RESPIRATORY DISORDERS: PART ONE

LECTURE 7: Overview UPPER RESPIRATORY TRACT (URT) INFECTIONS: u RHINITIS u INFLUENZA & IMMUNIZATION u COVID-19 (PART 2)

LOWER RESPIRATORY TRACT (LRT) INFECTIONS: u PNEUMONIA u COMMUNITY-ACQUIRED BACTERIAL PNEUMONIA u NOSOCOMIAL PNEUMONIA u PRIMARY ATYPICAL PNEUMONIA u VIRAL PNEUMONIA u PNEUMOCYSTIS CARINII PNEUMONIA (PCP) u PULMONARY EDEMA u TUBERCULOSIS u ATELECTASIS COMMON COLD: INFECTIOUS RHINITIS u Viral infection of the Upper Respiratory Tract (URT) u Most common pathogen is Rhinovirus, however, there are more than 200 possible causative pathogens (adenovirus, parainfluenza, etc.), making it difficult to ever develop immunity against all colds u More frequently acquired in children, than adults COMMON COLD: Transmission - Spread through respiratory droplets which are directly inhaled or by secretions on hands and/or contaminated objects (indirect transmission)

• Virus can survive for hours outside of the body COMMON COLD: Pathophysiology & S/S u Initially: mucous membranes of nose and pharynx are red and swollen with increased secretions  nasal congestion, watery discharge (rhinorrhea, sneezing, watery eyes), mouth breathing, change in tone of voice u Sore throat, headache, low fever may develop u Secretions drip into pharynx  cough & throat irritation, “stuffiness” u If infection spreads  pharyngitis, laryngitis, acute bronchitis u Also more vulnerable to a secondary bacterial infection – eg. strep

COMMON COLD: Treatment Ø Colds are a self-limiting infection! Ø Acetaminophen  fever, headache Ø Decongestants (vasoconstrictors) Ø Antihistamines Ø Humidifiers Ø Vitamin C

Ø Antibiotics do NOT cure viral infections, but are sometimes taken as preventative measure if risk of secondary bacterial infection is high

INFLUENZA (FLU) u Viral infection that affects both the Upper and Lower Respiratory Tracts (URT & LRT) u 3 groups: u Type A – most common u Type B and Type C u These viruses constantly mutate, making long-term immunity difficult u Differs from a cold in the swiftness and aggression of manifestations INFLUENZA (FLU): S/S & Tx - Transmissible 1 day before or 5 days after symptoms appear – very contagious

• Sudden acute onset with fever, notable fatigue, and myalgia with achiness throughout the body

• Can lead to viral pneumonia (most common cause of flu-related deaths)

• Treatment with antiviral drugs: amantadine, zanamivir, or oseltamivir; Tamiflu

INFLUENZA: Immunization - Vaccination recommended annually for all individuals

• Vaccinated against all strains/mutations from the previous season

• Does not protect you against newly mutated strains (from current season)

• Takes 2-3 weeks after vaccination to develop immunity - body susceptible to mild infections during this time

PNEUMONIA u Inflammation of the lung, particularly affecting the alveoli – i.e. Lower Respiratory Tract Infection u Fluid or pus will enter the alveoli rather than air u Associated with fever, chest pain, and consolidation (decreased air space) u Most commonly caused by an infection: u Steptococcus pneumoniae – 50% of cases u Hemophilus influenzae – 20% of cases u Other pathogens: C. pneumoniae, Myocoplasma pneumoniae, staph aureus, Legionella u Susceptibility also highly influenced by changes in pulmonary, immunological, and cardiovascular health -Pneumonia fills the lung alveoli w/ fluid, hindering oxygenation

PNEUMONIA: S/S u Fever u Cough, with or without sputum u SOB u Pleuritic chest pain u Altered mental status – in the elderly u Crackles u Dullness with percussion u Vibration with tactile fremitus u Enhanced voice sounds on auscultation (egophony and whispered pectoriloquoy) – d/t consolidation u Non-specific symptoms PNEUMONIA: Risk Factors Ø Prior viral respiratory infection Ø Alcohol use Ø Institutionalized/hospitalized Ø Tobacco use Ø Congestive heart failure Ø COPD Ø Extremes of age (very old or very young) Ø Immunocompromised/immunosuppressed PNEUMONIA: Classifications Most commonly classified according to where or how it was acquired: • COMMUNITY-ACQUIRED BACTERIAL (TYPICAL) • NOSOCOMIAL • VIRAL • PRIMARY ATYPICAL (“WALKING”) • PNEUMOCYSTIS CARINII (PCP)

1. COMMUNITY-ACQUIRED BACTERIAL PNEUMONIA u Aka Typical Pneumonia or Pneumococcal Pneumonia u Most common in adults u Mostly caused by strep pneumoniae in adults; H.influenzae more common in children u Patient presents with fever, chills, nausea, vomiting u *Productive cough – purulent blood-streaked rusty-coloured sputum u *Pleuritic chest pain, *Leukocytosis (Neutrophilia) u Tachypnea and tachycardia u Consolidated alveoli (on chest x-ray) u Increased tactile fremitus, dullness with percussion, and consolidation heard with auscultation (whispered pectoriloquy)

PLEURITIC CHEST PAIN u PLEURISY = PLEURITIS – inflammation of the lung pleura; most commonly caused by infection (as in pneumonia) u PLEURAL EFFUSION – accumulation of excess fluid between the pleura layers (ie. in the pleural cavity between the visceral and parietal pleura); can impair breathing and limit lung expansion during inspiration u PLEURAL EMPYEMA – accumulation of pus in the pleural cavity; result of infection or pneumonia u PLEURITIC CHEST PAIN – severe, sharp pain with inspiration as a result of pleuritis and pleural effusion; seen in pneumonia

BACTERIAL PNEUMONIA: Pathophysiology u Bacteria will typically enter the lung when airborne droplets are inspired u Can also reach the lung via the bloodstream when there is already an existing infection in another part of the body u Very common for bacteria to live in parts of the upper respiratory tract (i.e. nose, mouth, sinuses) – these can become easily inhaled into the alveoli (lower respiratory tract) u Once inside the alveoli, the bacteria may invade the spaces between the alveoli via connecting pores  invasion  triggers immune response u Get infiltration of neutrophils (white blood cells) in the lungs in attempts to engulf and kill the bacteria u This immune response leads to the s/s of pneumonia – i.e. fever, chills, and fatigue u The neutrophils, bacteria, and fluid from the surrounding blood vessels will fill the alveoli (leading to consolidation) and interrupt the normal transport of oxygen (i.e. poor gas exchange) u BACTERIAL PNEUMONIA: Complications • Since there is a decrease in gas exchange, this will lead to hypoxemia and hypercapnea • Hypercapnea will lead to increased carbonic acid  Respiratory Acidosis • Typically, the body will compensate for acidosis via hyperventilation to expel the excess CO2 • As a result of the present infection consolidating the alveoli, this will often not occur in the case of pneumococcal pneumonia, and the acidosis will remain until there is compensation by the renal system • May require a ventilator for breathing assistance d/t severe dyspnea • May trigger respiratory failure via ARDS response – may also require need for mechanical ventilation • Can lead to sepsis and shock – sepsis more common in bacterial pneumonia – bacteria enter bloodstream and affect the body systemically  systemic immune response  can lead to liver, kidney, and heart damage • May even be fatal 2. NOSOCOMIAL PNEUMONIA u Aka Hospital-acquired pneumonia (HAP) u Refers to any pneumonia (bacterial or viral) contracted by a patient in a hospital at least 48-72 hours after being admitted u More typically caused by a bacteria u Second most common nosocomial infection after UTI; most common in ICU u Also refers to Ventilator-associated pneumonia (VAP) – occurs in people who receive mechanical ventilation while in a hospital d/t pathogen-affected intubation u Typically have purulent sputum and fever (fever lower than in typical pneumonia)

NOSOCOMIAL PNEUMONIA: Pathophysiology • Most nosocomial infections are caused by microaspiration of the upper airway secretions into the lower respiratory tract • Can also occur by macroaspirations of esophageal or gastric material • Risk factors include mechanical ventilation, old age, decreased filtration of inspired air, intrinsic respiratory, neurologic, or other disease states that can result in respiratory tract obstruction, trauma, surgery (especially abdominal – leads to aspiration), certain medications, diminished lung volume, or decreased clearance of secretions (as in COPD) • These will all decrease the defense of the lungs • Poor hand-washing and inadequate disinfection of respiratory devices may also lead to cross-contamination and infection in this setting • More common in the right lung (more vertical bronchus) 3. ATYPICAL PNEUMONIA u Aka. Walking Pneumonia u Pneumonia that is NOT caused by one of the more traditional pathogens u Has a clinical presentation that is inconsistent with typical pneumonia u Can be caused by a variety of microorganisms u When developed independently from another disease, is referred to as “Primary” Atypical Pneumonia (PAP) u Present with more ‘atypical’ or general s/s: fever, headache, myalgia u Most commonly caused by bacteria: mycoplasma pneumonia in children, Legionella in adults  Legionnaire’s disease (high mortality rate) u Viral causes include Respiratory Syncytial virus (RSV), Influenza, Parainfluenza, Adenovirus, SARS, and Measles

ATYPICAL PNEUMONIA: S/S u *Lack of response to common antibiotics (eg. beta-lactams – penicillin, or sulfonamides) u *Absence of leukocytosis u Extrapulmonary s/s u No or little sputum (ie. non-productive) u Lack of alveolar exudate (NO consolidation) u Fever, headache, dry irritating cough, myalgia u *Few physical signs – patient looks better than symptoms indicate u Have constitutional s/s rather than respiratory u No findings of consolidation u Slower course u Maculopapular rash – raised, circular, red u On chest x-ray – *snowstorm appearance all over, rather than a consolidated lobe u Typically, a more mild, spontaneous recovery u 4. VIRAL PNEUMONIA u Pneumonia caused by a virus u Most common cause of pneumonia in children (bacterial more common in adults) u In adults, most common viral agents include Influenza, RSV, and Adenovirus (especially in military) u In children, most causative agents include Human parainfluenza virus, rhinovirus, RSV, and bocavirus u S/S include fever, *non-productive cough, runny nose, and systemic symptoms (myalgia, headache) – recall that viruses cause more diffuse/systemic s/s while bacteria are more locally invasive

VIRAL PNEUMONIA: Pathophysiology u Virus will typically reach the lungs by traveling droplets through the mouth and nose via inspiration u The virus will then invade the cells lining the airways of the respiratory tract and eventually, the alveoli  cell death via viral death or apoptosis u Further damage to the lungs will occur when the immune system responds  LYMPHOCYTOSIS (NOT neutrophilia as in bacterial infections) will occur  causes leaking of fluid into alveoli  disruption of oxygen transport u In addition to the effects on the lungs, many viruses will also affect the other organs of the body, leading to decreased function throughout the body u Can also make the body more susceptible to bacterial pneumonia infections  complicated by both bacterial and viral infections

VIRAL PNEUMONIA: Greatest Risk

• Those most at risk for serious complications arising from viral pneumonia include: • Chronic pulmonary disease patients • Heart disease patients • Pregnancy – 3rd trimester • Elderly and very young • Bed-ridden 5. PNEUMOCYSTIS PNEUMONIA (PCP) u Formerly, Pneumocystis Carinii Pneumonia (PCP) u Pneumonia caused by the yeast-like fungus Pneumocystis jirovecii u This pathogen is commonly found in the lungs of healthy people but is an opportunistic infection – ie. will only invade and become an infection in those with a weakened immune system u Most commonly affiliated with HIV-positive and AIDS patients, along with others who are immunocompromised u Named based on incorrect thought of the causative agent – P. carinii (which is now known to be the causative agent in rats) versus P. jirovecii

PCP u Relatively rare in people with normal immune function u Occurs in severely malnourished children, the elderly, and especially those with HIV/AIDS; also, in those on immunosuppressive medications (post-transplant) u S/S include fever, non-productive cough, SOB (especially on exertion), weight loss, night sweats u The fungus can also invade other visceral organs – liver, spleen and kidney – not that common u Most common complication is pneumothorax – air in the pleural cavity  chest pain with breathlessness and diminished breath sounds

PCP: Pathology Ø Increased risk of invasion when immune cells CD4 are < 200 cell/uL = immunosuppression Ø Affects the lungs interstitially, leading to fibrous tissue and marked thickening of the alveolar septa and alveoli  severe hypoxia Ø Fatal if not treated aggressively Ø One of most common causes of death in AIDS patients PULMONARY EDEMA Ø Fluid accumulation in the alveoli and interstitial area of the lungs (vs. pleural effusion) Ø Decreases oxygen exchange with blood and reduces lung expansion which further decreases oxygenation  hypoxemia Ø Caused by Left CHF, protein loss (hypoalbuminemia) as seen in liver and/or kidney disease, pleuritis, blocked lymphatic drainage from tumours or lung fibrosis, and pulmonary hypertension (often secondary to obstructive sleep apnea)

PULMONARY EDEMA: S/S Ø Cough Ø Orthopnea Ø Rales Ø Hemoptysis Ø Sputum – often blood-tinged Ø Labored breathing Ø Feeling of “drowning” Ø Paroxysmal nocturnal dyspnea TUBERCULOSIS (TB) Ø Tuberculosis is short for Tubercle Bacillus Ø A common chronic recurrent infectious disease caused by different strains of Mycobacterium tuberculosis Ø Typically attacks the lungs, but can also affect other parts of the body Ø Spreads through the air when people who have active TB cough, sneeze, or transmit their saliva through the air Ø Usually asymptomatic and latent (i.e. inactive) – only 10% will progress to active disease – which if left untreated, will kill 50% of those infected Ø Diagnosis by chest x-ray and tuberculin skin test Ø Bacillus-Calmette-Gerin (BCG) vaccination available Ø Common s/s include chronic cough with blood-tinged sputum, fever, night sweats and weight loss Ø Affects one third of the world’s population – mostly in developing countries – 80% in Asia and Africa

TUBERCULOSIS: Cause • Main cause is Mycobacterium tuberculosis – a small, aerobic, non-motile bacillus (sausage-shaped microbe) • Also includes other mycobacterium: M.bovis (spread by cows, but eliminated with pasteurization of milk), M.africanum (limited to Africa), M.canetti (rare), and M.microti (common in immunodeficient) • Other agents recognized include M.avium and M.leprae – these are non-tuberous mycobacterium and only cause pulmonary disease resembling TB, rather than TB itself • Relatively slow dividing pathogen – every 20 hours, compared to other gram-positive bacteria • Can withstand weak disinfectants and survive a dry environment for weeks d/t its cell wall • An acid-fast bacillus (retains certain stains)Ø TB: Transmission Ø Transmission occurs when people with active TB cough, sneeze, speak, sing or spit, expelling infectious aerosal droplets into the environment Ø A single sneeze can release up to 40,000 droplets Ø Inhaling fewer than 10 droplets can lead to infection Ø Those with prolonged or frequent contact are most at risk Ø On average, a person with active but untreated TB will infect another 10-15 people per year Ø Those at risk include drug users, residents or employees of infected persons, children, healthcare workers, and immunocompromised Ø Transmission can ONLY occur from an active form (NOT latent) of TB Ø An active TB patient will only stop being contagious after two weeks of confined anti-tuberculous therapy Ø If you become infected, it will take 3-4 weeks before the person becomes contagious (ie. Latency period is 3-4 weeks!!) Ø TB: Pathophysiology Ø 90% of those infected are asymptomatic with a latent infection (LTBI) Ø Infection begins when the mycobacteria reach the alveoli where they replicate Ø Site of infection referred to as the Ghon complex – as seen on x-ray Ø Typically located in upper portion of lower lobe, or lower portion of upper lobe Ø Bacteria get picked up by dendritic cells which transport the bacilli to local lymph nodes in the mediastinum Ø At this point, further spread occurs via the bloodstream to other tissues and occurs = SECONDARY TB – causes lesions in other parts of the lungs (especially apex of upper lobes), peripheral lymph nodes, kidneys, brain, and bones – rarely affects the heart or muscles Ø Considered granulomatous – forms granulomas in lungs via aggregation of macrophages, lymphocytes and fibroblasts – when bacteria get caught in granuloma, they become latent or dormant Ø Granulomas will also cause necrosis in the center of tubercles known as caseous necrosis because of its appearance to soft-white cheese which fills the cavities Ø If TB bacteria do gain entry into the bloodstream from an area of damaged tissue, they will spread through the body and set up multiple foci of infection – appear as tiny white tubercles in the tissue – most common in infants and elderly – referred to as MILIARY TB – almost 100% fatal if untreated Ø Often have a mix of destruction and necrosis with healing and fibrosis Ø If left untreated, can also lead to lobar pneumonia Ø Ø Ø TUBERCULOSIS: S/S When active: PULMONARY TB: u Chest pain (Pleurisy) u Hemoptysis u Productive, prolonged cough for more than 3 weeks u Fever, chills u Night sweats u Decreased appetite, weight loss u Pallor, fatigue EXTRAPULMONARY TB (more common in immunocompromised and kids): u Meningitis u Lymphadenopathy u Urogenital TB u Pott’s Disease – in bones and joints of the spineØ TUBERCULOSIS: Risk Factors Ø Silicosis – 30 times greater risk for developing TB – silica in paint, concrete, cement, etc. Ø Chronic renal failure, Hemodialysis – 3-fold increase Ø Diabetes Mellitus – 2-4 times greater risk Ø Gastrectomy Ø Neoplasm Ø Renal or cardiac transplantation Ø Low body weight (BMI < 18.5) – 3-fold increase; an increase in body weight decreases the risk Ø IV drug users Ø Recent infection or history of TB Ø Prolonged corticosteroid therapy Ø Immunocompromised Ø Intestinal bypass or other malabsorption problems Ø Some drugs – those for RAØ TB: Antibiotics Ø Treatment for TB includes antibiotics to kill the mycobacteria Ø Unfortunately, effective treatment is difficult d/t the unusual structure and composition of the cell wall – makes many antibiotics ineffective Ø Most commonly used drugs include isoniazid and rifampicin Ø Requires much longer periods of treatment (around 6 to 24 months) compared to other bacteria Ø Latent TB usually attacked with a single antibiotic, whereas active TB is best treated with combination of several antibiotics to decrease risk of antibiotic resistance Ø High drug-resistance in TBØ ATELECTASIS Ø Incomplete expansion of the lungs (neonatal) or the collapse of a previously inflated lung Ø May affect all of one lung or part of the lung Ø Alveoli become deflated – very distinct from pulmonary consolidation (eg. pneumonia, neoplasm) Ø May be caused by normal exhalation or by a medical condition Ø Not to be confused with a pneumothorax (air escaping the lungs into the pleural cavity) which can lead to atelectasis Ø May occur as a post-operative complication, or as a result of surfactant deficiency in premature neonates  Infant Respiratory Distress Syndrome Ø ACUTE ATELECTASIS Ø Common, post-operative complication – especially after chest or abdominal surgery Ø Can also occur with injury to chest (MVA, fall, stabbing) Ø Degree of alveolar collapse tends to be quite consistent and complete Ø Increased risk with large dose opioids or sedatives, tight bandages, chest or abdominal pain, abdominal swelling, or immobility following injury or surgery Ø If d/t poor surfactant – will not cause collapse of all alveoli, non-uniform collapse Ø Can also arise in adults from excessive oxygen therapy or mechanical ventilation Ø ACUTE ATELECTASIS Resorption Atelectasis u Result of complete obstruction by mucous (plugs) – eg. bronchial neoplasm u Something is blocking the air from getting to the distal part of the airway, so the air that is already in the distal airway will eventually be absorbed and the local alveoli will collapse 2. Compression Atelectasis u Result of pleural cavity being filled by fluid, tumour, blood, or air (as in a tension pneumothorax) u Something is compressing the lung (fluid, air, blood) in the pleural cavity so there is no space for the lung to expand  alveoli collapse 3. Contraction Atelectasis u Result of fibrosis preventing full expansion u Something occurs that causes the lung to contract (occurs with fibrotic changes)  decreased ability to expand lung, so as you exhale, the lung’s recoiling system becomes enhanced during expiration = decreased ventilation u Only form of atelectasis that is usually irreversible ATELECTASIS: Risk Factors Ø Most common cause: post-surgical atelectasis  restricted breathing after abdominal surgery Ø Smokers and elderly at increased risk Ø Carcinoma of the lung, infection (obstruction or compression atelectasis) Ø Poor surfactant spreading during inspiration (preterm neonates)  high surface tension  collapse of smaller alveoli Ø Suction – air is withdrawn from lungs along with the sputum Ø Pulmonary embolism (airway obstruction) CHRONIC ATELECTASIS Ø Right Middle Lobe Syndrome Ø Aka Andy Wilson’s Disease Ø Middle lobe of right lung contracts because of pressure on bronchus from enlarged lymph glands or tumour  develop pneumonia  chronic inflammation, scarring, bronchiectasis (dilated bronchus) Ø 2. Rounded Atelectasis Ø Aka Folded Lung Syndrome Ø Outer portion of lung slowly collapses d/t scarring and shrinkage of pleura  rounded appearance on x-ray; usually a result of Asbestosis Ø u 1. ATELECTASIS: S/S Ø Cough (not prominent) Ø Chest pain Ø Dyspnea Ø Low SaO2 Ø Pleural effusion Ø Cyanosis (late sign) Ø Tachycardia Ø Does NOT typically cause fever (as often believed) Ø