Week 7 Lecture 1 Flashcards
What is atelectasis?
Atelectasis is a medical condition characterized by the collapse or incomplete expansion of a part or all of the lung.
What can cause atelectasis?
Various reasons including blockage of the airways, pressure from outside the lung, or weakened lung tissue.
What is resorption atelectasis?
Resorption atelectasis occurs when the airway leading to a portion of the lung is blocked, preventing air from reaching the alveoli.
What are the major causes of resorption atelectasis?
- Aspiration of a foreign body blocking a conducting airway
- Tumor or other growth
- A mucous plug
What is compression atelectasis?
Compression atelectasis happens when there is external pressure on the lung, preventing it from expanding fully.
What are common causes of compression atelectasis?
- Tumor
- Enlarged lymph nodes
- Fluid accumulation in the pleural cavity
- Pneumothorax
What is the role of the pleura?
The pleura provides protection, lubrication, and support to the lungs during breathing.
What are the two layers of the pleura?
- Visceral Pleura
- Parietal Pleura
What is pleural effusion?
Pleural effusion is an abnormal collection of fluid in the pleural space.
What are the two major types of pleural effusions?
- Transudative
- Exudative
What characterizes transudative pleural effusion?
Transudate is protein- and cell-poor fluid that accumulates due to an imbalance of Starling forces.
What are common causes of exudative pleural effusions?
- Malignant diseases
- Inflammatory conditions
- Infectious diseases
- Vascular issues
What is a parapneumonic effusion?
Parapneumonic effusion is an accumulation of fluid in the pleural space that occurs as a complication of pneumonia.
What are the stages of a parapneumonic effusion?
- Exudative phase
- Fibrinopurulent stage
- Organization stage
What is empyema?
Empyema is a collection of pus within the pleural cavity.
What are the clinical features of pleural effusions?
- Dyspnea
- Chest pain
True or False: Transudates tend to be bilateral.
True
What is the normal intrapleural pressure?
Normal intrapleural pressure is around -10 cm water at the lung bases.
What can cause a pneumothorax?
Trauma and obstructive lung disease can cause a pneumothorax.
What is the primary function of mesothelium?
To provide a smooth, protective surface that allows organs to move against one another with minimal friction.
What is the typical volume of pleural fluid present in the pleural cavity?
Normally, between 10 – 25 ml of pleural fluid.
What happens to pleural fluid production in certain medical conditions?
Conditions can disrupt the balance of pleural fluid production and absorption, leading to pleural effusion.
What is the function of the pleural fluid?
The pleural fluid acts as a lubricant, allowing smooth movement of the lungs during breathing.
What is the significance of the phrase ‘the sun cannot set on a parapneumonic effusion’?
It emphasizes the urgency of diagnosing and treating parapneumonic effusions promptly.
What are the two main types of influenza viruses?
- Influenza A
- Influenza B
What type of virus is influenza?
Influenza viruses are negative-sense single-stranded RNA viruses.
What role does hemagglutinin play in influenza?
Hemagglutinin allows the virus to bind to and invade the host cell.
What is the function of neuraminidase in influenza?
Neuraminidase allows the virus to disengage from the cell and spread.
What characterizes uncomplicated infectious pleural effusions?
Exudate with neutrophils, no microbes found on thoracocentesis.
What indicates a complicated parapneumonic effusion?
Bacteria invade but are cleared rapidly, with more neutrophils and protein.
What is the treatment for empyema?
Empyema may require drainage or more invasive therapy.
What do hemagglutinin and neuraminidase do in the influenza virus life cycle?
Binding and budding of the virus
Hemagglutinin binds to sialic acid-containing glycolipids or glycoproteins on respiratory cells, while neuraminidase allows the virus to disengage from the cell.
What is the function of PB protein in influenza viruses?
RNA-dependent RNA polymerase
This protein is responsible for synthesizing viral mRNAs.
What are the two types of proteins that act as ion channels in influenza?
- Influenza A – M2
- Influenza B – NB
What is the primary site of infection for influenza viruses?
Respiratory epithelium
This includes the cells lining the nose, throat, and lungs.
How does the influenza virus enter the host’s respiratory tract?
Through inhalation of respiratory droplets, direct contact, or contact with contaminated surfaces.
What happens once the influenza virus is inside the host cell?
Viral RNA is released and serves as a template for replication.
What immune responses are activated in response to influenza infection?
- Innate immune response
- Adaptive immune response
What is a cytokine storm in the context of influenza?
Excessive inflammation and cytokine release contributing to severe symptoms.
What are the potential severe complications of influenza infection?
- Bacterial pneumonia
- Exacerbation of chronic respiratory conditions
- Systemic complications
What is antigenic shift?
A sudden and major change in the antigenic properties of the influenza virus due to genetic reassortment.
What is antigenic drift?
Gradual changes in the antigenic properties of the influenza virus due to mutations.
What does the ‘H’ and ‘N’ in influenza virus naming refer to?
- H refers to hemagglutinin type
- N refers to neuraminidase type
What are the most common influenza subtypes in humans?
- H1
- H2
- H3
- N1
- N2
What is the typical transmission method for influenza?
Direct droplet transmission, usually through coughing.
What are the clinical features of influenza?
- Cough
- Sore throat
- Rhinorrhea
- Systemic symptoms like fatigue and myalgias
What is a common complication of influenza in children?
Reye syndrome
This can occur due to the administration of salicylate drugs.
What is the role of neuraminidase inhibitors in influenza treatment?
They are beneficial for severe disease if given within 48 hours of onset.
What is the R0 rate for SARS-CoV-2 compared to influenza?
R0 for SARS-CoV-2 is between 5 and 6, while for influenza it is between 1 and 2.
What structural proteins are encoded by the SARS-CoV-2 genome?
- S (spike)
- E (envelope)
- M (membrane)
- N (nucleocapsid)
How does SARS-CoV-2 enter host cells?
By binding to the ACE2 enzyme after cleavage of the spike protein by TMPRSS2.
What is the consequence of the cytokine storm in COVID-19?
Acute respiratory distress syndrome (ARDS) and multi-organ system stimulation.
What is the primary mechanism of viral replication for SARS-CoV-2?
Translation in the cytoplasm followed by cleavage by host and viral proteases.
What is a significant difference between antigenic shift and drift?
Antigenic shift involves major changes through gene swapping, while drift involves minor mutations.
What are the common respiratory symptoms of influenza?
Cough, sore throat, and nasal congestion.
What is the incubation period for influenza symptoms?
Typically averages 2 days (1-4 days).
What promotes viral uptake by cleaving ACE2 and activating the SARS-CoV-2 S-protein?
The serine protease TMPRSS2
During early infection, where can viral copy numbers be high?
In the lower respiratory tract
Which types of cells release inflammatory signaling molecules during infection?
- Infected cells
- Alveolar macrophages
- Recruited T lymphocytes
- Monocytes
- Neutrophils
What activates kinin receptors on the lung endothelium during late lung inflammation?
Plasma and tissue kallikreins release kinins
What effect do kinins have on vascular smooth muscle?
Leads to vascular smooth muscle relaxation and increased vascular permeability
Which receptor controls the process of vascular leakage in the lungs?
ACE2 receptor
What are the consequences of dysregulated proinflammatory cytokine release?
- Pulmonary edema fills the alveolar spaces
- Hyaline membrane formation
- Compatible with early-phase acute respiratory distress syndrome
What can anomalous coagulation result in during COVID-19?
Formation of microthrombi and subsequent thrombotic sequelae
What types of immunity play important roles in acute SARS-CoV-2 infection?
- Cell-mediated immunity
- Humoral immunity
Which immune response is thought to be more important in controlling infection during COVID-19?
T cell responses
What is observed about T cell responses in mild COVID-19 patients compared to moderate to severe patients?
T cell responses were higher in mild COVID-19 patients
What do studies suggest about antibody responses in moderate to severe COVID-19 patients?
More robust antibody responses compared to mild disease patients
What is the incubation period for COVID-19?
2 to 14 days (median 5-6 days)
What percentage of COVID-19 patients remain asymptomatic?
Approximately 30%
What are some mild to moderate symptoms of COVID-19?
- Fever or chills
- Cough (can be productive)
- Shortness of breath
- Fatigue
- Muscle or body aches
- Headache
- Loss of taste or smell (10%)
- Sore throat
- Congestion or runny nose
- Conjunctivitis
- Nausea or vomiting
- Diarrhea
What are some severe symptoms of COVID-19?
- Dyspnea (severe)
- Cyanosis
- Chest pain (could be angina)
- Confusion
- Inability to wake or stay awake
What percentage of COVID-19 patients may require oxygen support due to lower respiratory symptoms?
15%
What unique condition can develop in COVID-19 patients regarding hypoxemia?
Significant hypoxemia (oxygen saturation < 90%) but limited dyspnea and respiratory discomfort
What is the estimated mortality rate of COVID-19?
Just over 2%
What are some risk factors for severe complications and viral pneumonia in COVID-19 patients?
- Advanced age (>80% of deaths occur in people over age 65)
- Male sex
- Racial and ethnic minorities
- Chronic conditions (cardiovascular disease, chronic kidney disease, diabetes, obesity, malignancy)
- Immunocompromised individuals
What are some complications associated with COVID-19?
- Death
- Heart attack & myocarditis
- Cerebrovascular disease
- Ischemic stroke due to hypercoagulability
- Acute kidney injury (acute renal failure)
What is atelectasis?
Atelectasis is a medical condition characterized by the collapse or incomplete expansion of a part or all of the lung.
What are the major types of atelectasis?
- Acquired atelectasis
- Resorption atelectasis
- Compression atelectasis
- Contraction atelectasis
What causes resorption atelectasis?
It occurs when the airway leading to a portion of the lung is blocked, preventing air from reaching the alveoli.
What can lead to contraction atelectasis?
Scarring or fibrosis within the lung tissue, which prevents proper expansion of the affected area.
True or False: Atelectasis is a disease.
False
What are some complications associated with atelectasis?
- Pulmonary infection (pneumonia)
- Ventilation-perfusion mismatching
- Underlying cause for restrictive pulmonary diseases
What is compression atelectasis?
It happens when there is external pressure on the lung, preventing it from expanding fully.
What role does the pleura play?
- Provides a protective barrier around the lungs
- Lubricates lung movement
- Supports lung structure
What are the two layers of the pleura?
- Visceral Pleura
- Parietal Pleura
What is pleural effusion?
An abnormal collection of fluid in the pleural space.
What are the two major types of pleural effusions?
- Transudative
- Exudative
What characterizes transudate fluid?
Protein- and cell-poor fluid that accumulates due to imbalance of Starling forces.
What are common causes of exudative pleural effusions?
- Malignant causes (e.g., mesothelioma, lung cancer)
- Inflammatory causes (e.g., lupus, RA)
- Infectious causes (e.g., parapneumonic effusion)
- Vascular causes (e.g., pulmonary emboli)
What is a parapneumonic effusion?
An accumulation of fluid in the pleural space that occurs as a complication of pneumonia.
What are the stages of a parapneumonic effusion?
- Exudative phase
- Fibrinopurulent stage
- Organization stage
What symptoms are caused by pleural effusions?
- Dyspnea
- Chest pain
What is the significance of the phrase ‘the sun cannot set on a parapneumonic effusion’?
It emphasizes the urgency of diagnosing and treating parapneumonic effusions promptly.
How much pleural fluid is normally present in the pleural cavity?
Between 10 – 25 ml.
What is empyema?
A collection of pus within the pleural cavity.
What is the normal intrapleural pressure?
Around -10 cm water at the lung bases.
What can cause a pneumothorax?
Presence of air in the pleural space, causing lung collapse.
What is the primary function of the mesothelium?
To provide a smooth, protective surface that allows organs to move against one another with minimal friction.
Fill in the blank: The space between the visceral and parietal pleura is called the _______.
pleural cavity
What is the lymphatic system’s role concerning pleural fluid?
It can accommodate 10 – 20X normal hourly production without accumulating significant volumes of fluid in the pleural space.
What is a decent initial study for diagnosing pleural effusions?
Chest radiograph (both upright and decubitus).
Which imaging technique is better than X-ray for detecting pleural effusions?
Ultrasound.
Which imaging technique is likely better than ultrasound for detecting pleural effusions?
CT.
What is thoracocentesis used for?
It can be diagnostic and therapeutic.
What is a potential complication of thoracocentesis?
Pneumothorax.
What is the prognosis for malignancies that have metastasized to the pleura?
Very poor prognosis.
What is the higher mortality and morbidity associated with?
Ineffectively treated parapneumonic effusions that progress to empyema.
How are parapneumonic effusions typically treated?
By draining the fluid and sometimes using clot-busting drugs and DNA-ase enzymes.
What two meanings does ‘influenza’ refer to?
- Syndrome
- Microbe.
What are the systemic symptoms of the influenza syndrome?
- Fever
- Malaise
- Myalgia.
What respiratory symptoms are associated with influenza?
- Dyspnea
- Cough (lower)
- URTI symptoms like rhinitis, sinusitis, or otitis.
What are the two most clinically important types of influenza?
- Influenza A
- Influenza B.
What type of virus are influenza A and B?
Orthomyxoviruses.
What kind of RNA do influenza viruses contain?
Negative-sense single-stranded RNA.
What is required to convert the RNA genome of influenza into a readable form?
RNA-dependent RNA polymerase.
What major proteins are clinically relevant for influenza?
- Neuraminidase
- Viral hemagglutinin
- RNA-dependent RNA polymerase proteins.
What does the hemagglutinin spike do?
Allows the virus to bind to and invade the host cell.
What does the neuraminidase spike allow the virus to do?
Disengage from the cell and spread.
What is the role of PB protein in influenza?
It is an RNA-dependent RNA polymerase transported into the nucleus for mRNA production.
What are the ion channel proteins specific to influenza A and B?
- Influenza A – M2
- Influenza B – NB.
What is the life cycle of Influenza A or B characterized by?
- Binding due to hemagglutinin
- Budding due to neuraminidase.
What is the pathogenesis of influenza primarily characterized by?
Complex interplay between the virus and the host’s immune response.
What cells do influenza viruses primarily infect?
Respiratory epithelium.
How does the virus enter the host’s respiratory tract?
Through inhalation of respiratory droplets, direct contact, or contact with contaminated surfaces.
What happens once the virus enters the host cell?
The viral RNA is released into the cytoplasm for synthesis and replication.
What immune responses are activated against influenza?
- Innate immune response
- Adaptive immune response.
What can excessive inflammation and cytokine release lead to?
Cytokine storm and severe complications.
What typically happens after the host’s immune response controls the virus?
Recovery from influenza illness.
What is antigenic shift?
Large changes in RNA sequence due to gene swapping between virus strains.
Which influenza type does antigenic shift occur in?
Influenza A.
What is the result of antigenic drift?
Smaller, point-mutation type changes in the RNA genome.
What does antigenic drift lead to?
Emergence of new variants or strains within the same subtype.
What does ‘H’ and ‘N’ refer to in influenza naming?
- H refers to hemagglutinin type
- N refers to neuraminidase type.
What influenza subtypes are most relevant in humans?
- H1
- H2
- H3
- N1
- N2.
What factors determine the severity of influenza epidemics or pandemics?
- Antibody effectiveness
- Ability to be passed from human to human
- Other virulence factors.
What is a characteristic of H5N1 (‘avian flu’)?
Has a very high mortality rate but poor human-to-human transmission.
What is usually the most common and severe complication of influenza?
Bacterial superinfection leading to pneumonia.
What are common systemic complications associated with influenza?
- Myositis
- Myocarditis
- Guillain-Barre syndrome.
What is the primary method of diagnosing influenza?
Clinical diagnosis.
What tests confirm influenza diagnosis?
NAAT tests (nasopharyngeal swab).
What type of treatment can reduce influenza symptoms?
Vaccinations.
What are neuraminidase inhibitors used for?
To treat severe disease or high-risk patients if given within 48 hours of onset.
What virus causes COVID-19?
SARS-CoV-2.
What kind of virus is SARS-CoV-2?
Betacoronavirus.
What is the genome type of SARS-CoV-2?
Single linear RNA segment of nearly 30,000 nucleotides.
What are the structural proteins encoded by the SARS-CoV-2 genome?
- S (spike)
- E (envelope)
- M (membrane)
- N (nucleocapsid).
What is the typical transmission method for SARS-CoV-2?
Droplet transmission.
What appearance does the virus give that resembles a crown?
Crown of thorns or a solar corona
Name three surface proteins of the virus.
- Hemagglutinin-acetylesterase glycoprotein
- Membrane glycoprotein
- Small envelope glycoprotein
What type of transmission involves larger droplets that fall to the ground quickly?
Droplet transmission
What type of droplets can remain airborne for much longer?
Smaller droplets (aerosols)
How can the virus be transmitted from surfaces?
Contact from colonized surface (hands, inanimate objects) to respiratory tract/eyes
What are the initial targets for viral colonization/replication?
Nasopharyngeal/oropharyngeal cells
List other cells that can be invaded/colonized by SARS-CoV-2.
- Bronchial epithelium
- Alveolar epithelial cells
- Vascular endothelial cells
- Alveolar macrophages
What cells in the body express ACE-2?
- Enterocytes
- Cholangiocytes
- Myocardial cells
- Kidney cells
- Bladder urothelial cells
Why is COVID-19 so transmissible?
It replicates in the upper airways
At what stages can the virus replicate in the upper airways?
- Symptomatic stage
- Pre-symptomatic stage
What are the R0 rates for COVID-19 compared to influenza?
COVID-19 R0 rate is between 5 and 6; influenza is between 1 and 2
Does enteric replication impact transmissibility?
No one is sure – likely not
What impact does enteric replication have during symptomatic phases?
It seems to exacerbate inflammation
What does the spike protein bind to on cells?
ACE2 enzyme
What allows for viral entry after the spike protein is cleaved?
Cleavage by TMPRSS2 (transmembrane protease serine 2)
What forms after the cleavage of the spike protein?
Endosome
What happens to the viral genome after it enters the cytoplasm?
Translation in a polyprotein followed by cleavage by host and viral proteases
List some functions performed by viral proteins.
- Continued replication (RNA-dependent RNA polymerase)
- Viral particle assembly
- Inhibition of type I interferons
What is the rate of mutation for the virus compared to influenza?
Relatively low rate of mutation due to exonuclease activity
What is a cytokine storm?
A hyperactive immune response leading to acute respiratory distress syndrome (ARDS) due to highly virulent viruses like H5N1, H1N1, and COVID-19.
Cytokine storms are characterized by the excessive release of proinflammatory cytokines.
Which proinflammatory cytokines are primarily involved in a cytokine storm?
Interferon-γ, TNF-α, IL-1, IL-6
These cytokines stimulate multiple organ systems and contribute to the immune response.
What role do T cells and natural killer cells play in a cytokine storm?
They are rapidly proliferating and highly activated by infected macrophages.
This activation is part of the immune response to combat viral infections.
What cells does SARS-CoV-2 infect during the early stage of disease?
Bronchial epithelial cells, type I and type II alveolar pneumocytes, capillary endothelial cells.
These infections are crucial for the onset of lung inflammation.
What is the function of the serine protease TMPRSS2 in SARS-CoV-2 infection?
It promotes viral uptake by cleaving ACE2 and activating the SARS-CoV-2 S-protein.
This mechanism facilitates the entry of the virus into host cells.
What occurs during late lung inflammation in COVID-19?
Release of kinins activates kinin receptors, leading to vascular smooth muscle relaxation and increased vascular permeability.
This process is controlled by the ACE2 receptor.
What are the consequences of ACE2 being blocked during COVID-19?
Increased vascular leakage, angioedema, and downstream activation of coagulation.
This can lead to significant lung damage and complications.
What are the early signs of acute respiratory distress syndrome (ARDS) in COVID-19?
Pulmonary edema fills alveolar spaces, followed by hyaline membrane formation.
This is a result of dysregulated proinflammatory cytokine release.
What types of immunity are involved in acute SARS-CoV-2 infection?
Cell-mediated and humoral immunity.
Both types play important roles in controlling the infection.
How do T cell responses differ between mild and severe COVID-19 patients?
T cell responses are higher in mild COVID-19 patients compared to moderate to severe patients.
This suggests a potential correlation between T cell activity and disease severity.
What is the incubation period for COVID-19?
2 to 14 days (median 5-6 days).
Symptoms typically develop within this timeframe.
What percentage of COVID-19 patients remain asymptomatic?
Approximately 30%.
This highlights the variability in disease presentation.
What are common mild to moderate symptoms of COVID-19?
Fever, cough, shortness of breath, fatigue, muscle aches, headache, loss of taste or smell, sore throat, congestion, nausea, diarrhea.
Approximately 80% of symptomatic cases fall into this category.
What severe symptoms may indicate a critical case of COVID-19?
Dyspnea, cyanosis, chest pain, confusion, inability to stay awake.
These symptoms can indicate respiratory failure or multi-organ issues.
What is the estimated mortality rate of COVID-19?
Just over 2%.
The death toll is approximately 7 million worldwide, primarily due to pneumonia.
What are some risk factors for severe complications from COVID-19?
Advanced age, male sex, racial and ethnic minorities, chronic conditions (cardiovascular disease, chronic kidney disease, diabetes, obesity, malignancy), immunocompromised status.
Over 80% of deaths occur in people over age 65.
