Respiratory system Flashcards
Define asthma?
Common chronic disorder of the airways that is complex and characterized by
variable and recurring symptoms, airflow obstruction, bronchial hyperresponsiveness and an underlying inflammation
Reversibility (hallmark)
Reversible spontaneously or after treatment
FEV1/FVC ratio increase 12% before and after bronchodilator (SABA) treatment
What is the assessment of severity of exacerbation for asthma?
What are asthma associated syndromes?
What is the classification of asthma?
What are RF for asthma?
Genetics
* Defects of genes that encode for β-adrenoceptors/ IFN-γ
o IgE upregulation
o Decreased bronchodilation
Atopy: Predisposition towards developing certain allergic hypersensitivity
* More than 80% of asthmatics are atopic Gender
* Severe and uncontrolled asthma usually occurs in females
Ethnicity: Caucasian has higher prevalence rate than the Chinese
Environment
* Tobacco smoke
* Air pollution
* Viral respiratory infections
* Diet and drugs
* Obesity
Airway hyper-responsiveness: Inborn
What are the triggering factors of atopy?
Allergens: dusts, pollen grains, animal dander, fecal pallets of household mites
Respiratory irritants: smoking, air pollution, cold air
What is the ddx for obstructive and restrictive lung diseases?
What is the ddx of asthma?
- Acute bronchiolitis
- Pneumonia
- Foreign body aspiration +/- aspiration pneumonia
- Bronchiectasis: recurrent infections
- GERD
- Bronchopulmonary dysplasia (BPD): history of prematurity
- Primary ciliary dyskinesia: recurrent infections
- Cystic fibrosis
What is the functional changes in asthma
Spirometry
What is the pathogenesis of asthma?
- Airway inflammation
Naive helper T cells become Th2 cells: Th2 response generates cytokines that mediate allergic inflammation. Mast cells are sensitized and contains allergen specific IgE. Inhaled allergens attach to specific IgE antibodies on the suface of mast cells. Cross linking of IgE receptors leads to intracellular signaling. Degranulation of mast cells and release of mediators.
Inflammation cells infiltration: increased vascularity permeability due to acute inflammation. Infiltration of eosinophils and lymphocytes. - Airflow obstruction
Bronchoconstriction: IgE mediated allergic response, smooth muscle constriction due to release of histamine, heparin and serotonin
Mucous plug formation: mucous hypertension: hypertrophy of mucous gland, hyperplasia of goblet cells
Airway edema: mucosal congestion and edema. Congestion refers to engorgement of blood within vessels.
Airway remodelling: chronic inflammation, affect reversibility of airway obstruction - Bronchial hyperresponsiveness
Airways narrow excessively in response to a variety of stimuli that provoke little or no bronchoconstriction in normal individuals
Caused by atopy, thickened bronchial wall, enhanced muscle contractility, epithelial damage
What is the assessment of asthma control?
Asthma control test (GINA assessment)
What triggering factors to asses in asthmatic attack?
- Allergens
o Dusts
o Pollen grains
o Animal dander (new pets)
o Fecal pellets of household dust mites (new curtains/ carpets/ mattress/ blanket/ dolls)
Requires frequent washing every week with water > 55oC - Respiratory irritants
o Smoking (first or second-hand)
o Air pollution
o Cold air
o Change of living environment (ongoing construction work) o Change in occupation (work-related exposure) - Medical conditions
o Upper respiratory tract infection (URTI)
o Gastroesophageal reflux disease (GERD) - Drug-induced
o Aspirin/ NSAIDs
o ACEI
o β-blockers - Exercise-induced
- Emotional stress
How to assess effect of asthmatic medication?
How to assess the severity of asthma using GINA 2009?
How to do a PE in asthmatic patient?
Inspection
Use of accessory muscles for breathing
Hyperinflation of chest
Seated position with use of extended arms to support upper chest (tripod position)
Pulsus paradoxus: occurs in acute exacerbation of asthma
Abd paradoxus: occurs in acute exacerbation of asthma, paradoxical movement
Auscultation
* Prolonged expiration phase
* Wheezing: widespread high pitched expiratory wheeze. Different from single pitch (monophasic) wheezing of local bronchial narrowing (e.g. aspiration of foreign body or bronchogenic cancer) which repeatedly begins and ends at the same point in each respiratory cycle.
* Silent chest: severe asthma exacerbation (status asthmaticus) or sever airway obstruction such that patient is unable to generate airflow to wheeze
Percussion: resonant
What dx tests can be done for athma?
Lung function test
Peak expiratory flow (PEF)
<80% personal best is consistent with poor control, <50% personal best is consistent with poor exacerbation
Brochial (metacholine) challenge test
Exclude airway hyperresponsiveness in patients with atypical presentation
Procedures: apply various dosage of metacholine that normally does not cause bronchoconstriction
E+ve early and late asthmatic reactions (bronchoconstriction) with decrease in FV1 >20%
-ve: straight line similar to normal pattern
Skin prick test: if not done before to confirm atopy.
Biochemical tests
CBC with DC: polycythemia (chronic hypoxia), leukocytosis (secondary infection ), eosinophilia (AGPA/Churg Strauss syndrome)
ABG: indicated when sO2 <92% on room air –> evaluate for resp failure
Aspergillus skin test +ve: suspected ABPA
Serum Ig level: suspected ABPA (increased total Ige level (typically >1000IU/ml)
When is step up and down treatment considered for asthma?
What are the 5 steps of treatment of asthma?
What must LABA be used with in asthmatic patients?
What are short acting, long acting B agonist used for asthma?
Muscarinic receptor antagonists?
mechanism
What complications?
What corticosteroids (inhaled, oral) used in asthma?
MoA
EA?
What is the mast cell stabilizer for asthma
MoA and Ae
What is the anti IgE antibodie for asthm
MoA and Ae
What are the leukotriene pathway inhibitors used for asthma?
MOA?
What are the different types of inhalers used for asthma?
What are the different types of delivery devices for asthamtic medication?
What is mx of asthmatic attack in children
mild to moderate
What is mx of asthmatic attack in children
severe asthmatic attack
What is mx of asthmatic attack in children
life threatening asthmatic attack
What is the management of asthmatic attack in adults?
What is asthmatic discharge plan in children?
What are the complications of severe asthmatic attack?
- Pneumothorax or pneumomediastinum
- Pulmonary infections: predisposed to mucous accumulation and stasis airflow e.g. pneumonia
- Resp failure: ventilatory failure (type 2 respiratory failure)
What other treatment modifications should be considered at this stage?
How do you distinguish exercise-induced asthma from exertional dyspnea?
Exercise-induced asthma
* Onset
o 5 – 15 mins after a brief (5 mins) exercise (OR)
o 15 mins after going into a prolonged exercise * Offset
o Resolve with rest after 30 – 60 mins
Exertional dyspnea
* Onset
o Shortly after onset of exertion
* Offset
o 5 mins after stopping exercise
What oxygen delivery systems are there and the O2 flow?
What are the indications of mechanical ventilation?
Indications of non invasive positive pressure ventilation (NPPV)?
What are the adv of mechanical ventilation?
Advantages of mechanical ventilation
* Improves gaseous exchange
o ↑ Oxygenation by improving V/Q matching
o ↑ Alveolar ventilation
o Reverse acute respiratory acidosis
* Relieve respiratory distress
o ↓ Work of breathing
o ↓Respiratory muscle fatigue
What are the variables on the ventilator?
FiO2 = Fraction of inspired air that is O2
VT = Tidal volume = Volume of breath delivered F = Respiratory rate
PEEP = Positive end-expiratory pressure
* Positive pressure applied during exhalation via resistor in exhalation port
* Beneficial in terms of preventing alveolar collapse, decrease shunting, increase O2 via
alveolar recruitment and improved compliance
* Cardiac effects
o ↓ Preload by increasing intrathoracic pressure which decrease venous return o ↓ Afterload by decreasing cardiac transmural pressure
What are the basic principles of ventilators?
What are the modes of non invasive positive pressure ventilation (NPPV)?
Define acute cough, subacute cough and chronic cough
- Acute cough: one lasting for <3 weeks
- Subacute cough: one latsing for 3-8 weeks
- Chronic cough: british thoracic cavity defined as one lasting for >8 week
What is the cough reflex arch?
What are the different phases of cough and its significance?
What are the disorders resulting in ineffective cough
What is the consequence of ineffective cough
What are the causes of acute cough in children?
What are causes of chronic cough in children?
What are the causes of chronic cough in adults?
What are the warning signs for severe cough in children?
Hypoxemia
Purulent sputum
Hemoptysis
Chest pain
Exertional dyspnea
Failure to thrive
Growth retardation
What is history taking for cough?
onset of cough: acute or subacute paroxysmal cough –> pertussis, chronic paroxysmal cough –> astham, present during day and disappaer at night –> psychogenic or habitual cough
Nature of cough
Productive cough –> bronchiectasis/bacterial bronchitis/asthma
Barking/brassy cough –> croup (laryngotracheobronchitis)/laryngotracheomalacia/foreign body aspiration
Whooping cough –> pertussis
Staccato cough –> chlamydai infection
Honking cough disappearing at night –> psychogenic or habitual cough
Triggering factors
Smoking, excercise, cold air, allergens, viral infection –> asthma
Swallowing –> laryngeal cleft/tracheoesophageal fistula
Exacerbating factors
Worse in the morning –> bronchiectasis
Worsen before sleep –> asthma (decreased cortisol at night by circadian rhythm which has anti inflammatory effect)
Worsen after meal or lying supine –> GERD
Associated symtpoms
Haemoptysis –> bronchiectasis/bronchitis/CA lung/TB
Failure to thrive and weight loss –> immuno deficiency and chronic infection
Medical history
History of atopy: eczema/ allergic rhinitis/allergic conjunctivitis
Previous URTI: post infectious cough
Recurrent pneumonia: immunodeficiency, tracheoesophageal fistula
Drug history
ACEI: increased kinins and substance P which are normally metabolized by ACE –> leads to activation of arachidonic acid pathway. Increased PG which stimulates C fibers in the airway. Increased thromboxane which potentiates bronchoconstriction
Antihistamiens
Bronchodilators
Family history: atopy, primary ciliary dyskinesia, cystic fibrosis
Social history: smoking, contact with pets, close contact with TB individuals
Birth history
Prematurity with low birth weight
Presidposes to atopic sensitization and asthma
Precursor for bronchopulmonary dysplasia
What is done for PE of coughing?
What Ix for cough?
CBC with differentials Nasopharyngeal aspirate Throat swab
Sputum smear
Sputum culture with sensitivity testing
Blood culture
Lung function test
* Spirometry to document obstructive or restrictive lung pattern
* FEV1.0/ FVC ratio post-bronchodilator (SABA) increase >12% in asthma
Ambulatory 24-hour esophageal pH monitoring
* Indicated in patients with suspected GERD
Tuberculin skin test (Mantoux test) (PPD test)
* Presentation of TB in children can be subtle and hence should be considered even in the absence of obvious signs and symptoms
Treatment for cough (requires management of underlying cause)
A patient presents with dull percussion note with decreased breath sound and vocal resonance over the right lower zone. There is fine inspiratory crackles bilaterally over middle and lower zones.
What ddx
what ix done
Pulmonary fibrosis with right pleural effusion
Bronchiectasis with pleural effusion
Heart failure with pleural effusion
CXR
HRCT thorax
Lung function test (restrictive pattern) Arterial blood gas (ABG)
Lung biopsy
Immunological blood test
* ANF * RF
What are the causes of pleural effusion in patients with idiopathic pulmonary fibrosis (IPF)?
Respiratory infection
* Especially for patients receiving corticosteroids
Associated CA lung
* IPF is a risk factor
Associated pleuritis in pulmonary fibrosis complicating connective tissue disease such as rheumatoid arthritis
A patient undergoes physical examination which is normal on inspection, palpation and percussion. On auscultation, there is fine end-inspiratory, lower zone crackles bilaterally. There is a small amount of clear whitish sputum in a cup at bedside.
What is most likely ddx?
What disease commonly give rise to clubbing together with inspiratory crackles?
Idiopathic pulmonary fibrosis
Bronchiectasis
Pulmonary fibrosis
CA lung with obstructive pneumonia
What are types of lung cancer?
SCLC: round nucleoli, absent nucleoli, hyperchromatic, scanty cytoplasm.
Produces ACTH, ADH.
NSCLC (more common)
SCC (20-30%): morphology (squamous differentiation, keratinization, keratin pearl formation, intercellular bridges). Location: found near hilum –> usually metastasize through lymphatics. Extensive necrosis: cavities within tumors (cavitations) seen in CXR
Adenocarcinoma (45-55%: most common). Morphology. Glandular patterns: papillary, micropapillary. Location: peripheral lung. Distant metastasis common –> lymphatic and blood spread common
Large cell carcinoma (5-10%). Remarks: high grade, aggressive tumor, poor prognosis
Compare SCLC and NSCLC in general features
What are the modes of spread of lung cancer?
What are the RF for lung cancer?
Smoking associated with SCC and SCLC. Adenocarcinoma is the most common type in non smokers
Occupation exposure: asbestos, arsenic compounds, radioactive substances, heavy metals (beryllium, cadmium, chromium, nickel)
Genetics
Diet: protective effects of antioxidants
What is the pathogenesis of lung cancer?
What is the carcinogenesis process of lung cancer
genes involved
What are the paraneoplastic syndromes of lung CA
What are endocrine disturbances in lung CA?
- PTH-rP: Hypercalcemia
- ADH: Hyponatremia (SIADH)
- ACTH: Hypokalemia (Cushing’s syndrome)
- ILP: Hypoglycemia
What Ix for lung CA?
CBC with DC: anemia (haemoptysis, anemia of chronic disease, bone marrow infiltration)
LFT: deranged liver function in liver metastasis, increased ALP in bone metastasis (increased bone turnover)
RFT: hypoNa due to SIADH, hypoK due to ectopic ACTH production, hyperK due to adrenal metastasis and destruction
LFT: preop assessment
Sputum cytology: gram smear and culture with sensitivity testing including acid fast bacilli (AFB)
Pathological tests
Cytological exam: sputum, pleural fluid, bronchial washing and brushing, fine needle aspiration of LN
Histological exam: bronchial or transbronchial biopsy, pleural biopsy, LN biopsy
Radiological tests
CXR
CT thorax, upper abdomen, brain
PECT
Fiberoptic bronchoscopy with endobronchial ultrasound guided biopsy (FOB-EBUS): fibreoptic bronchoscopy: assess airways and sampling of specimen, BAL or lung biopsy. Endobronchial ultrasound: transbronchial needle aspiration (EBUS-TBNA) can be performed: assess subcarinal, upper and lower paratracheal and hilar LN, indicated for staging of cancer (N)
Pleuroscopy: assess pleural metastasis
What must be tested before treatment of lung cancer?
Genetic testing: EGFR mutation, ALK and ROS1 translocation and PD-L1
Guide decision on targeted therapy. EGFR mutation have better survival when treated with targeted therapy. Wild type EGFR have better survival when treated with conventional chemotherapy
Indicated in patients with confirmed lung cancer, patients required systemic therapy due to inappropriate candidateas for surgery: stage 3b/4 lung cancer
Types of mutations: hotspots for EGFR mutations are exons 18-21 of tyrosine kinase domain
Mechanism of acquired EGFR mutation: secondary mutation in T790M, amplification of HER2, activation of Met pathway
Sample collection: tissue biopsy at time of progression is now the gold standard. Liquid biopsy gaining popularity. Sample sources: surgically resected cancers, biopsy (bronchoscopy/pleural biopsy/LN biopsy), cytology (FNA/pleural fluid aspiration)
Sample limitations: small DNA amount leading to FP result due to random amplifcation, low tumor to normal cell ratio leading to FN result.
TKI sensitive: L856R mutation/exon19 mutations
Known resistnace T790M mutation
What is the treatment strategy of lung cancer?
- SCLC
- AD
- SCC
- LCC
What are the principles of targeted therapy in lung cancer?
What is medical treatment for lung cancer?
What is the prognosis for lung cancer?
SCLC
* Worst prognosis
* Few patients survive more than a year
NSCLC
* Better prognosis for patients with early surgical excision
* 30 – 40% of patients with completely excised early stage cancer may survive for >5 years
CA right lung Pneumonia TB
What ix should be done?
What are the principles of underlying treatment of carcinoma of lung?
What are the causes of hypoNa in CA lung patients?
Syndrome of inappropriate ADH (Most common)
Depletional hyponatremia due to poor oral intake
Cortisol insufficiency due to bilateral adrenal metastasis
How are patients with brain metastasis from CA lung treated?
Whole brain radiotherapy
* Gamma knife for isolated brain metastasis
Systemic corticosteroids (i.e. dexamethasone)
* Relieve cerebral edema
What is the classification of pneumothorax?
Primary pneumothorax
* Always spontaneous and thus called primary spontaneous pneumothorax (PSP)
* Without underlying respiratory disorder
* Presence of emphysematous lung blebs or bulla formed on lung surface usually at apices: blebs are probably formed after puberty but its origin is still idiopathic. Rupture of blebs because they are so thin walled
Secondary pneumothorax
* TB
* Asthma
* COPD
* Bronchiectasis
* Lung abscesses
* Marfan syndrome
Tension pneumothorax
* Pneumothorax state where interpleural pressure becomes more +ve than atmospheric pressure
What are the causes of pneumothorax?
- Spontaneous: idiopathic emphysematous lung blebs or bulla
- COPD: thin walled, diseased lung bulla can spontaneously rupture, most common cause (50-70%) of secondary pneumothorax
- TB: infection or inflammation damages lung parenchyma can spontaneously rupture
- Pneumonia
- Neoplasm: sinus formation and fistulation results from internal necrosis in tumor –> creates a path for air to leak out from the lung
- Connective tissues diseased (leads to weakened parenchyma which spontaneously rupture) e.g. Marfan syndrome, RA, dermatomyositis, systemic sclerosis
- Trauma: perforation of lung: rib fracture, penetration of chest wall: stabbing or gunshot
- Iatrogenic: thoracentesis, bronchoscopy, FNAC of pulmonary nodules, percutaneous/transbronchial lung biopsy, positive pressure ventilation, insertion of central venous catheter (CVC)
What is the pathophysiology of pneumothorax?
Chest pain
* Visceral pleura is insensitive to pain since it is innervated by autonomic nerve fibers: visceral pleura contains stretch receptors. Increased relative collapsing or stretching of the partly deflated lung in pneumothorax leads to chest pain
* Parietal pleura is sensitive to pain since it is innervated by somatic intercostal nerve and phrenic nerves. Parietal pleura contains pain receptors but chest pain in pneumothorax is not attributable to this since air is not irritant to pleura at all
Dyspnea
* Air enters pleural space leads to loss of normal -ve pleural pressure
* Partial deflation of lung means collapse of small terminal airways and alveoli: less gas exchange surface can be recruited for respiration
* Relative compressibility or expansibiloity of air impedes ability to inflate chest wall and deflate: muscles expend more than expected effort with each breath as some work is used to expand and compress the air of pneumothorax instead of ventilating the lung
What is the pathogenesis of tension pneumothorax?
- Air sucked into pleural space during inspiration
Opening of a ruptured bleb on lung surface. Opening of a pleuro-cutaneous fistula or wound - Air cannot escape out of pleural space during expiration
Collapse of the defect or bleb or wound on collapsing the chest during exhalation - Results in rapid addition of a volume of air to pleural space with each breath
Building up of tension within pleural space. Lethal when pressure in chest rise to higher than RA pressure (central venous pressure) leading to loss or reversal of pressure gradient. Allow caval blood to return to the chest. Consequent loss of cardiac output and patient dies of shock.
What are the SS for pneumthorax/tension pneumothorax?
What PE for pneumothorax?
Palpation
* Tracheal & mediastinal deviation away from affected side
* Displaced apex beat away from affected side
* ↓ Chest expansion (Affected side)
Auscultation
* ↓ Breath sounds
* ↓ Tactile fremitus
Percussion
* Hyper-resonance
What Ix and results for pneumothorax?
CXR should be done in erect position: 2cm separation between visceral pleural line to the chest wall at the level of hilum approximate to a radiographic pneumothorax volume of 50% of hemithoraxi volume
Small pneumothorax <2cm separation
Large pneumothorax: >2cm separation
Lung fields
Area of blackness: border: present with a lung edge, distribution: unilateral
Lung edge
Lung markings (bronchi and blood vessels)
Decreased vasscular markings since lung is replaced by air
Primary or secondary spontaneous pneumothorax
* Presence of ipsilateral lung edge
* Translucent lung without lung markings
* Contralateral mediastinal shift
* Deep sulcus sign: air collects anteriorly and basally in costophrenic angle, dark and deep costophrenic angle
Tension pneumothorax
* Flattening of diaphragm
* Widening of intercostal sapce
* Deviation of mediastinum to contralateral side
* Deviation of trachea to contralateral side
* Hearat is shifted to contralateral side
ABG: assess degree of hypoxemia, hypercapnia and respiratory acidosis
pO2<80mm in 75% of patients
What treatment for pneumothorax?
Observation for primary pneumothorax, lung edge <2cm from chest wall, non breathless patient
O2 supplementation: speeds resolution of spontaneous pneumothorax –> breathing in high flow O2 leads to increased O2 content and decreased N2 content in serum
Not given to treat breathless, not given to treat desaturation
Giving excessive O2 can lead to oxygen toxicity in lungs, O2 therefore not given at 100% via a mask or nasal cannula. O2 should be given intermittently rather than continously for 24h daily
Surgical
Percutaneous needle aspiration at 2nd ICS at MCL for tension pneumothorax. 60-80% chance of avoiding a chest drain
Intercostal tube drainage (chest drain)
indications: secondary pneumothorax, significant underlying chronic lung disease, patients >50 years old
inserted at 5th ICS MAL or safety triangle (anterior: lateral border of pectoralis major, posterior: anterior border of latissimus dorsi, superior: horizontal line drawn from nipple, apex: below axilla)
Structures that causes pain during chest drain insertion: skin –> subcutaneous fat –> serratus anterior –> intercostal muscle –> parietal plerua.
Skin, periosteum and parietal pleura are most sensitive to pain and should be specifically targeted when giving LA
What is the mechanism of 3 bottle system in chest drain?
What are the components of a chest drain?
What does swinging and bubbling indicate?
What are the precautions, risks and how to remove the chest drain?
What procedure may be indicated in patients with recurrent pneumothorax or persistent air leaks?
Lifestyle modification of pneumothorax?
What is the classification of atelactasis?
What are the different causes of atelactasis?
What is the physiology of maintaining an open alveoli?
What is the PE and results for atelactasis?
What Ix for atelactasis?
CBC with DC: absence of changes in CBC help to differentiate atelactasis from pneumonia
Sputum smear, culture and cytology. Smear and culture for acid fast bacilli, cytology for malignant cells
What is treatment for atelactasis?
Depends on etiology
What are the causes of pleural effusion?
What is the pathophysiology of pleural effusion?
What is PE and results for pleural effusion?
What are the biochemical tests for pleural effusion and results?
What radiological Ix and specific tests for pleural effusion?
What is the general principles for treatment of pleural effusion?
Treatment of non malignant pleural effusion
* Primarily involves treatment of underlying etiology
Treatment of malignant pleural effusion
* Repeat therapeutic thoracentesis
* Indwelling pleural catheter placement: indicates in patients with shorter life expectancy
* Chest drain insertion + pleurodesis: indicated in patients with longer life pleurodesis
What are the treatment options for pleural effusion?
Thoracentesis
* Pleural tapping should not be performed for bilateral pleural effusion in clinical setting strongly suggestive of transudate process unless there is a presence of atypical features or failure to respond
* Large volume thoracentesis refers to removal of >1L of pleural effusion confiremd by PE and CXR (not recommended)
Indications
* Large non purulent pleural effusion >40% of hemithorax
* Frank pus or turbid pleural fluid on thoracentesis
* Pleural fluid analysis shows: positive gram + positive culture, LDH>1000IU/L, glucose <2.2mmol/L, pH <7.2
* Radiological findings: loculation on CXR, pleural thickening with contrast enhancement on CT thorax
Complications: pain at puncture site, bleeding, soft tissue infection, splenic or liver puncture, tumor seedling along needle tract
Reexpansion pulmonary edema (non cardiogenic pulmonary edema), related to negative pleural pressure created during pleural fluid removal in the setting of an unexpandable lung (atelactasis/endobronchial obstruction)
Pneumothorax: risk of pneumothorax increases with the volume of fluid withdrawn. Related to negative pleural pressure created during pleural fluid removal in the setting of an unexpandable lung
Chest drain insertion indications
* Haemothorax
* Empyema
* Complicated parapneumonic effusion
* Symptomatic malignant pleural effusion
Pleurodesis
* Induction of pleural inflammation and fibrosis
* Chemical pleurodesis: achieved with sclerosants such as talc instilled via chest tube, indwelling catheter or at time of thoracoscopy. Clamp drain for 1-2 hours post sclerosant application than release clamp. Chest tube kept unclamped thereafter for drainage until daily output <150ml/day and CXR shows reexpansion of lung with most of the effusion drained
* Surgical pleurodesis; achieved through mechanical irrigation of the pleura
A patient presents with dull percussion note with decreased breath sound and vocal resonance over the right lower zone. There is fine inspiratory crackles bilaterally over middle and lower zones.
What ddx?
Pulmonary fibrosis with right pleural effusion
Bronchiectasis with pleural effusion
Heart failure with pleural effusion
What are the causes of pleural effusion in patients with idiopathic pulmonary fibrosis (IPF)?
Respiratory infection
* Especially for patients receiving corticosteroids
Associated CA lung
* IPF is a risk factor
Associated pleuritis in pulmonary fibrosis complicating connective tissue disease such as rheumatoid arthritis
How can one proceed to make dx?
Define pulmonary hypertension?
Elevated mean arterial pressure >25mmHg at rest
PA mean = CO x PVR +PA wedge pressure
Transpulmonary pressure gradient (TPG) = PA mean -PA wedge pressure
What is the classification of pulmonary hypertension?
Group 1: pulmonary arterial hypertension
Idiopathic PAH, heritable PAH, drug induced, associated conditions (connective tissue diseases: SLE, RA, scleroderma, mixed connective tissue disease), congenital heart disease (ASD/VSD/PDA), portal hypertension)
Group 1’: pulmonary venoocclusive disease (PVOD) and/or pulmonary capillary haemangiomatosis (PCH): characterized by extensive diffuse occlusion of pulmonary veins resulting in tortuous dilation of pulmonary capillaries
Group 1’’: persistent pulmonary hypertension of the newborn: occurs when pulmonary vascular resistance remains abnormally elevated after birth
Group 2: PT due to left heart disease: left ventricular systolic/diastolic dysfunction. Left sided valvular disease. Mitral valve: MS/MR, aortic valve: AS/AR
Group 3: PT due to lung disease an/or chronic hypoxemia (COPD, ILD, OSA, alveolar hypoventilation disorders, chronic exposure to high altitude)
Group 4: chronic thromboembolic pulmonary hypertension (CTEPH): pulmonary embolism
Group 5: PT due to unclear multifactorial mechanism.
Haematological disorders: chronic hemolytic anemia (thalassemia), spherocytosis, sickle cell anemia. Myeloproliferative disorders, splenectomy. Metabolic disorders: thyroid disorders, glycogen storage disease.
Systemic disorders: sarcoidosis. langerhans cell histiocytosis (pulmonary), neurofibromatosis (NF), vasculitis
Others: tumor obstruction, fibrosing mediastinitis, chronic renal failure
What are the SS of right sided HF?
What are the SS of pulmonary hypertension?
Dyspnea
Exertional chest pain
* Subendocardial hypoperfusion caused by increased RV wall stress and myocardial oxygen demand (RV ischemia)
* Dynamic compression of left main coronary artery by an enlarged pulmonary artery
Exertional syncope
* Inability to increase CO during activity or reflex bradycardia secondary to
mechanoreceptor activation in RV
Fatigue
What is the PE and results for pulmonary hypertension?
What Ix for pulmonary hypertension?
CBC with DC (group 5): assess for chronic hemolytic anemia
LungFT (group 1): rule out pulmonary hypertension
Serum autoantibodies (group 1): ANA, Anti dsDNA, Anti Scl 70, RF
HIV serology: rule out HIV associated PAH
Radiological Ix
* CXR
* ECG: RBBB, RVH, right atrial enlargement (P pulmonale with peaked P wave)
* Excercise testing (6 min walk test 6MWT) or cardiopulmonary excercise testing
* Echocardiography: estimation of pulmonary artery systolic pressure. Technique takes advantage of TR that usually exists and measures the maximum TR jet velocity (TRV). RA pressure estimated from the size and respiratory variation of flow in IVC. Assess RV size, thickness and function, assess LA size (group 2), assess for valvular heart lesions
* Right heart catheterization (gold standard in dx of pulmonary hypertension). Pulmonary HT confirmed when mean pulmonary arterial pressure >25mmHg at rest (normal =8-20mmHg)
Spirometry and DLCO (group 3): rule out obstructive or lung restrictive lung diseases with FEV1/FVC. ILD will give a restrictive pattern on spirometry with FEV1/FVC>70% and decreased DLCO
Polysomnography (Group 3)
Ventilation perfusion VQ scan (group 4): normal VQ scan excludes chronic thromboembolic disease
CT pulmonary angiography (group 4): indicated when PE suspicion is high
What is the general management of patients with pulmonary hypertension?
What is medical and surgical treatment for pulmonary hypertension?
What are the types of sleep apnea?
Obstructive sleep apnea
* Recurrent obstructive apnea and hypopneas caused by repetitive collapse of upper airway (functional occlusion) during sleep
* Presence of respiratory effort meaning thoracic and abd movement
* No resulting inspiratory flow
Central sleep apnea
* Can be due to central (lack of resp drive), NMJ (myasthenia gravis) or muscular diseases (muscular dystrophy)
* Absence of respiratory effort
* No resulting inspiratory flow
What are the RF for OSA?
What is the physiology of sleep?
What is the effect of sleep on respiratory mechanics?
What are the SS of OSA?
What is the ddx of OSA?
Insufficient sleep
Central sleep apnea
Periodic limb movement of sleep
Obesity hypoventilation syndrome
Primary respiratory diseases
Narcolepsy
* Excessive daytime sleepiness with cataplexy, hypnagogic hallucination and sleep paralysis
Depression
Fibromyalgia
What is the diagnostic criteria for OSA?
What assessment tool used to assess OSA in history taking?
What is gold standard Ix for OSA?
What are the treatment options for OSA?
CPAP
indications for ugent CPAP
* Pickwanin syndrome with daytime alveolar hypoventilation
* Pulmonary hypertension or cor pulmonale
* Nocturnal malignant arrhythmia related to OSA
* Nocturnal angina related to OSA
* Severe excessive daytime sleepiness that may impose risk to patient and others
Mechanism: maintenance of positive pharyngeal pressure so that intraluminal pressure exceeds surrounding pressure. Stabilize upper airway through increased end expiratory volume to prevent airway collapse
Oral applianaces
Protrude the mandible forward or hold the tongue in a more anterior position
Surgical treatment
Nasal procedures: turbinectomy (turbinate reduction), septoplasty, rhinoplasty, nasal valve surgery
Upper pharyngeal prodecures: tonsillectomy and adenoidectomy, uvulopalatopharyngoplasty (UPPP)
Lower pharyngeal and laryngeal procedures: genioglossus advancement
Global upper airway procedures: upper airway stimulation (upper airway stimulation via an implantable neurostimulator device activates the protrusion muscles of tongue via hypoglossal nerve (CN12) stimulation
Lifestyle modication
Weight loss
Alcohol avoidance: depress CNS, exacerbate OSA, worsen sleepiness and promote weight gain
Change sleep position: supine to lateral recumebnt position
Drug avoidance: BDZ receptor agonist, antiepileptics, antidepressants, antihistamines and opaites
What are the complications of OSA?
Asthma attacks
Pulmonary edema
Obstructive sleep apnea (OSA)
Rhinitis with severe nasal blockage
Panic attacks
What further questions asked regarding the breathing difficulty?
Symptoms of wheezing
* Suggest asthma or pulmonary edema
Characteristics of breathing difficulty
* OSA: Suffocation/ Gasping/ Choking
* OSA: Resolves immediately on waking
* Pulmonary edema: Relief by sleeping with several pillows
* Asthma: Cough with expiratory wheeze
What other cardinal symptoms should be asked for if OSA is suspected?
Snoring
Witnessed breathing pauses during sleep
Excessive daytime sleepiness despite adequate hours of sleep
Feeling unrefreshed on waking up
What are the causes of acute adult respiratory distress syndrome?
What are the pathological hallmarks of acute adult respiratory distress syndrome?
Diffuse alveolar damage
* Alveolar edema and focal hemorrhage
* Acute inflammation of alveolar wall
* Hyalinzation of membrane
What is the pathogenesis of acute adult respiratory distress syndrome?
- Alveolar injury produces diffuse alveolar damage –> release inflammatory cytopkines such as TNF, inflammatory cytokines recruit and activate neutrophils –> release of toxic mediators such as ROS and proteases –> damage of capillary endothelium and alveolar epithelium
- Allows proteins to escape from the vascular space and the oncotic gradient that favors resopriton of fluid is lost with fluid pouring hte interstitium to overwhelm the lymphatics
- Increase in interstitial fluid combined with damage to alveolar epithelium causes air spaces to fill with bloody, proteinaceous edema fluid and debris from degenerating cells
Consequences
* Impaired gaseous exchange: V/Q mismatch due to physiological shunting and physiological dead space
* Pulmonary hypertension: hypoxic pulmonary vasoconstriction, vascular compression by positive airway pressure, parenchymal destruction, airway compliance
* Decreased lung compliance: due to stiffness of poorly non aerated lungs
What is the ddx for acute adult respiratory distress syndrome (ARDS)?
- Cardiogenic pulmonary edema
- Acute exacerbation of interstitial lung disease
- Idiopathic acute eosinophilic pneumonia
- Cryptogenic organizing pneumonia
- Acute interstitial pneumonia
What is the diagnostic guidelines to make the dx of acute ARDS?
What is the diagnostic criteria for acute ARDS?
1 week, new or worsening
Bilateral opacities, not other pathologies
Not cardiac failure/ fluid overload, hydrostatic pulmonary edema
Mod – Severe impairment of oxygenation
What PE and Ix for ARDS?
PE: auscultation: diffuse crepitations
Biochemical tests
ABG: hypoxemia, diffusion impairment, respiratory alkalosis (excess ventilatory compensation)
CXR: bilateral alveolar infiltrates (opacities)
CT thorax
Echocardiography
What is treatment for ARDS?
Complications?
What are the modes of transmission of the common cold
Incubation period
Period of infectivity
Hand contact: direct contact via an infected person (self inoculation of ones own conjunctiva or nasal mucosa after touching a person being contaminated the cold virus. Indirect contact with a contaminated environmnetal surface
Small particle droplet (droplet transmission)
Large particle droplet (droplet transmission): requires close contact with an infected person
Incubation perdio: time between contact with infectious material until onset of symptoms
Most common cold virus = 24-72 hours
Period of infectivity: low level of viral shedding may persist for up to 2 weeks
What are the seasonal patterns of common cold?
- Rhinovirus infections in september (autumn months)
- Parainfluenza virus infecton in october and november (autumn monhts)
- Coronavirus, influenza virus and respiratory syncytial virus infection in december to february (winter months)
What are the viral etiologies of the common cold?
What are the specific features of adenovirus infection?
Clinical, biochemcial and radiological
What is the mechanism of common cold infection?
What are the SS of common cold?
How to differentiate URTI and LRTI from SS?
What is the ddx for common cold?
What are the medications for common cold?
Analgesics (headache, ear pain, muscle and joint pain): acetaminophen/NSAIDs
Antihistamine/decongestant combination: combination is more effective than either component alone
* H1 receptor antagonist (antihistamine): diphenhydramine
* Decongestant (alpha adrenergic agonist causing vasoconstriction): phenylephrine
Cough suppressant: NMDA receptor antagonist (Decreases sensitivity of cough receptors –> interrupts cough impulse transmission by depressing medullary cough center through sigma receptor stimulation): dextromethorphan
Expectorants: increases effective hydration of respiratory tract –> improves ciliary clearance and reduces viscosity of respiratory mucus
Relief of nasal symptoms: cromolyn sodium (mast cell stabiizer), ipratropium bromide (intranasal): anticholinergic agents –> inhibits serous and seromucous gland secretions to reduce rhinorrhea
Vit C: reduction in duration of cold symptoms. Vit C given after symptom onset does not reduce symptoms duration or severity
Panadol
Acetaminophen: analgesia
Phenylephrine hydrochloride: nasal decongestant
Nasocapine: cough susppressant
Terpin hydrate: expectorant to increase bronchial secretion
Caffeine: relieve tiredness
Ascorbic acid: facilitate recovery
What are the types of influenza virus?
Influenzae virus A: may lead to pandemics –> divided into 18H (H1-H18) and 11N (N1-11) subtypes
Influenza virus B: do not lead to pandemics
Influenzae virus C: do not lead to pandemics
What is the terminology of influenza?
Seasonal influenza (H1N1/H3N2): common respiratory tract infection caused by human seasonal influenza viruses
Avian influenza (H5N1/H7N9/H9N2): influenza viruses that mainly affect birds and poultry. People may become infected through direct contact with infected birds and poultry, their droppings and contaminated environment
Influenza pandemics (H1N1/H2N2/H3N2): caused by emergence and global spread of a new influenza virus originated from an animal influenza virus such as avian influenza virus and is marked different from viruses circulating in the population
What are the kind of mutations that can occur in influenza?
Antigenc shift: major change in envelop glycoproteins (hemagglutinin and neuraminidase): only occurs in influenza A
Host infected by 2 different strains of influenza viruses –> gene reassortment occurs among influenza viruses whose genomes consist of 9 distinct segmetns of RNA. Changes in antigenic composition resulting in appearance of a new haemagglutunin or neuraminadase
Antigenic drift
* Minor changes in envelop glycoproteins (haemagglutinin and neuraminidase)
* Occurs in both influenza A and B viruses
Physiology: point mutations in RNA gene segments that code for haemagluttunin and neuraminidase. Mutations result in new strains of viral particles which cannot be inhibited effectively by antibodies that were originally targeted against previous strains.
What is the structure of the influenza virus?
- Enveloped RNA virus
- Haemagglutinin: attached to host cells by binding their cell receptors. Binds to sialic acid residues on respiratory epithelial cell surface glycoproteins. Interaction is necessary for initiation of infection
- Neuraminidase: promotes viral release after viral infection in cells –> facilicatetes release and spread of virus through mucin of respiratory tract
What history taking and biochemical tests for influenza patient?
What patient counselling done for influenza patients
What are indications for more targeted treatment
What antiviral medications can be given for influenza?
When are they indicated to be given
What AE?
What are the complications of influenza?
What is done for prevention of influenza?
What indications and contraindications?
Season influenza vaccination: requires about 2 weeks after vaccination for antibodies to develop and provide protection against influenza virusr infection. Efficacy in individuals age <65 years = 70-90% protection
Indications
All people aged >6 months except those with contraindications
High priority groups
* Persons aged >50
* Children between age 6 months-11 years
* Pregnant women: inactivated seasonal vaccine is safe in pregnancy but not for live attenuated virus
* Elderly living in residential care homes
* Long stay residents of institutions for persons with disability
* Healthcare workers
* Poultry workers
* Pig farmers and pig slaughtering industry personnel
* Chronic medical problems: children and adolescents aged 6 months-18 years on long term aspirin therapy. Chronic CVS, lung, liver or kidney diseases. Chronic neurological conditions taht can compromise respiratory functions or handling of respiratory secretions. History of invasive pneumocococcal disease. CSF leakage. Immunocompromised states related to weakened immune system due to conditions such as asplenia, HIV/AIDS or cancer/steroid treatment
Contraindications
* Allergy to previous dose of inactivated influenza vaccine or other vaccine components
* Allergy to egg if severe or history of anaphylaxis
What are the eligible groups for seasonal influenza vaccine?
What are the possible complications of seasonal influenza vaccine?
- GBS: paralysis and respiratory distress
- Meningitis/encephaliits
- Anaphylaxis
- Can seasonal influenza vaccine cause influenza?
- Is it necessary to get vaccinated against seasonal influenza every year?
- Can I receive seasonal influenza vaccination when receiving another vaccination?
- No. The virus in the inactivated vaccine are dead virus
- Yes. The circulating seasonal influenza strains change from time to time and the vaccine composition is updated every year to enhance protection. The immunity built up in a vaccinated person in prior season will decrease over time and insufficient to provide protection in next season.
- Yes. Injectable inactivated vaccine does not interfere with effectiveness of other vaccines.
Different vaccines should be given at different injection sites.
What precaution for influenza
What other diseases require this precaution?
Droplet precautions: particles do not remain suspended in air for extended periods of time. Particles do not travel beyond several feet (usually <1m)
Placement of patient: spatial separation of >1cm between infected patients and other patients
Transport of patient: place a surgical mask, only move if essential
Healthcare workers: wear surgical asmk
Other diseases requiring droplet precaution: neisseria meningitiditis, bordetella pertussis
What is the classification of sinusitis based on symptom duration or etiology/clinical manifestation?
What are the RF for sinusitis?
What are the bacterial and viral causes of sinusitis?
Acute bacterial rhinosinusitis
* Streptococcus pneumoniae
* Haemophilus influenzae
* Moraxella catarrhalis
Acute viral rhinosinusitis
* Rhinovirus
* Influenza virus
* Parainfluenza virus
What are the different nasal sinuses, blood and nerve supply?
What are the SS of sinusitis?
What is the diagnostic criteria for sinusitis?
What is the PE for sinusitis?
What radiological Ix for sinusitis if suspicious of complications?
- X ray sinuses
- CT sinuses with/without contrast: common findings include air fluid levels, mucosal edema and thickening, air bubbles within sinuses and opacification. CT with contrast is required to identify complications of sinusitis and evaluate disease location and extent of involvement beyond the sinuses
- MRI sinuses
What treatment for sinusitis?
What are the complications of acute rhinosinusitis?
What is the classification of pneumonia according to source of infection?
- Community acquired pneumonia
- Hospital acquired pneumonia
- Healthcare associated pneumonia
What is the classification of pneumonia according to causative agents?
Typical organisms: include S. pneumoniae, H.influenzae, S. aureus, S. pyogenes, aerobic gram-ve bacteria and anaerobes
Atypical pneumonia: chlamydia pneumoniae, chlamydia psittaci, mycoplasma pneumoniae and legionella pneumophila
Afebrile pneumonia of infancy: syndrome seen between 2-4 months of life: classically caused by chlamydia trachomatis but other agents such as mycoplasmsa hominis, ureaplasma urealyticum and CMV are also implicated.
Clinical presentation: insidious onset of rhinorrhea, conjunctivitis and tachypnea followed by a staccato cough (individual cough separated by inspiration)
What are the patterns of pneumonia?
What are the RF for pneumonia?
What are the RF for MDR pathogens in pneumonia?
Use of antibiotics in preceding 90 days
Hospitalization for ≥ 2 days in preceding 90 days
High frequency of antibiotic resistance in community or hospital
Home wound care
Residence in nursing home or extended care facility
Family member with MDR pathogens
Immunosuppressive therapy
What are the pathogens of pneumonia in children vs adults?
Etiological agents of pneumonia in adults?
What are the pathogens causing pneumonia in children?
Define recurrent pneumonia in children
What disorders must you suspect in recurrent pneumonia?
What is the micbio of bacteria causing pneumonia?
What is the micbio of virus and fungi causing pneumonia?
What is the ddx for pneumonia?
- Bronchiolitis
- Lemierre syndrome (jugular vein suppurative thrombophlebitis): vessels of the carotid sheath become infected typically by fusobacterium sp leading to bacteremia and metastatic spread of infection to lungs and mediastinum
What are the different stages of pneumonia?
What are the SS of pneumonia in adults?
What are the SS of pneumonia in children?
What history taking for pneumonia?
What PE and results for pneumonia?
What Ix for pneumonia?
- CBC with DC: leukocytosis with leftward shift suggestive of pyogenic bacterial disease
- Inflammatory markers: increased ESR and CRP
- LFT
- RFT: hypoNa due to SIADH
- Blood culture
- Sputum smear and culture
- NPA for viral IF/PCR + mycoplasma PCR: Rapid diagnostic testing including enzyme immunoasay (EIA) immunofluorescence or PCR for viruses
- Throat swab for PCR: PCR for mcyoplasma pneumoniae
- Urine antigen detection: antigen detection for legionalla pneumophila
- Bronchoalveolar lavage (BAL): indicated in not responsive to treatment, recurrent pneumonia, suspected unusualy organism or suspected aspiration in children
Radiological Ix
* CXR
Consolidation: homogenous opacification in lobar pattern in lobar pneumonia. Multiple small nodular or reticulonodular opacities in bronchopneumoniae
Infiltrations: alveolar infiltrates indicates bacterial pneumonia
Air bronchogram: black airways against white background: alveolar space filled with fluid and thus appear white. Airways retain air and thus appear black.
Left heart border: not clearly seen –> leson in LLL
Right heart border: right heart border not clearly seen –> lesion in RML
Bronchoscopy with bronchoalveolar lavage (BAL): ideal specimen for dx of pneumocystic jirovecci pneumonia
What is antibiotics duration for pneumonia
Choice of antibiotics in pregnancy and infants
What antibiotics not used alone?
What antibiotics for mycoplasma pneumoniae due to resistance?
What is treatment for community acquired pneumonia?
What is treatment for hospital acquired pneumonia?
What is treatment for pneumonia according to casuative organisms?
How to managem mycoplasma or MRSA pneumonia?
What is used to assess whether patient should be admitted for pneumonia?
What are the complications of pneumonia?
What is the classification of TB?
- Primary TB: describes new TB infection or active disease in a previously naive host
- Latent TB: 90% of individuals with intact immunity can control further replication of bacilli after primary infection
- Reactivation TB: chronic TB or post primary TB
- Miliary TB: haematogenous dissemination of mycobacterium tuberculosis. Radiological appearance of small firm white nodules resembling millet seeds. Results from both progressive primary infection or via reactivation of latent focus with subsequent haematogenous spread via bloodstream
- Endobronchial TB: tuberculous infection of the tracheobronchial tree. Develop via direct extension to bronchi from an adjacent parenchymal focus or via spread of organisms to bronchi via infected sputum. Complications of endbronchial TB include atelactasis, bronchiectasis, obstruction and tracheal stenosis
How to make dx of latent TB and active TB?
What are the sites of extrapulmonary TB?
Are they infectious?
What are general features of TB lymphadenitis
How to make dx
Treatment
What are general features of TB pleuritis
How to make dx
Treatment
What are general features of TB skeleton
How to make dx
Treatment
What are general features of TB meningitis?
How to make dx
Treatment
What is tuberculoma and how to make dx?
- Rounded mass lesions that can develop during primary infection or when a focus of
reactivation TB becomes encapsulated - Fine needle aspiration or lung biopsy may be necessary for diagnosis
What are the RF for TB?
What are the RF for progression or dissemination of TB?
Immunocompromised patients
* HIV infection
* Malignancy
* Chronic renal failure
* Uncontrolled DM
* Organ transplant recipients
* Immunosuppressant
* Malnutrition
* Alcoholism
What is the micbio of TB?
MTB
NTM
- Mycobacterium avium complex
- Mycobacterium kansasii
- Mycobacterium abscessus complex
- Mycobacterium marinum
- Others: M. ulcerancs, M. chelonae, M.fortuitum
What is the ddx for TB?
Bronchiectasis
Pneumonia
Lung abscess
Lung cancer
Sarcoidosis
Silicosis
What is the natural history of TB infection?
1 of 4 possible outcomes
* Immediate clearance of the organism
* Primary disease: immediate onset of active disease
* Latent infection
* Reactivation disease: onset of active disease many years following a period of latent infection
Primary disease: tubercle bacilli establish infection in the lungs after they are carried in droplets small enough to reach alveolar spaces. Failure to eliminate the infection by innate defense system leads to proliferation of bacilli inside alveolar macrophages –> macrophages and neutrophils form a nodular granulomatous structure known as tubercle. Progressive destruction of lung with development of caseating necrosis. Tubercle enlarges and bacilli enters local draining LN leading to lymphadenopathy. Continous bacterial growht leads to haematogenous spread to bacilli to produce disseminated TB infection
What is the pathogenesis of TB?
Host response to infection by tubercle bacilli is primary cellular and specific acquired immune response is largely cell mediated. Local tissue damgae caused by delayed (type 4) hypersensitivity reaction to mycobacterial protein antigens
Pathogenesis
* Dendritic cells carry the MTB antigen to LN: MTB induces the dendritic cells to produce IL12
* Activated Th1 and B cells migrate to the site of infection
* Activated macrophage by MTB is unable to clear the infection: macrophages will continously present MTB antigens to Th1 clels –> MTB inhibits fusion of lysosomes with phagosomes. Granuloma fence off infectious agents and prevents dissemination providing a local environment for multiplication of MTB
* Chronic inflammation occurs with mycobacteria in the center: cellular immunity results in control of infection as well as tissue damage
What are SS of TB?
What PE and results for TB?
General examination
* Lymphadenopathy
Palpation
* ↓ Chest wall expansion
Percussion
* Stony dullness in pleural effusion
Auscultation
* ↓ Breath sounds
* Bronchial breathing
* Pain-inspiratory crackles
* Wheezing in endobronchial TB
What Ix done for TB?
- CBC with DC: leukocytosis, thrombocytopenia/thrombocytosis, pancytopenia occurs in bone marrow infiltration
- Inflammatory markers: CRP, ESR
- Electrolyte profile: HypoNa in SIADH
Microbiological tests
* Sputum
* Bronchoalveolar lavage and brushings
* Tissue biopsy
Other specimens
* Pleural fluid by tapping or pleural biopsy in TB pleuritis
* LN fine needle aspiration or biopsy in TB lymphadenitis
* Lumbar puncture for CSF fluid analysis in TB meningitis
* Paracentesis for ascitic fluid analysis in TB peritonitis
AFP smear microscopy: ZN stain (bacilli stained red with a blue background)
Mycobacterial culture: LJ medium. Allow drug sensitivity testing for HREZ. Disadv: time consuming with solid media requiring 3-8 weeks and liquid media requiring 1-3 weeks
NAAT (PCR): does not replace the roles of AFB smear and culture in diagnostic algorithm for TB
Adv high sensitivity and specificity: rapid dx requiring 1-2 days old.
Histopathology: demonstrates caseating granulomatous inflammation. Characteristic caseation necrosis. Contains epithelioid macrophages, langhans giant cells (horseshoe appearance with nuclei locate peripherally) and lymphocytes.
Specific tests for TB infection
Tuberculin skin test
Based on Type 4 hypersensitivity reaction to M.tuberculosis –> for dx of latent TB infection.
Procedure: intradetrmal injection of 0.1mL purified protien derivative (PPD).
Interpretation: results should be read at 48-72 hours, palpation with finger or use ballpen method. Measure maximal transverse diameter
Inferferon gamma release assay: IGRA (designed for latent TB infection): +ve results supports dx of active TB but -ve results does not rule out active TB
Other tests: urine lipoarabinomannan (LAM) antigen detectin but not routinely available in HK
CXR
CT chest
Bronchoscopy: BAL or bronchial brushing
How to interpret the results of tuberculin test?
Causes of FN and FP results?
What are CXR features of TB?
What is the types of drug resistance of TB?
What is treatment regimen for TB and for how long?
What side effects
What are the different types of TB drugs?
What is treatment regimen of TB in immunocompromised hosts?
How to manage the AE of drug treatment in TB?
- Hepatotoxicity (drug induced hepatitis): isoniazid/rifampicin/pyrazinamide. Ehionamide/prothionamide
Withhold treatment if ALT >3x ULN or bilirubin >2x ULN.
Management: stop anti-TB treatment. Reintroduction may be considered when ALT is <2x ULN in case treatment is prompty required
Non hepatotoxic interim S-L-E regimen (S+fluoroquinolone (L)+E) is initiated.
Subsequent addition of H,R and Z with the aim of administering HR together if possible. R at maximum dosage at day 1. H at maximum dosage at day 8, Z at maximum dosage at day 15. -
Ocular toxicity caused by ethambutol
Management: stop anti TB treatment –> both isoniazid and ethambutol should be stopped immediately if severe ocular toxicity occurs. Isonidazid should also be stopped 6 weeks after stopping ethambutol if ocular condition does not improve. - Nephrotoxicity: rare complication of rifampicin administration. Due to type 2/3 hypersensitivity reaction: forms immune complexes that are deposited in renal vessels, glomerular endothelium and interstitial area
-
GI disturbances
Exclude hepatitis with blood tests when ALT <3x ULN, total bilirubin <2x ULN
Management: administer drugs with food, adminsiter medication at bedtime, prescribe anti-emetics for symptomatic relief -
Peripheral neuropathy due to isoniazid
Prophylactically given vit B6 at 10-20mg daily, high dose vit B6 at 50-100mg daily given to patients complicated by peripheral neuropathy -
Cutaneous hypersensitivity
Stop all chemotherapy until reaction has subsided. Consider use of antihistamines/topical steroids. Reintroduction of TB drugs one by one. Start with drug least likely to be responsible for reactin (HR) at a small challenge dose (isoniazid at 50mg)
What is the strategy for TB control in HK?
- Case finding
- Effective chemotherapy - DOTS
- Treatment of latent TB infection
- BCG vaccination
- Health education
How is case finding done for TB?
What is effective chemotherapy in TB?
How is treatment for latent TB infection done?
Targeted groups for LTBI treatment in Hong Kong
* Patients age < 35 years old if tuberculin response ≥ 15 mm
* Infants close contacts of smear +ve patients
* Tuberculin skin test +ve patients with HIV
* Tuberculin skin test +ve patients with silicosis
What is done for BCG vaccination and health education in TB?
What is the complications of TB?
What are some common medications that have drug interactions with rifampicin
Rifampicin
* Potent inducer of CYP450 system including CYP3A and CYP2C, which account for more
than 80% of CYP450 isoenzymes
* Results in a decrease in the serum concentrations of many drugs
Oral hypoglycemic agents
Warfarin
Oral contraceptives
Immunosuppressant
Phenytoin
Protease inhibitor and NNRTI in HIV patients
What recommendations would you give to patients if they are receiving therapies that interact with rifampicin?
Oral contraceptives
* Recommend female patients of reproductive age to use other contraceptive methods
Warfarin
* Inform cardiologist that the patient will require an unusually high maintenance dose of warfarin in order to produce a therapeutic INR
* Warn cardiologist to decrease dosage of warfarin on withdrawal of rifampicin after TB treatment
Steroids
* Increase dosage of steroids for SLE patients so as to achieve the desired therapeutic level
What is the pathogenesis of bronchiectasis?
What are the causes of bronchiectasis (infectious insult, airway obstruction)?
What are the causes of bronchiectasis (impaired drainage, defective host response, miscallenous)?
What is ddx for bronchiectasis?
Asthma
* Presents with dyspnea, coughing, tenacious sputum production and recurrent exacerbation in
patient who might not have been a smoker
COPD
* Classically presents with virtually identical symptoms in a smoker
* High prevalence of bronchiectasis among patients diagnosed to have COPD
TB
Chronic rhinosinusitis
* Affects up to 60% of cases with bronchiectasis
Interstitial lung disease
* Idiopathic pulmonary fibrosis (Cryptogenic fibrosing alveolitis)
GERD
What is SS for bronchiectasis
PE and results
What Ix for bronchiectasis?
- CBC with DC: leukocytosis
- Sputum smear and culture
- Lung function test (spirometry)
- Pulse oximeter
- Arterial blood gas
- Immunoglobulin measurement
- Serum alpha1-antitrypsin levels
- Sweat chloride level or mutation analysis of CFTR gene (evaluate for cystic fibrosis –> more in Western countries)
CXR: ring shadows, tramline shadows
HRCT thorax: airway dilatation and lack of tapering, signet ring sign, thickening of bronchial wall, mucopurulent plugs, cyst off the bronchial wall
distribution of bronchiectasis:
* Central distribution = allergic bronchopulmonary aspergillosis
* Upper lobe predominance = cystic fibrosis/post radiation fibrosis
* Middle lobe predominance = primary ciliary dysfunction/non tuberculous mycobacterium infection
* Lower lobe predominant
Bronchoscopy: BAL when sputum studies are negative and MTB suspected
Specific tests
24 hour esophageal pH monitoring to exclude GERD
Ciliary study
What features in CXR and HRCT thorax for bronchiectasis?
What is the medical treatment of bronchiectasis?
A patient presents with cachexia and moderate finger clubbing. Physical examination shows tracheal deviation to the left, decreased chest movements bilaterally, particular the left upper part. There is increased dullness to percussion over the left upper part. Coarse inspiratory crackles over the whole lung bilaterally and a full cup of purulent sputum at the bedside.
Q1: What is the most likely diagnosis?
Q2: What common diseases give rise to finger clubbing together with inspiratory crackles?
Q3: What common diseases cause apical fibrosis?
1.
Bronchiectasis and left-sided apical fibrosis
2.
Bronchiectasis
Idiopathic pulmonary fibrosis
CA lung with localized pathology
3.
TB
Post-radiation
Ankylosing spondylitis
What is the lung function test pattern in bronchiectasis?
What are the important sputum diagnosis?
Obstructive pattern on spirometry in 60% of patients
H. influenzae in early disease P. aeruginosa in late disease
Suggest antibiotics useful for exacerbations of bronchiectasis?
Early or mild cases (against H. influenzae)
* Amoxicillin with clavulanic acid (Augmentin)
* Azithromycin
Late or severe cases (against P. aeruginosa)
* Ceftazidime
* Levofloxacin
What is the long-term management for bronchiectasis??
Inhaled corticosteroids (e.g. fluticasone)
* Anti-inflammatory drugs to prevent further damage and enhance QOL
* Reduce exacerbation frequency and sputum production
Antibiotics
* Indicated for each exacerbations
Chest physiotherapy
* Useful as retained infected mucus is harmful
Remarks
* Disease is greatly irreversible
* Treatable causes such as immunodeficiency and GERD should be looked for and treated
How do you manage hemoptysis in bronchiectasis?
Bed rest
Antibiotics
* Until sputum volumes or coughing returns to baseline values or fever settles
Thrombotic agents (e.g. transamine)
* Not recommended routinely as they could obstruct airways leading to lung collapse, further infection and respiratory failure
* Also pose risk to stroke, MI or peripheral vascular obstruction
What is done for PE of lung CA?
What are symptoms caused by metastatic disease?
