Week 6 PDF

WEEK SIX: ALTERATIONS OF PULMONARY FUNCTIONS (2 HR) OBJECTIVES 1. Alterations of pulmonary function 2. Pharmacotherapy for COVID- 19 - Monoclonal antibodies: Tocilizumab - Antivirals: nirmatrelvir/ritonavir - Systemic glucocorticoids: dexamethasone - Anticoagulants: hep...

WEEK SIX: ALTERATIONS OF PULMONARY FUNCTIONS (2 HR) OBJECTIVES 1. Alterations of pulmonary function 2. Pharmacotherapy for COVID- 19 - Monoclonal antibodies: Tocilizumab - Antivirals: nirmatrelvir/ritonavir - Systemic glucocorticoids: dexamethasone - Anticoagulants: heparin - Antidote for heparin therapy: protamine sulfate 3. Pharmacotherapy for bacterial pneumonia - Macrolides: azithromycin - Penicillin: amoxicillin List and explain factors that influence the capacity of a microorganism to cause disease (pathogenicity). COVID-19 ○ Explain the etiology, pathophysiology, and manifestations of COVID-19. ○ Discuss the screening and diagnostic tests used to identify cases of COVID-19. ○ Explain the complications associated with COVID-19, focusing on acute respiratory distress syndrome (ARDS) and post-acute COVID-19 syndrome. Acute respiratory distress syndrome (ARDS) ○ Describe the pathophysiology of ARDS, including its clinical course and alterations in blood gases. ○ Discuss pediatric ARDS, highlighting any specific differences in pathophysiology, manifestations and management. Pneumonia across lifespans ○ Explain the etiology, pathophysiology, manifestations, diagnostic tests, and management of pneumonia. ○ Discuss differences and specific concerns in managing pneumonia in adults versus children. Specific pediatric respiratory disorders ○ Describe croup in children and explain its clinical manifestations. ○ Identify the most common etiologic agent of bronchiolitis and describe its pathophysiology and clinical course in children. ○ Articulate and plan for the interprofessional care required for clients these conditions. Pharmacotherapy of pulmonary disorders: ○ Identify the classifications of drugs used in treating pulmonary disorders.  ○ Discuss the indications, mechanisms of action, desired therapeutic outcomes, and potential adverse effects of drugs used for pulmonary disorder ​Microorganisms and Humans: A Dynamic Relationship​ Infectious disease: a significant cause of death and morbidity because of the following: ○ Reemergence of old infections thought to be controlled ○ Emergence of previously unknown infections ○ Development of infections resistant to multiple antibiotics Capacity to cause disease Communicability​: Ability to spread from person to person​ Immunogenicity​: Ability to produce an immune response​ Infectivity​: Ability to invade and multiply in the host​ Mechanism of action​: How microorganism damages tissue​ Pathogenicity​: Ability to produce disease​ Portal of entry​: Route microorganism takes​ Toxigenicity​: Production of toxins​ Virulence​: Capacity to cause severe disease​, potent ID50​: Estimated number of organisms or virus particles required to produce infection in 50% of a population​ How infectious Diseases can be classified Endemic: Diseases with relatively high, but constant, rates of infection in a population Epidemic: Number of new infections in a population that greatly exceeds the number usually observed (New infections, numbers exceeds the number normally observed) Pandemic: An epidemic that spreads over a large area such as a continent or worldwide (spreads over a large area such as continent or worldwide) Note: → Endemic: Diseases with high constant rates of infection →Epidemic: New infections, numbers exceeds the number normally observed →Pandemic: Spreads over a large area such as continent or worldwide SARS-COV-2 (COVID-19): Severe Acute Respiratory Syndrome- Coronavirus-2 COVID-19 Outbreak of pneumonia in Wuhan, China in December 2019​ Led to identification of severe acute respiratory syndrome coronavirus -2 (SARS-CoV-2)​ Virus has distinctive spikes on its surface making it look like a solar corona​ Thus, its name, coronavirus​ Virus origin. in bats → transferred to humans through exposure from unidentified animal vector​  Genomic studies have identified related coronaviruses in bats in China, Cambodia, Thailand, and Laos​ Global pandemic called coronavirus disease-2019 (COVID-19) ensued​ Human-to-human transmission resulted in hundreds of millions of cases worldwide and millions of deaths​ Structure of SARS-CoV-2​(Don't memorize structure of covid​ Just understand spike protein makes the virus invasive, and escaping immunity ​ Viral Mutations of SARS-CoV-2​ Viral mutations of SARS-COV-2 have led to emergence of variants​ Have increased infectivity!​ Variants include:​ B.1.1.7 (alpha) variant emerged in United Kingdom​ B.1.1.351 (beta) variant emerged in South Africa​ B.1.1.33 (P.1) variant emerged in Brazil​ In 2021, two new variants emerged​B.1.617.2 (delta) & B.1.1.529 (omicron) - B.1.617.2 (delta) variant and the B.1.1.529 (omicron) variant​ ○ Increased infectivity compared to previous forms of virus and have been cause of surges in new infections worldwide​ ○ More new variants are emerging!​ Stages of Viral Infection of Host Cell​ Steps in viral life cycle of SARS-CoV-2 are same as for many other viruses​ (1) Virus recognize and attach to host receptor or cell wall molecule​ (2) Virus penetration into host cell by fusion or endocytosis​ (3) Uncoating of viral genome within cell cytoplasm​ (4) Replication of viral genome using host or viral transcriptases and polymerases​  (5) Translation with viral structural protein synthesis in host cell endoplasmic reticulum and Golgi apparatus​ (6) Assembly of virus​ (7) Release of virus by budding or exocytosis, or by lysis of host cell​ Transmission of COVID-19​ ➔ Covid-19 levels are highest in sputum, pharyngeal swabs, feces​ ➔ Transmitted via droplets released during cough, sneezing, talking***​Ontario health update: Covid-19 transmitted via aerosol ➔ Infected person transmitting virus that remains completely asymptomatic is rare ◆ But, pre-symptomatic transmission is a major contributor to spread of virus​ ➔ 3 to 7 days between infection & symptoms → shedding of virus can be high from respiratory tract​ ◆ But infected individuals do not realize they are ill​ ➔ Viral shedding peaks during early symptomatic illness (3-5 days after symptom onset) ​ ➔ Viral shedding then declines approx. 5 to 7 days after onset of symptoms​ ◆ No longer readily transmissible ​ ➔ Risk of transmission is greatest in indoor environments with poor ventilation and close contact (less than 6 ft) with infected individuals​ ➔ Transmission of virus from surfaces to hands and then to mouth, nose, or eyes is inefficient​ ◆ Risk of developing infection from contacting infected surfaces (fomites) is less than 1 in 10,000 exposures​ COVID-19: Pathophysiology​ Virus evades early innate responses, especially interferons​. ○ Unopposed viral replication and slows initiation of adaptive immune response​ As disease progresses → neutrophil and natural killer cell dysfunction develops​ ○ Also effective in killing T cells (found in bone marrow, important type of white blood cells of immune system, plays a central role in the adaptive immune response) resulting in a profound lymphopenia​(low white blood cells) Once infection established, powerful inflammatory response is initiated, sometimes progressing to a “cytokine storm”​ ○ Numerous interleukins (Il-1, IL-6, IL-8, IL-17), TNFα, and other inflammatory cytokines are produced at high levels​ ○ Hyperinflammatory response causes increased permeability of vascular and epithelial membranes, edema, and tissue necrosis, especially in lung tissue​ Hyperinflammatory response causes endothelial injury, microangiopathic changes, and platelet activation​  ○ Hypercoagulable state like disseminated intravascular coagulation (DIC) characterized by clotting but without bleeding​ Severe inflammation of lung tissue results in acute respiratory distress syndrome (ARDS)​ Inflammatory and immune changes in myocardium​ ○ Contributes to cardiomyocyte death​ Neuroinflammation is common​ ○ Damage to brain parenchyma and cerebral vasculature​ AKI may occur, especially in critically ill clients​ ○ Nephropathy characterized by ATN, followed by glomerulosclerosis in some clients​ - Covid-19 Pathophysiology: Covid-19 virus evades innate response and interferons→ development of neutrophil and T cell dysfunction → kills T cells → lymphopenia → established infection → powerful inflammatory response initiated → cytokine storm (increase production of interleukins & inflammatory cytokine) → hyperinflammatory → endothelial injury → microangiopathy → platelet activation (hypercoagulable state)→ severe lung inflammation (ARDS) → inflammatory and immune changes in myocardium (myocardium cell death) → can lead to neuroinflammation → AKI may also occur → characterized by Acute tubular necrosis (ATN) followed by glomerular necrosis Host response primarily determines the progression and severity of COVID-19 rather than the virulence of the virus (Host response over virulence of the virus) Clinical Manifestations of COVID-19​ Average intubation period: Approx. 6 days from exposure to symptoms onset  25% of all cases remain asymptomatic Most infected ind. Only have mild symptoms but older adults and those with underlying medical conditions i.e CV disease, diabetes, cancer at risk for severe disease and death Many of the organ systems are affected Common symptoms of COVID-19: ○ fever ○ Cough ○ Shortness of breath ○ Myalgia ○ Fatigue ○ Loss o f smell and taste - Additional symptoms result from/caused by: neurologic, cardia, endocrine, hepatic and renal injury COVID-19 Complications ○ Thrombotic issue linked to increase risk for stroke and venous thromboembolism ○ Respiratory failure and septic shock are primary causes of mortality ○ Most recover within 3 to 4 weeks after infection ○ Nearly ⅓ of affected persons have persistent symptoms→ last  for weeks → months ○ Prolonged syndrome are called: post-acute COVID -19 or long Covid-19 Clinical Manifestations of Acute ​COVID-19​ - Evidence: cells contain one or both of the receptors that SARS-COV-2 uses to enter cells - Studies identified viral RNA, suggesting virus is present - Cell-culture work shows that SARS-cov-2 can infect cells isolated from tissue organs SARS-COV-2 wide ranging effects on the body: - Brain and olfactory neurons: Stroke, encephalitis, loss of smell and taste, confusion, memory loss, brain fog, anxiety, and depression - Eyes: photophobia and eye irritation - Ears: hearing loss and vertigo - Heart: heart failure, palpitations, chest pain, shortness of breath - Liver: Elevated liver enzymes - Pancreas: Abdominal pain, hyperglycemia - Kidney: acute renal failure - Gastrointestinal: Nausea, anorexia, diarrhea, abdominal pain - Vasculature: Thrombosis with ischemic symptoms in multiple organs SARS-Cov 2 receptor binds with ACE2 - Receptor-binding portion of spike protein binds w/ high affinity to ACE2 receptor on cells - ACE2 receptor is highly expressed in: Lung, Brain, Fat - ACE receptor is exp. lesser extent: Heart, Kidney, Pancreas,Intestine Emerging Science COVID-19 infection in children - Most have no or mild symp. during acute SARS-COVID 2-infection - Significant number develop serious illness that occurs days to few weeks after initial infection; → Multisystem inflammatory syndrome in children (MIS-C) - SARS-COV-2 serves as a superantigen causing → overwhelming immune response  - Hyperinflammation results → Neurological, Cardiac, pulmonary, GI, renal injury & thrombotic complications & shock - Approx. 60% require intensive care​, 15% require mechanical ventilation ​ EMERGING SCIENCE: POST-ACUTE COVID-19 (LONG COVID; LONGHAULERS) - POST-ACUTE COVID-19 is the continuation of covid-19 symptoms or complications after 3-4 weeks post acute infection - Approx. 1/2 of infected with SARS-CoV-2 develop some post-acute symptoms within 12 months after acute infection​ - POST-ACUTE COVID-19 can occur after hospital discharge and in those who suffered only mild-moderate acute illness​ - POST-ACUTE COVID-19 → continued viral toxicity, microvascular injury, immune system dysregulation, and persistent hyperinflammatory state​ - Underlying comorbidities, recurrent infections also play role​ - Common persistent symptoms: Fatigue and dyspnea (reduction in diffusion capacity in lung): - Occurs in 50%–75% of ind. at 2–3 months​ - Persists 6 months after acute illness in approximately 25% of individuals ​ - Neurologic disorders constitute second most common sequelae​→ Persistent neuroinflammation associated with cognitive and behavioral changes, decreased memory and ability to concentrate​ - Common disturbances: Muscular weakness, joint pain, anxiety, hair loss, and sleep - Risk of thromboembolic events increased​ - Overall QOL significantly reduced​ - Worsening abnormalities in physical, cognitive and psychiatric health after critical illness compound symptoms ​ - Individuals with acute COVID-19 should be screened​→ Respiratory, psychiatric and thromboembolic sequelae → screened at 4–6 weeks, again at 12 weeks after discharge​ TESTING FOR COVID-19 - Reason for testing: those with symptoms, known exposures, or who are required to be tested for com. Or employment purpose - Two types of viral tests are used - Polymerase chain reaction (PCR) - Rapid antigen tests - Laboratory findings include: - Decreased lymphocytes in blood - Elevated levels of inflammatory cytokine and D-dimer - Bilateral lung infiltrates on CT Immunization Against COVID-19​  ➔ Several vaccines developed globally to prevent SARS-CoV-2 infection​ ➔ Two use mRNA carrying spike protein sequence​ ◆ mRNA vaccines: Moderna, Pfizer/BioNTech​ mRNA vaccines → use host cells’ own translation machinery → to make harmless pieces of viral spike proteins that → elicit immune response to virus​ ➔ Other vaccines use conventional viral vector technologies​ ◆ Viral vector vaccines: AstraZeneca, Janssen (Johnson & Johnson)​ Viral vector vaccines → use modified version of one virus as a vector → to deliver genetic material coding into hosts’ cells → to elicit immune response to virus​ ➔ Unknown whether prolonged immunity to virus can be achieved​ ◆ Booster immunizations recommended​ Note: Effectiveness of all vaccines will need to be retested as new variants emerge!​ PHARMACOTHERAPY FOR COVID-19​ - note: Info in this section pertain to drugs approved in Canada and is not reflective of our textbooks.​ - List of drugs is growing as new discoveries are made!!!​ Drugs can prevent and treat covid-19 Prophylaxis Treat mild to moderate covid-19 (no hospitalization) Treat severe acute COVID-19 What are Monoclonal Antibodies (MAB)?​ In 1980s, Monoclonal antibody (mab)​technique was developed → to harvest antibodies produced by a single B cell​ ○ This is called Monoclonal antibody (mab)​because a single B cell produces a single antibody ○ The MABs have similar names that end in -mab ​ A Monoclonal antibody (mab) is very specific → targets a single type of target cell or receptor​ ○ This allows greater effects on the target cell or receptor at lower doses and with fewer adverse effects than using polyclonal antibodies (mixture of different antibodies)​ Scientists have created approximately 30 different MABs to attack a diverse number of targets​ Monoclonal Antibodies: Tixagevimab and Cilgavimab​  Evusheld (a combination of tixagevimab and cilgavimab) is administered as two separate 3.0 mL, sequential, IM injections of tixagevimab and cilgavimab ​ Indications for prophylaxis: ○ Pre-exposure prevention of COVID-19 in adults and children (12 years of age and older, weighing at least 40 kg) who are not currently infected with COVID-19 and have not had recent known contact with someone infected with COVID-19​ ○ Who are immune compromised and unlikely to mount an adequate immune response to COVID‐19 vaccination; or,​ ○ for whom COVID-19 vaccination is not recommended​ Indications for treatment: Given as soon as possible after a positive viral test for SARS-CoV-2 & within 7 days after onset of symptoms ​→ give Evusheld (a combination of tixagevimab and cilgavimab) as soon as possible MOA: Tixagevimab & cilgavimab attach to the receptor-binding portion of the SARS-CoV-2 spike protein → Their combination blocks virus’ interaction with human ACE2 receptor required for viral fusion with the host cell​ Desired effects: Prevention of COVID-19​ Adverse effects: Hypersensitivity, anaphylaxis, injection site reaction​ NOTE: Ontario Health no longer recommends routine use of Evusheld (Tixagevimab and Cilgavimab) for pre-exposure prophylaxis for any patient group, including immunocompromised patients.​ SARS-CoV-2 and receptors​  - DON'T HAVE TO MEMORIZE Antivirals: Nirmatrelvir/Ritonavir​​(DON’T MEMORIZE CRITERIA) Paxlovid contains nirmatrelvir tablets co-packaged with ritonavir tablets ​ ○ Recommended Nirmatrelvir dosage and Ritonavir → 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) with all three tablets taken together orally twice daily for 5 days ​ Antivirals: Nirmatrelvir/Ritonavir - Strongly considered. for individ. with confirmed COVID-19 diagnosis, present within 5 days of symptom onset, and meet one or more of the following criteria:​ ○ 60 years of age or older​ ○ 18 years of age or older and is immunocompromised ​ ○ 18–59 years with one or more comorbidity that puts - Those with inadequate immunity:​ - Unvaccinated or incomplete primary series OR​ - Completed primary series AND last COVID-19 vaccine dose was more than 6 months ago AND last SARS-CoV-2 infection was more than 6 months ago​ - Drugs Can Prevent and Treat COVID-19 ​ - Higher risk of severe COVID-19 include: - 18–59 years with one or more comorbidity that puts - Indications for use:​ - Treat mild to moderate COVID-19 in clients who have​a positive result from a viral test and​a high risk of getting severe COVID-19, including hospitalization or death​ - MOA: - Co-packaged drugs have very different MOAs!​ - Nirmatrelvir inhibits SARS-CoV-2’s main protease/enzyme​ - When this protease/enzyme is inhibited, it cannot process polyprotein precursors​, → Blocks part of virus’ life cycle and prevents viral replication​  - Ritonavir acts as a pharmacokinetic enhancer​ →Inhibits cytochrome P450-mediated metabolism of nirmatrelvir​→Increases plasma concentrations of nirmatrelvir! ​ - Desired effects​ - Stops virus from multiplying​ - Reduces severe outcomes​ - Adverse effects​ - Common: hypertension, severe allergic reaction​ - Rare: Stevens-Johnson syndrome, toxic epidermal necrolysis, liver problems​ → Stevens-Johnson Syndrome & Toxic Epidermal Necrosis (SJS/TEN) are very serious skin peeling conditions, caused by allergic reaction to medications or an illness. Hospitalized treatment includes stopping the problem medication, replacing electrolytes, applying skin dressings, and providing pain medications and antibiotics. Systemic glucocorticoids​ Wide therapeutic application​ Short-term use due to potential serious adverse effects​ Suppress inflammatory response such as histamine release and→ inhibit the synthesis of prostaglandins by COX-2; → → inhibit the immune system by suppressing certain functions of phagocytes and lymphocytes reduce inflammation (tested)​ Adverse effects​ ○ Don’t STOP abruptly ○ Suppression of normal functions of adrenal gland (adrenal insufficiency), hyperglycemia, peptic ulcers (don't take drug in empty stomach), electrolyte imbalances (check urine); mask infections​(because with infection, person can have inflammation) Systemic Glucocorticoid: Dexamethasone​(TESTED) Indications for use: For clients needing supplemental O2 for severe acute COVID-19​→ Other indications: inflammation, allergies, cerebral edema, septic shock​ MOA: Suppresses migration of polymorphonuclear leukocytes, fibroblasts, and normal immune response​ Desired effects: Decreases inflammation, reverses increased capillary permeability, causes lysosomal stabilization​ Adverse effects: Hypertension, seizures, hyperglycemia​ Anticoagulants: Heparin ​→ works on thrombin, does not thin blood but just prevent blood getting bigger - Indications for use: Prevention dose anticoagulation for severe acute COVID-19 - Moa: biding of heparin to antithrombin III inactivates several clotting factors and inhibits thrombin act. - Desired effects: reduces chance client will develop blood clots - Adverse effects: - Severe bleeding & serious hemorrhaging​ - Heparin-induced thrombocytopenia​ - Caused by abnormal antibodies that activate platelets, causing clots to form and depleting platelet counts in blood​ Antidote For Heparin Therapy: Protamine​(not helpful if pt. Is bleeding and not on heparin) - Protamine reverses anticoagulant activity of heparin - Indications - If serious hemorrhage occurs - Onset action → 5 minutes - MOA: binds to heparin to form stable ion pair that does not have anticoagulant activity - Desired effects: neutralizes anticoagulant activity of heparin, makes heparin ineffective - Adverse effects: severe respiratory distress, anaphylaxis, pulmonary edema Acute Respiratory Distress Syndrome (ARDS)  - Form of acute lung inflammation & diffuse alveolocapillary capillary injury ​(prof) - Results from direct pulmonary injury or from severe systemic inflammation​ - Acute onset of bilateral infiltrates on chest x-ray (i.e., pulmonary edema) and persistent hypoxemia despite supplemental oxygen​(prof: ARDS characteristics) - 10% of ICU clients and 23% of all clients requiring mechanical ventilation have ARDS​ - Despite advances in diagnosis and therapy, mortality remains at approximately 30% to 40% - Emergence of COVID-19 → dramatic increase in number of ARDS cases worldwide​ Stages: (TESTED) - Exudative - Proliferative - fibrotic even if you're body is recuperating, there will still be lw oxygen level in the blood “Pediatric Acute Respiratory Distress Syndrome (PARDS)” in Children​ - COVID-19 and pneumonia cause direct lung injury​ - Inflammatory response​→ causes alveolocapillary injury followed by leakage of fluid into alveoli, coagulation, surfactant degradation, and fibrosis​ - Pulmonary edema, acute onset and severe hypoxemia, pulmonary infiltrates, decreased pulmonary compliance, progressive respiratory distress ​ - Most children require mechanical ventilation​  - Life-threatening​→ Mortality is high, approx. 24%​ Emerging Science: Pathogenesis of ARDS in COVID-19 Infection Begins when SARS-COV-2 binds its viral S spike protein with ACE-2 receptors on host respiratory epithelial cells, followed by: a. Virus first enters and replicates in epithelial cells of upper respiratory tract b. Virus then enters ciliated lower airway epithelial cells and alveolar ​→ Both express ACE-2 receptors Stages a. Inflammatory response follows → infiltration of macrophages, neutrophils, release of cytokines, and activation of complement and clotting systems “cytokine storms” → (a) results in diffuse alveolar and microvascular damage and thrombosis (b) fluid leaks into pulmonary interstitium resulting in V/Q mismatch and hypoxia b. As disease progresses, interstitial fibrosis and formation of hyaline membrane develops c. Pathologic changes causes hypoxic pulmonary vasoconstriction, right-to left shunting , and decreased pulmonary compliance → Pathologic changes causes hypoxic pulmonary vasoconstriction, right-to-left shunting, and decreased pulmonary compliance → severe dyspnea due to increased work of breathing. Require mechanical ventilation with high levels o positive end-expiratory pressure (PEEP) ARDS Pathophysiology: All of this Happens in Stages!​ Stages of ARDS ​(TESTED: ALSO KNOW THE TIME FRAME FOR EACH) - Characterized by acute lung inflammation and diffuse alveolocapillary injury​ a. Exudative (inflammatory)​ b. Proliferative​ c. Fibrotic​ a. Exudative Stage (Inflammatory)​ - Within 72 hours​(3-4) - Alveolocapillary membrane damage​ - Increased capillary membrane permeability​ - Pulmonary edema​ - Surfactant inactivated​ b. Proliferative Stage​ - 4–14 days​ - Resolution of pulmonary edema​ - Proliferation of type II pneumocytes, fibroblasts, and myofibroblasts begins​ - Intra-alveolar exudate becomes cellular granulation tissue​  - Appears as hyaline membranes (ARDS) that form diffusion barrier for oxygen exchange ​→ Decreased diffusion of O2 from alveoli into blood​→ Results in continued hypoxemia - Proliferative stage: (pus is gone but hyaline appears, which makes diffusion difficult, low oxygen level) Fibrotic Stage (scar tissues) - 14-21 days - Remodeling and fibrosis of lung tissue - Fibrosis obliterates alveoli, respiratory bronchioles, interstitium - Long-term respiratory compromise - Severe right to left shunting - Acute respiratory failure Clinical Manifestations of ARDS (know accumulation of co2, acidosis, poor O2) - Inadequate Gas exchange - Dyspnea and hypoxemia (tachypnea, tachycardia)​→ Poor response to O2 supplementation​ - Initial hyperventilation and respiratory alkalosis​ - Decreased tissue perfusion, metabolic acidosis, and organ dysfunction​ - Increased work of breathing, decreased tidal volume, and hypoventilation​ - Hypercapnia (PaCO2 is ≥50 mmHg), respiratory acidosis, and worsening hypoxemia​ - pH is ≤7.25​ - PaO2 is ≤50 mmHg​ - Respiratory failure, decreased cardiac output, hypotension, multiple organ dysfunction syndrome (MODS), death​ How Do We Diagnose ARDS?​ - ARDS Dx. based on: ​History of lung injury, physical examination, blood gas analysis, chest x-rays​​ - Three major criteria for diagnosis of ARDS​(NOt tested) (1) Onset within 1 week of known clinical insult or new or worsening respiratory symptoms; ​ (2) Bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules on chest x-ray or CT; and ​ (3) Respiratory failure not fully explained by cardiac failure or fluid to exclude hydrostatic edema if no ARDS risk factor is present​ - Measurement of serum biomarkers (i.e., surfactant proteins, B-type natriuretic peptide [BNP], C-reactive protein [CRP], and interleukins) aid in diagnosis and prognosis of ARDS ​ - Tested: Blood work Management of ARDS (Know some of these but not all) - Mechanical ventilation with PEEP and high oxygen concentrations - Prophylactic immunotherapy - Antibodies against endotoxins - Antioxidants - Surfactant replacement - Nitric oxide inhalation - Inhibition of various inflammatory mediators - Gene therapy - Stem cells Alterations of Pulmonary Function in Children Viral Croup (tested: age range and causes) - Most commonly caused by parainfluenza - Acute laryngotracheobronchitis - Almost always occurs in children between 6 months-3 yrs old (peak incidence at 2 yrs old) - Higher incidence during winter months - SARS-CoV-2 infection has been diagnosed in several children with croup  - Other causes include: - Respiratory syncytial virus (RSV), rhinovirus, adenovirus, rubella virus, or atypical bacteria Viral Croup Pathophysiology​TESTED Result of subglottic (area containing vocal cords) inflammation & edema from infection​ Mucous membranes of larynx tightly adhere to underlying cartilage, but those of subglottic space are looser and allow accumulation of mucosal and submucosal edema​ Cricoid cartilage is structurally narrowest point of airway, making edema in this area critical to development of airway obstruction​ Increased resistance to airflow leads to increased work of breathing​ Generates more negative intrathoracic pressure that may exacerbate dynamic collapse of upper airway​ Upper Airway Obstruction With Croup​ Inflammation and edema → upper airway obstruction → increased resistance to airflow → increased intrathoracic negative pressure → collapse of upper airway → respiratory failure Manifestations of Viral Croup​(TESTED) Child experiences: - rhinorrhea, sore throat, low-grade fever for - few days​ → Then develops harsh (seal-like), barking cough, hoarse voice, and inspiratory stridor​ - Quality of voice, cough, and stridor may suggest location of obstruction​ - Most cases resolve spontaneously within 24 to 48 hours​ - Young child with severe croup usually displays deep retractions, agitation, tachycardia, and sometimes pallor or cyanosis​ Evaluation and Treatment of Viral Croup​ - Westley Croup Score - Estimates severity - Tx: - Most cases: - No Tx - Glucocorticoids, either injected or oral (dexamethasone) or nebulized (budesonide) - Severe cases - Nebulized epinephrine - Oxygen Use Your Clinical Judgment!​ A child has laryngotracheobronchitis (croup). Which information should the nurse remember when planning care for this child? ​Laryngotracheobronchitis:​ a. is caused by subglottic edema from infection​ b. usually occurs in children from 2 to 5 months ​ c. produces supraglottic edema and airway obstruction ​ d. requires antibiotic therapy​(does not req. Because its viral, should be glucocorticoid steroids) Most common cause of hypoxemia a. reduced diffusion distance ​ b. hyperventilation with hypocapnia ​ c. ventilation-perfusion mismatch​ d. traveling to a low altitude ​ Bronchiolitis​(tested: what causes it, its consequences) Bronchiolitis (Bronchiolitis​(tested: what causes it, its consequences) - Leading cause of hospitalization for infants during winter season​ - Linked to increase in asthma later in childhood​ - Common viral-induced, lower respiratory tract infection of small airways​; Respiratory syncytial virus (RSV) is most common cause​; Occurs almost exclusively in children younger than 2 years​ - Causes edema, atelectasis, ventilation-perfusion mismatch, hypoxemia, obstructed airway​ - Healthy infants usually make a full recovery from RSV bronchiolitis​ - Infants who were premature (birth weight less than 2500 g) or who have underlying chronic lung disease of prematurity, heart disease, or immune deficiency​ - Have higher risk for more severe or even deadly course!​ Bronchiolitis Pathophysiology​(how is this different from croup) - Viral infection causes necrosis of bronchial epithelium and destruction of ciliated epithelial cells​ - Infiltration of lymphocytes around bronchioles and a cell-mediated hypersensitivity to viral antigens with release of lymphokines​→ Causes inflammation and activation of eosinophils, neutrophils, monocytes​ - Edema of bronchial wall, bronchospasm narrow many peripheral airways​ - Cellular debris, mucus, fibrin form plugs in bronchioles​ - Airways become partially or completely occluded​ - Atelectasis occurs in some areas of lung and hyperinflation in others​ - Mechanics of breathing disrupted by bronchiolitis​ - Airway narrowing causes obstruction of airflow that is worse on expiration​ - Leads to air trapping, hyperinflation, and increased functional residual capacity​  - Airway resistance and hyperinflation result in increased work of breathing and development of hypercapnia in severe cases​ So…What is Bronchiolitis Obliterans?​(can occur with adults and children) (EMERGENCY) Manifestations of Bronchiolitis​ - Significant rhinorrhea, followed by tight, dry cough over next several days​ - Systemic signs of decreased appetite, lethargy, fever​ - Increasing respiratory distress: ​ - Wheezing​ - Tachypnea​ - Chest retractions​ - Very young infants may present with severe apnea before lower respiratory tract symptoms appear!​ - Apnea frequently requires mechanical ventilation ​ - Many children also present with conjunctivitis or otitis media​ Prevention and Treatment of Bronchiolitis​ Preventive treatment with RSV-specific monoclonal antibody (palivizumab)​ Can reduce morbidity in infants with RSV bronchiolitis​ Other preventive measures include​ Use of hand washing and alcohol-based decontamination​ Prevention of exposure to tobacco smoke​ Promotion of infant breast feeding until at least 6 months of age​ For mild cases​ No specific treatment​  Monitored at home​ When treatment indicated, primarily supportive​ High-flow nasal oxygen or noninvasive ventilation​ Pneumonia (HAP defined) Community-acquired pneumonia (CAP) most common​ Leading cause of morbidity and mortality​ In developing countries​  Risk factors ​ Age younger than 2 years​ Overcrowded living conditions​ Winter season​ Recent antibiotic treatment​ Daycare attendance​ Passive smoke exposure​ Viral Pneumonia​ Accounts for approx. 66% of childhood CAP requiring hospitalization​ RSV is most common viral pneumonia in young children​ Other viruses​: ○ SARS-CoV-2 (COVID-19 pneumonia), parainfluenza, influenza, human rhinovirus, human metapneumovirus, and adenoviruses​ Direct inoculation of upper respiratory tract through inhalation of infectious secretions (droplet transmission), aerosol exposure, or from fomites in child’s environment​ Viral Pneumonia: Pathophysiology​(it woul heal itself but still have damage in lung tissue) Viruses target airway and alveolar epithelial cells​, especially pneumocytes​ Destruction of ciliated epithelium of distal airway with sloughing of cellular material and initiation of inflammatory response​ Alveolar injury results in loss of surfactant formation, hyaline membrane formation, and edema of alveolar-capillary membrane​ Viral pneumonia usually self-limiting and alveolar regeneration results in complete resolution of lung injury​ In severe viral pneumonias (influenza and COVID-19), cytokine storm!​ ARDS​ Viral Infections Can…​(TESTED: viral pneumonia can become bacterial, because you have colonizig bacteria in airway) - Set the stage for secondary bacterial infections!​ - Viruses damage ciliated epithelial cells​ - Reduced mucociliary clearance in trachea and major bronchi​ - Pathogens reach lower airways ​ - Reduced immune response ​ Bacterial Pneumonia​(Tested: but not on typical vs. atypical) ➔ Streptococcus pneumoniae (S. pneumoniae) most common cause​ ➔ Other causative bacteria include​: ◆ Staphylococcus aureus (S. aureus)​ ◆ Atypical bacteria (Mycoplasma pneumoniae -M. Pneumoniae ◆ Chlamydophila pneumoniae - C. pneumoniae)​ ◆ Most common cause of CAP for school-age children (ages 5 and older)​ ➔ Usually begins with aspiration of one’s own nasopharyngeal bacteria into the trachea​ ➔ Another route of infection​  ◆ Inhalation of certain microorganisms (M. pneumoniae, C. pneumoniae, Legionella pneumoniae)​ ◆ Released into air when infected individual coughs, sneezes, or talks, or from contaminated respiratory therapy equipment ​ Bacterial Pneumonia: Pathophysiology​ Bacteria encounter antibodies, complement, cytokines​ Prepare bacteria for ingestion by alveolar macrophages​ Alveolar macrophages phagocytose bacteria​ Macrophages release inflammatory cytokines​ Neutrophils recruited into lung​ Intense, cytokine-mediated inflammation begins​ Vascular engorgement, edema, and fibrinopurulent exudate occur​ Alveolar filling interferes with gas exchange​ If extensive, can lead to respiratory failure​ - Staphylococcal and streptococcal pneumonia have high incidence of empyema, pneumatocele, and sepsis!​ Pathophysiologic Course of Bacterial Pneumonia​ Clinical Manifestations of Pediatric Pneumonia​  Common​ Fever​ Dyspnea, tachypnea​ Cough​ Crackles, wheezing​ Tachycardia​ May develop​ Chest retractions​ Nasal flaring​ Emesis​ Dehydration​ Occasional​ Blood streaking in sputum​ Has overlapping features with other respiratory tract conditions like asthma and bronchiolitis​ Diagnosis of Pediatric Pneumonia​ Several microbiological tests​ Sputum, blood cultures​ Antigen detection assays ​ Chest x-rays and oximetry​ Determining extent of pulmonary involvement​ Serum surfactant protein D biomarker​ Predict pneumonia severity in children​ Degree of elevated temperature, absolute neutrophil counts, percent of bands are consistently higher in bacterial versus viral pneumonia​ Prevention and Treatment of Pediatric Pneumonia​ - Prevention​ - Vaccines for influenza and pneumococcal pneumonias​ - Important in infants and young children​ - Tx: - Many treated as outpatients​ - More severely ill children​ - Oxygen supplementation, assisted ventilation​ - Proper nutrition, adequate hydration ​ - May require enteral feeding​ - Aspiration is risk with tachypneic infants ​ - Cannot coordinate breathing with swallowing​  - Antibiotic administration for bacterial pneumonias is dependent on age and severity assessment​ Pharmacotherapy for Bacterial Pneumonia​ Antibiotics​ Macrolides: Azithromycin​ Indications for use​ Infections of respiratory track​ Pneumonia​ Mechanisms of action​ Binds to ribosomal subunits of susceptible bacteria​ Suppresses protein synthesis​ Prevents production of protein needed for bacteria to grow​ Desired effects​ Bacteriostatic​ Prevents growth of bacteria​ Adverse effects​ Skin reactions, hepatotoxicity ​→ check liver enzyme Penicillins: Amoxicillin​(What is special about amoxicillin within the penicillin family?​) Indications for use​ Infections of respiratory tract​ Pneumonia​ Mechanisms of action​ Binds to bacterial cell wall​ Interferes with cell wall replication in susceptible bacteria​ Causes bacterial cell wall autolysis​ Desired effects​ Bactericidal​ Kills bacteria ​ Adverse effects​ Allergic reactions, anaphylaxis​ Use clinical judgment A client has pneumococcal pneumonia. Which pathophysiologic process has occurred? ​ Progressive airflow limitation is associated with an abnormal inflammatory response and is not fully reversible ​ Continual bronchial inflammation causes bronchial edema and increases the size and number of mucous glands and goblet cells ​  Abnormal permanent enlargement of the acini is accompanied by the destruction of alveolar walls without obvious fibrosis ​ Inflammatory cytokines cause alveolar edema, which creates a medium for microorganisms that leads to consolidation​ Which pathophysiologic response is correctly matched to its disease? ​ ​Bronchiolitis: Is caused by a surfactant deficiency, which decreases the alveolar surface area​ Pneumonia: Is a viral-induced lower respiratory tract infection of the small airways in children younger than 2 years of age​ Bronchiolitis obliterans: Is caused by fibrotic obstruction of the respiratory bronchioles and alveolar ducts​ Croup: Is an infection and inflammation in the terminal airways and alveoli​