Block 1 - Respiratory Flashcards
Give an overview of the basic elements involved in neural control of ventilation.
- Which 4 nerves are involved and what do they innervate?
Innervation:
- Phrenic Nerve (C3-C5): Innervates diaphragm (autonomic) **MAIN**
- Vagus Nerve (CN X): Innervates diaphragm, abdominal viscera and muscles, larynx and pharynx (autonomic)
- Posterior Thoracic Nerves: Intercostal muscles located around the pleura (somatic)
- Intercostal Nerves: Internal intercostal muscles
Give an overview of the basic elements involved in neural control of ventilation.
- Which 3 controllers are involved and what do they do?
Controllers:
Brainstem (Pons and Medulla): Autonomic control
Spinal Cord: Reflex responses (breathing, sneezing, coughing, closure of glottis, and hiccups)
Cerebrum: Voluntary control
Give an overview of the basic elements involved in neural control of ventilation.
- Which 4 sensors are involved and what do they do?
Sensors:
- Central Chemoreceptors (Medulla): Detects ↑CO2 (indirectly) and ↑H+
- Peripheral Chemoreceptors (Aortic Bodies and Carotid Bodies): Detects ↓O2, ↑CO2 and ↑H+
- Lung and Upper Airway Receptors: Monitor ventilation
- Muscle Proprioceptors: Monitor respiratory effort
Give an overview of the basic elements involved in neural control of ventilation.
- Which are the 4 respiratory muscles and what do they do?
Effectors: Respiratory muscles
- Diaphragm: Pulls down when it contracts, increasing the size of the thoracic cavity (passive inspiration).
- External Intercostal Muscles: Pull the ribs up and out when they contract, increasing the size of the thoracic cavity (passive inspiration).
- Abdominal Muscles: Pull lower ribs inwards when they contract, cause intestines & liver to push upwards on diaphragm (active expiration).
- Internal Intercostal Muscles: Pull ribs inwards when they contract (active expiration).
Explain the probable location and function of the ‘central controller’ that regulates ventilation.
Ventilation
Central Controller:
Location: Reticular Formation of the medulla and pons
Function: Sets and modulates the respiratory rhythm in response to sensory input
What are the 2 medullary respiratory centres, their locations and their functions?
Medullary Respiratory Centres: Sends signals to the muscles involved in breathing
1) Ventral Respiratory Group (Nucleus Ambiguus and Nucleus Retroambiguus): Controls mainly expiration (including active expiration) as well as inspiration. Also operates as an overdrive mechanism when high levels of pulmonary ventilation are required, especially during heavy exercise.
2) Dorsal Respiratory Group (Nucleus Tractus Solitarius): Controls mainly inspiratory movement and rhythmicity. Integrates sensory information from glossopharyngeal (CN IX) and vagus (CN X) nerves and receives sensory input from viscera of thorax and abdomen and peripheral chemoreceptors and lung receptors.
What are 3 functions of the pontine respiratory centre?
- What is the Apneustic Centre?
- What is the Pneumotaxic Centre?
Pontine Respiratory Centre:
- Controls the rate of involuntary breathing
- Modifies the output of medullary centres
- Interacts with medulla to smooth respiration and inspiration/expiration transition
1) Apneustic Centre: Stimulates the inspiratory neurons of the DRG and VRG
2) Pneumotaxic Centre: Sends inhibitory signals to the inspiratory centre of the medulla (“switches off”) and so controls inspiratory time
Explain the various sensory inputs into the respiratory ‘central controller’.
- What are 7 Sensory Inputs into the respiratory central controller?
Sensory Inputs into the respiratory central controller:
- Other receptors such as nociceptors and emotional stimuli acting via the hypothalamus.
- Higher brain centres such as cerebral cortex for voluntary control
- Pulmonary stretch receptors that protect against barotrauma and hyperinflation.
- Airway irritant receptors that produce cough and help clear foreign particles
- Peripheral chemoreceptors in response to ↓O2, ↑CO2 and ↑H+
- Chemical chemoreceptors in response to ↑CO2 (indirectly) and ↑H+
- Receptors in muscles and joints relying information on oxygen demand
Explain the importance of central and peripheral chemoreceptors in regulating ventilation and identify whether these detect changes in CO2, pH/H+ or O2 in arterial blood or CSF.
- Location and function of central and peripheral chemoreceptors?
Explain the integrated responses of arterial pCO2, [H+] and arterial pO2 in the regulation of pulmonary ventilation.
- What is the most powerful respiratory stimulant?
*** Rising CO2 levels are the most powerful respiratory stimulant (“ hypercapnic drive to breath”) **
What happens when pCO2 levels rise in the blood?
Influence of PCO2:
- PCO2 levels rise in the blood and CO2 accumulates in the brain
- As CO2 accumulates, it is hydrated to form carbonic acid
- The acid dissociates, H+ is liberated, and the pH drops
- The increase in H+ excites the central chemoreceptors, which synapse with the respiratory control centres
- Depth and rate of breathing increase
- Enhanced alveolar ventilation quickly flushes CO2 out of the blood, raising blood pH
- Low PCO2 levels depress respiration
- Normally, arterial PCO2 is 40 mmHg and is maintained within 3mmHg
- Small changes in arterial PCO2 (and pH) produce major changes in ventilation
What effect does declining pO2 have on ventilation?
Influence of PO2:
- Declining PO2 has only a slight effect on ventilation, mostly limited to enhancing the sensitivity of peripheral receptors to increased PCO2
- Arterial PO2 must drop substantially (below 60 mmHg) before PO2 levels become a major stimulus for increased ventilation
- Ventilation is increased via reflexes initiated by the peripheral chemoreceptors in efforts to increase PO2 in the blood
What effect does declining pH have on ventilation?
Influence of pH:
- As arterial pH declines (due to CO2 retention or metabolic factors), respiratory system controls attempt to compensate and raise the pH by increasing respiratory rate and depth to eliminate CO2 from the blood
- Changes in arterial pH can modify respiratory rate and rhythm even when CO2 and O2 levels are normal
- H+ does not cross the blood brain barrier, so changes to ventilation are mediated through peripheral chemoreceptors
Summarise the pathways of the protective respiratory reflexes such as cough and sneeze.
- What are the 3 pulmonary receptors, where are they located and what is their function?
Pulmonary Receptors:
1) Pulmonary Stretch Receptors: Mechanoreceptors in the tracheobronchial region that detect stretch
2) Irritant Receptors: Sensory nerve endings in the epithelium of the trachea, bronchi, and bronchioles sensitive to mechanical and chemical stimuli (bradykinin, PGs and serotonin)
3) C-Fibre Receptors: Sensory nerve endings in the alveolar walls that are stimulated especially when the pulmonary capillaries become engorged with blood or when pulmonary edema occurs in such conditions as congestive heart failure
What are the Pulmonary Irritant Reflexes and what is their function?
Pulmonary Irritant Reflexes:
The lungs contain receptors that respond to an enormous variety of irritants. When activated, these receptors communicate with the respiratory centers via vagal nerve afferents. Accumulated mucus, inhaled debris such as dust, or noxious fumes stimulate receptors in the bronchioles that promote reflex constriction of those air passages. The same irritants stimulate a cough in the trachea or bronchi, and stimulate a sneeze in the nasal cavity.
Describe the steps in the cough reflex pathway.
Describe the steps in the sneeze reflex pathway.
Explain the effects of exercise on the respiratory system.
Discuss a microbiological framework for common lower respiratory tract infections giving examples for each category.
Discuss a microbiological framework for common lower respiratory tract infections giving examples for each category.
Discuss a microbiological framework for common lower respiratory tract infections giving examples for each category.
What are 4 types of virulence factors of Streptococci pneumonia? Examples of each?
Examples of Streptococci pneumoniae Virulence Factors:
1) Adhesion to Epithelial Cells and Mucus
- Pneumococcal surface protein C
- Pneumococcal surface antigen
- Pneumococcal adhesion and virulence factor A
- Enolase
- Capsule
- Pneumolysin
2) Invasion of Host Cells
- Translocation through vascular endothelium related to interaction with platelet activating factor
receptor (PAF-R) and endocytosis
- Membrane pore creation by pneumolysin (cytotoxin)
Evasion of Host Defence
- Polysaccharide capsule (antiphagocytic)
- Bacteria surface coat is changed via gene expression to avoid host defences
- Change Serotype via transformation DNA uptake to evade vaccine
Damage to Host
- Cell wall components and capsule activate classical and alternative complement pathways inducing
inflammation
- Cell wall proteins, autolysin and DNA induce cytokines and inflammation
What are 4 types of virulence factors of Streptococci pneumonia? Examples of each?
Examples of Streptococci pneumoniae Virulence Factors:
1) Adhesion to Epithelial Cells and Mucus
- Pneumococcal surface protein C
- Pneumococcal surface antigen
- Pneumococcal adhesion and virulence factor A
- Enolase
- Capsule
- Pneumolysin
2) Invasion of Host Cells
- Translocation through vascular endothelium related to interaction with platelet activating factor receptor (PAF-R) and endocytosis
- Membrane pore creation by pneumolysin (cytotoxin)
3) Evasion of Host Defence
- Polysaccharide capsule (antiphagocytic)
- Bacteria surface coat is changed via gene expression to avoid host defences
- Change Serotype via transformation DNA uptake to evade vaccine
4) Damage to Host
- Cell wall components and capsule activate classical and alternative complement pathways inducing inflammation
- Cell wall proteins, autolysin and DNA induce cytokines and inflammation
What are 3 examples of Streptococci pneumoniae Resistance Mechanisms?
Examples of Streptococci pneumoniae Resistance Mechanisms:
1) Change Surface Proteins/Alter Target: Produce modified, low-binding-affinity versions of the native Penicillin Binding Proteins (PBPs), inferring resistance to penicillins
2) Alter Target: Erythromycin ribosomal methylase (ermB) enables methylation of a single adenine in the bacterial 50s ribosome that binds to erythryomycin inferring macrolide resistance (COMMON)
3) Remove Antibiotics: Efflux pumps (low level resistance)
List 6 Virulence Factors and 3 Resistance Mechanisms of Other Respiratory Pathogens?
Explain the systemic defence mechanisms, using respiratory system as an example.
- 2 primary immune tissue organs?
- Secondary immune tissue organs?
Systemic Defence Mechanisms: Occurs all over the body
1) Primary Immune Tissue: The developmental site for lymphocytes that are functional but naïve (development independent of antigen)
Organs: Bone marrow and thymus
2) Secondary Immune Tissue: Sites of initial encounter with antigen that drives lymphocytes to their effector state (site of lymphocytes activation)
Organs: Lymph nodes, spleen, Peyer’s patches, MALT, tonsils, appendix etc.
3) Tertiary Immune Tissue: Actual site of the immune response
4) Humoral Immunity: Immune response mediated by antibodies that are secreted by plasma cells (B cells)
5) Cell-mediated Immunity: Immune response mediated by the activation of cells (MOs, NOs, CTL, NK cells) and and the release of various cytokines in response to an antigen
What are the 3 INNATE mucosal defense mechanisms of the respiratory tract?
Mucosal Defence Mechanisms: Limited to mucosal associated areas (respiratory, gastrointestinal, urogenital and reproductive systems) including tonsils, appendix, Peyer’s patches and MALT
Innate Immunity:
- Mechanical: Mucus barrier prevents microbial penetration, cilia traps foreign bodies, debris and
pathogens and mucociliary escalator provides motility
- Chemical: Enzymes and antimicrobials peptides (defensins, cathelicidin, lysozymes, lactoferrins) destroy pathogens
- Microbiological: Commensals protect against colonisation of invading pathogens (deprive potential invasive pathogens of the essential nutrients needed to replicate)
What are the ADAPTIVE mucosal defense mechanisms of the respiratory tract?
- What is MALT? 3 types?
- What are M cells?
- Which specific antibodies? Activated by which ILs?
- Which cells?
- Tolerance?
What is the importance of the mucosal defense mechanisms?
What occurs when they fail?
Mucosal Defence Mechanisms - Importance:
- Mucosal surfaces cover an area of ~400m2 in the average adult
- Often the site where foreign bodies, debris and pathogens are introduced into the body (via airway or gastrointestinal tract) so provides local defence against pathogens
- ALSO provides tolerance to foreign substances (food, commensals, air etc.)
- SO when we get an infection, the body can produce a local mucosal response limited to the intraluminal mucosal surface, independent to- or with, a systemic cellular and humoral response
Failures of Mucosal Immunity: Serious/chronic infection, chronic inflammation, malignancy and allergy
Discuss how particular immune defects predispose to infection with certain types of pathogens using glucocorticoid treatment as an example.
- What are glucocorticoids?
- How do they predispose to infection?
- 5 Complications?
Glucocorticoids: Medication (steroids) which have anti-inflammatory and immunosuppressive effects
Cause: Iatrogenic
Complications: Immunosuppression.
- Decreased production of cytokines
- Decreased production of eicosanoids (messengers to CNS inflammation)
- Decreased production of IgG
- Decreased complement components in blood
- Increased IL-10 and annexin 1 (anti-inflammatory molecules).
Discuss how particular immune defects predispose to infection with certain types of pathogens using glucocorticoid treatment as an example.
- How does cough reflex suppression predispose to infection?
- 7 Causes?
- 2 Complications?
Cough Reflex Suppression: Loss of mechanical clearance
Causes:
- Coma
- General anaesthetic
- Pain
- Neuromuscular disease
- Kyphoscoliosis
- Endotracheal tube
- Drugs
Complications: Increased susceptibility to infection or prolonged duration of infection.
Discuss how particular immune defects predispose to infection with certain types of pathogens using glucocorticoid treatment as an example.
- How does injury to the mucociliary escalator predispose to infection?
- 6 Causes?
- 2 Complications?
Injury to Mucociliary Escalator: Loss of mechanical clearance
Causes:
- Smoking
- Virus
- Alcohol
- Hot corrosive gases
- Ostruction
- Cystic fibrosis
Complications: Increased susceptibility to infection or prolonged duration of infection
Discuss how particular immune defects predispose to infection with certain types of pathogens using glucocorticoid treatment as an example.
- How does decreased macrophage function predispose to infection?
- 5 Causes?
- 3 Complications?
Decreased Macrophage Function:
Causes:
- Alcohol
- Smoking
- Anoxia
- O2 toxicity
- Phagocyte killing defects
Complications: Increased susceptibility to bacterial infections and increased duration and severity of infection
Discuss how particular immune defects predispose to infection with certain types of pathogens using glucocorticoid treatment as an example.
- How does impairment of the immune system predispose to infection?
- 8 Causes?
- Complications?
Impairment of Immune System: Immunosuppression
Causes: Chronic disease, immune deficiency, medications, recent infection, co-morbidities, AIDS, leukopenia, ageing, etc.
Complications: Increases opportunistic infections or infections from normally low-virulent microbes e.g. pneumocystis
Explain the effect of immune defects on response to treatment.
What is Pneumonia?
4 Pathological Classifications of Pneumonia?
Pneumonia: Microbial infection of lung parenchyma distal to terminal bronchiole
- Lobar Pneumonia
- Bronchopneumonia
- Interstitial (Atypical) Pneumonia
- Aspiration Pneumonia
What is Lobar Pnuemonia?
- What is the usual pathogenic cause?
- 5 clinical features?
- Appearance on CXR?
Lobar Pneumonia: Characterised by consolidation of an entire lobe of the lung, and is usually bacterial (Streptococcus pneumoniae and Klebsiella pneumoniae)
- Intra-alveolar exudate
- Bronchi are relatively spared
- CXR: Air bronchogram (phenomenon of air-filled bronchi (dark) made visible by the opacification of surrounding alveoli (grey/white)) and non-segmental consolidation
- No ventilation: Shunt with hypoxia
- Acute onset
What is Bronchopnuemonia?
- What are the usual pathogenic causes?
- Clinical features?
- Appearance on CXR?
Bronchopneumonia: Characterised by scattered patchy consolidation centered around bronchioles, often multifocal (patchy) and bilateral caused by a variety of bacterial organisms (Staphylococcus aureus, Hemophilus influenzae, Pseudomonas aeruginosa, Moraxella catarrhalis and Legionella pneumophila)
- Inflammation of conducting airways (terminal bronchioles)
- Minimal intra-alveolar spread
- CXR: No air bronchograms, no segmental distribution and patchy consolidation
What is Interstitial (Atypical) Pneumonia?
- What are the usual pathogenic causes?
- Clinical features?
- Appearance on CXR?
Interstitial (Atypical) Pneumonia: Characterised by diffuse interstitial infiltrates (connective tissue in lungs), presents atypically with relatively mild upper respiratory symptoms (minimal sputum and low fever), and caused by atypical bacteria or viruses (mycoplasma pneumoniae, chlamydia pneumoniae, RSV, CMV, influenza virus and Coxiella burnetii)
- Defined clinically based on presence of extrapulmonary manifestations (confusion, hypoxia and sepsis etc.), not just confined to the lungs like with typical pneumonia
- Moderate sputum production
- No evidence of consolidation
- Moderate elevation of WCC
- Lack of alveolar exudate
- CXR: May be less impressive than clinically expected, lower lung fields, bilateral and perihilar distribution and “interstitial” pattern.
- Pathology can include type II pneumocyte hyperplasia, hyaline alveolar membranes, and an increased number of mononuclear cells within the alveolar septa
Who is at risk of Aspiration Pneumonia?
What commonly causes it?
Aspiration Pneumonia: Seen in patients at risk for aspiration (alcoholics, seizures and comatose patients), most often due to anaerobic bacteria in the oropharynx (Bacteroides, Fusobacterium, and Peptococcus)
What are the 4 Different Stages of Consolidation seen in pneumonia?
- Give the characteristics and clinical features of each.
PNEUMONIA - Different Stages of Consolidation
1) Congestion (1-2 Days): Due to congested vessels and oedema
- Characteristics: Heavy boggy red lungs, intra-alveolar exudate, few neutrophils, bacteria, vascular congestion
- Clinical: Fine crackles and watery sputum
2) Red Hepatisation (2-4 Days): Due to exudate, neutrophils, and hemorrhage filling the alveolar air spaces, giving the normally spongy lung a solid consistency
- Characteristics: Firm red airless lung, fibrinopurulent pleuritis, some intra-alveolar exudate and cells (erythrocytes, neutrophils and fibrin)
- Clinical: Bronchial breathing and rusty sputum
3) Grey Hepatisation (4-8 Days): Due to degradation of red cells within the exudate
- Characteristics: Dry grey brown cut surface, increased intra-alveolar fibrin and macrophages, degradation of erythrocytes and polymorphs
- Clinical: Moist rhonchi (continuous low pitched, rattling lung sounds)
4) Resolution (8-9 Days):
- Characteristics: Enzymatic digestion of exudate and resorption via phagocytosis
- Clinical: Expectoration (coughing up) of sputum
Compare Community-Acquired vs Hospital Acquired pneumonia in terms of:
- Definition
- Clinical Classification/Pathology
- Microbiology
- Epidemiology
Community Acquired Pneumonia (CAP): Occurs in people who are not or have not been in hospital recently, and who are not institutionalised or immunocompromised. Normally infection with S. pneumoniae (majority) or H. influenzae.
Hopsital Acquired (Nosocomial) Pneumona: An acute lower respiratory tract infection that is acquired after at least 48 hours of admission to hospital and is not incubating at the time of admission (often gram negative drug resistant bacteria such as Pseudomonas aerogenesis).
Compare Typical vs Atypical pneumonia in terms of:
- Pathology
- Microbiology
- Epidemiology
Outline the clinical presentation of common lower respiratory tract infections such as acute laryngotracheobronchitis (croup).
- Definition?
- 5 Clinical features?
Laryngotracheobronchitis (Croup): Inflammation of the larynx, trachea, and bronchi caused by an acute infection (parainfluenza virus most common cause) and subsequent swelling, excess mucus secretion and obstruction of the airways
- Characteristic hoarse “barking” cough with inspiratory stridor - Sounds like a dog barking or a seal
- Children 9 months to 3 years
- Usually 11 pm to 2 am
- Auscultation confirms inspiratory stridor
- Occurs in small local epidemics
Outline the clinical presentation of common lower respiratory tract infections such as acute bronchitis.
- Definition?
- 7 Clinical features?
Acute Bronchitis: Acute inflammation of the tracheobronchial tree that usually follows an upper respiratory infection. Although generally mild and self-limiting, it may be serious in debilitated patients.
- Cough and sputum (main symptoms)
- Wheeze and dyspnoea
- Usually viral infection
- Can complicate chronic bronchitis (often due to Haemophilus influenzae and Streptococcus pneumonia)
- Scattered wheeze on auscultation
- Fever or haemoptysis (uncommon)
- Improves spontaneously in 4–8 days in healthy patients
Outline the clinical presentation of common lower respiratory tract infections such as Bronchiolitis.
- Definition?
- Epidemiology?
- 9 Clinical features?
Bronchiolitis: Inflammation of the bronchioles due to an acute viral infection (usually RSV)
- The commonest acute LRTI in infants
- Usual age 2 weeks to 9 months (up to 12 months)
- Prodromal symptoms for 48 hours (e.g. coryza, irritating cough, then 3–5 days of more severe symptoms)
- Squeaks worsened upon inspiration
- Wheezy breathing (often distressed)
- Tachypnoea
- Hyperinflated chest: Barrel-shaped, usually subcostal recession
- Widespread fine inspiratory crackles (not with asthma) upon auscultation
- Frequent expiratory wheezes upon auscultation
- Hyperinflation of lungs with depression of diaphragm upon x-ray (but chest X-ray should not be used for diagnosis or routinely performed)
- Dehydration is a serious problem, especially with exhausted infants
Recognise clinical symptoms and signs of different types of pneumonia.
- What is pneumonia?
- When does it occur?
- Clinical features?
- Diagnostics?
Pneumonia: Inflammation of lung tissue (lung parenchyma)
- Occurs when normal defenses are impaired (impaired cough reflex, damage to mucociliary escalator, or mucus plugging)
- Clinical features include: 1. fever and chills, 2. productive cough with yellow-green (pus) or rusty (bloody) sputum, 3. tachypnea with 4. pleuritic chest pain, 5. decreased breath sounds, 6. dullness to percussion, and 7. elevated WBC count.
- Often history of viral respiratory infection
- Lethargy, poor appetite, weight loss
- Evidence of sepsis
- Diagnosis is made by chest x-ray, sputum gram stain and culture, and blood cultures
- X-ray and examination show focal chest signs and consolidation
What is lobar pneumonia? (pattern of involvement)
Causative pathogens?
Lobar Pneumonia: Characterised by consolidation of an entire lobe of the lung, and is usually bacterial (Streptococcus pneumoniae and Klebsiella pneumoniae)
What is Bronchopneumonia?
Causative organisms?
Histology?
Bronchopneumonia: Characterised by scattered patchy consolidation centered around bronchioles, often multifocal (patchy) and bilateral caused by a variety of bacterial organisms (Staphylococcus aureus, Hemophilus influenzae, Pseudomonas aeruginosa, Moraxella catarrhalis and Legionella pneumophila)
Bronchopneumonia: mostly commonly a descending infection that affects the bronchioles and adjacent alveoli
- Primarily caused by pneumococci and/or other streptococci
- Characterized by acute inflammatory infiltrates that fill the bronchioles and the adjacent alveoli (patchy distribution)
- Usually involves the lower lobes or right middle lobe and affects ≥ 1 lobe
- Manifests as typical pneumonia
- Necrotizing bronchopneumonia and pneumatocele are caused by Staphylococcus aureus and are often preceded by an influenza infection.
Histology
Relatively normal lung tissue (green overlay) can be seen next to pathologic lung tissue (white overlay) with alveolar infiltrates of mainly neutrophils as well as exsudation of erythrocytes. A crosssection of an airway (white outline) also shows infiltrates of a purulent infiltrate (examplary marked with black arrows) consisting of predominantly neutrophils.
What is Interstitial (Atypical) pneumonia?
Clinical presentation?
Pathogenic cause?
Interstitial (Atypical) Pneumonia: Characterized by diffuse interstitial infiltrates (connective tissue in lungs), presents atypically with relatively mild upper respiratory symptoms (minimal sputum and low fever), and caused by atypical bacteria or viruses (mycoplasma pneumoniae, chlamydia pneumoniae, RSV, CMV, influenza virus and Coxiella burnetii)
Recognise radiological signs of pneumonia.
- What are the radiological features of lobar, lobular, interstitial and aspiration pneumonia?
What is the importance of microbiological diagnosis in the management of pneumonia?
- Which antibiotics would you use for pneumococcus (S. pneumonia)?
- What are 3 atypical organisms of pneumonia and which antibiotics would you use for them?
- Which antibiotics are used for antibiotic resistant bacteria such as extended spectrum beta-lactamases (ESBLs)?
Pneumococcus (S. pneumonia) → β-lactam antibiotics (amoxycillin, benzylpenicillin or 3rd generation cephalosporin)
Atypical organisms such as Mycoplasma pneumoniae,Chlamydia pneumoniaeandLegionellaspecies → Doxycycline or macrolides
Antibiotic-resistant bacteria eg. ESBLs → Ticarcillin/Clavulanic Acid or Piperacillin/Tazobactam, 3rd generation cephalosporin (ceftriaxone or Cefepime) or Carbapenems such as meropenem are used for
What are 6 Routine Microbiological Investigations for pneumonia?
- Sputum Sample: To identify the likely pathogen via gram stain and culture (collected before starting antibiotic therapy)
- Blood Sample: To identify the likely pathogen via culture (ideally before starting antibiotic therapy)
- Pneumococcal Urinary Antigen Assay: Performed on routine urine specimens (either before or after starting antibiotic therapy) for the early identification of Streptococcus pneumonia
- Legionella Urinary Antigen Assay: Detects Legionella pneumophila serotype 1
- Nose and Throat Swabs: For PCR for respiratory viruses including influenza, and are becoming available for Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella
- IgM Serology: For M. pneumoniae, and acute and convalescent serology for M. pneumoniae, Legionella, C. pneumoniae and influenza. The M. pneumoniae IgM result can assist in making a diagnosis during the acute phase of the illness, but the other tests usually only provide a retrospective diagnosis (looking for a change in IgG titre between acute and convalescent serology). In acute illness, interpret a low positive IgG result with caution, as it may reflect past infection rather than current infection.
What are 4 Non-Routine Microbiological Investigations for pneumonia?
- Bronchoalveolar Lavage: Performed to identify a pathogen in a severely ill patient who has not responded to empirical antibiotic therapy, BUT balance the likelihood of a pathogen being identified with the potential risks of the procedure
- Bronchoscopy/Tracheal Aspiration: For the sick, immunocompromised or those not improving
- Pleural Aspiration
- Fine Needle Aspiration of Abscess
What are 8 factors you would consider when clinically assessing the severity of pneumonia?
Clinical Assessment of Severity of Pneumonia:
- Severity Scales: PSI, CURB-65, SMART-COP (Australia), ATS and BTS (URB)
- Vital Signs
- Age
- X-Ray or CT Appearance: Number of lobes or pleural effusion
- Comorbidities: Neoplasms, liver disease, heart failure, renal failure, CVA
- Physiological Impairment: Respiratory rate, heart rate, blood pressure, oxygen saturation and renal, hepatic and metabolic function
- Altered Mental Status (GCS)
- Smoking Status
What is the SMART-COP tool for assessing severity of community acquired pneumonia (CAP) in adults?
What are 5 signs of clinical deterioration of pneumonia?
Signs of Clinical Deterioration:
- Presence of focal chest signs (decreased chest expansion, dullness on percussion, decreased entry of air, bronchial breathing, and crackles)
- Multilobar infiltrates
- Altered mental status
- Altered vital signs (hypotension, raised respiratory or heart rate, hypothermia)
- Sepsis, multi-organ problems and pleural effusion can lead to rapid deterioration
Discuss the principles of choosing empiric antibiotic therapy for pneumonia.
Discuss the efficacy of major antibiotic classes outlining their microbiological spectrum.
- Penicillins?
Cell Wall Synthesis Inhibitors (Bactericidal): Penicillins
- Active against Gram-positive organisms
- Inactivated by beta-lactamase enzymes
- Dicloxacillin and flucloxacillin are stable to β-lactamase enzymes produced by staphylococci
- Piperacillin and ticarcillin have activity against Pseudomonas aeruginosa
- B-lactamase inhibitors with penicillin to cover anaerobe activity
Discuss the efficacy of major antibiotic classes outlining their microbiological spectrum.
- Cephalosporins?
Cell Wall Synthesis Inhibitors (Bactericidal): Cephalosporins
- Excellent Gram-positive activity
- Poor anaerobe activity
- 3rd generation = Gram-negative activity
- 4th generation = Pseudomonas activity
- 5th generation = MRSA (minus pseudomonas activity)
Discuss the efficacy of major antibiotic classes outlining their microbiological spectrum.
- Carbapenems?
Cell Wall Synthesis Inhibitors (Bactericidal): Carbapenems
- Broad-spectrum activity against many resistant Gram-negative organisms
- Anaerobe cover
- ESBLs and Pseudomonas aeruginosa cover
- Inactive against MRSA, VRE, Enterococcus faecium, Mycoplasma, Chlamydia, and Stenotrophomonas maltophilia
Discuss the efficacy of major antibiotic classes outlining their microbiological spectrum.
- Monobactams?
Cell Wall Synthesis Inhibitors (Bactericidal): Monobactams
- Gram-negative bacteria
- β-lactamase producing Haemophilus influenzae
- Enteric Gram-negative rods
- Pseudomonas species
- Inactive against Gram-negative anaerobic organisms and all Gram-positive organisms
Discuss the efficacy of major antibiotic classes outlining their microbiological spectrum.
- Glycopeptides?
Cell Wall Synthesis Inhibitors (Bactericidal): Glycopeptides
- Gram-positive organisms only (including MRSA)
Discuss the efficacy of major antibiotic classes outlining their microbiological spectrum.
Protein Synthesis Inhibitors (Bacteriostatic):
- Aminoglycosides
- Tetracyclines
- Macrolides
- Lincosamides
- Oxazolidinone (Linezolid)
- Chloramphenicol
Discuss the efficacy of major antibiotic classes outlining their microbiological spectrum.
Protein Synthesis Inhibitors (Bacteriostatic):
- Quinolones
- Metronidazole
- Co-Trimoxazole
- Rifampicin
- Fusidic Acid
Discuss the efficacy of major antibiotic classes outlining their microbiological spectrum.
Cell Membrane Disruptors:
- Daptomycin
- Polymyxin
What is Respiratory failure?
Acute vs. Chronic? Examples of each?
Respiratory Failure: Inability to maintain adequate oxygenation (reduced O2) or ventilation (increased CO2)
- A condition in which the respiratory system fails in one or both of its gas exchange functions, oxygenation of and/or elimination of carbon dioxide from mixed venous blood
-
Acute: Occurs suddenly and is treated as an emergency (hours to days)
- Examples: Drug overdose (ventilatory) and pneumonia (oxygenation)
-
Chronic: Develops over time, becomes “usual state” and requires long-term treatment (months to years)
- Examples: Neuromuscular disease (ventilatory) and pulmonary fibrosis (oxygenation)
What is the difference between Type I and Type II Respiratory Failure?
Type I RF: Failure of Oxygenation
Oxygenation: Uptake of O2 molecule onto the haemoglobin molecule
O2 decreased and CO2 low or normal
PaO2 < 55-60mmHg
Failure: Hypoxaemia (low PaO2 in blood)
Mechanisms of Hypoxaemia:
Impaired diffusion
Ventilation-perfusion (V/Q) mismatch
Hypoventilation
Shunt
Reduced inspired O2 concentration
Ventilation: Removal of CO2 from the blood
CO2 increased and O2 decreased
PaCO2 > 45-50mmHg
Failure: Hypercapnoea (Low PaCO2 in blood)
Mechanisms of Hypercapnoea:
i. Hypoventilation
What is the difference between Type I and Type II Respiratory Failure?
- What are the O2/CO2 levels like in each?
- What is the PaO2 of Type I RF?
- What are the 5 mechanisms of hypoxemia in Type I RF?
- What is the PaCO2 in Type II RF?
- What ar the 2 Mechanisms of Hypercapnoea in Type II RF?
Type I RF:** **Failure of Oxygenation
- Oxygenation: Uptake of O2 molecule onto the haemoglobin molecule
- O2 decreased and CO2 low or normal
- PaO2 < 55-60mmHg
- Failure: Hypoxaemia (low PaO2 in blood)
-
Mechanisms of Hypoxaemia:
- Impaired diffusion
- Ventilation-perfusion (V/Q) mismatch
- Hypoventilation
- Shunt
- Reduced inspired O2 concentration
Type II RF:** **Failure of Ventilation
- Ventilation: Removal of CO2 from the blood
- CO2 increased and O2 decreased
- PaCO2 > 45-50mmHg
- Failure: Hypercapnoea (Low PaCO2 in blood)
-
Mechanisms of Hypercapnoea:
- Hypoventilation
- Ventilation-perfusion (V/Q) mismatch
What is ventilation? What is perfusion?
What is a V/Q physiological deadspace?
What is a V/Q Shunt?
Describe the acute management of a dyspnoeic patient?
Acute Management of Dyspnoeic Patient:
Explain principles of supportive management (8) and clinical monitoring (6) of respiratory tract disease?
Supportive Management: To prevent or treat as early as possible the symptoms of a disease, side effects caused by treatment of a disease, and psychological, social, and spiritual problems related to a disease or its treatment
- Correct hypoxaemia via oxygen therapy
- Deal with hypercapnoea via non-invasive or mechanical ventilation
- Nutrition
- Prevent DVT
- Maintain acid-base balance
- Maintain fluid balance
- Maintain homeostatic balances
- Manage pain
Clinical Monitoring: The observation of a disease, condition or one or several medical parameters over time.
- Vital signs (HR, RR, BP, temperature, O2 saturation)
- Blood glucose levels
- Consciousness (Glasgow Coma Scale)
- Urine output
- Medication chart
- General observations
Demonstrate knowledge in oxygen therapy and delivery systems.
- What is oxygen therapy?
- 6 Delivery systems?
Oxygen Therapy: Supplemental oxygen administered as a medical treatment through nasal canulae, masks or a breathing tube
Delivery Systems:
- Nasal Canulae
- Simple (Hudson) Masks
- Non Re-Breathing Masks
- Partial Non Re-Breather Masks
- Face Tent
- Venturi Masks
What is the oxygen delivery flow rate and advantages of the different oxygen delivery devices?
Develop skills in using problem solving approach to clinical reasoning.
- What is clinical reasoning and what does it involve?
- Steps?
Clinical Reasoning: An ability to integrate and apply different types of knowledge, to weigh evidence, critically think about arguments and to reflect upon the process used to arrive at a diagnosis.
- To construct, evaluate, refine and distinguish diagnoses
- Involves gathering information, reasoning to a diagnosis and refining diagnosis (challenging assumptions, hypothesis testing, progression from differential diagnoses to provisional diagnosis to final diagnosis)
- It is important because it supports accurate diagnosis, timely diagnosis and evaluation of response to treatment
- Depends upon critical thinking and metacognitive abilities
- Practice by considering differentials, verbalising reasoning, identifying triads, pathognomic features (signs and tests) and syndromes and developing illness scripts
Clinical Reasoning Steps:
- Pattern Recognition: Spot diagnoses (important in time pressured situations!)
- Reflection and Re-Evaluation: Reduces uncertainty, cognitive errors and bias
- What are differential diagnoses?
- What is the diagnostic approach?
- What are 5 Questions to Foster Clinical Reasoning?
- What are 5 questions on the Diagnostic Model for Presenting Complaint (Murtagh’s GP)?
Differential Diagnoses: Refer to the possible alternative diagnoses that could account for the observed symptoms and signs.
Diagnostic Approach: The process followed to determine which disease process or condition explains a patient’s symptoms and signs (Murtagh’s diagnostic model, red/yellow flags or systematic approach)
Questions to Foster Clinical Reasoning:
- What are your differential diagnoses?
- What are your differential diagnoses, based on your history?
- What signs are you seeking to elicit to refine (confirm or exclude) your differential diagnoses?
- What symptoms and signs support your differential diagnoses?
- What investigations would you order and why?
- Given x result, how does this change your differential diagnosis list?
Diagnostic Model for Presenting Complaint (Murtagh’s GP):
- What is the probability diagnosis?
- What serious disorders must not be missed?
- What conditions are often missed (the pitfalls)?
- Could this patient have one of the ‘masquerades’ in medical practice?
- Is this patient trying to tell me something else (cues, concerns, anxieties, communication)?
Outline the basic aetiological categories of granulomatous lung diseases (infectious and non-infectious) giving examples for each.
- What are 3 Infectious Granulomatous Lung Diseases?
- What are 7 Non-Infectious Granulomatous Lung Diseases?
What is a Granuloma?
- Purpose?
- Classic Granuloma Morphology?
- How do they form? (8 steps)
Granuloma: A compact, organised collection of epithelioid macrophages (“histiocytes”) which may or may not be accompanied by accessory features such as central necrosis or the infiltration of other inflammatory leukocytes (T lymphocytes)
Purpose: Cellular attempt to contain an offending agent that is difficult to eradicate
Classic Granuloma Morphology: Central pale macrophage rich area with a lymphocyte cuff (border)
Formation:
Noxious stimulus cannot be removed by macrophages (persistent intracellular microbial survival or foreign body)
Macrophage activation and secretion of IL-1, TNF-a and IL-12
T Cell (CD4) proliferation, activation and differentiation to Th1 and secretion of IL-2 and IFN-y
Further activation of macrophages leads to maturation into epithelioid macrophages
Epithelioid change characterised by pale granular cytoplasm and indistinct cell membranes
Epithelioid macrophages combine to form the characteristic multi-nucleate giant cell
Surrounded by lymphocytes in attempts to wall off agent
Peripheral fibrosis whilst enhanced killing ability by macrophages leads to tissue destruction
What are the Basic Pathological Features of Tuberculosis?
- 2 macroscopic?
- 5 microscopic?
Basic Pathological Features of Tuberculosis:
Macroscopic
- Central caseous necrosis
- Fibrosis
Microscopic
- Necrotising granulomatous inflammation
- Central necrosis without residual cell outlines
- Acid Fast Bacilli (AFBs) with Ziehl-Neelsen stain
- Necrosis surrounded by activated epithelioid macrophages and giant cells including Langhan’s cells
- Outer layers of lymphocytes and fibrosis
What are the Specific Pathological Features of Primary Tuberculosis?
- Where do bacteria tend to implant?
- What is a Ghon focus?
- What is a Ghon complex?
- What is a Ranke complex?
Primary TB
- Typically, bacteria implant in the distal airspaces of the lower part of the upper lobe or the upper part of the lower lobe, usually close to the pleura.
- As sensitization develops, a 1-1.5cm area of grey-white inflammation with consolidation emerges, known as the Ghon focus.
- The combination of parenchymal lung lesion and nodal involvement is referred to as the Ghon complex, which will undergo progressive fibrosis, often followed by radiologically detectable calcification .
- Ranke complex is seen in healed primary pulmonary TB and consists Ghon lesion (calcified parenchymal tuberculoma) and ipsilateral calcified hilar node.
What are the Specific Pathological Features of Secondary Tuberculosis?
Secondary TB
The upper parts of both lungs are riddled with grey-white areas of caseation and multiple areas of softening and cavitation.
Hilar LNs not usually involved.
What are the Specific Pathological Features of Progessive Tuberculosis?
Progessive TB
- The apical lesion expands into adjacent lung and eventually erodes into bronchi and vessels.
- This evacuates the caseous center, creating a ragged, irregular cavity that is poorly walled off by fibrous tissue.
- Erosion of blood vessels results in hemoptysis.
What are the Specific Pathological Features of Miliary Tuberculosis?
Miliary TB
Numerous grey-white tubercles on cut surface of organs.
What are the pathological features of other granulomatous lung diseases:
- Sarcoidosis?
- Wegener Granulomatosis?
- Bronchiectasis?
Sarcoidosis
- Interstitial epithelioid granulomas distributed along lymphatic pathways (bronchovascular bundles, interlobular septa, pleura).
- Granulomas are non-necrotising and often contain asteroid, Schaumann and conchoid bodies and birefringent crystalline material.
Wegener Granulomatosis
- Necrotising granulomas and ulceration URT
- May see loosely formed granulomas in interstitium of lung, but more commonly a capillaritis (neutrophils in alveolar capillaries)
- Alveolar haemorrhage
- Glomerular necrotising lesions and crescents
Bronchiectasis
- Dilated bronchi can extend almost to pleural surface
- Contain mucopurulent material, surrounding scarring, exaggerated transverse ridging and trabeculation of bronchial mucosa.
Discuss the mode of transmission and the microbiology of tuberculosis.
- Mycobacterium tuberculosis?
- Mycobacterium bovis?
- 9 microbiological features?
What are 8 Virulence Factors of TB?
TB Virulence Factors
- Waxy Coat: Protects against macrophage killing
- High Lipid Cell Wall: Impermeable and resistant to antimicrobial agents, resistant to killing by acidic and alkaline compounds in both the intracellular and extracellular environment, and resistant to osmotic lysis via complement deposition or attack by lysozyme
- Cord Factor: Surface glycolipids allow organism to form cords, prevents phagolysosomal fusion
- Lipoarabinomannan (LAM): Inhibits macrophage activation and phagolysosomal fusion (escapes killing by MO)
- Sulfolipids: Impairs macrophage activation by inhibiting phagosomal maturation
- Induces delayed (type IV) hypersensitivity reaction
- Lacks Toxins
- Resistant to routine antibiotics
List the steps in the Immunology and Pathogenesis of Primary Pulmonary Lesion of TB?
- TEERDATGL
Immunology and Pathogenesis of Primary Pulmonary Lesion:
- Transmission
- Entry
- Evasion
- Replication
- Detection
- Activation of Immune Response
- TH1 Response and Macrophage Activation
- Granulomatous Inflammation and Tissue Damage
- Latency
Describe the Immunology and Pathogenesis of Primary Pulmonary Lesion of TB?
- Transmission?
- Entry?
- Evasion?
- Replication?
- Detection?
Immunology and Pathogenesis of Primary Pulmonary Lesion
Transmission: Inhalation of infected aerosol droplet
Entry: Mycobacterium tuberculosis land in the alveoli where they are phagocytised by alveolar macrophages (mediated by MBL and CR3).
Evasion: Mycobacterium tuberculosis inhibits maturation of the phagosome and blocks formation of the phagolysosome (by inhibiting Ca2+ signals and the recruitment and assembly of the proteins that mediate the phagosome-lysosome fusion).
Replication: Evasion from macrophage killing allows Mycobacterium tuberculosis to reside in macrophage lysosomes for several weeks and replicate unchecked within the vesicle. The bacteria proliferate in the pulmonary alveolar macrophages and air spaces, resulting in bacteremia and seeding of multiple sites, yet most people at this stage are asymptomatic or have a mild flu-like illness.
Detection: Bacterial MAMPs (lipoproteins and glycolipids) are detected by innate receptors (TLRs) which initiates an immune response.
Describe the Immunology and Pathogenesis of Primary Pulmonary Lesion of TB?
- Activation of Immune Response?
- TH1 Response and Macrophage Activation?
- Granulomatous Inflammation and Tissue Damage?
- Latency?
Immunology and Pathogenesis of Primary Pulmonary Lesion:
Activation of Immune Response (~3 Weeks Post Infection): Mycobacterial antigens enter draining lymph nodes and are displayed to T cells. T cells differentiate to TH1 cells (dependent on IL-12 from APCs).
TH1 Response and Macrophage Activation: TH1 cells in lungs and LNs produce IFN-γ which activates macrophages and promotes bactericidal action (delayed type IV hypersensitivity reaction)
- a. IFN-γ stimulates maturation of the phagolysosome in infected macrophages, exposing the bacteria to a lethal acidic, oxidizing environment.
- b. IFN-γ stimulates expression of inducible nitric oxide synthase, which produces nitric oxide (NO), NO combines with other oxidants to create reactive nitrogen intermediates, for killing of mycobacterium
- c. IFN-γ mobilises antimicrobial peptides (defensins) against the bacteria
- d. IFN-γ stimulates autophagy, a process that sequesters and then destroys damaged organelles and intracellular bacteria
- *Granulomatous Inflammation and Tissue Damage:** TH1 response orchestrates the formation of granulomas and caseous necrosis. Macrophages activated by IFN-γ differentiate into the “epithelioid histiocytes” that aggregate to form granulomas; some epithelioid cells may fuse to form giant cells. Activated macrophages also secrete TNF and chemokines, which promote recruitment of more monocytes
- *NB:** TH17 also drives granuloma formation via IL-17 (and IL-21, IL-22) release and cell-mediated inflammation
Latency: Viable organism may remain dormant in lesions for decades
What is the difference between primary and secondary TB?
Primary TB: Occurs in the nonimmune host (delayed type IV hypersensitivity reaction)
Secondary TB: Occurs in a previously sensitised host
What is the Pathogenesis of Post Primary Tuberculosis (Pulmonary)?
What is the Pathogenesis of Post Primary Tuberculosis (Extrapulmonary)?
Pathogenesis of Post Primary Tuberculosis (Extrapulmonary):
Extrapulmonary TB: Spread of TB outside of lungs via blood or lymphatic spread
Miliary TB: Diffuse hematogenous dissemination of the bacteria (via arterial system) to the liver, bone marrow, spleen, adrenals, meninges, kidneys, fallopian tubes, and epididymis (or any other organ) following progressive pneumonia
What are the 7R’s of Medication Administration?
7R’s of Medication Administration:
- Right Patient
- Right Medication
- Right Dose
- Right Time
- Right Route
- Right Documentation
- Right Reason
What are the Ten Principles of Good Prescribing?
Ten Principles of Good Prescribing:
- Be clear about the reasons for prescribing
- Consider the patient’s medication history before prescribing
- Identify other factors that might alter the benefits and risks of treatment
- Take into account the patient’s ideas, concerns, and expectations
- Select effective, safe, and cost-effective medicines appropriate for the patient
- Adhere to national and hospital guidelines
- Write unambiguous legal prescriptions using the correct documentation
- Monitor the beneficial and adverse outcomes of treatment
- Communicate and document prescribing decisions and the reasons for them
- Prescribe within limitations of knowledge, skills, and experience
Define what is meant by drug interaction.
- What is a Synergistic Reaction?
- What is an Antagonistic Reaction?
- What is an adverse effect?
- What is a Precipitant?
- What is an object?
Drug Interaction: A reaction between two (or more) drugs or between a drug and a food, beverage, or supplement
Synergistic Reaction: Drug’s effect is increased
Antagonistic Reaction: Drug’s effect is decreased
Adverse Effects: Drug interaction causes undesired harmful effect
Precipitant: The substance causing the interaction
Object: The substance being modified by the interaction
What are 6 types of drug interactions?
What is a source where you can find info on drug interactions?
Types of Interaction:
- Drug-Drug
- Drug-Herbal
- Food-Drug
- Chemical-Drug
- Genetics-Drug (Pharmacogenetics)
- Drug-Lab Test
Source for Drug Interactions: Australian Medicines Handbook
What is a Pharmacokinetic (PK) Interaction?
- Absorption? (4)
- Distribution? (2)
- Metabolism and Elimination? (3)
Pharmacokinetics = What body does to the drug
Pharmacokinetic (PK) Interactions: Occur when ADME of the drug is affected by another drug
What is a Pharmacodynamic (PD) Interaction?
Example?
Pharmacodynamic (PD) Interactions: Occur when the drug is altered by another drug producing an antagonistic, synergistic or additive effect.
• Example: CNS depressants such as narcotics (morphine) and antihistamines (diphenhydramine) can produce enhanced effects such as increased drowsiness when taken together
Describe the clinical features (symptoms and signs) of pulmonary and extrapulmonary tuberculosis.
Clinical Features of Pulmonary Tuberculosis:
DxT: Malaise + Cough + Weight Loss (± Erythema Nodosum)
Suspect TB: Cough >3 Weeks + Travel/Migration (Recent or 30yrs Later)
Describe the clinical features (symptoms and signs) of pulmonary and extrapulmonary tuberculosis.
Discuss investigations for the diagnosis of pulmonary tuberculosis. (7)
1) Chest X-Ray:
- Typically upper lobe infiltrates and cavitation (particularly with haemoptysis)
- Good screening tool as usually abnormal
- Not specific and doesn’t confirm activity
- CT rarely adds anything!
2) Sputum Sample:
- Acid-Fast Bacilli (AFB)/Ziehl Neelson Stain
- Culture (9-14 days at least!)
- PCR
- Drug Susceptibility Tests
- Can also do with urine, fine needle aspiration (LN biopsy), fibre-optic bronchoscopy, CSF sample if TB suspected in other organs etc.
Other Investigations:
3) Mantoux Tuberculin Test: Detects delayed type IV hypersensitivity reaction to tuberculin
4) Immunochromatographic Finger-Prick Test: New and promising test which uses blood from a finger prick to test for proteins that are part of the TB biosignature
5) Interferon Gamma Release Assay (IGRA): QuantiFERON GOLD TB Assay which measures IFN-γ from lymphocytes in blood sample by enzyme-linked immunosorbent assay (EIA)
6) Biopsies on Lesions/LNs (may be necessary)
7) HIV Studies
Explain important principles of management of tuberculosis, especially the rationale and evidence base for current treatment guidelines.
- Management?
- Standard Short-Course Therapy?
Management of Patients with TB:
- Close consultation with specialists who have appropriate training and experience
- Reference to local policies and guidelines
- Prompt notification of all cases to the relevant jurisdictional public health authorities
- Contact tracing, performed by specially trained professionals liaising closely with treating physicians (see the Australasian Contact Tracing Manual for more information)
Standard Short-Course Therapy (eTG):
- Treatment is standardised, evidence-based, usually 4 drugs over 6 months (2HREZ4HR)
- 2 months of treatment with isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E), followed by 4 months of treatment with isoniazid and rifampicin (daily regimen)
- Directly observed therapy
- Extend the duration of therapy if the response is not satisfactory
- Modified if there are difficulties, drug resistance or extrapulmonary TB
- Multiple drugs prevent resistance
What are the Minor (5) and Major (4) TB Drug side effects?
Apply skills in recognising key diagnostic features of tuberculosis (TB) on plain chest x-rays and in constructing a differential diagnosis of focal x-ray lesions.
- ABC Method ox CXR interpretation?
- Key Diagnostic Features of TB on CXR?
Key Diagnostic Features of TB on CXR:
- Active TB typically presents with upper lobe infiltrates, consolidations and/or cavitation (particularly with haemoptysis) with or without mediastinal or hilar lymphadenopathy
- In HIV and other immunosuppressed persons, any abnormality may indicate TB or the chest X-ray may even appear entirely normal
- Old healed tuberculosis usually presents as pulmonary nodules in the hilar area or upper lobes, with or without fibrotic scars and volume loss, bronchiectasis and pleural scarring may also be present
What is the pathology present on this CXR?
What is the pathology present on these CXRs?
A pneumothorax = a collapsed lung. A pneumothorax occurs when air leaks into the space between your lung and chest wall. This air pushes on the outside of your lung and makes it collapse. A pneumothorax can be a complete lung collapse or a collapse of only a portion of the lung.
A tension pneumothorax = a severe condition that results when air is trapped in the pleural space under positive pressure, displacing mediastinal structures, and compromising cardiopulmonary function.
What is the pathology present on this CXR?
Be able to recognise the following pathologies on CXR?
- Cardiomegaly?
- Pneumothorax?
- Tension pneumothorax?
- Wide mediastinum?
- Pleural effusion?
- Haemothorax?
- Pulmonary oedema?
- Pneumonia?
- COPD?
https://www.msdmanuals.com/professional/injuries-poisoning/thoracic-trauma/pneumothorax-tension
Illustrate, with examples, how vascular invasion/breach may occur through vessel damage, obstruction, and changes in pressure.
- What are 3 Mechanisms of Vascular Breach of the lungs resulting in haemoptysis? Examples of each?
Mechanisms of Vascular Breach:
-
Vessel Damage: Direct injury to vessel walls can cause breach and extravasation of blood, leading to haemoptysis
* *Examples:** Inflammation, toxins released due to immune response, and repetitive coughing in pneumonia can cause direct injury to vessels -
Obstruction: Luminal or extra-luminal obstruction of blood vessels causes pre-obstruction dilation, necrosis of the mucosa, and local inflammation
* *Examples:** Pulmonary embolus in a distal vessel in the lungs causes upstream dilation, inflammation and necrosis, weakening the blood vessel, potentially causing rupture and haemoptysis -
Changes in Pressure: Increased vascular pressure is a risk factor for vessel injury
* *Examples:** Pulmonary hypertension as a result of COPD or left-sided heart failure can cause rupture of vessels, leading to haemoptysis
Outline the differential diagnosis of haemoptysis.
Haemoptysis: Blood-stained sputum
- Must be distinguished from blood-stained saliva caused by nasopharyngeal bleeding or sinusitis and also from hematemesis
- Always consider malignancy or TB
- Often diagnosis can be made by chest x-ray
Apply skills in explaining a respiratory disease diagnosis and prognosis, and in explaining treatment and follow-up.
- What is Murtagh’s 10-Point Plan for Consultation?
- What is Restrictive Lung Disease?
- Characteristics?
Restrictive Lung Disease:
- Characterised by restricted lung expansion and total lung capacity
- ↓TLC, ↓FEV1, ↓↓FVC and FEV1:FVC ratio is increased (>80%)
- The compliance of the lung is reduced, which increases the stiffness of the lung and limits expansion (a greater pressure than normal is required to give the same increase in volume)
- Common causes of decreased lung compliance are pulmonary fibrosis, pneumonia and pulmonary edema
What is Interstitial Restrictive Lung Disease?
- Examples?
- Aetiology of IPF? PCS? HP?
Interstitial Restrictive Lung Disease
Examples: Idiopathic pulmonary fibrosis (IPF), pneumoconiosis (PCS, coal worker’s lung, silicosis, berylliosis, asbestosis) and hypersensitivity pneumonitis (HP)
Aetiology:
- IPF: Idiopathic (could be smoke, infections, occupational/environmental exposures)
- PCS: Occupational exposures (coal dust, asbestos, silica etc.)
- HP: Occupational/environmental exposures (mould, pigeon droppings, microbial spores)
What is the pathophysiology Interstitial Restrictive Lung Disease?
- IPF? PCS? HP?
Pathophysiology of Interstitial Lung Diseases
IPF: Multiple micro-injuries to the alveolar cells → Secretion of growth factors that recruit fibroblasts → Synthesise collagen and aggregate to form fibrotic foci
PCS: Inhalation of particle → Impaction at alveolar duct bifurcations → Macrophages accumulate and engulf trapped particles → Pro-inflammatory factors → Inflammation → Alveolar damage → Fibroblast proliferation and collagen deposition → Fibrosis
HP: Inhaled antigen → Initial infiltration of the small airways and alveolar walls with NOs followed by T lymphocytes and MOs →
Small noncaseating granulomas → Continued antigenic exposure → Chronic
inflammation → Fibrosis
What are the macroscopic and microscopic features of Idiopathic pulmonary fibrosis?
Restrictive Lung Diseases - Interstitial → Idiopathic Pulmonary Fibrosis
Macroscopic Features: Firm, rubbery white areas of fibrosis at subpleural regions and interlobular septa of cut surfaces, cobblestoned pleural surfaces due to retraction of scars along the interlobular septa, honeycombing (can be seen on CT scan)
Macroscopic Features: Patchy fibrosis of the interstitium, minimal or absent inflammation, acute fibroblastic proliferation and collagen deposition (fibroblastic foci), absence of type 1 pneumocytes with a lack of differentiation of type 2 into type 1 pneumocytes resulting in a dysfunctional alveolar epithelium, honeycombing
What are the macroscopic and microscopic features of pneumoconiosis?
Restrictive Lung Diseases - Interstitial → Pneumoconiosis
Macroscopic Features: Collagen deposits around fibres producing nodules and fibrosis.
Microscopic Features: Pigmented macrophages and reticulin fibres (collagen) in peribronchial, paraseptal and perivascular areas, nodules often located near respiratory bronchioles surrounded by collagen, macrophages, lymphocytes, and fibroblasts, may find emphysematous blebs or even necrotic cavitations near nodule due to inflammation.
What are the macroscopic and microscopic features of hypersensitivity pneumonitis?
Restrictive Lung Diseases - Interstitial → Hypersensitivity Pneumonitis
Macroscopic Features: Non-specific, diffuse involvement with mild to moderate increase in lung weight, bronchocentric fibrotic changes may be seen
Microscopic Features: : Airway-centred infiltration and inflammation with fibrotic changes, lymphocytic infiltration with granulomas or giant cells (loosely formed granulomas)
What are some examples of restrictive lung diseases that are Neuromuscular, Pleural and Chest Wall?
- Examples?
- Aetiology?
- Pathophysiology?
- Macroscopic Features?
- Microscopic Features?
Examples: Neuromuscular diseases such as poliomyelitis, Duchenne’s muscular dystrophy, ALS and myasthenia gravis, severe obesity, pleural diseases, pectus excavatum, kyphosis, scoliosis and rib fractures.
Aetiology: Underlying condition
Pathophysiology: Underlying condition → External compression of lung parenchyma → Prevents lungs from expanding
Macroscopic Features: Reduced lung size & Features specific to underlying condition
Microscopic Features: Perhaps cellular compression or involution and tissue atrophy & Features specific to underlying condition
What is Obstructive Lung Disease?
Characteristics?
Obstructive Lung Disease:
- Increased resistance to airflow due to partial or complete obstruction at any level
- ↓FVC, ↓↓FEV1 and ↓FEV1:FVC ratio (<70%), and usually ↑TLC due to air trapping
- Airway obstruction, greater pressure is needed to overcome the resistance to flow, lung does not empty, and air is trapped
- Common obstructive diseases include asthma, chronic bronchitis, and emphysema (subtypes include centriacinar (most common, smoking-related), panacinar (seen in α1-antitrypsin deficiency), distal acinar and irregular)
What is COPD?
- Examples? (5)
- Aetiology
- Patho-physiology? (8)
- Macroscopic Features of Chronic Bronchitis?
- Macroscopic Features of Emphysema?
- Microscopic Features of Chronic Bronchitis?
- Microscopic Features of Emphysema?
Describe how abnormalities of gas exchange, alterations in airway resistance and pulmonary compliance contribute to the pathology of obstructive lung disease.
- What happens to airway resistance in chronic bronchitis? Why?
- What happens to airway resistance in emphysema? Why?
- Effect of increased airway resistance?
- 6 factors Affecting Airway Resistance?
Airway Resistance:
- Increased in Chronic Bronchitis: Caused by partial block of the lumen due to excessive mucous production, thickening of the airway wall due to edema or muscle hypertrophy and increased tone of bronchial smooth muscle
- Increased in Emphysema: Caused by loss of alveolar attachments to the airways which will mean loss of support for the small airways and greater narrowing of the small airways in expiration
- Effect: Increased airway resistance causes airflow obstruction/limitation, which increases work of breathing and limits expiratory flow rates. The time available for lung emptying (expiratory time) during spontaneous breathing is insufficient to allow end expiratory lung volume (EELV) to decline to its natural relaxation volume. Expiration is interrupted by the next inspiratory effort, trapping air and causing hyperinflation.
-
Factors Affecting Airway Resistance:
- Lung parenchyma resistance
- Lung elasticity
- Lung volume
- Bronchiolar radius and bronchial/bronchiolar smooth muscle tone (autonomic control)
- Velocity of flow
- Alveolar pCO2
Describe how abnormalities of gas exchange, alterations in airway resistance and pulmonary compliance contribute to the pathology of obstructive lung disease.
- What happens to gas exchange in Obstructive Lung Disease?
- Effect?
- 4 factors affecting gas exchange? Which law of physics explains this?
Gas Exchange:
- Reduced in Obstructive Lung Disease: Deteriorated or damaged lung tissue causes areas of reduced ventilation whilst inflammatory oedema and vasodilation causes areas of increased perfusion (ventilation low relative to perfusion)
- Effect: Low ventilation in highly perfused areas (V/Q mismatch) causing reduced PO2 of blood leaving lungs, resulting in hypoxemia
-
Factors Affecting Gas Exchange:
- Magnitude of partial pressure gradient
- Membrane thickness
- Diffusion coefficient
- Surface area of membrane
Explain how chronic air flow limitation arises from intrinsic airway disease and parenchymal lung disease in obstructive lung disease.
Chronic Airflow Limitation:
- Loss of elasticity and alveolar attachments of airways due to emphysema. This reduces the elastic recoil and the airways collapse during expiration (EPP lowered).
- Inflammation and scarring cause the small airways to narrow.
- Mucus secretion, which blocks the airways.
Each of these narrows the small airways (<2 mm in diameter) and causes air trapping leading to hyperinflation of the lungs, V/Q mismatch, increased work of breathing and breathlessness (Kumar and Clark, Page 813).
What is a Pneumothorax?
- Spontaneous?
- Traumatic?
- Tension?
Pneumothorax: Accumulation of air in the pleural space
- Spontaneous Pneumothorax: Due to rupture of apical pleural blebs, small cystic spaces that lie within or immediately under the visceral pleura. Primary SP occurs commonly in tall, thin, young males whilst secondary SP occurs in smokers or those with underlying lung condition.
- Traumatic Pneumothorax: Caused by blunt (i.e. rib fracture) or penetrating trauma (i.e. gunshot).
- Tension Pneumothorax: Air enters the pleural space but cannot exit, increasing trapped air leads to pressure on lungs. Trachea is pushed opposite to the side of injury. This is a medical emergency and treated with insertion of a chest tube.
What is a Pleural Mesothelioma?
Clinical Presentation?
Pleural Mesothelioma: Malignant neoplasm of mesothelial cells, highly associated with occupational exposure to asbestos. Presents with recurrent pleural effusions, dyspnea, and chest pain given that tumor encases the lung.
Compare Restrictive Lung Disease and Obstructive Lung Disease in terms of:
- Definition
- Examples
- Clinical Features
- Physical Examination
Compare Restrictive Lung Disease and Obstructive Lung Disease in terms of:
- Laboratory Findings?
- Radiological Findings?
- Spirometry?
Compare the patterns of pathology of lung diseases on spirometry?
Compare the patterns of pathology of lung diseases on spirometry?
Apply knowledge in acid-base abnormalities to interpret arterial blood gas reports.
- Method for Interpreting ABGs?
Method for Interpreting ABGs:
1) Use pH to determine acidosis or alkalosis
- Normal: 7.35-7.45 (or compensated)
- Acidosis: < 7.35
- Alkalosis: > 7.45
2) Use PaCO2 to determine respiratory effort
- Normal 35-45 (or compensated)
- Acidosis: > 45
- Alkalosis: < 35
3) Assume metabolic cause when respiratory cause is ruled out
- If PaCO2 does not correlate with pH, may be metabolic cause
- Respiratory Acidosis: Low pH and high PCO2
- Respiratory Alkalosis: High pH and low PCO2
- Metabolic Acidosis: Low pH and low PCO2 (suggests respiratory compensation)
- Metabolic Alkalosis: High pH and high PCO2 (suggests respiratory compensation)
4) Use HCO3 to verify metabolic effort
- Normal 24 +/- 2
- Acidosis: < 22
- Alkalosis: > 26
What is the Non-Pharmacological Managements of Restrictive and Obstructive Lung Disease?
Describe the contribution of smoke and smoking to lung disease.
- What percentage of respiratory disease is tobacco responsible for?
- Link between smoking and COPD?
- Link between smoking and Cancer?
Identify the major occupational risks for lung disease.
Identify the major occupational risks for lung disease.
= Central Nervous System
At the cellular level, anaesthetics enhance tonic inhibition, reduce excitation and inhibit excitatory synaptic transmission. Their effects on axonal conduction are relatively unimportant.
a. it affects glycine-activated channels
b. it affects acetylcholine-activated channels
c. it potentiates the action of GABA by binding to GABAA receptors
d. it affects 5-hydroxytryptamine-activated channels
e. it activates K+ channels
= c. it potentiates the action of GABA by binding to GABAA receptors
Individual anaesthetics do not exert their function through a single mechanism of action. However, they have a principal mechanism of action, with the other mechanisms of action bearing minor effects. Beside propofol, other intravenous anaesthetic drugs include thiopental (a barbiturate), etomidate, ketamine and midazolam (a benzodiazepine).
As a short-acting agent for the induction of general anaesthesia, propofol has multiple indications. However, one indication is elective.
Which is the main, and elective, indication of propofol?
**= b. short surgical procedures
**
Propofol is widely available and cheap, it dulls airway reflexes to prevent coughing and it is well tolerated by patients. It is particularly useful for day surgery, because it causes less nausea and vomiting than do inhalation anaesthetics.
The metabolism of propofol follows first-order kinetics, in contrast to thiopental. The list of disadvantages of propofol include pain on the injection site, myoclonic movements, direct cardiac depression with haemodynamic instability (hypotension, bradycardia), respiratory depression and accumulation after prolonged administration (e.g., in intensive care units - ICUs). Propofol as a drug of abuse has been reported. Moreover, there is one particular side effect to propofol which is well known in the clinical practice.
What particular side effect of propofol is well known in the clinical practice?
= c. propofol infusion syndrome
As a general rule, the margin between surgical anaesthesia and potentially fatal respiratory and circulatory depression is quite narrow. Therefore, general anaesthesia requires careful and frequent monitoring by the anaesthetist.
Ketamine is an intravenous sympathomimetic anaesthetic. With a half-life of 16 min, the effects start in 1–2 min. Ketamine produces an effect known as “dissociative anaesthesia”, in which there is a marked sensory loss and analgesia, as well as amnesia, without complete loss of consciousness. During anaesthesia induction and recovery, involuntary movements and peculiar sensory experiences can occur. Ketamine has some effects on the cardiac function, such as hypertension and tachycardia, but not on the respiratory function (except bronchodilation).
What is the mechanism of action of ketamine?
= e. inhibition of N-methyl-D-aspartate (NMDA) receptors
Patients infused with ketamine maintain airway reflexes, the analgesia is intense, and despite the cardiac effects the haemodynamic remains stable.
a. preoperative sedation
b. endoscopy
c. long surgical procedures
d. emergency situations (e.g., accidents)
e. postoperative analgesia
= d. emergency situations (e.g., accidents)
Other indications of ketamine include treatment-resistant asthma (due to bronchodilation), treatment-resistant depression and minor procedures in paediatrics, because psychiatric symptoms are less marked in children.
Ketamine is chemically close to phencyclidine, a piperidine derivative with analgesic, amnestic, and dissociative properties. Phencyclidine was first synthesized in the 1950s and appeared as a substance of abuse in the 1970s, with the name of PCP or “angel dust”.
Which is/are the side effect/s of ketamine at therapeutic (that is: no recreational abuse) concentrations?
= d. answers a and b are correct
(increased ICP & psychiatric symptoms)
Neuromuscular blockers (also known as skeletal muscle relaxants) hold an essential role in general anaesthesia by blocking the neuromuscular transmission post-synaptically. Postsynaptic block is either achieved by blocking acetylcholine (Ach) receptors (or, in some cases, the ion channel) or by activating ACh receptors, with consequent persistent depolarisation of the motor endplate. In the clinical practice, suxamethonium is the only blocker of depolarisation still in use, whereas all other drugs, such as tubocurarine, pancuronium, rocuronium, vecuronium, atracurium and mivacurium are non-depolarising agents which act by blocking the neuromuscular transmission. Neuromuscular blockers used in general anaesthesia are cathegorised by the duration of their action: ultra-short/short, intermediate and long.
What is the primary site of action of neuromuscular blockers used in general anaesthesia?
** = a. neuromuscular junction**
Neuromuscular block can also be achieved by presynaptic action, through the inhibition of ACh synthesis or release, but no drugs with this mechanism of action are used for general anaesthesia.
Suxamethonium is the only depolarising agent used clinically, it has an ultra-short duration of action and several adverse effects, including bradycardia and increased intraocular pressure. Suxamethonium has one elective indication and multiple life-threatening side effects.
Which is the elective indication and which are the most dangerous/life-threatening side effects of suxamethonium?
= c. Suxamethonium is indicated for short-lasting procedures, the most dangerous side effects are cardiac arrythmias, malignant hyperpyrexia and prolonged paralysis.
Rocuronium is a non-depolarising agent with an intermediate onset (1-3 min) and duration (40 min) of action. It is similar to vecuronium, also widely used. Like all neuromuscular blockers, they are administered parenterally. The initiation dose of rocuronium is 0.45-1.2 mg/kg, and their elimination is mainly performed by the liver, with a smaller fraction eliminated by the kidneys.
Which is/are the indication/s and side effect/s of rocuronium?
= a. Rocuronium is used as a substitute when suxamethonium is contraindicated. Side effects are few and mild.
Define Anaesthesia.
What are the 4 components of Anaesthesia (MALL)?
4 General principles of anaesthesia?
- Solubility?
- MAC?
How do Local anaesthetics work?
- 2 classes? Which are preferred?
- MOA?
What renders local anaesthetics ineffective?
**Infection Inefficiency: **Increasing the acidity of the external solution would favour ionisation and render local anaesthetics ineffective (polar charged drugs cannot cross cell membrane), so most local anaesthetics are ineffective in infected tissue (acidic environment).
What is the Order of Nerve Blockade of LAs?
What is Inhaled Anaesthetic (General)?
- Examples?
- Mechanism?
- Effects?
- Adverse Effects?
What is Intravenous Anaesthetic (General)?
- Examples?
- Mechanism?
- Effects?
- Adverse Effects?
What is Topical Anaesthetic (Local)?
- Examples?
- Effects?
- Adverse Effects?
What is Infiltration Anaesthetic (Local)?
- Effects?
- Adverse Effects?
What is Epidural Anaesthetic (Local)?
- Effects?
- Adverse Effects?
What is Spinal (Intrathecal) Anaesthetic (Local)?
- Effects?
- Adverse Effects?
Summarise the concept of balanced anaesthesia and the anaesthetic process.
Demonstrate clinical skills in localisation and interpretation of clinical signs in focal lung disease such as lung cancer.
- 4 clinical signs of lung cancer?
Clinical Signs of Lung Cancer:
1. Main Symptoms: Hemoptysis and constitutional symptoms (weight loss, fever and night sweats). Usually silent until disease progresses.
2. Palpation: Chest wall expansion possibly reduced.
3. Percussion: Percussion note possibly dull.
4. Auscultation: Breath sounds and vocal fremitus possibly decreased.
What is Lambert-Eaton Syndrome?
What are 3 key diagnostic features of lung cancer on CXR?
Key Diagnostic Features of Lung Cancer on CXR:
* Nodules: Solitary central or peripheral nodules (commonly primary tumour) or multiple nodules (commonly metastasis). “Coin-shaped lesion”.
* Size: Nodules normally 1cm wide or larger. Small tumours may not show up or may be hidden by other organs within the chest cavity.
* Indirect Signs: Atelectasis, post-obstructive pneumonia, pleural effusion (particularly unilateral), mediastinal widening and cavitary lesions
Interpretation of CXR (ABC Method)?
Discuss the Aetiology of Respiratory Tract Cancer? (5 points)
Pathogenesis of Respiratory Tract Cancer - 7 steps?
Describe the pathogenesis of smoking/nicotine in lung cancer?
How are Respiratory Tract Cancers Classified?
a. Small Cell Carcinoma (Central)
b. Non-Small Cell Carcinoma
1 - Adenocarcinoma (Peripheral)
2 - Squamous Cell Carcinoma (Central)
3 - Large Cell Carcinoma (Peripheral)
4 - Carcinoid Tumour
c. Precursor lesions
What is Small Cell Lung Cancer?
- Pathology?
- Types?
- Signs & Symptoms?
- Diagnosis/Lab results?
- Histology?
** Small Cell Carcinoma (Central):**
- Tumour arising from small, immature neuroendocrine cells (15% of cases).
- Associated with l-myc mutation and several paraneoplastic syndromes.
- Strong correlation with cigarette smoking. Develops near main bronchus.
- Very aggressive with early metastases but responsive to chemotherapy.
What is Small Cell Lung Cancer?
- Treatment?
- Characteristic cytological features?
What are Non-Small Cell Carcinomas?
- 4 Types?
- Signs & Symptoms?
Pathogenesis and Clinical Findings of Bronchial Carcinomas?
Epidemiology of Lung Cancer?
Histological Features of Lung Cancers:
- Small Cell Carcinoma? (7)
- Small dark blue cells (Kulchitsky cells), chromogranin, neuron-specific enolase and Synaptophysin positive.
- May arise in major bronchi or in the periphery of the lung
- No known preinvasive phase.
- Comprised of relatively small cells with scant cytoplasm, ill-defined cell borders, finely granular nuclear chromatin (salt and pepper pattern) and absent or inconspicuous nucleoli.
- Cells are round, oval or spindle-shaped, nuclear molding is prominent and they grow in clusters that exhibit neither glandular nor squamous organisation.
- Necrosis is common and often extensive.
- Basophilic staining of vascular walls due to encrustation by DNA from necrotic tumour
cells (Azzopardi effect) is frequently present.
What lung cancer type is this?
= Small cell carcinoma
There are sheets of small cells with hyperchromic, pleomorphic nuclei, and minimal cytoplasm. Mitotic figures are present. The stroma appears delicate and scant compared to the sheets of abnormal cells.
What type of lung cancer is this?
**= small cell lung cancer **
Sheets of small round cells with scanty cytoplasm and deep blue nuclei are visible throughout the image. The stroma (pink hypocellular tissue) is scanty.
This is the typical appearance of small cell lung cancer at high magnification.
Histological Features of Lung Cancers: Adenocarcinoma?
What type of lung cancer is this?
**= Adenocarcinoma **
Several confluent tubular glands lined by atypical epithelium (examples indicated by green outline) and surrounded by desmoplastic hypercellular stroma are visible. There is nuclear stratification (nuclei located at different heights within the epithelium rather than basally only), nuclear hyperchromasia (darker stained nuclei), and pleomorphism (different sizes of cells and nuclei). These are typical findings in acinar adenocarcinoma of the lung.
Histological Features of Lung Cancers:
Squamous Cell Carcinoma?
What type of lung cancer is this?
= Squamous cell carcinoma of the lung
There are several islands of large, polygonal, atypical squamous cells with polymorphic nuclei and mitotic figures (arrow). There is also evidence of keratinization (green circles). These findings are consistent with a moderately differentiated squamous cell carcinoma with keratinization.
Histological Features of Lung Cancers:
Large Cell Carcinoma? (4)
What type of lung cancer is this?
= Large cell carcinoma of the lung
A tumor consisting of multiple round cell nests can be seen. The tumor cells (examples indicated by green overlay) present with pale eosinophilic cytoplasm and pleomorphic nuclei with prominent nucleoli. There are no certain signs of cornification and there is no evidence of glandular, or neuroendocrine differentiation. For a definite diagnosis, large cell carcinoma needs to be verified via immunohistochemical stains (negative for TTF-1, p63, neuroendocrine markers, positive for cytokeratins).
Differentiate the histological variants of lung carcinoma?
A - Adenocarcinoma
B - Squamous cell carcinoma
C - Small cell carcinoma
D - Large cell carcinoma
Clinical Presentation of Lung Cancer:
- Pulmonary Symptoms? (5)
- Extrapulmonary symptoms? (3)
- Symptoms of metatstatic spread? (4)
Describe common causes of asymptomatic lung nodules and of secondary lung cancers in men and women.
- 6 Common Causes of Asymptomatic Lung Nodules?
Common Causes of Asymptomatic Lung Nodules:
1. Primary Tumour
2. Secondary Tumour
3. Lymphoma
4. Abscess
5. Granuloma (Infectious and Non-Infectious)
6. Hamartoma
Outline the principles of diagnosis of primary lung cancer? (5)
Diagnosis of Lung Cancer:
1. Chest X-Ray: Chest x-ray and comparison to previous images if available.
2. CT Scan: CT imaging for further evaluation indicated if new lesion detected on chest x-ray, there are changes (e.g. enlargement) compared to previous chest x-ray or there is no previous CXR available.
3. Assessment: Assessment of lesion size and probability of malignancy (based on CT findings and patient characteristics). Increased probability of malignancy with history of smoking, patients over 40 years of age and other known risk factors such as positive family history and asbestos exposure.
4. NB: Other investigations include sputum cytology, Full blood count to detect anaemia and biochemistry for liver involvement, hypercalcaemia and hyponatraemia.
5. NB: In patients aged > 40 years, any pulmonary nodule detected on CXR is considered lung cancer unless proven otherwise!
Diagnostic Imaging Pathway:
- Haemoptysis?
- Solid pulmonary nodules?
How is Staging of Diagnosed Lung Cancer performed?
Staging of Diagnosed Lung Cancer:
1. CT Scan (Chest, Liver, Adrenal Glands):
- Nodules (localisation, size, margins and calcifications)
- Regional spread (hilar lymph nodes, mediastinal invasion and pleural effusions)
- Distant metastasis (hepatic lesions or adrenal gland mass).
2. Blood Tests: FBC and serum chemistry (calcium, alkaline phosphatase, LFTs and kidney function test)
3. Further Radiographic Imaging:
- Abdominal Ultrasound and CT: Assesses lymph node involvement and extent of metastatic disease
- Skeletal Scintigraphy: Detects bone metastases
- Cranial MRI: Detects CNS metastases
- Whole Body PET-CT: Best method for detection of occult disease
4. Preoperative Evaluation: For thoracic surgery
Summarise basic principles of staging and grading of primary lung cancer?
Outline the principles of management of primary lung cancer? (6 points)
Management of Lung Cancer:
1. Smoking Cessation: After cessation, the risk of lung cancer reduces by half within 5–10 years. After approximately 15–20 years, the risk decreases to the corresponding level in non-smokers.
2. While early stages of lung cancer are treated with a curative approach, the majority of cases are diagnosed in advanced stages and can therefore only be treated palliatively.
3. Surgery (lobectomy, sub-lobar resection, pneumonectomy or systematic LN dissection) is often not possible due to distant metastases or because the patient has poor pulmonary reserve.
4. In such cases, chemotherapy is the mainstay of treatment.
5. Radiation therapy is also frequently necessary.
6. An individual treatment approach is usually determined by an interdisciplinary tumour board and discussed with the patient.
Prognosis of Lung Cancer?
Prognosis of Lung Cancer:
* Overall: 5-year survival rate is approximately 17%.
* SCLC: Limited disease has a 5-year survival rate of 12–15% whilst extended disease has a 5-year survival rate of 2% (median survival 8–13 months).
* NSCLC: Better prognosis but depends primarily on extent of disease and lymph node status. Locally confined stages (no lymph node involvement and no metastasis) have a survival rate of up to 60–70%.
Describe the steps in the Calgary-Cambridge model?
IGEPCT
What is a Pancoast Tumour?
- Pathology & Causes?
- Signs & Symptoms?
- Diagnosis?
- Treatment?
What is Mesothelioma?
- Pathology & Causes?
- Types?
- Signs & Symptoms?
- Diagnosis?
- Treatment?
- Histology?
Haemostasis is defined as the arrest of blood loss from damaged blood vessels. If the mechanism is defective it leads to haemorrhage, if it is excessive it leads to thrombosis. Thrombotic diseases are prevalent on haemorrhagic disease, and are treated with anticoagulant, antiplatelet and fibrinolytic drugs. Drugs affect haemostasis and thrombosis by acting on three stages: blood coagulation (fibrinogenesis), platelet function and fibrin removal (fibrinolysis).
On which stage of haemostasis do anticoagulant drugs exert their function?
= e. fibrinogenesis
Haemostasis involves a vascular mechanism (with transient vasoconstriction and activation of von Willebrand factor), a platelet multiple-step reaction (adhesion, activation, aggregation) and the activation of the coagulation cascade. The final result is the formation of a fibrin thrombus. A thrombus forms in vivo and presents a distinct microstructure, as opposed to a clot, which forms in vitro (e.g., blood in a glass tube) and is amorphous.
a. acute conditions
b. long term therapy
c. acute conditions and long term therapy
= b. long term therapy
The duration of treatment with warfarin is usually long term. Beside the oral route of administration, other advantages of warfarin are the well-known effects (and side effects), the low cost and the possibility of direct reversal of unwanted effects by replacement (e.g., with prothrombin complex concentrate, FFP or vitamin K).
The long half-life of warfarin makes it generally difficult to manage. Furthermore, it needs regular monitoring of the PT/INR , needs to be discontinued before surgery, and has a broad range of drug interactions.
What is the main adverse effect of warfarin?
= haemorrhage
Beside haemorrhage, especially into the bowel or the brain, another dangerous effect of warfarin is teratogenicity (disorders of fetal bone development). Warfarin crosses the placenta and appears in milk during lactation. However, since infants are routinely prescribed vitamin K to prevent haemorrhagic disease, warfarin treatment of the mother does not generally pose a risk to the breastfed infant. Hepatotoxicity and necrosis of soft tissues are rare.
a. acute conditions
b. long term therapy
c. acute conditions and long term therapy
a. acute conditions
In urgent situations, the treatment with unfractionated heparin starts as a bolus intravenous dose, followed by a constant-rate infusion.
LMWHs are used in the prolonged treatment for the prophylaxis of venous thrombosis. They are as safe and effective as unfractionated heparin, but easier to manage, because patients can be taught to inject themselves at home and there is generally no need for blood tests and dose adjustments. LMWHs are mainly eliminated by renal excretion.
Beside drug interactions, e.g., with aminosalicylates and tetracycline, heparin is a rather complex drug to manage. The effects of heparin can be reversed by protamine sulfate, administered intravenously.
What is/are the adverse effect/s of heparin?
= all of the above is correct
Hypersensitivity reactions are rare with heparin but more common with protamine. Unfractionated heparin is used in patients suffering from renal failure (Creatinine Clearance < 30mL/min), in whom LMWHs are contraindicated.
Rivaroxaban is administered orally and does not require the monitoring of plasma concentration.
What is/are the main indication/s of rivaroxaban?
= deep vein thrombosis, prophylaxis and treatment
Beside the side/adverse effects of all anticoagulants, of which the main one is haemorrhage, rivaroxaban has an elective side effect.
What is the elective side effect of rivaroxaban?
= nausea
In the case of life-threatening bleeding, the effect of dabigatran is reversed by idarucizumab (monoclonal antibody), and the effect of apixaban and rivaroxaban is reversed by andexanet alfa (a recombinant modified Factor Xa protein).
Veins
- Function?
- Properties?
- Flow?
- Venous return?
Describe the Systemic Venous Circulation.
Describe the veins of the head and neck.
Veins of the upper limbs and thorax?
Veins of the abdomen?
Veins of the Lower Limb and Pelvis?
What are 2 pulmonary diseases of vascular origin?
Pulmonary Hypertension
Pulmonary Embolism
Pulmonary Hypertension
- Definition?
- Risk Factors?
- Pathology & Causes?
Pulmonary Hypertension = Chronically elevated mean pulmonary arterial pressure at rest ≥ 25 mm Hg (normal is 10–14 mm Hg) or systolic > 30 mm Hg, usually not symptomatic until 60 mm Hg. Due to chronic pulmonary and/or cardiac disease or unknown reasons (idiopathic).
Pulmonary Hypertension
- Aetiology?
- WHO Classification - 5 groups?
- Group I?
Pulmonary Hypertension
- Group II?
- Group III?
Pulmonary Hypertension
Group III Causes:
1. COPD
2. ILD
3. Mixed restrictive/obstructive pattern
4. Alveolar hypoventilation
5. Sleep apnoea
6. Chronic exposure to high altitude
Pulmonary Hypertension
- Group IV?
- Group V?
Pulmonary Hypertension
- Pathogenesis?
- Clinical Findings?
Pulmonary Hypertension
- Microscopic & Macroscopic Features? (6)
Pulmonary Hypertension - Microscopic & Macroscopic Features
1. Luminal narrowing and intimal thickening of muscular arteries plus elastic layer hyperplasia, smooth muscle hyperplasia and hyaline change (pink homogeneity due to protein accumulation into wall) if elastic arterioles
2. Small vessels have medial hypertrophy and intimal fibrosis which may narrow lumina to pinpoint
3. Pulmonary artery atherosclerosis and plaque formation
4. Thromboembolism and organising thrombi (suggests recurrent pulmonary emboli)
5. Diffuse interstitial fibrosis if hypoxia
6. Plexiform lesion, a tuft of capillaries that forms a web around the lumen of dilated small arteries), which is characteristic of advanced disease
Pulmonary Hypertension
- Clinical Features?
Pulmonary Hypertension
- Investigations/Diagnosis? (4)
Pulmonary Hypertension
- Treatment? (3)
- Treat underlying cause!
- Consider diuretics, physical exercise, oxygen therapy and pulmonary vasodilator therapy such as calcium channel blockers, long-acting prostacyclin analogues (iloprost), endothelin receptor antagonists (bosentan) and phosphodiesterase-5-inhibitors (sildenafil)
- Patients who are refractory to medical treatment consider atrial septostomy ( right-to-left shunt) or lung transplantation
Pulmonary Embolism
- Definition?
- Pathology & Causes?
- Sources of emboli?
Pulmonary Embolism = The obstruction of one or more pulmonary arteries by solid, liquid, or gaseous masses. In most cases, the embolism is caused by blood thrombi, which arise from the deep vein system in the legs or pelvis (deep vein thrombosis) and embolise to the lungs via the inferior vena cava.
Pulmonary Embolism
- Aetiology?
Pulmonary Embolism
- Pathophysiology? (7)
- Pathogenesis & Laboratory findings?
Pulmonary Embolism
- Microscopic and Macroscopic Features? (9)
Pulmonary Embolism
- Risk Factors?
Pulmonary Embolism
- Epidemiology?
Pulmonary Embolism
- Clinical Features/Signs & Symptoms? (10)
Clinical Features of PE
1. Acute onset of symptoms, often triggered by a specific event such as on rising in the morning or sudden physical strain or exercise
2. Dyspnoea and tachypnea
3. Sudden chest pain worse with inspiration
4. Cough and hemoptysis
5. Possibly decreased breath sounds, dullness on percussion and split second heart sound audible in some cases
6. Tachycardia and hypotension
7. Jugular venous distension
8. Low-grade fever
9. Syncope and shock with circulatory collapse in massive PE (saddle thrombus)
10. Symptoms of DVT such as unilaterally painful leg swelling
Pulmonary Embolism
- Pretest probability/Well’s score?
Pulmonary Embolism
- Diagnostic imaging?
- Approach?
Pulmonary Embolism
- Investigations? (8)
Pulmonary Embolism
- Investigations: D-dimer?
Pulmonary Embolism
- Investigations: CXR?
Hampton hump
X-ray chest (PA view) of a patient with pleuritic chest pain
A peripheral opacity (Hampton hump) obscures the adjacent margin of the right hemidiaphragm. The Hampton hump appearance is most commonly due to pulmonary infarction.
A Hampton hump is a subpleural opacity caused by pulmonary hemorrhage or infarction. It may be wedge-shaped or the apex of the infarction spared and the contour dome-shaped as a result of collateral bronchial arterial blood flow. Differential diagnosis includes pneumonia and malignancy. Of note, the patient is rotated slightly to the right since the distance from the spinous processes to the right clavicle (C) is greater than the distance to the left clavicle.
Dashed lines: margins of medial clavicles; White line and ellipses: spinous processes
Pulmonary Embolism
- Investigations: ECG?
Pulmonary Embolism
- Treatment?
- General? (4)
- Non-Life-Threatening PE? (4)
- Life-Threatening PE? (2)
Define:
- Embolus?
- Embolism?
- Thrombosis?
- Thrombus?
- Thromboembolism?
Embolus = A detached intravascular solid, liquid, or gaseous mass that is carried by the blood from its point of origin to a distant site, where it often causes tissue dysfunction or infarction.
Embolism = Is passage through venous or arterial circulations of any material that can lodge in a blood vessel and obstruct its lumen.
Thrombosis = Refers to the formation of a thrombus, defined as an aggregate of coagulated blood containing platelets, fibrin, and entrapped cellular elements, within a vascular lumen.
Thrombus = A thrombus, by definition, adheres to vascular endothelium and should be distinguished from a simple blood clot.
Complications of a Pulmonary Embolism?
Explain Virchows Triad?
Predisposing Factors (Virchow’s Triad):
1. Stasis or Turbulent Blood Flow
2. Hypercoagulability
3. Endothelial Injury
Virchow’s triad?
What is Chronic Thromboembolic Pulmonary Hypertension?
Describe the Evolution of a Thrombus:
- IPEDOR?
Outline the different types of embolism and describe their origin = 7
List the clinical and pathological outcomes of systemic and pulmonary emboli.
- Origin?
- Arises from?
- Causes what?
- Consequences?
Discuss the principles of management of a haemodynamically stable pulmonary embolism.
Discuss the principles of management of a haemodynamically UNstable pulmonary embolism.
DVT vs PE Clinical Features?
Haemorrhages:
- Causes? (8)
- Consequences? (6 - by system)
Hyperaemia:
- Causes? (10)
- Consequences? (7)
Oedema:
- Causes? (7)
- Consequences? (10)
List 7 Common Causes of Calf Pain and explain their mechanism.
List 6 Common Causes of Chest Discomfort and explain their mechanism.
List 9 Common Causes of Breathlessness and explain their mechanisms.
Describe the Genetic Aetiology of Obesity? (4)
Describe the Environmental Aetiology of Obesity? (6)
Describe the Secondary Aetiology of Obesity? (6)
What are the medical complications of obesity?
List 11 Complications of Obesity and their pathogenesis?
6 Principles of Obesity Management?
Dietary Strategies for Obesity? (3)
Medical Therapy for Obesity? (4)
3 Types of bariatric surgery? Pros and cons of each?
Lipid Digestion:
- Lingual cavity?
- Stomach?
- Duodenum & Jejunum?
Outline the metabolic processes by which fat is metabolised in the body.
- Absorption?
What is Lipogenesis? When does it occur? Storage?
What is Lipolysis?
- Triglycerides?
- Glycerol?
- Energy?
What is ketogenesis?
7 FA Metabolic Pathways in Liver?
FA Metabolic Pathways in Liver:
1. FA in liver can be converted to liver lipids for cellular requirements
2. FA can leave the liver and bind to serum albumin to be transported to heart and skeletal muscle as fuel
3. FA in liver can enter into the mitochondrial matrix for B-oxidation where it is eventually oxidised to Acetyl CoA (stored energy in the form of FADH2 and NADH travel to the ETC to produce ATP)
4. Acetyl CoA can also be metabolised via the TCA to produce energy
5. Acetyl CoA can go on to produce ketone bodies (acetoacetate and 3 -hydroxybutyrate) to transport fuel around the body
6. Acetyl CoA can be used for cholesterol synthesis
7. Acetyl CoA can be used for synthesis of TAGs for lipoproteins which carry lipids (TAGs, cholesterol,
phospholipid) around the body and to adipose tissue for energy and storage
What is Hypertension?
- What does it predispose you to?
- Primary HTN?
- Secondary HTN?
Hypertension
- Pathology & Causes?
- Risk Factors?
- Complications?
- Signs & Symptoms?
- Diagnosis?
Hypertension
- Pathology & Causes?
- Risk Factors?
- Complications?
- Signs & Symptoms?
- Diagnosis?
Complications of Chronic Hypertension?
3 Types of Arteriosclerosis?
Atherosclerosis
- Pathogenesis?
- Complications?
Aneurysms
- Causes?
- 5 Types?
Aneurysms
- Pathology & Causes?
- Risk Factors?
- Signs & Symptoms?
Aneurysms
- Diagnosis?
- Treatment?
Abdominal Aortic Aneurysm
- Pathogenesis?
- Clinical Findings & Complications?
What is a Dissection?
- Pathogenesis, Complications and Clinical Findings of an Aortic Dissection?
Dissection: Blood enters wall and resulting haematoma dissects between layers and is often aneurysmal. Blood splays apart the laminar planes of the media forming a blood-filled channel within aortic wall. Can be accompanied by an aneurysm. Begins with intimal tear followed by extension. Caused by hypertension (90%), connective tissue pathology in younger adults (10%) and iatrogenic. Rare when atherosclerosis is extensive. Rupture of blood into peritoneum, pericardium and pleura can result in death.
Aortic Dissection
- Pathology?
- Types?
- Causes?
- Risk Factors?
- Complications?
- Signs & Symptoms?
- Diagnosis?
- Treatment?
List 3 Vascular Tumours?
Vascular Tumours
1. Hemangioma
2. Angiosarcoma
3. Kaposi Sarcoma
Vascular Tumours: Hemangioma
- What is it?
- Causes
- Signs & Symptoms?
What is a hemangioma?
Hemangiomas, also known as strawberry marks, are benign tumors of blood vessels, most commonly seen in children. They have a characteristic clinical appearance of bright red papules, or plaques (i.e., bumps on the skin surface) of a few millimeters to a few centimeters, that may occur anywhere in the body. However, most frequently they are found on the face, scalp, chest, and back. The majority of lesions are solitary, but multiple lesions may occur in up to 20% of infants. Although most hemangiomas are superficial, they can also appear deeper in internal organs, such as the liver. There are two common types of hemangiomas: congenital hemangiomas, which are present from birth at their maximal size, and infantile hemangiomas, which appear weeks after birth and increase gradually in size until they spontaneously disappear. Congenital hemangiomas can be further subcategorized into RICH (rapidly involuting congenital hemangioma), which regress like infantile hemangiomas, and NICH (non-involuting congenital hemangioma),
Vascular Tumours: Angiosarcoma
- Pathology & Causes?
- Risk Factors?
- Complications?
- Signs & Symptoms?
- Diagnosis?
- Treatment?
Vascular Tumours: Kaposi Sarcoma
- Pathology & Causes?
- Types?
- Risk Factors?
- Staging?
- Complications?
- Signs & Symptoms?
- Diagnosis?
- Treatment?
What is the link between smoking and obesity?
List 6 Hormones associated with obesity?
- Insulin = lipogenesis & anti-lipolysis (reduces effect of adrenalin & cortisol) = far more bioactive than glucagon
- Glucagon = Glycogen to glucose in the liver (Lipolysis)
- Catecholamines - eg. adrenaline, noradrenaline from the adrenal medulla = lipolysis
- Glucocorticoids = lipolysis
- Growth Hormone = lipolysis
- Testosterone = lipolysis
What is the link between stress and obesity?
What is the link between
What does Leptin do?
What does Ghrelin do?
Leptin - suppresses appetite, so obese people should have a reduced appetite but obese people develop leptin insensitivity
Ghrelin - stimulates appetite, however, ghrelin secretion is reduced in obese people
What is Vasculitis?
List the primary forms of vasculitis?
Vasculitis: Vessel wall inflammation. Can be infectious with direct invasion by organism or immune-mediated with immune complex deposition, antineutrophil cytoplasmic antibodies (ANCA) or anti-endothelial antibodies. Clinical expression dependent on vessel type, organ location, age, type and distribution of inflammatory process and extent of healing. Inflammation can cause local tissue destruction which causes vessel wall weakness, aneurysms or rupture and hemorrhage in large vessels or oedema and RBC leakage in small vessels. Can also cause endothelial damage and thrombosis, ischaemia, infarction and ulceration or epithelium.
Describe the 4 Steps of normal haemostasis?
**Normal hemostasis. **
1. A - After vascular injury local neurohumoral factors induce a transient vasoconstriction.
2. B, Platelets bind via glycoprotein Ib (GpIb) receptors to von Willebrand factor (vWF) on exposed extracellular matrix (ECM) and are activated, undergoing a shape change and granule release. Released adenosine diphosphate (ADP) and thromboxane A2 (TxA2) induce additional platelet aggregation through platelet GpIIb-IIIa receptor binding to fibrinogen, and form the primary hemostatic plug.
3. C, Local activation of the coagulation cascade (involving tissue factor and platelet phospholipids) results in fibrin polymerization, “cementing” the platelets into a definitive secondary hemostatic plug.
4. D, Counter-regulatory mechanisms, mediated by tissue plasminogen activator (t-PA, a fibrinolytic product) and thrombomodulin, confine the hemostatic process to the site of injury.
List 5 differences between a thrombus vs. a postmortem clot.
What are some primary and secondary Hypercoagulable States?
What are the 4 Grades of Hypertensive Retinopathy?
4 Causes of PE?
Describe the Pathophysiology of PE and how it results in the clinical features?
Diagnosis of PE
- Initial investigations?
Diagnosis of PE
- Imaging investigations?
Classification of PE by Severity
- Nonmassive PE?
- Submassive PE?
- Massive PE?
Classification of PE by overall prognosis
- Low risk?
- Intermediate risk?
- High risk?
Management of PE by severity and bleeding risk?
