Block 1 - Respiratory Flashcards

Question

What are 3 examples of *Streptococci pneumoniae* Resistance Mechanisms?

Answer 1

**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)

Answer 2

**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

Answer 3

**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)

Answer 4

**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

Answer 5

**Glucocorticoids:** Medication (steroids) which have anti-inflammatory and immunosuppressive effects **Cause:** Iatrogenic **Complications:** Immunosuppression. 1. Decreased production of cytokines 2. Decreased production of eicosanoids (messengers to CNS inflammation) 3. Decreased production of IgG 4. Decreased complement components in blood 5. Increased IL-10 and annexin 1 (anti-inflammatory molecules).

Answer 6

**Cough Reflex Suppression:** Loss of mechanical clearance **Causes:** 1. Coma 2. General anaesthetic 3. Pain 4. Neuromuscular disease 5. Kyphoscoliosis 6. Endotracheal tube 7. Drugs **Complications:** Increased susceptibility to infection or prolonged duration of infection.

Answer 7

**Injury to Mucociliary Escalator:** Loss of mechanical clearance **Causes:** 1. Smoking 2. Virus 3. Alcohol 4. Hot corrosive gases 5. Ostruction 6. Cystic fibrosis **Complications:** Increased susceptibility to infection or prolonged duration of infection

Answer 8

**Decreased Macrophage Function:** **Causes:** 1. Alcohol 2. Smoking 3. Anoxia 4. O2 toxicity 5. Phagocyte killing defects **Complications:** Increased susceptibility to bacterial infections and increased duration and severity of infection

Answer 9

**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

Answer 10

**Pneumonia:** Microbial infection of lung parenchyma distal to terminal bronchiole 1. Lobar Pneumonia 2. Bronchopneumonia 3. Interstitial (Atypical) Pneumonia 4. Aspiration Pneumonia

Answer 11

**Lobar Pneumonia:** Characterised by consolidation of an entire lobe of the lung, and is usually bacterial (*Streptococcus pneumoniae* and *Klebsiella pneumoniae*) 1. Intra-alveolar exudate 2. Bronchi are relatively spared 3. CXR: Air bronchogram (phenomenon of air-filled bronchi (dark) made visible by the opacification of surrounding alveoli (grey/white)) and non-segmental consolidation 4. No ventilation: Shunt with hypoxia 5. Acute onset

Answer 12

**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

Answer 13

**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

Answer 14

**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*)

Answer 15

**_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

Answer 16

**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*).

Answer 17

**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 1. Characteristic hoarse "barking" cough with inspiratory stridor - Sounds like a dog barking or a seal 2. Children 9 months to 3 years 3. Usually 11 pm to 2 am 4. Auscultation confirms inspiratory stridor 5. Occurs in small local epidemics

Answer 18

**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. 1. Cough and sputum (main symptoms) 2. Wheeze and dyspnoea 3. Usually viral infection 4. Can complicate chronic bronchitis (often due to *Haemophilus influenzae* and *Streptococcus pneumonia)* 5. Scattered wheeze on auscultation 6. Fever or haemoptysis (uncommon) 7. Improves spontaneously in 4–8 days in healthy patients

Answer 19

**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) 1. Prodromal symptoms for 48 hours (e.g. coryza, irritating cough, then 3–5 days of more severe symptoms) 2. Squeaks worsened upon inspiration 3. Wheezy breathing (often distressed) 4. Tachypnoea 5. Hyperinflated chest: Barrel-shaped, usually subcostal recession 6. Widespread fine inspiratory crackles (not with asthma) upon auscultation 7. Frequent expiratory wheezes upon auscultation 8. Hyperinflation of lungs with depression of diaphragm upon x-ray (but chest X-ray should not be used for diagnosis or routinely performed) 9. Dehydration is a serious problem, especially with exhausted infants

Answer 20

**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

Answer 21

**Lobar Pneumonia:** Characterised by consolidation of an entire lobe of the lung, and is usually bacterial (*Streptococcus pneumoniae* and *Klebsiella pneumoniae*)

Answer 22

**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](https://next.amboss.com/us/article/ap0QLS#Zd789b8bc27469b31e8919583fe00ff8d) and adjacent [alveoli](https://next.amboss.com/us/article/ap0QLS#Z7355062fcb9a5de029f4665967b6f713) * Primarily caused by [pneumococci](https://next.amboss.com/us/article/Sn0ysg#Zfce18259c025350213b3850dc734f8bb) and/or other [streptococci](https://next.amboss.com/us/article/Sn0ysg#Zc55380d620c82ec8d6a1edfc63b9bfbf) * Characterized by acute inflammatory infiltrates that fill the [bronchioles](https://next.amboss.com/us/article/ap0QLS#Zd789b8bc27469b31e8919583fe00ff8d) and the adjacent [alveoli](https://next.amboss.com/us/article/ap0QLS#Z7355062fcb9a5de029f4665967b6f713) (patchy distribution) * Usually involves the lower lobes or right middle lobe and affects ≥ 1 lobe * Manifests as [typical pneumonia](https://next.amboss.com/us/article/mh0Vef#Zf03008f93afa99eeea3c7544e8a9d8f3) * Necrotizing bronchopneumonia and pneumatocele are caused by [*Staphylococcus aureus*](https://next.amboss.com/us/article/Vl0GDT#Zaf074edfb4940be0ed1d4fcfc4ea0dee) and are often preceded by an [influenza](https://next.amboss.com/us/article/Bm0z3g#Z7f6a08ed676ff91e0fd1a38ea649ecbd) 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.

Answer 23

**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*)

Answer 24

**Pneumococcus** (*S. pneumonia*) → β-lactam antibiotics (amoxycillin, benzylpenicillin or 3rd generation cephalosporin) **Atypical organisms such as** ***Mycoplasma pneumoniae*****,*****Chlamydia pneumoniae*****and*****Legionella*****species** → 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

Answer 25

1. **Sputum Sample:** To identify the likely pathogen via gram stain and culture (collected before starting antibiotic therapy) 2. **Blood Sample:** To identify the likely pathogen via culture (ideally before starting antibiotic therapy) 3. **Pneumococcal Urinary Antigen Assay:** Performed on routine urine specimens (either before or after starting antibiotic therapy) for the early identification of *Streptococcus pneumonia* 4. ***Legionella*** **Urinary Antigen Assay:** Detects *Legionella pneumophila* serotype 1 5. **Nose and Throat Swabs:** For PCR for respiratory viruses including influenza, and are becoming available for *Chlamydia pneumoniae*, *Mycoplasma pneumoniae* and *Legionella* 6. **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.

Answer 26

1. **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 2. **Bronchoscopy/Tracheal Aspiration:** For the sick, immunocompromised or those not improving 3. **Pleural Aspiration** 4. **Fine Needle Aspiration of Abscess**

Answer 27

**Clinical Assessment of Severity of Pneumonia:** 1. **Severity Scales:** PSI, CURB-65, SMART-COP (Australia), ATS and BTS (URB) 2. Vital Signs 3. Age 4. X-Ray or CT Appearance: Number of lobes or pleural effusion 5. Comorbidities: Neoplasms, liver disease, heart failure, renal failure, CVA 6. Physiological Impairment: Respiratory rate, heart rate, blood pressure, oxygen saturation and renal, hepatic and metabolic function 7. Altered Mental Status (GCS) 8. Smoking Status

Answer 28

**Signs of Clinical Deterioration:** 1. Presence of focal chest signs (decreased chest expansion, dullness on percussion, decreased entry of air, bronchial breathing, and crackles) 2. Multilobar infiltrates 3. Altered mental status 4. Altered vital signs (hypotension, raised respiratory or heart rate, hypothermia) 5. Sepsis, multi-organ problems and pleural effusion can lead to rapid deterioration

Answer 29

**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

Answer 30

**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)

Answer 31

**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*

Answer 32

**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

Answer 33

**Cell Wall Synthesis Inhibitors (Bactericidal): _Glycopeptides_** * Gram-positive organisms only (including MRSA)

Answer 34

**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)

Answer 35

**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

Answer 36

**_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:** 1. Impaired diffusion 2. Ventilation-perfusion (V/Q) mismatch 3. Hypoventilation 4. Shunt 5. 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:** 1. Hypoventilation 2. Ventilation-perfusion (V/Q) mismatch

Answer 37

**Acute Management of Dyspnoeic Patient:**

Answer 38

**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 1. Correct hypoxaemia via oxygen therapy 2. Deal with hypercapnoea via non-invasive or mechanical ventilation 3. Nutrition 4. Prevent DVT 5. Maintain acid-base balance 6. Maintain fluid balance 7. Maintain homeostatic balances 8. Manage pain **Clinical Monitoring:** The observation of a disease, condition or one or several medical parameters over time. 1. Vital signs (HR, RR, BP, temperature, O2 saturation) 2. Blood glucose levels 3. Consciousness (Glasgow Coma Scale) 4. Urine output 5. Medication chart 6. General observations

Answer 39

**Oxygen Therapy:** Supplemental oxygen administered as a medical treatment through nasal canulae, masks or a breathing tube **Delivery Systems:** 1. Nasal Canulae 2. Simple (Hudson) Masks 3. Non Re-Breathing Masks 4. Partial Non Re-Breather Masks 5. Face Tent 6. Venturi Masks

Answer 40

**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:** 1. Pattern Recognition: Spot diagnoses (important in time pressured situations!) 2. Reflection and Re-Evaluation: Reduces uncertainty, cognitive errors and bias

Answer 41

**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:** 1. What are your differential diagnoses? 2. What are your differential diagnoses, based on your history? 3. What signs are you seeking to elicit to refine (confirm or exclude) your differential diagnoses? 4. What symptoms and signs support your differential diagnoses? 5. What investigations would you order and why? 6. Given x result, how does this change your differential diagnosis list? **Diagnostic Model for Presenting Complaint (Murtagh's GP):** 1. What is the probability diagnosis? 2. What serious disorders must not be missed? 3. What conditions are often missed (the pitfalls)? 4. Could this patient have one of the ‘masquerades’ in medical practice? 5. Is this patient trying to tell me something else (cues, concerns, anxieties, communication)?

Answer 42

**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

Answer 43

**_Basic Pathological Features of Tuberculosis:_** **Macroscopic** 1. Central caseous necrosis 2. Fibrosis **Microscopic** 1. Necrotising granulomatous inflammation 2. Central necrosis without residual cell outlines 3. Acid Fast Bacilli (AFBs) with Ziehl-Neelsen stain 4. Necrosis surrounded by activated epithelioid macrophages and giant cells including Langhan's cells 5. Outer layers of lymphocytes and fibrosis

Answer 44

**Primary TB** 1. 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. 2. As sensitization develops, a 1-1.5cm area of grey-white inflammation with consolidation emerges, known as the Ghon focus. 3. 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 . 4. Ranke complex is seen in healed primary pulmonary TB and consists Ghon lesion (calcified parenchymal tuberculoma) and ipsilateral calcified hilar node.

Answer 45

**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.

Answer 46

**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.

Answer 47

**Miliary TB** Numerous grey-white tubercles on cut surface of organs.

Answer 48

**Sarcoidosis** 1. Interstitial epithelioid granulomas distributed along lymphatic pathways (bronchovascular bundles, interlobular septa, pleura). 2. Granulomas are non-necrotising and often contain asteroid, Schaumann and conchoid bodies and birefringent crystalline material. **Wegener Granulomatosis** 1. Necrotising granulomas and ulceration URT 2. May see loosely formed granulomas in interstitium of lung, but more commonly a capillaritis (neutrophils in alveolar capillaries) 3. Alveolar haemorrhage 4. Glomerular necrotising lesions and crescents **Bronchiectasis** 1. Dilated bronchi can extend almost to pleural surface 2. Contain mucopurulent material, surrounding scarring, exaggerated transverse ridging and trabeculation of bronchial mucosa.

Answer 49

**_TB Virulence Factors_** 1. **Waxy Coat:** Protects against macrophage killing 2. **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 3. **Cord Factor:** Surface glycolipids allow organism to form cords, prevents phagolysosomal fusion 4. **Lipoarabinomannan (LAM):** Inhibits macrophage activation and phagolysosomal fusion (escapes killing by MO) 5. **Sulfolipids:** Impairs macrophage activation by inhibiting phagosomal maturation 6. Induces delayed (type IV) hypersensitivity reaction 7. Lacks Toxins 8. Resistant to routine antibiotics

Answer 50

**Immunology and Pathogenesis of Primary Pulmonary Lesion:** 1. Transmission 2. Entry 3. Evasion 4. Replication 5. Detection 6. Activation of Immune Response 7. TH1 Response and Macrophage Activation 8. Granulomatous Inflammation and Tissue Damage 9. Latency

Answer 51

**_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.

Answer 52

**_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

Answer 53

**Primary TB:** Occurs in the nonimmune host (delayed type IV hypersensitivity reaction) **Secondary TB:** Occurs in a previously sensitised host

Answer 54

**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

Answer 55

**7R's of Medication Administration:** 1. Right Patient 2. Right Medication 3. Right Dose 4. Right Time 5. Right Route 6. Right Documentation 7. Right Reason

Answer 56

**Ten Principles of Good Prescribing:** 1. Be clear about the reasons for prescribing 2. Consider the patient’s medication history before prescribing 3. Identify other factors that might alter the benefits and risks of treatment 4. Take into account the patient’s ideas, concerns, and expectations 5. Select effective, safe, and cost-effective medicines appropriate for the patient 6. Adhere to national and hospital guidelines 7. Write unambiguous legal prescriptions using the correct documentation 8. Monitor the beneficial and adverse outcomes of treatment 9. Communicate and document prescribing decisions and the reasons for them 10. Prescribe within limitations of knowledge, skills, and experience

Answer 57

**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

Answer 58

**Types of Interaction:** 1. Drug-Drug 2. Drug-Herbal 3. Food-Drug 4. Chemical-Drug 5. Genetics-Drug (Pharmacogenetics) 6. Drug-Lab Test **Source for Drug Interactions:** Australian Medicines Handbook

Answer 59

**Pharmacokinetics** = What body does to the drug **Pharmacokinetic (PK) Interactions:** Occur when ADME of the drug is affected by another drug

Answer 60

**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

Answer 61

**Clinical Features of Pulmonary Tuberculosis:** **DxT:** Malaise + Cough + Weight Loss (± Erythema Nodosum) **Suspect TB:** Cough \>3 Weeks + Travel/Migration (Recent or 30yrs Later)

Answer 62

**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

Answer 63

**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

Answer 64

**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

Answer 65

**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.

Answer 66

https://www.msdmanuals.com/professional/injuries-poisoning/thoracic-trauma/pneumothorax-tension

Answer 67

**Mechanisms of Vascular Breach:** 1. **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 2. **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 3. **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

Answer 68

**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

Answer 69

**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

Answer 70

_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)

Answer 71

**_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

Answer 72

**_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

Answer 73

**_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.

Answer 74

**_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)

Answer 75

**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

Answer 76

**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)

Answer 77

**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:** 1. Lung parenchyma resistance 2. Lung elasticity 3. Lung volume 4. Bronchiolar radius and bronchial/bronchiolar smooth muscle tone (autonomic control) 5. Velocity of flow 6. Alveolar pCO2

Answer 78

**_Pulmonary Compliance:_** * **Increased in Emphysema:** Caused by reduction of elastic tissue in the pulmonary parenchyma due to alveolar wall destruction, making it easier to inflate the lungs and increasing lung functional residual capacity (FRC) * **Effect:** The diaphragm becomes flattened and disadvantaged (chest wall volume increases and intra-alveolar pressure decreases), plus reduced elastic recoil means work of breathing increases and there is greater difficulty with expiration than inspiration. Expiration is interrupted by the next inspiratory effort, trapping air and causing hyperinflation. * **Factors Affecting Pulmonary Compliance:** 1. Lung elasticity 2. Alveolar surface tension

Answer 79

**_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:** 1. Magnitude of partial pressure gradient 2. Membrane thickness 3. Diffusion coefficient 4. Surface area of membrane

Answer 80

**Chronic Airflow Limitation**: 1. Loss of elasticity and alveolar attachments of airways due to emphysema. This reduces the elastic recoil and the airways collapse during expiration (EPP lowered). 2. Inflammation and scarring cause the small airways to narrow. 3. 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).

Answer 81

**_Pleural Effusion: Accumulation of fluid in the pleural cavity_** * **Inflammatory Pleural Effusion:** Due to inflammation of the underlying lung and increased vascular permeability * e.g. pneumonia and TB * **Non-Inflammatory Pleural Effusion:** Due to: 1. Increased hydrostatic pressure → e.g. congestive heart failure) 2. Decreased osmotic pressure → e.g. nephrotic syndrome) 3. Increased intrapleural negative pressure → e.g. atelectasis) 4. Decreased lymphatic drainage → e.g. mediastinal carcinomatosis

Answer 82

**Empyema:** Collection of pus in the pleural cavity caused by microorganisms. Often it happens in the context of a pneumonia, injury, or chest surgery. It is a type of pleural effusion.

Answer 83

**Pleuritis:** Inflammation of the parietal pleura resulting in sharp chest pain (pleuritic pain) that worsens on breathing, due to underlying inflammation of the lungs and pleural cavity and increased vascular permeability (e.g. viral infection, pneumonia and TB)

Answer 84

**Pneumothorax:** Accumulation of air in the pleural space 1. **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. 2. **Traumatic Pneumothorax:** Caused by blunt (i.e. rib fracture) or penetrating trauma (i.e. gunshot). 3. **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.

Answer 85

**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.

Answer 86

**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

Answer 87

**Goals of Management:** 1. Relieve symptoms 2. Improve exercise tolerance 3. Prevent and treat exacerbations 4. Prevent disease progression 5. Prevent and treat complications 6. Improve health status 7. Reduce mortality

Answer 88

**_Pharmacological Management of Restrictive and Obstructive Lung Disease_** **Restrictive** 1. **Immunosuppressive Medications:** For inflammatory conditions e.g. ILD 2. **Anti-Fibrotic Medications:** For fibrotic conditions e.g. IPF 3. **Antibiotics:** Prophylaxis for IPF and fibrotic disease **Obstructive** 1. **Short Acting β2 agonists (SABA):** To relieve symptoms e.g. Salbutamol and bricanyl 2. **Anticholinergic Agents:** To improve lung function, reduce exacerbations (does not reduce frequency), improve exercise tolerance and quality of life e.g. Triotropium and glycoporonium 3. **Long Acting β2 Agonists (LABA):** To improve lung function and symptoms e.g. Efomoterol and salmeterol 4. **Inhaled Corticosteroids (ICS):** To reduce frequency of exacerbations and improve lung function e.g. Fluticasone, budesonide 5. **Systemic Corticosteroids:** For acute exacerbations 6. **Antibiotics:** For acute exacerbations

Answer 89

**_Restrictive LD_** **Lung Transplant:** To improve quality of life in selected patients **_Obstructive LD_** **Lung Volume Reduction Surgery (LVRS):** Improves quality of life and lung function in some patients (bronchoscopically or surgically) **Lung Transplant:** To improve quality of life in selected patients

Answer 90

**= 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.

Answer 91

**= 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).

Answer 92

**= 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.

Answer 93

**= 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.

Answer 94

**= 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.

Answer 95

**= 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.

Answer 96

= d. answers a and b are correct (increased ICP & psychiatric symptoms)

Answer 97

** = 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.

Answer 98

= c. Suxamethonium is indicated for short-lasting procedures, the most dangerous side effects are cardiac arrythmias, malignant hyperpyrexia and prolonged paralysis.

Answer 99

= a. Rocuronium is used as a substitute when suxamethonium is contraindicated. Side effects are few and mild.

Answer 100

**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).

Answer 101

**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.

Answer 102

**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

Answer 103

**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**

Answer 104

** 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.

Answer 105

**Precursor Lesions: ** 1. Squamous dysplasia and carcinoma in situ 2. Atypical adenomatous hyperplasia 3. Adenocarcinoma in situ 4. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia

Answer 106

1. Small dark blue cells (Kulchitsky cells), chromogranin, neuron-specific enolase and Synaptophysin positive. 2. May arise in major bronchi or in the periphery of the lung 3. No known preinvasive phase. 4. 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. 5. Cells are round, oval or spindle-shaped, nuclear molding is prominent and they grow in clusters that exhibit neither glandular nor squamous organisation. 6. Necrosis is common and often extensive. 7. Basophilic staining of vascular walls due to encrustation by DNA from necrotic tumour cells (Azzopardi effect) is frequently present.

Answer 107

**= 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.

Answer 108

**= 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.

Answer 109

**= 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.

Answer 110

**= 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.

Answer 111

**= 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).

Answer 112

A - Adenocarcinoma B - Squamous cell carcinoma C - Small cell carcinoma D - Large cell carcinoma

Answer 113

**Common Causes of Asymptomatic Lung Nodules:** 1. Primary Tumour 2. Secondary Tumour 3. Lymphoma 4. Abscess 5. Granuloma (Infectious and Non-Infectious) 6. Hamartoma

Answer 114

**Common Causes of Secondary Lung Cancers: ** 1. Breast Cancer 2. Colorectal Cancer 3. Renal Cell Carcinoma 4. Prostate Cancer 5. Bladder Cancer 6. Melanoma

Answer 115

**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!

Answer 116

**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

Answer 117

**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.

Answer 118

**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%.

Answer 119

**= 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.

Answer 120

**Warfarin = a Vitamin K antagonist** The effect of warfarin takes several days to develop. The treatment with warfarin, like other vitamin K antagonists, requires frequent blood tests to determine and maintain a therapeutic and safe dose. Numerous medical and environmental conditions modify sensitivity to warfarin, including interactions with other drugs (e.g., many antifungal azoles and NSAIDs, some antibiotics, Vitamin K, carbamazepine and colestyramine). The effect of warfarin is monitored by measuring Prothrombin Time (PT), expressed as an international normalised ratio (INR) which should remain between 2 and 4.

Answer 121

**= 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).

Answer 122

**= 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.

Answer 123

**Heparin activates antithrombin III** Antithrombin III deficiency is very rare but can cause thrombophilia and resistance to heparin therapy.

Answer 124

**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.

Answer 125

**= 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.

Answer 126

** Rivaroxaban directly inhibits factor Xa.** Other NOACs include apixaban, betrixaban, dabigatran etexilate and edoxaban. Direct inhibitors act on factor Xa or thrombin, a group of elective thrombin inhibitors is hirudins, e.g., lepirudin and bivalirudin.

Answer 127

**= deep vein thrombosis, prophylaxis and treatment**

Answer 128

**= 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).

Answer 129

Pulmonary Hypertension Pulmonary Embolism

Answer 130

**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).

Answer 131

**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

Answer 132

**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

Answer 133

1. Treat underlying cause! 2. 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) 3. Patients who are refractory to medical treatment consider atrial septostomy ( right-to-left shunt) or lung transplantation

Answer 134

**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.

Answer 135

**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

Answer 136

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

Answer 137

**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.

Answer 138

Predisposing Factors (Virchow's Triad): 1. Stasis or Turbulent Blood Flow 2. Hypercoagulability 3. Endothelial Injury

Answer 139

**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

Answer 140

**Arteriosclerosis**: Hardening of arteries, with arterial wall thickening and loss of elasticity. Artery aging secondary to chronic exposure to normal or elevated blood pressure. Artery tries to resist dilatation of blood pressure through spasm to reduce hyper-perfusion of capillaries supplying living tissue. This results in medial changes including smooth muscle hypertrophy, elastic reduplication and intimal fibrous thickening. Artery elongates and becomes tortuous.

Answer 141

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.

Answer 142

**Vascular Tumours** 1. Hemangioma 2. Angiosarcoma 3. Kaposi Sarcoma

Answer 143

**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),

Answer 144

1. **Insulin** = lipogenesis & anti-lipolysis (reduces effect of adrenalin & cortisol) = far more bioactive than glucagon 2. **Glucagon** = Glycogen to glucose in the liver (Lipolysis) 3. **Catecholamines** - eg. adrenaline, noradrenaline from the adrenal medulla = lipolysis 4. **Glucocorticoids** = lipolysis 5. **Growth Hormone** = lipolysis 6. **Testosterone** = lipolysis

Answer 145

**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

Answer 146

**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.

Answer 147

**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.

Block 1 - Respiratory Flashcards

(309 cards)