulses** to stimulate respiratory **muscles** to produce ventilation **Behavioral** control system: **higher** **centers** of brain **coordinate** ventilation with talking and can take over if no metabolic control (but not when you're sleeping!)

Answer 9

**Idiopathic** (Ondine's Curse) CNS disease (**stroke**) Disease of **carotid** **bodies** (autonomic dysfunction) Endocrine or metabolic diseases (**hypothyroidism**, metabolic alkalosis) Analgesics, sedatives, **drugs** are most common cause (morphine, valium, barbiturates)

Answer 10

1) Respiratory muscles **cannot** **generate** enough minute ventilation to **overcome** **inefficiency** of breath to breath CO2 elimination 2) **Work** of breathing very **high** due to **airway resistance** 3) Muscles at mechanical disadvantage due to **hyperinflation**

Answer 11

**Acidosis** Increases SNS and systemic vasodilation --\> **headache**, cerebral edema and **papilledema**, **cutaneous** **flushing** and **diaphoresis** Headache, **confusion, coma**

Answer 12

**Pneumoconioses**: asbestosis, silicosis, talc, coal worders' pneumoconiosis **Idiopathic interstitial pneumonias** (IIP): interstitial pulmonary fibrosis (**IPF**), NSIP, COP, RB-ILD, DIP, lymphoid interstitial pneumonitis (LIP), AIP Infections: TB, cocci, histoplasmosis, CMV, PCP **Drugs/radiation**: nitrofurantoin, amiodarone, methotrexate, gold, dilantin **Hypersensitivity** reactions: hay/straw (farmer's lung), cotton (byssinosis), TDI (chemical worker's lung), red cedar (cedar worker's lung), sugar cane (bagassosis) **Collagen-vascular diseases**: RA, SLE, systemic sclerosis, polymyositis-dermatomyositis, sjogren's syndrome, ankylosing spondylitis and psoriatic arthritis **Vasculitis**/autoimmune diseases: granulomatosis with polyangitis (GPA; Wegner's), Churg Strauss, Goodpasture's Miscellaneous: **sarcoid**, pulmonary infiltrates with eosinophilia (PIE), chronic aspiration, pulmonary Langerhans' cell histiocytosis (histiocytosis X)

Answer 13

**Acute** illness (days to weeks**): viral** infections, acute **sarcoidosis** or **Goodpasture's** **Sub-acute** illness (weeks to months): PCP, **TB**, sarcoidosis, alveolar hemorrhage syndromes, cryptogenic organizing pneumonia (COP), **hypersensitivity** pneumonitis, **drug-induced lung disease** **Chronic** (months to years): idiopathic pulmonary fibrosis **Cough**, **dyspnea**, abnormal PFTs, abnormal imaging

Answer 14

**Hypersensitivity** **pneumonitis**: western cedar, cotton, plastics **Pneumoconiosis**: asbestos, silica **Infection**: TB, coccidiomycosis **Drugs**

Answer 15

**Churg-strauss syndrome**: asthma **Wegner's/GPA**: more than 50% have **sinusitis**, **nasal** complaint or **otitis media** Any **collagen vascular disease** will have more than just pulmonary involvement

Answer 16

**Infiltrating** diseases may be **silent** or may have Velcro rales (**dry crackles**) **Sarcoidosis** will have **erythema** **nodosum**, **ocular** manifestations, **arthritis** **Langerhans' cell histiocytosis** (histiocytosis X) will have **lymphadenopathy** and **hepatosplenomegaly**

Answer 17

**Reticulonodular** pattern with interstitial disease (lines all over, maybe small nodules) **Nodular** changes: **Wegner's/GPA**, **sarcoidosis**, pulmonary Langerhans' cell histiocytosis (histiocytosis X), **pneumoconiosis**, granulomatous infections **Cavitation**: **Wegner's/GPA**, **infection** Bilateral **hilar** **adenopathy** with **right paratracheal nodes**: **sarcoid** Bilateral **hilar adenopathy** with **hilar nodes**: pulmonary **Langerhans' cell histiocytosis** Bilateral **hilar adenopathy** with **eggshell calcifications**: **silicosis** **Pleural** disease: **rheumatoid** lung, **asbestosis**, **SLE** Diffuse pulmonary disease with **spontaneous pneumothorax**: pulmonary **Langerhans' cell histiocytosis**

Answer 18

**Blood**: alveolar hemorrhage **Water**: pulmonary edema (ARDS) **Pus**: pneumonitis (infectious, SLE, etc) **Mass**

Answer 19

**Chest wall** **Pleura** (costophrenic angles) **Lung parenchyma** (vasculature vs. other?) **Mediastinum** (look for border of aortic arch, descending aorta, left heart, RA, SVC)

Answer 20

Finding on CXR of a **dense consolidation of alveoli** but **clear bronchi**! Alveoli become densely consolidated then see border you don't normally see, and see the larger airways

Answer 21

**Right middle lobe**: see **minor** **fissure** (**horizontal** line); lateral subsegment if you can still see right border of heart, but medial subsegment if you cannot see right border of heart **Right lower lobe**: see **major fissure** (**diagonal**/oblique line); will **not** be able to see **diaphragm** border

Answer 22

This is prototypical **restrictive** **diffuse parenchymal lung disease** Specific form of **chronic**, **progressive** **fibrosing** **interstitial** **pneumonia** of **unknown cause**, occurring primarily in older adults, **limited to lungs** and associated with histopathologic and/or radiologic pattern of **UIP** Pathophysiology: chronic inflammation and fibrosis leading to **reduced lung compliance**; involves macrophages, lymphocytes, neutrophils, eosinophils, epithelial cells, endothelial cells, fibroblasts; mediated by chemotactic factors, adhesion molecules, cytokines, arachidonic acid metabolites, ROS, growth factors, matrix proteins and enzymes **Fatal** lung disease and natural history is variable and **unpredictible** (most develop gradual worsening of lung function over years, minority remain stable, some decline rapidly but impossible to tell who will react this way) Diagnosis of IPF requires: **exclusion of** other ILDs, presence of usual interstitial pneumonia (**UIP**) pattern on high-resolution CT (**HRCT**) in patients without lung biopsy, specific combinations of HRCT and **surgical** **lung biopsy** pattern in patients subjected to surgical lung biopsy **Treatment** of IPF is **different** from other IIPs (desquamative interstitial pneumonia (DIP), nonspecific interstitial pneumonia (NSIP), respiratory bronchiolitis-associated interstitial lung disease (RBILD), acute interstitial pneunomia (AIP), cryptogenic organizing pneumonia (COP), lymphocytic interstitial pneumonia (LIP)); there is **no effective treatment**, just supportive/symptomatic care or clinical trial or lung transplant **Peripheral involvement, honeycombing, UIP**

Answer 23

Airway **size**/caliber Airway **geometry** Gas **viscosity** Gas **density** Flow = diff in pressure/resistance

Answer 24

Most resistance is at the **7th generation** of airway (within **conducting zone**) Note: **narrowest** place is larynx/**vocal cords** Note: **small airways** have very **little resistance** in healthy people (have laminar flow) but have **highest cross-sectional area**

Answer 25

**Airway** **lumen**: secretions, tumors, foreign bodies **Airway** **wall**: bronchoconstriction (smooth muscle), mucous gland hypertrophy, inflammatory cell infiltration, collagen and fibrosis, loss of cartilaginous support **Peribronchial region**: **lymph** **nodes** (may enlarge and collapse the RML), peribronchial edema **Upper airway**: vocal cords, epiglottitis, oropharynx, nasal **Lung parenchyma**: loss of **elastic** **recoil** so decreased driving pressure and loss of radial traction

Answer 26

**Small airway disease** (COPD) **Parenchymal destruction** (COPD) with less radial traction **Asthma**: edema and bronchospasm

Answer 27

**Laminar** **flow**: smooth, orderly with parallel currents, flow increases with increasing driving pressure, increasing size of airway, decreasing gas viscosity (thickness not density), decreasing airway length **Turbulent** **flow**: disorganized, eddies and swirls, flow is approximately square root of laminar flow (so much lower), likely to be present with large airways, higher average velocity, higher density, lower viscosity, if Reynolds number exceeds 2000-4000

Answer 28

**Heliox** (He with 20-40% O2) used because much more likely to have **laminar flow** in upper airway to get **more gas through** (flow rate is now squared in previously turbulent airways) Viscosity is 13% higher though so results in **slightly reduced flow** in **small** **airways** with laminar flow (so not as useful in COPD small airway disease)

Answer 29

V = diff in pressure/resistance **Static elastic recoil** of lung parenchyma due to **elastin** and **collagen** fibers and due to surface tension of alveoli (reduced by surfactant) Static elastic recoil of chest wall balances lung recoil at FRC When **forced exhalation**, use muscles to increase intraabdominal pressure **(rectus abdominis, internal and external oblique, transversus abdominis**), and to compress chest wall (**internal** **intercostal** **muscles**)

Answer 30

In emphysema, elastic recoil of lung is **reduced** due to destruction of elastin, collagen and lung tissue in general Lungs at **bigger volume** Note: static elastic recoil tends to **collapse** the lung as a **whole**, but tends to hold **airways** **open**

Answer 31

**Higher** **tension** during **inflation** when surface film is being stretched **Lower** **tension** during **deflation** when surface film is collapsing

Answer 32

There is a **limit** to how much you can use the muscles As apply pressure to alveoli, you also apply that pressure to the **airways** so if you continue to increase pleural pressure further, you cause **airway to collapse** (especially if you have **COPD** and radial traction keeping airways open is already decreased)

Answer 33

**Increasing transpleural pressure** is applied to alveolus, resulting in increased driving pressure but also to airways resulting in narrowing and **collapse** Max expiratory flow is limited by airway collapse (if expiratory muscle strength and effort are adequate) In **emhpysema** airways become more **easily collapsed** due to destruction of airway support structure (**radial** **traction** and cartilage) --\> **premature airway closure** results in unexhaled air being trapped behind collapsed airways (**airtrapping**; increased residual volume)

Answer 34

Some lung "units" empty more slowly due to **increased** **compliance** (less recoil pressure to drive flow due to parenchymal destruction) or **increased airway resistance** (small airway disease) If flow is slow then as you breathe **faster** and faster, get **more air trapping** and no time for air to be exhaled through narrow airways (new breath **initiated** before complete exhalation so less ventilation and **air remains trapped** because no time to exhale) **Overinflated lungs**, high residual volume (RV)

Answer 35

**Wheeze**: continuous **musical** sounds longer than 250 ms; may be inspiratory or **expiratory**; oscillation of opposing walls of airways narrowed to point of near closure; pitch not related to location **Prolonged** **exhalation**: long time constant **Hyperinflation**: **hyperresonance** on percussion, **barrel** **chest**, **low flat diaphragm**

Answer 36

**Common**, preventable and treatable Characterized by persistent **airflow limitation** that is progressive and associated with enhanced **chronic inflammatory response** in airways and lung to **noxious particles or gasses** **Exacerbations** and **comorbidities** contribute to severity in people Chronic airflow limitation is mixture of **small airway** disease (**obstructive** **bronchiolitis**), **parenchymal destruction** (**emphysema**), and relative contributions vary from person to person Slow and progressive with continued smoking Measure airflow limitation by spirometry

Answer 37

**Cough, sputum, wheezing, dyspnea** Get cough before obstruction, but get obstruction before you're bothered by the symptoms

Answer 38

**Alpha-1-antitrypsin deficiency** leads to **emphysema/COPD** Hyperresponsiveness to tobacco predicts accelerated rate of decline compared to non-hyperresponsive smokers

Answer 39

**Tobacco** **smoke** by far most important **Occupational** **dust** and chemical exposure (**coal** dust = airflow obstruction, **cadmium** fumes = emphysema) **Indoor pollution**: biomas fuel, environmental tobacco smoke **Outdoor air pollution** (not so much though) **Infections**: lung growth, airway hyperresponsiveness, HIV infection, stepwise decline Socioeconomic status

Answer 40

**Noxious particles** and **gases** combined with host factors --\> **lung inflammation** --\> normal protective and/or repair mechanisms overwhelmed or defective --\> **oxidative** **stress** and **proteinases** --\> **repair** mechanisms --\> **COPD pathology** Note: inflammatory response in COPD is **cytotoxic TH1** (?) cells that activate **macrophages**, which is markedly different from that in asthma (TH2 cells that recruit B cells)

Answer 41

**Proteases** **destroy** tissue: **neutrophil** **elastase** (elastase and collagenase), neutrophil cathepsin G, neutrophil proteinase-3, cathepsins B, L, S; matrix metalloproteases (collagenase, gelatinase, elastase) **Antiproteases** **limit** **destruction** by proteases: **alpha-1-antitrypsinase**, secretory leukoproteinase inhibitor (SLPI) and tissue inhibitors of MMPs (TIMPs)

Answer 42

Alpha-1-antitrypsin is a **protease inhibitor** (antiprotease enzyme) **Normal** allele is Pi **M** Most **common** abnormality is **point mutation** where protein **doesn't make it out of the golgi in the liver** (Pi **Z**) --\> may cause **liver** **disease** in children, or cause **emphysema** at **age 50** in a nonsmoker Pi **S** allele is mutation causing decreased serum half life of alpha-1-antitrypsin, is more common in Spain/Portugal and is **intermediate** but if combined with Pi Z allele then increased risk for disease Heterozygotes are fine! **Smoking** increases **neutrophil** **elastase** from WBCs (increased parenchymal destruction) and smoking **inactivates alpha-1-antitrypsin** (less inhibition of neutropil elastase) --\> **MORE destruction** of lung parenchyma

Answer 43

**Oxidants** and **free radicals** are released by **neutrophils** in respiratory burst (O2-, H2O2, OH, ONOO-) Inhaled as **tobacco smoke** Damage **matrix proteins**, lipids, nucleic acids; activate protease precursors; inactivate antiproteases Limited and localized by antioxidants

Answer 44

**Small airway disease** **Parenchymal destruction** **Mucous hypersecretion** **Pulmonary HTN, cor pulmonale** Systemic effects **Hypoxemia** and **hypercapnia**

Answer 45

**Chronic inflammation** Subsequent **fibrotic repair** reaction **Thickening** of **airway walls** from inflammatory edema and cellular infiltrates **Bronchiolar fibrosis**, smooth muscle **hyperplasia**, **goblet cell hyperplasia** may also be present Airway distortion may result from **fibrous scarring** Note: membranous bronchioles not supported by collagen (are small conducting airways right before respiratory alveoli)

Answer 46

Condition of lung characterized by **abnormal** permanent **enlargement** of the **airspace distal to the terminal bronchiole**, accompanied by destruction of their walls, and without obvious fibrosis **Centrilobular** **emphysema**: dilation and destruction (not just blowing up lung too much but actually tearing open parts of lung and getting holes!) of respiratory bronchioles and beyond (but **not** affecting **alveolar** ducts/alveoli distally) Loss of alveolar attachments to bronchioles; **decreased** lung **elastic recoil** **Hyperinflation** **Destruction** of **pulmonary capillary bed** occurs with destruction of rest of **parenchyma** Gas exchange abnormalities (**decreased DLCO**)

Answer 47

In **smoking**, damage starts at center of lobule (**centrilobular** emphysema) In **alpha-1-antitrypsin**, destruction throughout entire lung (**panacinar** emphysema) Note: in **asthma**, have **no destruction** of the parenchyma at all

Answer 48

**Emphysema** is a **TYPE** of **COPD**, however... **Emphysema** is a **pathologic** diagnosis: parenchymal destruction including destruction of vessels, alveolar attachments to airways, alveolar surface area For **COPD**, you **do not perform a biopsy**! Have destruction leading to airflow obstruction and loss of gas exchange surface area and capillaries, but **cannot prove** whether this is emphysema histologically since no tissue sample!

Answer 49

**Clinical** definition; **mucous hypersecretion** (**hypertrophy** and **hyperplasia** of the subepithelial tracheobronchial mucus glands) Production of any **sputum** whether expectorated or swallowed, and in most instance accompanied by chronic cough for **\>3 months** per year and for **\>2 consecutive years** Disease of **small airways** Does not correlate with FEV1 or impairment but may predict future obstruction **Excludes bronchiectasis** and **chronic infections** Since many COPD patients cough up mucus, prior definition included chronic bronchitis in COPD but just turns out that it's not that important in terms of functional/exercise limitation (its the small airway disease that is important in this)

Answer 50

Get **pulmonary** **hypertension** late in course of COPD: body tries to **compensate for hypoxemia** (poor ventilation) so get hypoxemic **vasoconstriction** in poorly ventilated lung units and destruction of capillaries; pathologic changes in pulmonary arteries Get **cor pulmonale** due to pressure building up as a result of pulmonary hypertension and get hypertrophy and eventual **failure of RV** --\> edema, etc COPD associated with **systemic inflammation** and **skeletal muscle dysfunction** that may contribute to limitation of exercise capacity and decline of health status

Answer 51

**Hypoxemia** may develop when have 35-30% of normal FEV1 (\<1L) due to **V/Q mismatch**: late disease **parenchymal destruction** reduces SA for gas exchange and capillary bed also contributing to hypoxemia during exercise **Hypercapnia** may develop with even lower FEV1 (\<0.75-1L) due to **inspiratory muscle dysfunction**: respiratory drive increased (even with hypercapnia) but respiratory **muscles insufficient** to overcome increased work of breathing due to airflow obstruction and increased inefficiency of ventilation

Answer 52

**Smoker's cough** (**nonproductive**) may start almost immediately with smoking (irritant effect) COPD onset is in **middle age** after long latent period of progressive pathologic and physiologic changes **Chronic bronchitis**: chronic **productive** **cough** due to **mucous gland hypertrophy** and loss of ciliated bronchial epithelium **Dyspnea**, an abnormal awareness of the act of breathing: slowly progressive over years, first with moderate to strenuous exercise, then progressively with less exercise then eventually at rest; late in course get **significant diffusion impairment** with exercise and **cor pulmonale** contributes to dyspnea

Answer 53

On inspection: **horizontal ribs** and **"barrel-shaped"** chest; **flattening** of hemi-**diaphragms**; use of **scalene (palpable)** and SCM muscles; central **cyanosis**; ankle or lower leg **edema** On auscultation: **reduced breath sounds**; **wheezing** during quiet breathing

Answer 54

Slow, progressively increasing **obstructive** ventilatory defect, **without** return to **normal** after **bronchodilators** FEV1 does not correlate well with degree of emphysema **FEV1/FVC ratio \<70%** predicts further decline of \>50 mL/yr **Prolonged exhalation time** (may result in under-estimation of FVC) Hyperinflation causes **increased TLC** **FRC increases** due to decrease in elastic properties of lung (**increased** **compliance**) **RV increases** due to premature airway closure and **air** **trapping** Hyperinflation **flattens** **diaphragm** and results in **mechanical disadvantage** for ventilatory pump

Answer 55

**Parenchymal** **destruction** (emphysema) **reduces both SA** (Dm) for gas exchange and **alveolar capillary bed** (Vc) **DLCO** **correlates** well with degree of **emphysema** (on resection or HRCT) if **FEV1 \>1L**

Answer 56

Graded by **FEV1%** predicted **post bronchodilator** Not all signs and symptoms correlate well with FEV1 Stage I: mild **FEV1 \>80%** Stage II: moderate **FEV1 50-80%** Stage III: severe **FEV1 30-50%** Stage IV: **very severe \<30%** or **FEV1 \<50% with respiratory failure** (PaO2 \< 60 with or without PaCO2 \> 50) or **right heart failure** Note: all stages have **FEV1/FVC \<70%**

Answer 57

**Exacerbation**: acute event characterized by a **worsening** of the patient's respiratory symptoms that is **beyond normal day to day** variations and which leads to a change in medication **Frequent**: **two or more** in the prior year (predictor of future exacerbations)

Answer 58

**Chronic inflammatory disorder** of airways involving **mast cells, eosinophils, neutrophils** (less so than COPD but esp in sudden onset, fatal exacerbations, occupational asthma and patients that smoke), **TH2 lymphocytes**, macrophages, epithelial cells In susceptible individuals, inflammation causes **coughing (at night** or early morning), **wheezing**, **breathlessness** and **chest tightness** Episodes associated with widespread but variable airflow **obstruction** that is often reversible either spontaneously or with treatment **Airflow limitation** due to bronchoconstriction, airway **hyperresponsiveness**, airway **edema** Airway wall remodeling

Answer 59

More common in people **under 18** (whereas COPD never symptomatic in those under 18) Risk factors: innate immunity (**TH2** cytokines, **IgE** levels, allergic sensitization, **atopy**); complex genetic influence, **environment** (airborne allergens, viral respiratory infections, tobacco smoke in utero, air pollution, maybe diet)

Answer 60

**Triggering** symptoms: **allergens**, **viral** infections, nonspecific **irritants**, **exercise** and **cold** air, **osmotic** stimuli **Foods** and **medications** (beta blockers, aspirin) Emotion (rare) Reflex bronchoconstriction (**acid reflux** triggers bronchospasm by NANC nerves then can get down into lung which is bad!) **Classic (Samter's) triad**: **aspirin sensitivity, nasal polyps** and **asthma**

Answer 61

**Early** phase: rapid activation of **mast cells** and **macrophages** already in airways; release of preformed mediators (**histamine**, eicosanoids (**leukotrienes**), **ROS**); smooth muscle contraction, **mucous** secretion, **vasodilation**, microvascular **leak**; result is obstruction (bronchoconstriction, airway wall edema, luminal mucous, exudate and cells); relieved by **beta agonists** and related drugs **Late** phase: recruitment of **new** cells (**eosinophils**, **TH2 helper cells**, basophils, neutrophils, **macrophages**); release of TH2 like cytokines (**IL-2, IL-5, GM-CSF**), recruitment and activation from adhesion molecules, **chemokines** and **cytokines**; enhanced nonspecific (methacholine) bronchial hyperresponsiveness; this is probably what **chronic asthmatics** are experiencing

Answer 62

**Mast cells** and **basophils**: histamine, PGD2, LTC4, tryptase and chymase **Eosinophils**: toxic granule release (major basic protein, eosinophilic cationic protein, eosinophil-derived neurotoxin, oxygen free radicals, eicosanoids (leukotrienes), TH2 like cytokines, growth factors, elastase and metalloproteases) **Lymphocytes**: CD4+ T helper cells (likely control chronic inflammation by release of TH2 like cytokines (IL-4, IL-5, etc) **Macrophages**, **epithelial** cells, **neutrophils**, **fibroblasts** and myofibroblasts **Neurogenic** **inflammation**, **eicosanoids**, endothelins and **NO**, substance P, neurokinins (NKA, NKB)

Answer 63

Occurs in all "types" of asthma **Acutely** **increased** with asthma **triggers** (allergens, viral infections, occupational triggers) Occurs **early** in course of disease (even in mild, intermittent and in remission) Asthma **severity** **correlates** with many inflammatory indices but inflammation **does not "define" asthma subtypes/phenotypes**

Answer 64

**Variable/episodic** with time and/or treatment **Dyspnea** **Wheezing** (more than in COPD; not always seen on physical exam) **Chest tightness** (bronchoconstriction and hyperinflation) **Cough** (sometimes its all it is!) **Sputum** production **Nocturnal awakening** **Exercise limitation**

Answer 65

**Airway obstruction** Variable with time, exposure, treatment **Decreased FEV1/FVC** **Reduced FEV1, PEF, FEF25-75%** PEF variable AM/PM and day to day May have **increased TLC, FRC, RV** **DLCO usually normal** but may be increased in acute attacks (large intrathoracic negative pressures draw in more blood and increase pulmonary capillary blood volume; kind of blood doping effect and get DLCO up a little IF you measured during an exacerbation, but don't usually)

Answer 66

Give **methacholine** to people who may have asthma If healthy, won't do much If severe, FEV1 will drop after having methacholine (**causes bronchoconstriction** because is a **muscarinic agonist**) Negative test has good negative predictive value for asthma!

Answer 67

Can be **intermittent** or **persistent** (mild, moderate or severe) **Symptoms** **Nighttime awakenings** Short acting **beta2 agonist** for symptom control used? Interference with normal activity **Lung function** Exacerbations requiring **oral prednisone** (consider frequency and severity)? Treatment level for initiating or after optimizing control

Answer 68

**Intrinsic** **intensity** of disease process (impairment or risk) Most easily measured when patient not taking long-term controller therapy Guides initial therapy Inferred from minimum therapy needed to maintain control

Answer 69

Well controlled, not well controlled and severe Degree to which **manifestations** of asthma are **minimized** **Current** impairment (symptoms and functional impairment) **Future** risk (exacerbations, decline in lung function, adverse events from medications) Guides treatment after initiation of long-term control medications

Answer 70

**Relax airway** of smooth muscle Don't treat the underlying problem, only treat symptoms (**bronchoconstriction**) **Albuterol/levalbuterol:** short-acting (4h), rapid onset (15s) **Salmeterol**: long-acting (12h), slower onset (15-20min) **Formoterol/arformoterol**: long-acting (12h), rapid onset (\<5min) **Indacaterol**: long-acting (24h), slower onset **Epinephrine**: has heart side effects from beta1

Answer 71

**Smooth muscle relaxation** and mild anti-inflammatory (likely cause bronchodilation by **inhibiting phosphodiesterase**, thereby decreasing breakdown of cAMP) **Theophylline** (PO) and **aminophylline** (IV) **Caffeine** (very weak bronchodilator) Side effects, toxicity and drug interactions (therapeutic range overlaps toxicity range, bad!) **Phosphodiesterase IV specific inhibitors**: raflumilast approved for COPD 3/1/11

Answer 72

Not used as commonly in asthma because don't work as fast as beta agonists, but use **ipratropium** if have beta2 tremor Used in **COPD** primarily (**tiotropium**) Relaxation of cholinergic (**muscarinic**) induced bronchoconstriction **Ipratropium** is **short** **acting** (6h) and **tiotropium** is **long acting** (24h) and selective for M3 and M1 receptor **Atropine** has **systemic side effects**

Answer 73

**Local** broad airway **anti-inflammatory** **Beclomethasone** HFA (dry powder inhaler) **Fluticasone** HFA or DPI, also with **salmeterol** (beta agonist) **Budesonide** DPI or nebulizer, also with **formoterol** **Mometasone** DPI, also with **formoterol** **Ciclesonide** HFA For **rescue**: **oral** prednisolone, methylprednisolone, **IV** methylprednisolone, hydrocortisone

Answer 74

**Only** help **15-20%** of people (can tell who won't respond genetically) Specific reduction in leukotriene mediators Acute bronchodilation and limited anti-inflammatory **Montelukast**: antagonizes **LTD4** and **LTE4** receptors (CysLT type 1) **Zafirlukast**: antagonizes **LTD4** and **LTE4** receptors **Zileuton**: inhibits **5 lipoxigenase**

Answer 75

**Cromolyn** nebulizer (doesn't actually work that well) **Omalizumab**: anti IgE antibody; helpful in severe cases to reduce exacerbation

Answer 76

**Trigger avoidance**: environmental modification, pneumococcal and influenza **vaccination** (because infection can cause exacerbation?), occupational assessment **Cigarette smoking**: reduces anti-inflammatory action of corticosteroids

Answer 77

**Step up** as needed if adherent and **step down** if possible if asthma **well controlled for 3 months** 1) PRN **beta2 agonist** 2) **Low**-dose inhaled **corticosteroid** (ICS) 3) **Medium** dose **ICS** or **low**-dose ICS + long acting beta2 agonist (**LABA**) 4) **Medium** dose **ICS** + **LABA** 5) **High** dose **ICS** + **LABA** and consider **omalizumab** 6) **High** dose ICS + **LABA** + **oral** **corticosteroids** and consider **omalizumab** **Quick relief** medication for all patients: **short**-acting **beta2 agonist** as needed for symptoms up to **3 doses at 20 minute intervals** depending on severity of symptoms

Answer 78

Reduce exposure to **tobacco** smoke, **occupational dusts** and chemicals and indoor and outdoor air pollutants **Smoking cessation** is single most effective (and cost effective) way to reduce risk of developing/progressing COPD Test for **alpha-1-antitrypsin deficiency** in non-smokers with COPD, family history of AAT and early presentation of COPD

Answer 79

**O2 administration** is only way (other than smoking cessation) to **improve survival** in patients with COPD

Answer 80

**Group A**: few symptoms, low risk = **PRN** beta agonists or anticholinergics **Group B**: many symptoms, low risk = long-acting beta agonists (**LABA**) or anticholinergics (**LAMA**) **Group C**: few symptoms, high risk = **LABA/ICS** or **LAMA** or **LABA/LAMA** **Group D**: many symptoms, high risk = LABA/ICS or LAMA, LABA/LAMA, LABA/LAMA/ICS, LABA/raflumilast

Answer 81

Purpose of ICS in **COPD** is to **reduce exacerbations** so if **no exacerbations then** **no need for ICS** Purpose of ICS in **asthma** is to **reduce inflammation** and disease as well as symptoms (so can take steroid daily)

Answer 82

**Bronchodilators**: continuous nebulized **albuterol** and **ipratropium** or frequent high dose MDI until improved then converted to metered dose inhaler; if come into the **ER**, may give **20 puffs** of **albuterol** to try to relieve bronchospasm **Corticosteroids**: IV at hospital or PO at home; steroids take **8 hours to work** so have to get them through that time with bronchodilators and potentially temporary ventilation; use **methylprednisone** once followed by prednisone usually tapered from 60 mg/d **Oxygen** to maintain **SpO2 \>92%** but don't want to give too high O2 or else will suppress respiratory drive **Rule out PE** In asthma, consider **magnesium**, **heliox** (FiO2 0.3 with He), **montelukast** Consider IV **terbutaline**, IV **aminophylline** (but make sure haven't already taken theophylline), intubation and **mechanical** **ventilation** with permissive hypercapnia, paralytic agents **Discharge**: oral steroid burst, good long-term medication regimen, rescue medication, plan for exacerbations, good follow-up

Answer 83

**Exposure** **Infection** **Didn't take their medications**

Answer 84

**Extrathoracic** **upper** **airway**: post nasal drip, Klebsiella rhinoscleroma, hypertrophied tonsils, laryngeal edema, laryngocele, epiglottitis (supraglottitis), retropharyngeal abscess, vocal cord dysfunction, bilateral vocal cord paralysis, vagus nerve compression due to increased ICP, postextubation granuloma, hemorrhagic vocal cord obstruction, abnormal arytenoid movement, cricoarytenoid arthritis, malignancy, obesity, Wegner's granulomatosis (GPA), anaphylaxis, sleep apnea **Intrathoracic upper airway**: tracheal stenosis due to prior intubation, acquired tracheomalacia, relapsing polychondritis, tracheobronchealmegaly, intrathoracic goier, right sided arotic arch, malignancies, tracheal chondroma, tracheal leiomyoma, herpetic tracheobronchitis, benign bronchial tumors, tracheal adenoma (HPV), malignancies, foriegn body aspiration **Lower airway obstruction**: asthma, COPD, bronchiectasis, CF, malignancies, bronchiolitis, pseudomembranous aspergillus tracheobronchitis, lymphangioleimyomatosis (LAM), lymphangitic carcinomatosis, aspiration, pulmonary embolism, anaphylaxis, carcinoid syndrome, parasitic infections, pulmonary edema

Answer 85

Both **obstructive** **COPD**: **small** **airway** disease and **parenchymal** **destruction** due to tobacco/AAT deficiency/chronic bronchitis; preventable (early) mortality, treatable morbidity (only treating symptoms) **Asthma**: **inflammation** of airways treatable with inhaled corticosteroids and bronchospasm relieved with beta2 agonist (treating underlying inflammation)

Answer 86

**Neurological** disease: postinfectious polyneuropathy (**Guillain-Barre syndrome**), motor neuron disease (**ALS**), **poliomyelitis** **Muscular disease**: muscular dystrophy, myopathy (metabolic or structural), connective tissue disease (SLE) **Chest wall deformity**: kyphosis, scoliosis, gibbus, secondary to muscle disease (muscular dystrophy, poliomyelitis)

Answer 87

**TLC decreases** **RV increases** **Lungs** **cannot** **expand** as much and **chest wall cannot shrink** as much

Answer 88

**Maximum voluntary ventilation (MVV)** Breathe deep and quickly for 12 seconds to calculate MVV Can estimate MVV by doing **FEV1 x 40** because you exhale for 40 seconds out of every minute

Answer 89

**Maximum inspiratory** and **expiratory** mouth **pressures** (PImax and PEmax) Better inspiratory force at lower lung volumes Better expiratory force at higher lung volumes

Answer 90

**Use DLCO**: uses **CO** to determine diffusion characteristics of the lung CO goes through alveolar duct to alveolar space across alveolar epithelium into tissue interstitium across capillary epithelium and into plasma From plasma gets across **RBC membrane**, into RBC cytoplasm and onto hemoglobin Measure **CO content of air breathed out** to figure out how much diffused into the lung

Answer 91

Factors **increasing** DLCO: body **size** (SA, Vc), lung **volume** (SA), **exercise**, **supine** (Vc, more uniform distribution of blood throughout lung) Factors **decreasing** DLCO: **age, anemia** (less Hb to bind CO), **diffusion impairment**, **resection** (SA)

Answer 92

In **muscular** disease, get **hypoventilation** which causes **higher PCO2** and **lower PO2** See these levels in both **acute** and **chronic** muscular disease

Answer 93

**Chronic** **hypoxemia** causes **reflex pulmonary vasoconstriction** and with chronicity get remodeling of pulmonary vasculature so resistance increases and get **secondary pulmonary hypertension** as a result of hypoxemia Pulmonary HTN causes **right heart failure** (cor pulmonale) which causes **hypoxemia**, **cyanosis**, **peripheral edema, large pulsatile liver, JVD** In chronic hypercapnia, get **respiratory acidosis** but **renal compensation** by retaining bicarb **PO2 is low** so can provide some supplemental O2 (if PO2 \<50) but don't want to give too much because that will cause **decreased** **ventilatory drive** and **worsen hypercapnia** via **DeJours effect**

Answer 94

**Increase** o**f PCO2 1 mmHg** will **decrease** **pH 0.01 units** **Retention** of **0.5 mEq/L of bicarb** will **restore pH 0.01** units toward normal

Answer 95

1) High **PCO2** in blood diffuses **into** **CSF** so you get high PCO2 in CSF 2) In the CSF, **CO2** combines with water, forms carbonic acid then dissociates to form **H+** 3) Kidney has retained **bicarb** to compensate for hypercapnia in peripheral blood and that bicarb is **actively transported into CSF** to balance the increased CO2 **(increased CSF buffering capacity)** 4) This bicarb in the CSF restores pH of CSF toward normal so there is **less H+** in CSF to stimulate central chemoreceptors and drive from **central chemoreceptors is now diminished** Overall have **less active central chemoreceptors** in presence of **high PCO2 in peripheral blood** --\> must be **more reliant on peripheral chemoreceptor**

Answer 96

**Peripheral** **chemoreceptors** sense **high O2** and low CO2 and **decrease ventilation** and get increased end tidal CO2 High PO2 makes carotid body disinterested in ventilatory control If you give oxygen you correct hypoxemia a little but **PCO2 rises even higher** and pH becomes more acidotic because hypoventilating! Want to maintain adequate O2, don't need it to be too high because you can manage with slightly high CO2

Answer 97

Progressive **loss of ventilatory muscle strength**: worsening **dyspnea** then impaired **cough** then worsening **hypercapnia** Increasing difficulty swallowing: **aspiration pneumonia**

Answer 98

Clinical considerations: chronic **ventilatory** **support** (noninvasive positive pressure ventilation (**NIPPV**) has higher pressure on inspiration and lower on expiration to make breathing easier), tracheostomy for **PPV** (removes half of dead space so get more alveolar ventilation), percutaneous gastrostomy (PEG) for nutrition Ethical considerations: advance directive, durable power of attorney

Answer 99

**Nasal** **cannula: 24-35%** (each L/min raises FiO2 3-4% from 21%) **Face mask: 35-60%** **Non-rebreather face mask: 70-95%** **Intubation: 100%**

Answer 100

**10-15 mmHg** PAO2 - **PaO2 (measured)** **Calculate PAO2**: 150 - (PaCO2/0.8)

Week 6 (Obstruction, Restriction and Respiratory Failure) Flashcards

(124 cards)