Cardiopulmonary Pathology PDF

RT REVIEW  ANATOMY MUSCLES OF INSPIRATION 1. Diaphragm – Most important muscle for inspiration – When diaphragm contracts, the abdominal contents are pushed downwards, the ribs are lifted upward & outward 2. External intercostal...

RT REVIEW  ANATOMY MUSCLES OF INSPIRATION 1. Diaphragm – Most important muscle for inspiration – When diaphragm contracts, the abdominal contents are pushed downwards, the ribs are lifted upward & outward 2. External intercostals and accessory muscles – Not used for inspiration during normal quiet breathing – Used during exercise, labored breathing  ANATOMY MUSCLES OF INSPIRATION 3. Scalene muscle- raise the rib cage & sternum during inspiration - active even during quiet breathing 4. Accessory muscles of inspiration a. Sternocleidomastoid d. Erector spinae b. Trapezius e. Serratus c. Pectoralis minor  ANATOMY Muscles for expiration  Expiration is normally passive  Because the lung/chest wall is elastic, it returns to resting position after inspiration  Used during exercise, increased airway resistance (e.g., asthma) 1. Abdominal muscles- internal oblique, ext oblique, transversus abdominis, rectus abdominis  Compress the abdominal cavity, push diaphragm up, & push air out of lungs 2. Internal intercostal muscles  Pull the ribs down & inward Airway Subdivisions Right Lung - Upper - Middle - Lower Left - Upper - Lower Lingula Transitional and Respiratory Zones  Respiratory zone - starts at the level of respiratory bronchioles  Respiratory bronchioles - Dual function: conduction and gas exchange - Transitional zone Terminal Respiratory Units  Alveolar ducts, with accompanying alveoli, that stem from the most proximal (first) respiratory bronchiole  100 alveolar ducts, 2000 alveoli  Terminal Respiratory Units Type I Pneumocytes Type II Pneumocytes  small, cuboidal cells with  Large, squamous cells stubby microvilli  Resembles a fried egg  < 5% of total peripheral lung cells  Pores of Kohn-  Source of pulmonary surfactant communication  Proliferate in cases of injury and between alveoli may give rise to new type 1 cells  Specialized for gas exchange Obstructive Lung Diseases  COPD - Emphysema - Chronic Bronchitis  ASTHMA  BRONCHIECTASIS  COPD  Disease state characterized by airflow limitation that is NOT FULLY REVERSIBLE.  The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles and gases  Global Initiative for Obstructive Lung Disease (GOLD)  Chronic Bronchitis  Chronic productive cough for 3 months during each of 2 successive years in a patient in whom others causes of chronic cough have been excluded. Emphysema  Abnormal permanent enlargement of the air spaces distal to the terminal bronchioles accompanied by destruction of their walls and without obvious fibrosis  Risk Factors Exposure to toxic fumes/gases  Cigarette smoking - most important risk factor  10-15% smokers lead to COPD  Farming dusty occupation  risk in combination w/ smoking increase to six- fold  Biomass fuel  Cadmium Risk Factors  Mutations in the serine proteinase inhibitor, alpha1–protease inhibitor (A1PI) - only proven genetic abnormality that predisposes to COPD  Cigarette smoking markedly accelerates loss of lung function in patients with A1PI deficiency as well  Clinical Features  Cough  Sputum production  Hemoptysis  Dyspnea with exertion – dynamic hyperinflation  Health status (quality of life)  Acute exacerbations Clinical Features  Coarse crackles on early inspiration  Wheezing  PROLONGED EXPIRATORY TIME- Expiratory phase longer than 4 seconds.  Barrel shaped chest, purse-lipped breathing, emaciation  Tripodding position  Pulmonary hypertension Clinical Features Pink Puffer/ Blue Bloaters  Laboratory Findings  Chest Radiography  Computed Tomography  Pulmonary Function Tests  Spirometry, lung volumes, volume-pressure relations, diffusing capacity arterial blood gases (ABG)  Erythrocytosis  Sputum Examinations Chest Radiography  Diagnosis of COPD EXPOSURE TO RISK SYMPTOMS FACTORS cough tobacco sputum occupation shortness of breath indoor/outdoor pollution  SPIROMETRY Pulmonary Function Tests Spirometry  Diagnosis and staging of COPD  FEV1- severity of COPD   FEV1/FVC - Diagnostic of obstruction Lung Volumes   TLC, RV, FRC   VC Volume-pressure relations  Increased lung compliance Pulmonary Function test  Treatment  Reduction of risk factors  Symptomatic Therapy  Therapy for Dyspnea  Pulmonary Rehabilitation  Nutrition  Chronic Ventilatory Failure  Surgical Treatment  Acute Exacerbations  Acute Respiratory Failure Symptomatic Therapy Bronchodilators  Improvement in airflow  Reduce airway smooth muscle tone  Reduced dyspnea  Improved exercise tolerance  Improvement in lung volume  Chronic basis and as needed for  “rescue” Symptomatic Therapy Bronchodilators  Beta agonist  Airway smooth muscle relaxation  Improve airflow  Short-acting agents  Onset: 5-15 minutes lasting 2 – 4 hours  Rescue during episodes of dyspnea  Long-acting  Formoterol – same onset of action to short acting agents  salmeterol Symptomatic Therapy Bronchodilators  Long –acting beta agonist (salmeterol)  anti-inflammatory effect  reduce edema  reduce airway epithelial cell injury  increase cilia beating  improve mucus transport  improve endurance of fatigued respiratory muscles  Reduce incidence of exacerbations  Symptomatic Therapy Bronchodilators  Metered dose inhaler/Dry powder inhaler - preferred mode of administering drug  Superior to oral administration for improving FEV1  effective as and less expensive than nebulized solution  Nebulizers  Too weak to use device  altered mental status  inspiratory capacity is limited to permit effective inhalation  Symptomatic Therapy Bronchodilators  Anticholinergics  Blocking the action of acetylcholine on M3 muscarinic receptors  Ipratropium, oxtropium  onset of 10-15 mins lasting 4-6 hrs  Tiotropium  slower in onset, peak after 1-2 hrs, prolonged duration of action Symptomatic Therapy Bronchodilators  Tiotropium  Prolonged duration of action dissociates from the receptors extremely slowly  Dissociates from the M2 receptors faster than from the M3 receptors  receptor selectivity  Improves airflow and lung volumes  Improve health status  Improve exercise performance (Reduction in hyperinflation)  Reduces exacerbation frequency and fewer hospitalizations  Symptomatic Therapy Bronchodilators  Combination therapy  Fixed combination of SABA+ SA anticholinergic (current guidelines)  Symptomatic Therapy Bronchodilators  Methylxanthines  Theophylline – currently used to treat COPD  Anti inflammatory effects  inotropic and diuretic effect  augment skeletal muscle strength  Target blood level: 5-10 ug/ml  Adverse effects: nausea, vomiting, seizures and arrhythmias  Symptomatic Therapy Corticosteroids  (Inhaled) Not recommended for routine use to prevent lung function decline  Benefits  Improvement in airflow  Reduced the frequency and severity of exacerbations frequent exacerbation  FEV1 decline of 5ml/year  Reduce the rate of health status decline  Reduced hospitalization and mortality  Adverse effects  increased bruising  reduce bone density  Symptomatic Therapy  Thinning and mobilization of airway secretions  Avoid inhaled irritants  Mucolytic agents (n-acetylcysteine)  Diminished symptoms and exacerbation frequency  Active antooxidant  Reverse epithelial metaplasia in animal models  Expectorants  Guaifenesin and glyceryl guiacolate provides little or no benefit  Physical therapy (postural drainage)  Therapy for Dyspnea (oxygen)  British Medical Research Council Trial  15 hrs/day vs no oxygen  National Institute of Health (NIH) Nocturnal Oxygen Therapy Trial  12 hrs vs 24 hrs  24 hr regimen more beneficial than 12 hr Oxygen Therapy  Indications  Resting arterial PO2 of 55 or less while breathing air  PO2 of 56 - 59 at room air  erythrocytosis (Hct > 55%)  cor pulmonale  Recovery from acute respiratory failure, re-evaluated after a month Oxygen Therapy  Oxygen during exercise  RA: PO2 of 60 or > worsened hypoxemia with exercise  Delay fatigue in exercising ventilatory muscle  Px on O2 even in the absence of hypoxemia: reduced ventilatory rate on O2 due to suppression of carotid body result to less dynamic hyperinflation Nutrition  Progressive weight loss  cachexia reduced muscle strength (inspiratory and expiratory muscles)  15-25% increase in resting energy expenditure (elevated work of breathing)  Increase in circulating inflammatory cytokines  Reduced caloric intake  Improve nutrition can restore respiratory and general muscle strength and endurance  Pulmonary Rehabilitation  Benefits  Improved independence and quality of life  Decreased hospital days  Improved exercise capacity  Lung function (FEV1) usually not improved  Exercise conditioning  single most important aspect  Improved exercise capacity and endurance Pulmonary Rehabilitation  Upper extremity exercises using light weights  Improve upper extremity performance and reduced fatigue  Controlled breathing techniques  Pursed-lip breathing with manual upper abdominal compression and standing bent-forward position  Control of resting dyspnea, anxiety and panic attack  Reduced respiratory rate and enhanced expiratory tidal volume  Improves diaphragmatic function Acute Exacerbations  Increasing symptoms to the increased need to utilize health care resources  Prevention  Inhaled glucocorticoids  Anticholinergic tiotropium and ipratropium  Long-acting beta agonist  Influenza vaccine Acute Exacerbations  Antibiotics  H. influenzae, s. pneumoniae and moraxella catarrhalis  Glucocorticoids  Reduce recovery time and treatment failures  Bronchodilators  Use aggressively (short acting)  IV aminophyliines improve lung function slightly  Definition of Asthma A chronic inflammatory disorder of the airways Chronic inflammation is associated with airway hyperresponsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing Widespread, variable, and often reversible airflow limitation Prevalence  10-12% - adults  15%- children  Childhood- Males > Females  Adult- Equal sex ratio Prevalence  Mortality - poorly controlled disease - frequent use of bronchodilators - lack of ICS use - near fatal asthma Definition  Associated with widespread but variable airflow obstruction  Reversible with treatment or spontaneously  Inflammation-causes hyperresponsiveness to variable stimuli Asthma Inflammation: Cells and Mediators Source: Peter J. Barnes, MD Mechanisms: Asthma Inflammation Source: Peter J. Barnes, MD Risk factors: Atopy Strongest risk factor: family history of atopic disease ( 3x-4x) - House dust mites - cat and dog fur - cockroaches - grass and tree pollens  Production of specific IgE antibodies Risk factors: Infections  Common triggers of exacaerbations  (?) role in etiology  RSV- development of asthma  Mycoplasma/Chlamydia - severe asthma - (?) etiology Asthmatic Triggers  Allergens: - Activate mast cells - Release of mediators Asthmatic Triggers  Viral Infections - Rhinovirus, RSV and Coronavirus - common triggers of exacerbations Asthmatic Triggers  Pharmacologic agents - beta blockers - aspirin Asthmatic Triggers  Exercise - Typically begins after exercise has ended - resolves spontaneously after 30 minutes - worse in cold dry climates - prevented by regular treatment with ICS Asthmatic Triggers  Food  Air pollution  Occupational factors  Hormonal factors - fall in progesterone - premenstrual worsening  GERD Pathophysiology  Airflow limitation - mainly due to bronchoconstriction  Reduction in: - FEV1 - FEV1/FVC Ratio - Peak Expiratory Flow rate Pathophysiology  Early closure of peripheral airways - hyperinflation - air trapping - increased residual volume Clinical Features  Wheezing, dyspnea and coughing  Variable  Resolves spontaneously or with treatment  Worse at night and typically awake in the wee hours of the morning  Increased mucus production Clinical Features  Inspiratory and expiratory rhonchi  Hyperinflation  Some patients present with nonproductive cough  Absence of physical findings in controlled asthma Diagnosis: PFT  Spirometry - reduced FEV1, FEV1/FVC ration and PEF  Reversibility - >12% and 200 ml increase in FEV1 post bronchodilator Diagnosis: PFT  Measurement of PEF - diurnal variation of asthma  Increased airway resistance, TLC and RV  DLCO is usually normal Diagnosis: Methacholine/Histamine Challenge Test  Increased AHR  Provocation with either metacholine or histamine  Provocative concentration that lead to a 20% decrease in FEV1 Diagnosis: Imaging  Chest radiograph: - usually normal - Hyperinflated lungs - rule out co- existing conditions Treatment  Relievers (Bronchodilators) - rapid relief of symptoms - relaxation of smooth muscles  Controllers - inhibit underlying inflammatory response Treatment: Bronchodilators  Reverses bronchoconstricion  Little or no effect on inflammation  B2 agonists, anticholinergics and theophyllines Treatment: B2 Agonists  Stimulates adenyl cyclase - increased intracellular CAMP - relaxes smooth muscles - inhibits certain inflammatory cells particularly mast cells Treatment: B2 Agonists  SABA - 3 to 6 hours - rapid onset - increased use uncontrolled asthma - nebulizer/MDI Treatment: B2 Agonists  LABA - 12 hours duration - should not be used as a monotherapy (without ICS) - improve control and reduce exacerbations when added to ICS - muscles tremors and palpitations Treatment: Anticholinergics  Anticholinergics - prevents cholinergic nerve induced bronchoconstriction and mucus secretion - less effective than b2 agonists - only used as an additional medication in uncontrolled asthma - dry mouth and urinary retention Treatment: Theophylline  Oral bronchodilator  Inhibition of phophodiesterases increases CAMP  Narrow Therapeutic range  Low doses anti-inflammatory effects Treatment: Theophylline  Slow release preparation: OD/BID  Add- on medication in poorly controlled asthma  Nausea, vomiting and headaches  Arrhythiams and seizures Treatment: Controllers  ICS - most effective controller - reduces inflammatory numbers and their activation - reduction of AHR Treatment: ICS  Given BID  Rapidly improve symptoms and lung function  Prevents exacerbations, EIA, AHR  Maximal improvement may taake several months Treatment: ICS  Prevents irreversible changes in airway function  1st line therapy for persistenmt asthma  Added to a LABA if still uncontrolled with ICS alone Treatment: ICS  Hoarseness and Oral candidiasis - reduced by a large volume spacer device  Minimal systemic side effects Treatment: Contoller  OCS - used for treatment of acute severe asthma - Prednisone/Prednisole 30-45 mg/day once daily for 5-10 days and no tapering needed Treatment: OCS  1% of asthmatics may require maintenance treatment with OCS  Systemic side effects: Trucal obesity, bruising, osteoporosis, diabetes, hypertension, gastric ulceration, depression and cataract Treatment: Antileukotrienes  Cysteinyl Leukotrienes - potenet bronchoconstrictors  Montelukast/Zafirlukas - LT 1 receptor blockers Treatment: Antileukotrienes  Less effective than ICS  Add on therapy  Less effective than LABA as add on  OD/BID  Bronchiectasis  defined by ectasia, or dilation, of the airways, or bronkos.  Abnormal & permanent dilatation of bronchi, may be either focal, (involving airways supplying limited region of pulmonary parenchyma) or diffuse (involving airways in a more widespread distribution).  primary clinical manifestations are recurrent, chronic, or refractory infections. Causes Infectious causes 1. Adenovirus and influenzae virus 2. S. aureus , K. pneumoniae & anaerobes  Potentially necrotizing organisms 3. HIV infection  At least partly due to recurrent bacterial infection 4. Tuberculosis  Necrotizing effect on lung parenchyma & airways (direct)  Consequence of airway obstruction from bronchostenosis or extrinsic compression by LN (indirectly) 5. MOTT  Mycobacterium avium complex  Primary, secondary infection or colonization 6. Mycoplasma, necrotizing fungal infection (rare)  Causes: Generalized impairment of pulmonary defense mechanisms  Panhypogammaglobulinemia  recurrent airway, sinus & skin infections & bronchiectasis  Selective IgG2 subclass  Primary ciliary dyskinesia  5-10% of bronchiectasis  Structural defects of dynein arms, radial spokes, & microtubules  Cilia becomes dyskinetic, their coordinated, propulsive action is diminished  Clinical effects: 1. Recurrent respiratory tract infections (sinusitis, OM, & bronchiectasis) 2. Males are generally infertile 3. Kartagener’s syndrome (situs inversus, bronchiectasis, sinusitis)  Cystic fibrosis  Impaired bacterial clearance due to tenacious secretions  Results to colonization & recurrent infection (e.g P. aeruginosa, S. aureus, H. influenzae, E. coli, B. cepacia) Clinical manifestations  Persistent or recurrent cough and purulent sputum production (typical presentation)  Hemoptysis (50-70%)  Bleeding from friable, inflammed airway mucosa (bronchial arteries)  Dyspnea, wheezing  Widespread bronchiectasis or underlying COPD  Infection  Exacerbation  Increased sputum production  Purulent sputum  More bloody  fever Physical examination of the chest/lungs  Crackles  Rhonchi  Wheezes  Clubbing*  Finding consistent with cor pulmonale & RV failure Diagnosis  Pulmonary Function Test  Demonstrate airflow obstruction  Presence of COPD  Sweat chloride test  For widespread involvement to rule out cystic fibrosis Treatment Major goals of therapy: 1. Elimination of an identifiable underlying problem 2. Improved clearance of tracheobronchial secretions 3. Control of infection, particularly during exacerbations 4. Reversal of airflow obstruction  Treatment  Secretions: 1. Chest physiotherapy 2. Postural drainage 3. Mucolytics 4. Recombinant DNAse  decreases viscosity of sputum by breaking down DNA released fro PMN  Improve pulmonary function in cystic fibrosis (not in other etiologies)  Appropriate treatment when a treatable cause is found: 1. Hypogammaglobulinemia- Ig replacement 2. Tuberculosis- Anti-TB drugs 3. ABPA- glucocorticoids  Antibiotics:  Given during acute exacerbation characterized by increase in quantity & purulence of sputum.  Use is guided by GS/CS  Empiric antibiotics  Ampicillin  Amoxicillin  Cotrimoxazole  Cefaclor  Short or prolonged course of single or rotating antibiotics Treatment  Bronchodilators  For airway obstruction  Aid in clearance of secretions  Lung transplantation  Disabled despite maximal therapy  Massive hemoptysis  Rest, antibiotics  Surgery  Bronchial artery embolization  Hypoxemia or cor pulmonale  Long term O2 Chest and Pleural Trauma  Flail Chest  Pneumothorax Flail Chest  Results as a complication of multiple rib fractures  Causes a part of the chest wall to be free floating  Paradoxical Movement of the chest wall: - Bowing out during expiration - Collapsing inward during inspiration  Result: A negative intrathoracic pressure gradient Flail Chest  Requires significant blunt force trauma to the torso to fracture the ribs in multiple areas.  Such trauma may be caused by motor vehicle accidents, falls, and assaults in younger, healthy patients.  Flail chest is an indicator of significant kinetic force to the chest wall and rib cage, but  May also may occur with lesser trauma in persons with underlying pathology, including osteoporosis, total sternectomy, as well as individuals with congenital absence of the sternum. Flail Chest Flail Chets Flail Chest  Frequently associated with a variety of other pulmonary injuries - mechanism of injury - force required to break multiple ribs - Pulmonary contusion,hemothorax and pneumothorax  Often necessitate urgent or emergent treatment of the trauma patient Flail Chest  Flail segment - dysfunction of the remaining unaffected segments - exhalation of the alveoli adjacent to the injury  Consequences - collapse, atelectasis, V/Q mismatch, decreased compliance and hypoxemia Flail Chest: Treatment  Positive pressure ventilation  Stabilization of the rib cage  Treatment of other organ problems Pneumothorax  Presence of air in the pleural space  Spontaneous Pneumothorax - Primary - Secondary  Traumatic Pneumothorax  Pleura - usually a negative pressure chamber  Pneumothorax - communication develops between an alveolus and the pleural space - air flows into the pleural space - communication develops between pleural space and atmosphere Pneumothorax  Main physiologic consequences - Decrease in vital capacity - Decrease in arterial PO2  Primary Spontaneous - decrease in VC is well tolerated  Secondary Spontaneous - may lead to respiratory insufficiency with alveolar ventilation and respiratory acidosis Primary SpontaneousPneumothorax - rupture of a subpleural bleb - pathogenesis of these blebs and trigger of rupture is unkwnon - strong association with smoking - tends to occur more commonly among patients who are tall and thinner Primary SpontaneousPneumothorax  Occurs commonly in their early 20’s and rarley after age of 40  Usually develops at rest and rare during exercise  Chest pain and dyspnea are the most common symptoms Primary SpontaneousPneumothorax  PE: Normal vital signs except for tachypnea and tachycardia  Decrease breath sounds. Percussion note is hyperresonant  Diagnosis: Demonstration of the visceral pleural line on chest x ray Primary SpontaneousPneumothorax  Treatment: (15%) - Observation - supplemental oxygen - simple aspiration - Tube thoracostomy with or without pleurodesis Secondary spontaneous Pneumothorax  COPD is the most common etiology  Symptoms - same with SSP but more severe  Should always be suspected among COPD patients who suddenly complains of chest pain and dyspnea  PE is less useful  Diagnosis: Visceral pleural line on chest xray Secondary spontaneous Pneumothorax  Treatment - Tube thoracostomy - VATS - Open thoracotomy Pulmonary Infections  Pulmonary Tuberculosis  Pneumonia Characteristics of the genus  Acid-fast  Intracellular parasite  Slow rates of growth (except for “rapid grower” category  Obligate aerobes  Induce granulomatous response in normal hosts Mycobacterium Tuberculosis  Obligate aerobe  Persists, even without multiplying, with a very limited oxygen supply  Remain viable but dormant in sequestered sites in the body Mycobacterium Tuberculosis  Source case  Environmental factors  Circumstances of exposure  Factors related to the potential host Source case  M. tuberculosis: air-borne infection  Acquired by inhaling 1 or more tubercle bacilli in an airborne particle (1 – 5 um)  Only patients with pulmonary tuberculosis can be regarded as infectious  Droplet nucleus  A single bacillus in a tiny droplet nucleus is more hazardous than a large number of bacilli in a larger particle Source case  Droplet nucleus  Do not settle but remain suspended in the air for long periods of time  coughing: most effective mechanism in producing droplet nucleus  1 cough = 5 minutes of loud talking  Character and volume of respiratory secretions may influence infectiousness  masks Source case  The most important factor to be considered in determining infectiousness is the number of organisms contained in the lungs of the source case  Extent and morphology of disease (Canetti)  Solid nodular lesion: 102 – 104 bacilli  Cavitary lesion: 107 – 109 bacilli  However, it SHOULD NOT be assumed that persons with lesions indicative of small bacillary populations are noninfectious Source case  Microscopic examination of properly stained sputum: most direct means of estimating bacillary population  5,000 – 10,000 organisms per millimeter of sputum required for organism to be seen in an acid-fast-stained sputum smear  Use of chemotherapy  Patients with positive sputum-smears but who receive anti-tuberculosis drugs were much less infectious Source case  The major factor associated with culture- positive aerosols was lack of effective treatment in the previous week 1stMost important 2 days: reduction inmechanism colony count byby which 2 logs/ mL sputum with Regimenreduces chemotherapy (INH, Rif, Pyrazinamide, S) infectiousness is the direct 2 weeks: effect decrease fromof107the drug to 104 on themL organisms/ bacillary sputum, population or a reduction in the lungs of 99.9% Jindani Circumstances of Exposure  Long duration of exposure = greater likelihood of transmission  Crowding and intimacy: important determinants of transmission  Rate of tuberculosis  15 per 1000 close contacts  3 per 1000 non-close contacts  Close contacts = high-priority for preventive isoniazid therapy Factors related to the potential host  Endogenous factors  Blacks > whites  Impaired immune response  Nonimmunologic and immunologic factors  Cell-mediated immune response  BCG: increases response of lymphocytes and macrophages to M. tuberculosis  Specific genetic defects  NRAMP-1, Vitamin D receptor Risk factors for developing tuberculosis  HIV infection  Conditions or therapies that interfere with cell-mediated immunity  Hematologic malignancies  Cancer chemotherapy  Risk-enhancing diseases  DM  Uremia  Silicosis Risk factors for developing tuberculosis  Genetic factors  Filipinos – decreased ability to develop potent cell-mediated immunity  Undernutrition  Gastrectomy, intestinal bypass  Body build  Thin for height (not related to nutritional status)  Detecting latent tuberculous infection  The tuberculin skin test  Reactivity is hallmark of a cell-mediated immune response to M. tuberculosis  Gold standard for detecting latent TB infection  Measurement of whole-blood interferon- release  Accomplished in 1 visit; more specific in presence of BCG, infection with MOTT; less reader variability; not recalling waned immunity Tuberculin skin test  5 TU (0.0001 mg PPD) intermediate test strength used for routine testing  Should cause a well-demarcated wheal 6 – 10 mm in diameter with hair follicles forming dimples  Read after 48-72 hrs after; may be delayed for up to 1 week  Only the extent of induration is important  Boosting  Occurs when a person who was infected in the past loses skin reactivity over the course of several years  Interpretation of tuberculin skin test Criterion  5 mm reactions Circumstances Known or suspected HIV infection or other immunosuppressed condition recent close contact with infectious TB chest film abnormalities suggestive of old TB ≥ 10 mm persons born in high prevalence areas injection drug users medically underserved, low-income populations: high-risk minority populations residents of long-term care facilities persons with medical conditions that increase the risk of tuberculosis ≥ 15 mm all others General Manifestations of Tuberculosis  Site of involvement  Effectiveness of host defense  Presence of associated disease  Systemic features  Fever, malaise, weight loss  Hematologic manifestations  Anemia  Leukocytosis  Metabolic disorders  hyponatremia Pulmonary tuberculosis  US data: 71% involve lungs 20% extrapulmonary sites 9% both  Symptoms  Cough  Pleuritic pain  Dyspnea  Hemoptysis Causes of Hemoptysis in PTB  Extensive parenchymal involvement  Bronchiectasis  Rupture of a dilated vessel in a wall of an old cavity (Rasmussen’s aneurysm)  Bacterial or fungal infection (mycetoma or aspergilloma) in an old residual cavity  Erosion of calcified lesions into the lumen of an airway (broncholithiasis) Radiographic Features  Primary tuberculosis  Middle or lower lung zone infiltrate  Ipsilateral hilar adenopathy  atelectasis  Endogenous reactivation  Upper lobes of one or both lungs  Cavitations  Fibrotic scar with shrinkage of lung parenchyma and calcification  Bronchogenic spread Radiographic Features Bacteriologic Evaluation  Definitive diagnosis  Isolation of tubercle bacilli in culture or  Identification of specific nucleic acid sequences  Sputum  Single early morning specimen  Gastric content sampling thru NGT  Lower yield than sputum induction  Fiberoptic bronchoscopy  BAL and transbronchial lung biopsy  Miliary TB Treatment  Bacillary populations are not uniform in their susceptibility to antimycobacterial agents  A bacillary population of > 1012 organisms would be required before one would expect to find a single bacillus resistant to both Isoniazid and Streptomycin Treatment  Streptomycin, Rifampicin, Isoniazid  bactericidal  Pyrazinamide, Rifampicin, Isoniazid  Effective in killing intracellular organisms  Rifampicin  Kills organisms that grows in spurts rather than continuously Drugs in Current Use  Isoniazid  Inhibits mycolate synthase  Resistance  Deletion of katG gene  Mutations of inhA gene  Major toxic effect: hepatitis  2nd most frequent adr: peripheral neuropathy  Prevention/ reversal  Pyridoxine (25 mg/ day) Drugs in Current Use  Rifampin  Binds to -subunit of RNA polymerase  Resistance  Mutations in rpoB gene  Rifamycins (Rifampin, Rifabutin, Rifapentine)  Protease inhibitors – decrease clearance of rifamycins  Rifamycins accelerate clearance of protease inhibitors  Interacts with non-nucleoside RT inhibitor classes Drugs in Current Use  Ethambutol  Target: arabinosyltransferase  Reduce risk of rifampin resistance caused by strains with primary resistance to isoniazid  Resistance  Mutations in embB gene  Main adr: retrobulbar neuritis  Blurred vision, central scotoma, red-green color blindness Drugs in Current Use  Streptomycin  Not a 1st line drug  Inhibits ribosomal protein synthesis by binding to 16S rRNA (inhibits initiation of translation)  Resistance  Mutations in rrs : low-level resistance  Mutations in rpsL: high-level resistance  Most serious adr: ototoxicity Drugs in Current Use  Pyrazinamide  MOA: unknown  Active against dormant and semidormant M. tb  Acidic environ within caseations; in macrophages  Resistance  Mutations in pncA gene  Most important adr: liver injury  Hyperuricemia occurs in nearly all Drugs in Current Use  2nd Line drugs  Para-aminosalicylic (PAS) Acid  Ethionamine  Cycloserine  Capreomycin, kanamycin, amikacin  Fluoroquinolones – DNA gyrase  Levofloxacin – most preferred agent Treatment  Short-course regimen 1. Initial, intensive or bactericidal phase (2 mos)  Majority of bacilli are killed  Symptoms resolve  Patient becomes noninfectious 2. Maintenance, continuation or sterilizing phase (4 mos.)  Eliminate semi-dormant “persisters”  TREATMENT  FIRST LINE ESSENTIAL DRUGS Isoniazid – bactericidal, extra-cellular Rifampicin – bactericidal, extra/intra-cellular  FIRST LINE SUPPLEMENTAL DRUGS Pyrazinamide – weakly bactericidal, w/in macrophages, acute inflam’n Ethambutol – bacteriostatic/cidal at higher doses; extra/intra cellular Streptomycin - bactericidal Pneumonia  Definition  Infection of the pulmonary parenchyma caused by various bacterial species, virus, fungi and parasites. Not a single disease, but a group of specific infection, each having different epidemiology, pathogenesis, clinical manifestations and clinical course.  Transmission  Aspiration  Inhalation  Hematogenous Aspiration  Most common mechanism  50 % of healthy adults aspirate oropharyngeal secretions during sleep Factors that increase risks for aspiration  Alcoholics  Stroke patients  Seizure  Drug abusers  General anesthesia Inhalation of infectious aerosols  Size factor:  >10 um diameter = nose and upper airway  < 5 um diameter (airborne) = deposited in small bronchiole and alveoli Etiologies acquired by inhalation:  TB  Influenza  Legionella  Psittacosis  Histoplasma  Q fever Hematogenous Dissemination from an extrapulmonary site  Staph aureus - IV drug user, abscess  Fusobacterium - from retrophangeal tissue  Direct inoculation and contiguous spread  Ex: stab wound, tracheal intubation  Etiology Factors that determine the etiologic agent 1. Setting from which infection is acquired  Community acquired  Hospital acquired  Health Care Associated 2. Age 3. Comorbid condition Community acquired infection  Streptococcus pneumonia  Haemophilus influenza  Chlamydia pneumonia  Mycoplasma pneumonia Hospital Acquired Pneumonia  Staphyloccocus aureus  Pseudomonas species Water storage system with warm temp, stagnation and sediment accumulation:  Legionella species Age Factor  Infants < 6 months:  RSV  Chlamydia trachomatis  6 months to 5 years:  H. influenza  Young adults:  M. pneumonia  S. pneumonia  C. pneumonia  Hantavirus  Elderly  H. influenza  M. catarhallis  S. pneumonia Clinical Manifestation Community Acquired Pneumonia  Atypical  Typical Nosocomial Pneumonia Aspiration Pneumonia  Atypical Pneumonia Typical Pneumonia Syndrome Syndrome Etiology M. pneumonia, S. pneumonia, C. pneumonia, H. influenza, Legionella sp, Klebsiella sp Mycoplasma, viruses Onset gradual Abrupt Cough Dry cough Productive cough Sputum Scanty Purulent Pulmonary Shortness of breath Shortness of breath signs and pleuritic chest pain symptom sign of pulmonary consolidation, rales Extrapulmonar Prominent (headache, Not prominent y symptoms myalgia, fatigue, nausea, vomiting, diarrhea) Nosocomial Pneumonia / HAP  Pneumonia occuring > 48 hours after admission and excluding any infection that is incubating at the time of admission  New or progressive pulmonary infiltrate  Purulent tracheobronchial secretion  Fever  Leukocytosis Aspiration Pneumonia  Sudden onset of dyspnea, wheezing, hypoxemia  CXR: Infiltrate in the right lower lobe Etiology:  Oropharygeal pathogen  Anaerobes  Chemical Pneumonitis  Health Care Associated Pneumonia 1. Hospitalization for 2 days more in the preceding 90 days 2. Residence in a nursing home or extended care facility 3. Home infusion therapy (infusion therapy) 4. Chronic dialysis within 30 days 5. Home wound care 6. Family member with multidrug resistant pathogen  Diagnosis A. History and Physical examination  60% accuracy  CHEST FINDINGS  RALES, CRACKLES, DECREASE BREATH SOUNDS, ETC… Laboratory Examination A. Chest X-ray (PA - Lateral views)  New parenchymal infiltrate  Confirms the diagnosis  Assess the severity / prognostication  May suggest the etiology  Laboratory Examination B. Sputum Examination  Gram stain  Good specimen: > 25 PMN; < 10 epith cell per LPF  Sensitivity: 60-80%  Specificity: 85% in identifying pneumococcus  Culture And Sensitivity  40-60% specificity  ETA, BAL, TTA  Not routinely done  Better specificity Laboratory Examination C. Serologic Test  Urinary antigen test  Legionella pneumophila  Indirect immunoflourescence  IgM>1:20, IgG>1:128 – diagnostic for Mycoplasma D. Blood Culture E. Other tests  CBC, electrolytes, liver function, creatinine F. Arterial Blood Gas Lung Cancer CLINICAL PRESENTATION  CLINICAL PRESENTATION  Chest pain is related to involvement of the pleura but can be related to extension into the mediastinum or chest wall  Dyspnea is occurring in half of all new patients at presentation  Reasons for dyspnea  Pulmonary embolism  Superior vena cava syndrome  Deconditioning  Reactive airway disease  Endobronchial obstruction with tumor  Prior obstructive pneumonia  Hemoptysis / hemorrhage  Malignant pleural effusion  Extrinsic compression of the airway by tumor  LUNG CANCER STAGING  Diagnostic and staging is the most critical in the management of lung cancer “GENERAL RULE “ Early-stage lung cancer (stage I and II) is a surgical disease  Staging Locally dictates advanced the lung cancer patient's (stage IIIA and B)treatment is treated with a options and predicts combination survival of chemotherapy and radiotherapy Stage IV (metastatic disease) is treated with chemotherapy alone  It is intuitive that early-stage disease has a much better survival than late-stage disease  The treatment options for lung cancer have now evolved so that treatment for patients in different stages is vastly different  LUNG CANCER STAGING  The staging of NSCLC uses the tumor-node- metastasis (TNM) classification  TNM staging system is applied to NSCLC  Small cell Lung carcinoma uses a more simplified version  Limited disease (LD) is disease that is limited to one hemithorax, and can include supraclavicular and mediastinal lymphadenopathy  Extensive disease (ED) is any disease outside of the hemithorax  The implication in this classification is that LD is treated with chemotherapy and radiotherapy, whereas ED is treated with chemotherapy alone  SPUTUM CYTOLOGY  Sputum cytology is the least invasive method  Accuracy depends on the expertise of the health care team in obtaining the sample (3 samples), the preservation technique, and the size and location of the lesion  Central lesions likely to yield positive cytologic results than peripheral lesions  Patients with hemoptysis with or without a mass on chest radiographs should have sputum cytology obtained  The sensitivity and specificity of sputum cytology are 66% and 99%, respectively  TRANSTHORACIC NEEDLE ASPIRATION  Transthoracic needle aspiration, usually under CT or fluoroscopic guidance, is an expedient and relatively safe way to diagnose the primary tumor mass and establish a diagnosis of lung cancer “As a general rule, if a lesion is less than 3 cm in size and lateral to the mid-clavicular line, bronchoscopy would not be the diagnostic procedure of choice”  If a patient presents with a solitary pulmonary nodule suspicious for malignancy the diagnosis, stage, and therapy can be accomplished simultaneously with a thoracotomy and surgical resection  FIBEROPTIC BRONCHOSCOPY More than 50% of patients with advanced-stage lung cancer will have involvement of the central airways  Patients with known or suspected lung cancer may have symptoms due to endobronchial involvement that require airway inspection with bronchoscopy Types  Small Cell Lung Cancer - most strongly associated among smokers; centrally located mass  Non Small Cell Lung Cancer - Adenocarcinoma: Women and non- smokers; peripherally located mass; usually presents with pleural effusion - squamous cell: Smoking; Centrally located masses  TREATMENT OF LUNG CANCER  The overall 5-year survival for patients diagnosed with lung cancer is aEarly-stage dismal 14% disease is surgically managed  The survival curves vary by stage, with Locally advanced disease is earlier stage lung cancer patients enjoying managed a much with chemotherapy better survival than do patients and disease with later stage radiotherapy Advanced disease is managed  Treatment is based with chemotherapy with  Stage of the disease supportive care or supportive  Patients' performance status at the time therapycare alone  SMALL CELL LUNG CANCER  SCLC accounts for 15% to 20% of all lung cancers  This cell type has the strongest association with cigarette smoking, and is rarely observed in a never smoker  SMALL CELL LUNG CANCER  Approximately 1/3 of patients have LD at diagnosis  LD-SCLC response rate of 80% to 90% with standard chemotherapy and thoracic radiotherapy, and a complete clinical response of 50% to 60% ARDS  Diagnostic Criteria ARDS ALI Acute Acute PaO2/Fio2