Week 9 Flashcards
List the anatomic/physical factors that make up the respiratory tract defense mechanisms.
List three of them and how they work.
- Physical and anatomic barriers
- Branching of airways – filters the air
-
Cough reflex – removes filtered particles
- Afferent irritant receptors stimulate efferent vagus response, leading to contraction of diaphragm and cough
- Mucociliary transport – moves particles trapped on mucus layer up and out
List some innate cell types.
Antimicrobial peptides, NK cells, phagocytic cells (macrophages, PMNs), dendritic cells
Where are antimicrobial peptides located in the respiratory system? Name 4 of them and each of their functions.
- Antimicrobial peptides – in the sol layer of the mucus (layer closest to cell membrane)
- Lysozyme – in proximal airway and lyses bacteria
- Lactoferrin – promotes neutrophil superoxide response
- Defensins – secreted peptide that increases cell wall permeability in foreign cells
- Collectins – surfactant protein that aggregates microbes
What are NK cells?
NK Cells – kill virus infected cells
- Resident cells
What do macrophages do in the respiratory system?
- Macrophages
- Prevents infections
- Homeostasis – “inhibit” immune responses
- Can process 109 bacteria without eliciting further immune response
- Keeps lungs sterile and not inflamed
What do PMNs do in the respiratory system?
- Responds to established bacterial infections
- In normal state, few are present in small airways and alveoli
- In infection, activated macrophages recruit PMNs to alveolar spaces
What do dendritic cells do in the respiratory system?
- Dendritic cells – process and present antigen to adaptive immune cells
- Present in alveolar walls
- Sample environment and present antigen to T lymphocytes
In the alveolar space, where are the following located:
- type I pneumocyte
- type II pneumocyte
- alveolar macrophage
What are the two types of systems involved in the adaptive immunity? What cells are involved in each?
Adaptive
- Humoral Immunity
- B cells
- ABs
- Cellular immunity
- T-cells
What is the funcitonal of humoral immunity and what cells are a part of it? What do they each do and where are they located?
- Humoral immunity – prevent microbe entry, clear extracellular bacteria, +/- fungi
- B cells
- ABs – agglutinates microorganisms, neutralizes
- IgA – in nasopharynx/upper airways, protects mucosal surfaces
- IgG – lower airways, complement activation
What is the function of cellular immunity? What cells are a part of this system?
- Cellular immunity – intracellular bacteria, viruses, fungi (with phagocyte help)
- T cells – helper, cytotoxic, regulatory
What are the two methods of physical clearance? What infections can occur if these mechanisms fail?
Physical Clearance
- Impaired cough = aspiration pneumonia
- Impaired mucociliary clearance = bacterial infections
Provide 4 clinical examples for impaired cough and what infection occurs?
-
Impaired cough = aspiration pneumonia (anaerobes)
- Clinical examples
- Muscular dystrophy (impaired diaphragm), tracheostomy, quadriplegia, vocal cord paralysis
- Clinical examples
Provide a genetic and an evnironemental clinical example for impaired mucociliary clearance. What type of infection generally occurs with impaired mucociliary clearance?
Name some clinical consequences of impared mucociliary clearance. A specific syndrome?
-
Impaired Mucociliary clearance = bacterial infections
- Clinical examples
- Genetic: primary ciliary dyskinesia (PCD)
- Environmental: viral infection, smoking, general anesthesia
- Clinical consequences
- Kartagener’s syndrome: PCD with situs inversus (internal organs are flipped) – rare
- Recurrent infections
- Clinical examples
What infections are common in phagocytic defects? What cells are affected in phagocytic defects (2)?
-
Phagocytic defects = fungal, bacterial infection
- Clinical examples
- Macrophage deficiency
- Neutrophil deficiency
- Clinical examples
What can cause macophage deficiency? What type of defect is macrophage deficiency?
-
Phagocytic defects = fungal, bacterial infection
- Clinical examples
- Macrophage deficiency
- Impaired killing – viral infections, smoking, hypoxia, starvation, alcoholism
- Impaired migration/function – chronic systemic steroids
- Macrophage deficiency
- Clinical examples
What can cause neutrophil deficiency? What type of defect is neutrophil deficiency?
-
Phagocytic defects = fungal, bacterial infection
- Clinical examples
- Neutrophil deficiency
- Decreased numbers: leukemia, chemotherapy, congenital
- Impaired migration/function: congenital
- Neutrophil deficiency
- Clinical examples
What are the clinical consequences of phagocytic defects?
- Clinical consequences: bacterial bronchitis/pneumonia (macrophages deficiency) and bacterial infections/fungal infections (neutrophil deficiency)
What type of infections are common with NK cell defects?
Viral infections
What kind of infections do you get with humoral cell defects?
- Humoral defects = bacterial (especially encapsulated) infections
What are some examples of humoral defects? Name one congenital and two secondary.
-
Humoral defects = bacterial (especially encapsulated) infections
- Clinical examples:
- Congenital: hyper-IgM syndrome
- Secondary: nephrotic syndrome (kidney damage), chemotherapy
- Clinical examples:
What infections occur as a consequence of humoral defects?
-
Humoral defects = bacterial (especially encapsulated) infections
- Clinical consequences
- Recurrent bacterial respiratory infections
- Bronchiectasis
- Clinical consequences
What are combined defects?
- Combined defects = features of both humoral and cellular immunity
What are antimicrobial peptide defects (4)? Name a clinical example and some clinical consequences?
- Antimicrobial peptide defects (defensins, lactoferrins, collectins, lysozymes)
- Clinical examples
- Cystic fibrosis
- Clinical consequences
- Require defect in multiple peptides for a true immunodeficiency
- Defensin defects: severe respiratory infections
- Clinical examples
Name 5 anti-histamines.
MNEMONIC ALERT (may or may not help): “_C_an’t _D_o _H_istamines _F_or _L_ife”
- Cetirizine
- Diphenhydramine
- Hydroxyzine
- Fexofenadine
- Loratadine
What is the general mechanism of action of antihistamines?
Competitive H1 receptor (Gq receptor); although increase in intracellular Ca2+, histamine stimulation causes production of prostacyclin and NO, outweighing histamine’s vasoconstrictive effects
What are the uses of antihistamines?
What are the adverse effects of antihistamines?
Use: Allergy-mediated pathologies
Adverse Effects: Diphenhydramine and hydroxyzine have anticholinergic effects (aka sedating)
Name 2 decongestants
- Pseudoephedrine
- Phenylephrine
For decongestants (pseudophedrine, phenylepherine):
- What is the MOA?
- What are the uses?
- What are some adverse effects?
- MOA: Alpha 1 agonists (Gq) – vasoconstriction
- Uses: Used to decrease mucus production
- Adverse effects: Tissue necrosis if use extends past 3 days
For intranasal corticosteroid:
- Name one.
- What is the MOA?
- What is its use?
- What are 3 adverse effects?
- Example: fluticasone
- MOA: Transcription factor that decrease capillary permeability, stabilize lysosomes, decrease mucus production
- Uses: Sinusitis
- AE: Candida infection, perforation of nasal septum, bone necrosis
For expectorant:
- Name one.
- What is the MOA?
- What is its use?
- Guaifenesin
- MOA: Increase respiratory tract fluid secretions and helps loosen phlegm
- Use: Sinusitis (may help – “expect” it to help)
For mucolytic agents:
- Name one.
- What is the MOA?
- What is its use?
- Example: acetylcysteine
- MOA: Splits the disulfide linkages that holds mucus together
- Use: Reduces sputum viscosity to improve secretion clearance
For opioid antitussives:
- Name three.
- What are the MOAs?
- What is its use?
- Adverse effects?
- Example: Codeine/Hydrocodone/Dextrmethorphan
- MOA: Acts on Gi receptors to hyperpolarize cell membranes – prevents neurotransmitter release
- Uses: Decreases cough (so people with colds can sleep)
- Adverse effects: Dextromethorphan (seen as DM in cold medications) is very weak; honey more effective
For non-opioid antitussives:
- Name one.
- What is the MOA?
- What is its use?
- Adverse effects?
- Example: Benzonatate
- MOA: Topical anesthetic action on respiratory stretch receptors (blocks sodium channels)
- Use: Decreases cough (so people with colds can sleep)
- AE: Sedating
Define the following terms:
- Nasopharyngitis
- Acute rhinosinusitis
- Acute otitis media
- Acute infection pharyngitis
- Rhinitis
- Nasopharyngitis: more commonly known as the Common Cold
- Acute rhinosinusitis: inflammation of the nasal cavity and sinuses
- Acute otitis media: bulging of tympanic membrane (TM) or otorrhea
- Acute infection pharyngitis: inflammation of the pharynx
- Rhinitis: inflammation of nasal cavity
What is the epidemiology of nasopharyngitis?
- What age group does it most occur in?
- How does transmission occur and what viruses?
- Epidemiology
- More frequent in children
- Transmission occurs from direct hand-to-mucus membranes (rhinovirus) or small droplet inhalation (only 15 micrometers, does not get into distal airways; influenza, RSV)
What is the pathophysiology of nasopharyngitis?
- What does yellow mucus mean? Green mucus?
- What can bradykinin cause?
- Pathophysiology – VIRAL
- Virus deposits on nasal/conjunctiva mucosa → attaches/enters to epithelium → virus replicates → epithelial cells release IL-8 and bradykinin → recruitment of PMN
- Yellow mucus = PMN aggregation
- Green mucus = PMN enzymatic activation
- Bradykinin causes dry cough
- Virus deposits on nasal/conjunctiva mucosa → attaches/enters to epithelium → virus replicates → epithelial cells release IL-8 and bradykinin → recruitment of PMN
For nasopharyngitis:
- What are the clinical symptoms associated with it?
- Risk factors?
- Complications as a result of the condition?
- Diagnosis?
- Treatment?
- Clinical
- Nasal congestion, sore throat, rhinorrhea, cough, sneezing, +/- headache
- Fever is uncommon but can be present
- Nasal congestion, sore throat, rhinorrhea, cough, sneezing, +/- headache
- Risk factors – exposure to children, parents, stress, lack of sleep
- Complications
- Otitis media, bacterial rhinosinusitis, asthma exacerbation, lower respiratory tract infection (virus affects cilia and can cause severe infection)
- Diagnosis
- Lungs are clear
- Treatment
- Decongestants, analgesics
For acute rhinosinusitis, provide pathophysiology of the viral and bacterial types?
- Indicate the 3 microorganisms that cause each
- How long are the symptoms for each? Do they get worse or better?
- What is the method of infection?
- Pathophysiology
- Viral – inoculation via direct mucosal contact
- Rhinovirus, influenza, parainfluenza
- Has < 10 days of symptoms without worsening
- Bacterial – secondary to viral infection; rare
- S. Pneumoniae, H. influenza, M. catarrhalis
- Has ≥ 10 days of symptoms without improvement/double worsening (getting better for a few days and then it gets worse)
- Viral – inoculation via direct mucosal contact
What are the symptoms associated with acute rhinosinusitis? Differentiate between complicated and uncomplicated bacterial rhinosinusitis. How do you diagnose both?
- Clinical
- Purulent discharge with nasal congestion +/- facial pain, pressure, fullness
- Uncomplicated acute bacterial rhinosinusitis – no evidence that the disease has spread outside of nasal cavity and sinuses
- No culture
- Complicated acute bacterial rhinosinusitis – disease has spread outside nasal cavity and sinuses
- Perform culture
- Possible to get fungal rhinosinusitis
What are two complications associated with acute rhinosinusitis? What are the treatments for the conditon (specifically for uncomplicated??)
- Complications
- Osteomyelitis
- Meningitis – sinuses are really close to the brain!
- Treatment
- Decongestants, analgesics
- Antibiotics if bacterial (amoxicillin)
- Uncomplicated may resolve by itself without Abx
For otitis media:
- What is the age group that the condition is most common in?
- What are four symptoms?
- How can it be diagnosed? Three indications.
- What are two complications?
- What is the general treatment?
- Epidemiology
- High prevalence in children between ages 6 and 18 months old
- Clinical
- Infants have no way to communicate pain: fever, irritability, headache and ear pain
- Diagnosis
- Bulging of TM and opacity and erythema
- Complications
- TM perforation and hearing loss
- Treatment
- Antibiotics (amoxicillin) or observation
Discuss the pathophysiology of acute otitis media. What are the three bacteria involved?
- Pathophysiology
- Bacteria involved: S. Pneumoniae, H. influenza, M. catarrhalis
- Occurs often in infants because the Eustachian tube is very horizontal and short (in adults, it is more angled and longer), allowing for easier infections
- URI → travels to Eustachian tube → inflammation/edema → negative ear pressure → bulging of TM
For acute infectious pharyngitis:
- What is the age group that the condition occurs in?
- What is the general pathophysiology?
- What microorganisms cause the condition?
- What are two ways to diagnose the condition?
- What is the VERY IMPORTANT COMPLICATION?
- Epidemiology
- School-aged children
- Pathophysiology
- Viral (most cases are viral): part of the common cold
- Bacterial (15% of cases): Group A Strep, N. gonorrhoeae
- Diagnosis
- Throat culture – gold standard
- Rapid antigen test – widely used
- Complications
- Rheumatic fever (main goal of treatment is to prevent)
For acute infectious pharyngitis, indicate the symptoms associated with bacterial and viral?
- Clinical
- Bacterial
- Age 5-15
- Fever
- White exudate on tonsils
- Tonsillopharyngeal inflammation
- Anterior cervical lymphadenopathy
- Viral
- Conjunctivitis
- Hoarseness
- Bacterial
Distinguish between allergic rhinitis and non-allergic rhinitis.
Allergic rhinitis:
- Associated pruritus, sneezing
- Have allergic triggers
- Other atopic diseases may be present
- Responds to antihistamines
- Positive allergy testing
- Inflammed turbinate in nose turns bluish/pale color from normal red
- Mast cells release histamine
Non-allergic rhinitis:
- Lack of irritative symptoms
- Mostly irritant triggers
- No other atopic diseases present
- Do not respond to antihistamines
- Negative allergy testing
- Inflammed turbinate without change in color
Define basic pleural anatomy
- Anatomy
- Visceral pleura lines the outer layer of the lung
- Parietal pleura line the inner chest wall
- Each pleural lining is made up of mesothelial cells
- Small amount of fluid in pleural cavity reduces friction between lung and chest wall during breathing cycle
Explain the Diffusion Mechanisms of fluids in the lung and pluera
- Diffusion Mechanisms
- Hydrostatic pressure from parietal pleura drives fluid into pleural space
- Oncotic pressure from proteins in pleural space drive fluid into parietal/visceral spaces
- In normal conditions, the lymph system drains fluid in the pleural space
Pleuritis versus Pleuritic Chest Pain
define and give examples
- Pleuritis – pain due to inflammation
- Idiopathic, viral
- Pleurtic chest pain – sharp, stabbing, well localized pain exacerbated by inspirations (not necessarily having to do with the pleura)
- Rib fractures, PE, pneumonia
pleural effusions - what do you see on different modes of imaging
- Imaging
- Chest X-ray: see a meniscus of fluid line
- MRI – see fluid build-up in axial view
- Ultrasound – see expansion of pleural space
Chylothorax
description/etiology
- Pleural effusion due to damage to thoracic duct
- Chylothorax
- Description: Build-up of lymph fluid in the pleural space
- Etiology: Trauma, Malignancy
- Chylothorax
Transudates
examples/treatments
- Transudates – due to hydrostatic or oncotic pressure
- Examples:
- CHF – increase in hydrostatic pressure in pulmonary artery
- PE – increase in hydrostatic pressure in pulmonary artery
- Cirrhosis – liver produces less albumin à decreases in oncotic pressure
- Treat underlying problem
- Examples:
Exudates
examples/treatment
- Exudates – due to inflammation or disease of the pleura
- Examples:
- Pneumonia
- Parapneumonic effusion – exudate with uninfected fluid
- Empyema – infection of pleural space à formation of pus
- Tx: Surgical resections
- Malignancy, PE, GI disease
- Pneumonia
- Find underlying problem
- Examples:
Light criteria
transudates
- Transudates
- Pleural fluid protein : Serum protein < 0.5
- Pleural fluid LDH : Serum LDH < 0.6
Light criteria
exudates
- Exudates (ONLY need ONE of following)
- Pleural fluid protein : Serum protein > 0.5
- Pleural fluid LDH : Serum LDH > 0.6
- Pleural fluid LDH > 2/3 upper limit of normal
Mesothelioma
description, signs/symptoms, prognosis, pathology
- Mesothelioma – associated with asbestos
- Signs & Symptoms: Dyspnea, chest pain
- Prognosis: poor, palliative care
- Pathology: black lung
Solitary fibrous tumor (SFT)
description, treatment
- Solitary fibrous tumor (SFT) – mesenchymal tumor from pleural surface
- Usually benign
- Become symptomatic when very large
- Treatment: surgical resection
Define ARDS
- A response to an injury (i.e. pneumonia, car accident, trauma) that causes a massive inflammatory response
- Cause of hypoxic respiratory failure
types of ARDS
- Types
- Pulmonary ARDS – due to direct lung injury (i.e. pneumonia, aspiration, inhalation, infection)
- Extrapulmonary ARDS – due to systemic processes (i.e. sepsis, pancreatitis, and trauma)
Criteris for ARDS
- Strict criteria for diagnosis
- Timing: less than 1 week following insult
- Imaging: bilateral opacities or infiltrates
- Origin of edema: infiltrates are not caused from heart failure (rule out via echo)
- Hypoxia: PF ratio < 300
PF ratio
PF Ratio = PaO2 / FIO2 = 100/0.21 = 480 (that’s really good!)
What happens to VQ in ARDS?
- ARDS is caused by filling of alveoli with edema – unable to ventilate, leading to a V/Q ratio close to 0
Types of Hypoxemia (7)
how to diagnosis each
- ARDS – bilateral infiltrates on CXR
- Pneumonias – unilateral infiltrates on CXR
- Pulmonary embolism – clear on CXR
- CHF – BNP and echo findings
- Interstitial lung disease – chronic history of lung issues
- Pulmonary hypertension – no pulmonary infiltrates on CXR
two phases of ARDS
exudative, proliferative
What happens inthe exudative phase of ARDS
- Exudative Phase – flooding of proteinaceous fluid and edema
- Increased permeability (and cellular swelling) of alveolar membrane/capillary
- Hyaline membrane
What happens in the proliferative phase of ARDS
- Proliferative Phase – pulmonary fibrosis
- Stiff lungs due to interstitial fibrosis
- Less edema due to diuretics
- Progressive pulmonary HTN
- Interstitial inflammation (causing recruitment of fibroblasts)
What are the key features in each slide - how does it relate to ARDS
hyaline membrane
fibrosis
common complications of patients with ARDS (5)
- Stiff lungs
- Refractory hypoxia – neurological deficits
- Paralytics – myopathy
- Pyschological trauma
- ICU related-complication – HAP, ulcers, blood clots
explain PEEP and tidal volume treatment in ARDS
- PEEP (positive end expiratory pressure) – keeps alveolar sacs open
- Low tidal volume – reduces mortality
- Start patients at 8cc/kg
- Wean down patients to 6cc/kg
- Permissive hypercapnia – reduced inspiratory and expiratory phases à buildup of pCO2 à acidosis
What are some other treatment techniques used in ARDS (4)
- Prone position (flipping patient on face) – relieves distension of dorsal alveoli/decreases V/Q mismatch
- ECMO – acts as dialysis for the lungs
- Paralytics – reduce oxygen demand from body
- No steroids
Describe the prognosis for ARDS patients and the long-term sequelae of survivors of ARDS.
- Bad, 75% who survive will have some deficit
- High mortality rate
- High rate of PTSD
