Respiratory Flashcards
Where is the central area for stimulation of inspiration
medulla- dorsal respiratory group
Where are the central chemoreceptors
Near ventral surface of the medulla
Anion Gap Equation
ANION GAP:
= Na – (Cl + HCO3) – 12
Normal anion gap = 12mmol/L +/- 2
Osmolar gap equation
OSMOLAR GAP: calculate if anion gap is increased and unclear cause
Difference in measured and calculated osmolality
Should be <10
Calculated osmolality =
(2xNa) +Glucose +Urea
Measured osmolality – calculated osmolality = Osmolar gap
Lung volume at which pulmonary vascular resistance is lowest
FRC
Definition of pulsus paradoxus
an inspiratory drop in blood pressure of 10mmHg or more during normal breathing
A-A Gradient equation
• PA02 = (Patm – Pwater)FiO2 – PaCO2/0.8
= 150 – PaCO2/0.8
• A-a gradient = PA02 – Pa02
= 150 – PaCO2/0.8 – PaO2
Indirect Bronchoprovocation drugs
Mannitol, adenosine monophosphate, eucapnic hyperventialtion
Direct Bronchoprovocation drugs
methacholine, histamine
Which histo subtype of malignant mesothelioma has the worst/best prognosis
Sarcomatoid - worst
Papillary mesothelioma -best
Mx of mesothelioma
Unresectable - Platinum +Pemetrexed
+/- bevacizumab
If progess on first line: Gemcitabine
Causes of Upper Lung Fibrosis
Upper lobe - Coal miners pneumoconiosis - Hypersensitivity pneumonitis (extrinsic allergic alveolitis)/ Histiocytosis - Ank Spond - Radiation - TB Silicosis/Sarcoidosis
Left shift in O2 curve
↓H+ (↑pH) and CO2 ↓Temperature ↓DPG-phosphate from metabolism COHb MetHb ↑HbF
Right shift in O2 curve
↑H+ (↓pH) and CO2 ↑Temperature ↑2-3 DPG-phosphate from metabolism Cyanide ↓HbF
Right shift in O2 curve
↑H+ (↓pH) and CO2 ↑Temperature ↑2-3 DPG-phosphate from metabolism Cyanide ↓HbF
Flow Volume loop: Flat bottom
Dynamic extrathoracic obstruction
Cause:
Structural or functional vocal fold abnormalities
Laryngomalacia
Tracheomalacia of the extrathoracic trachea
Flow Volume loop: Flat top
Dynamic intrathoracic obstruction
Cause:
Tracheomalacia of intrathoracic airway
Bronchogenic cysts
Malignant tracheal lesions
Flow Volume loop: Flat both top and bottom
Fixed obstruction
Cause:
Firm tracheal lesions (e.g. tracheal stenosis)
Extraluminal Tracheal Obstruction (goitre)
Flow Volume loop: Sawtooth
Cause:
OSA
NMD
Parkinsons
Methaemoglobinaemia
- Iron is in Fe3+ state rather than Fe2+, so reduced oxygen affinity for Hb while remaining O2 bound to normal Hb binds tighter (left shift)
- Can be congenital (eg. Haemoglobin M disease or acquired (eg. Dapsone)
- Cyanosis with normal PaO2.
- Treatment: methylene blue
Lights Criteria
- Pleural fluid protein/serum ratio >0.5
- Pleural fluid LDH/serum LDH ratio >0.6
- Pleural fluid LDH > 2/3 the upper limits of the laboratory’s normal serum LDH
Transudative pleural effusion
Serum: Pleural protein - >31g/L most likely transudative
If <31 g/L consider measuring albumin gradient (particularly if hepatic hydrothorax is likely)
• >12 g/L most likely transudate
• Ratio <0.6 the most sensitive for transudate
Mesothelioma malignancy markers
– Mesothelin, Fibulin 3; SMRP (Serum mesothelin related protein good for sarcomatoid mesothelioma), Calcretin
Pleural pH when testing for empyema
• Pleural pH is only reliable if checked within 1 hour of obtaining otherwise it begins to rise; pleural glucose <2.2 is just as sensitive as pH and can be stable for up to 24 hours
Management of pleural infection
IVABx
Drainage
Treatment Failure:
-Surgical: VATS/Thoracotomy
Not a surgical candidate:
-TPA and DNase
Mx of malignant pleural effusions:
- USS guided thoracocentesis
- If NO lung expansion:
- Survival >1 week Consider IPC
- Survival <1 week then palliate and consider repeat thoracocentesis - If Lung expansion occurs:
- IPC (indwelling pleural catheter - improved length of hospital stay, increased risk of infections)
- VATS pleurodesis
- Combo IPC and talc (increased rate of pleurodesis in 35 days)
Varenicline (Champix)
Partial agonist of nicotinic receptors
o Most effective monotherapy
o CIs: Pregnancy, psychiatric disease, CVD, reduce dose in renal disease, SEs: Nausea
Bupropion (Zyban)
o Antidepressent with uncertain mechanism
o CI: bipolar, seizures, pregnancy, MAO-I use
AAT Pathophysiology
• Emphysema thought to result from imbalance between neutrophil elastase (destroys elastin) and elastase inhibitor (AAT) – toxic loss of function
o Pathogenesis of liver disease is a “toxic gain of function” – accumulation of AAT within hepatocyte
CF PAthogenesis
• Pathogenesis – CFTR protein dysfunction: functions as cAMP-regulated Cl- channel (also other ions)
o Located on apical plasma membranes in lungs (regulates secretions)
CF Genetics
AR
Delta F508 mutation with deletion of phenylalanine at position 508
Kalydeco/Ivakaftor
Oral active inhibitor for G551d stop mutation in CF
Potentiates CFTR channel
Definition of classic CF
homozygous mutations or positive sweat test with >1 organ system affected
Non Classical CF Definition
Milder symptoms with either heterozygote or no mutations detected
ABPA diagnostic Criteria
Major Criteria:
o Clinical: Asthma
o Radiographic: Pulmonary opacities (transient or chronic); central bronchiectasis
o Immune: Eosinophilia; immediate skin reactivity to Aspergillus antigen; serum IgE > 1000 IU/ml
Minor Criteria
o Fungal elements in sputum; expectoration of brown plugs/flecks; delayed skin reactivity to fungal antigens
ABPA Mx
Steroids; Itraconazole as second line
ABPA XR
Finger in glove appearance
Sarcoid PFTs
Restrictive pattern, decreased DLCO
Pulm HTN Classification
o Group 1: PAH (eg. idiopathic, heritable (BMPR2, ALK1), drugs (eg. Amphetamines, IFN), CTD
o Group 2: Left heart disease (most common): Elevated LA pressure (mLAP >14mmHg)
o Group 3: Lung disease (+/- hyoxaemia) Eg. COPD, ILD
o Group 4: CTEPH - V/Q best screening test, special phase CTPA gold-standard
o Group 5 – Multifactorial - Eg. Chronic haemolytic anaemia, myeloproliferative disorders, sarcoid
STOP BANG Screening OSA
o Snoring, Tiredness, Observed apnea, Pressure (BP), BMI, Age, Neck circumference, Gender; Score 3 or more = 88-93% sensitivity
Diagnosis of OSA
Clinical diagnosis – AHI >5/hr plus 1 symptom or AHI of >15/hr
o Symptoms: fatigue, insomnia, PND, snoring, breathing interruptions HTN, mood disorder, cognitive dysfunction, CAD, stroke, CCF, AF, T2DM
• General consensus – AHI <5 is normal, 5-15 mild, 15-30 moderate and >30 severe
Strongest correlation with CVS events in OSA
oxygen desaturation index of 4% - number of times oxygen dips by 4% from baseline per hour of sleep
Mx OSA
o Weight loss can reduce severity of OSA and in some cases eliminate OSA altogether
Calorie counting, Very low energy diet, Bariatric intervention
o Positional treatment – efficacious in 25% of patients with OSA when laying on back
o Mandibular splint – For mild to moderate OSA; Brings lower jaw forward; 75% efficacious
o CPAP – Most effective Tx
RCT for severe OSA and CPAP use: NO improvement in CVS event rates (maybe reduces stroke rate, but post hoc analysis)
Reduced BP and actually increases weight due to reduced WOB
o Uvulolaryngopharyngeal plasty – Not usually done; only 40% undergoing this have resolution or major improvement in OSA
Cause of narcolepsy
Loss of neuropeptides (orexin A and B aka Hypocretin 1 and 2); ?Autoimmune component (Assoc with HLADQB1*06:02 in >90% of people with Type 1)
Diagnosis of narcolepsy
Multi-sleep latency test – Mean latency <8 minutes and 2 or more naps associated with REM sleep
Mx of narcolepsy
Modafinil 1st line
Idiopathy hypersomnolence
Typical presentation – young adult with chronic and disabling excessive daytime sleepiness
Multi-sleep latency test – Mean latency <8 minutes BUT number of naps with REM sleep <2
Pathophysiology unclear
Generally treat the same as narcolepsy
Subtypes of OHS
- OHS in the context of obstructive sleep apnoea; this is confirmed by the occurrence of 5 or more episodes of apnoea, hypopnea or respiratory-related arousals per hour (high apnea-hypopnea index) during sleep.
- OHS primarily due to “sleep hypoventilation syndrome”; this requires a rise of CO2 levels by 10 mmHg (1.3 kPa) after sleep compared to awake measurements and overnight drops in oxygen levels without simultaneous apnoea or hypopnea
Cause and Mx of restless leg syndrome
- Iron defiency is most common cause (it is a co-factor for dopamine, and defiencies of DA transport are thought to be key in pathogenesis)
- Treatment: Dopamine agonists – PRAMIPEXOLE or gabapentin and pregabalin
Causes of REM behavior disorder
LBD/MSA (alpha syneuclein neurodegeneration)
Mx: Melatonin
PJP Prophylaxis
o Bactrim 160/800 daily or 3 times per week
If contraindicated: Dapsone 100 mg daily
Role for adaptive servo ventilation in CSA
Cannot be used with decreased LVEF as increases mortality
-Better to treat underlying CCF
Primary ciliary dyskinesia
AR
Dx - Examination of ciliary ultrastructure is the definitive test
–Low levels of nasal NO are suggestive of need for further investigation
Diagnosis of CF
Clinical feature os CF or FHx of CF AND EITHER
- 2 CF causing mutations
- Positive sweat chloride on 2 occasions (60mmol/L)
- Nasal potential difference tracing typical for CF
Lumacaftor-Ivacaftor
CFTR Corrector and potentiator
For homozygous Phe508del
Small improvement in FEV1, decrease in pulmonary exacerbations
Role for macrolides in CF
Inhibits biofilm
Modifies mucus production
Suppresses inflammatory mediators
Always rule out nontuberculous myobacteria before starting as it can cause resistance when started
Definition for pulm arterial HTN
mPAP >25 mmHg
PASP (Pulm arterial systolic pressure)
PASP=RVSP=tricuspid pressure gradient +CVP (in the absence of RV outflow obstruction or pulmonary stenosis)
RVSP
RVSP >40 mmHg = estimated mPAP >25 mmHg
mPAP severity rating
mild = 25-40
Mod=41-55
Severe >55
PCWP indicative of LHF as cause of increased PAP
PCWP = LVEDP
> /=15 mmHg suggest LHF
PBS listed treatment for IPF that have shown to slow progression of disease
Pirfenidone
Nintendanib
Diagnosis of IPF
Confirmed at MDT
- No tissue needed
- Radiological features of UIP pattern IPF + Combined with appropriate clinical features
HRCT Findings of UIP pattern
- Subpleural and basal predominance
- Reticular abnormality
- Honeycombing (with or w/o traction bronchiectasis)
- Absence of features listed as inconsistent with UIP (mid or upper zone, peribronchovascular changes, extensive ground glass opacity, profuse micronodules, cysts, mosaic attenuation, consolidation)
Choice of oxygenation method for T1RF
HFNP better than NIV except in APO when CPAP/NIV are beneficial
Contraindications to Lung Tx
- End stage concurrent organ disease
- Active malignancy
- Active IVDU
- Active untreated infection
Treatment of PJP
IV Bactrim
OR
-Clinda + Primaquine OR IV pentamadine
If Severe (PaO2 <70 mmHg) add stress pred/hydrocort
CMV Prophylaxis in Tx
Recipient +ve
IV ganciclovir for first 7 days
Change to oral valganciclovir 450mg BD
Duration 5-11 months
High risk: lifelong
CMV Prophylaxis in Tx
Recipient -ve/ Donor +ve
IV ganciclovir for first 7 days + CMV immunoglobulin for first 3 days then weekly for a month
Change to oral valganciclovir 450mg BD
Duration 11-17 months
CMV Prophylaxis in Tx D-ve/R-ve
3 months valganciclovir
Most common type of Lung Tx rejection
Acute cellular rejection
-T cell mediated via HLA
Mx of Lung Tx Acute cellular rejection
Azithromycin for immunomodulatory properties 3x/wk
Increase immunosuppression
Diagnosis and Mx of AMR in lung transplant
AMR usually hyperacute rejection and due to DSAs
Definite AMR: Allograft dysfunction (drop in FEV1) plus DSA plus histological (neutrophil capillaritis) and immunological (C4d positivity) changes on lung biopsy. ACR and AMR can be concurrent but other causes have been excluded.
Mx:
MMF, IVIG, increase immunosuppression dependent on stage of rejection
Bortezomib if refractory
CLAD Definition
Chronic lung allograft dysfunction
Two types:
Bronchiolitis obliterans syndrome (obstructive)
OR
Restrictive allograft syndrome
Definition:
Substantial or persistent decline of >20% FEV1 from baseline
If it persists for >3 months then it is definitive
Pathogenesis of IPF
Perpetuated by abberant wound healing rather than by chronic inflammation
Pirfenidone Evidence
Combined activity as antifibrotic, antiinflammatory, and antioxidant
Unknown MOA
Evidence:
- Reduced FVC, 6MWT
- Improved progression free survival
- No reduction in dyspnea or death though
Pirfenidone SE
Photosensitivity
Rash
N+D
Nintedanib MOA and evidence
TKI
Evidence
- Reduction in FVC decline
- No change to time to first exacerbation
- No difference in QOL
Nintedanib SE
GI upset
N+D
Prognosis for NSIP vs UIP
NSIP has a better prognosis
RAPID Score
Assessing outcome in pleural infection
- Renal: Urea
- Age
- Purulence of fluid (more better)
- Infection source (CAP vs HAP)
- Dietary factors: Albumin <27
Serum neurone specific enolase is assosciated with?
Small cell Lung Cancer
Major indication for Thrombolysis in PE
Cardiogenic shock/persistent hypotension
ILD type associated with sjogren’s
Lymphocytic interstitial pneumonitis
Risk factors for Spontaneous primary pneumothorax
Smoking FHx Marfa's Homocytinuria Thoracic endometriosis
Risk factors for spontaneous secondary pneumothorax
COPD PCP AIDS CF TB
Which type of ILD resolves with smoking cessation
Respiratory associated Bronciolitis Associated ILD (RBILD)
DIP - Distal interstitial pneumonia
Tx of choice for a lung abscess
IV Clindamycin
Riociguat
Soluable guanylate cyclase stimulator
for Pulm HTN associated with CTEPH
Best measure to predict mortality in patients with IPF
DLCO and FVC
PSP Mx
<2 cm - O2 and observe for 6 hours and repeat CXR
> 2 cm or symptomatic - Fine needle aspiration/chest tube
Unstable - chest tube or emergency cannula
Most common causes of chylothorax
- Malignancy is typically the leading cause of nontraumatic chylothorax while thoracic surgery is the major cause of traumatic chylothorax
Fluid MCS for chylothorax: lots of lymphocytes, chylomicrons, and triglycerides
Extrinsic allergic alveolitis/Hypersensitivity pneumonitis
Will need trigger - bird’s, farmer
Abrupt onset
fever, chills, malaise, nausea, cough, chest tightness, and dyspnea without wheezing. With removal from exposure to the inciting antigen, symptoms subside within 12 hours to several days and clinical and radiographic findings resolve completely within several weeks
CXR: fleeting, micronodular pattern
ABPA
- Major Criteria:
o Clinical: Asthma
o Radiographic: Pulmonary opacities (transient or chronic); central bronchiectasis
o Immune: Eosinophilia; immediate skin reactivity to Aspergillus antigen; serum IgE > 1000 IU/ml - Minor Criteria
o Fungal elements in sputum; expectoration of brown plugs/flecks; delayed skin reactivity to fungal antigens - Management: Steroids; Itraconazole as second line
COPDX
Confirm the diagnosis
Sx and spirometry
RF:
§ Smoking!!
§ Organic and inorganic dust and fume exposure
§ Smoke from cooking (solid fuel fires)
§ Bronchial hyper responsiveness
§ Respiratory infections/mucus hypersecretion
Genetic: alpha 1 antitrypsin deficiency
COPD Severity based on FEV1
Mild: FEV1 60-80%
Mod: 40-59%
Severe: <40%
COPDx
Optimise function
Essentially.
- Start SABA
- Mod: Add LAMA/LABA or both
- Severe: Add ICS to above
Indication for Long term O2 therapy in COPD
- PO2 <55 mmHg
- PO2 <60 mmHg w/ Pulmonary HTN/RHF
§ Mortality benefit only if greater than 16 hours use per day No benefit of LTOT in COPD with moderate resting or exercise induced O2 therapy
Lung volume reduction surgery for COPD
® Overall increase early mortality and no change at 2 years, increased exercise capacity
Predominantly upper lobe emphysema benefitted the most
COPD X
Prevent Deterioration
Vaccines
Smoking cessation
Mx for comorbidities
COPDX
Develop Supports
○ Self management plans ○ Education - exacerbations, Sx Mx ○ Exercise ○ Psychological support ○ Manage anxiety and depression ○ Overall improves QoL and respiratory admissions
COPDX
Exacerbations
- Bronchodilators
- SABA - No evidence for nebulizer more efficacious than MDI and spacer
- Mixed evidence for adding ipratropium - Steroids ® Improve symptoms, FEV1, PaO2 ® Reduce treatment failure, relapse and length of stay
- No advantage of IV except speed of onset - ABx
If Increased SOB, Sputum volume, purulence, and ?CRP - O2 therapy
-Sats 88-92%
◊ High flow O2 associated with: HDU admission, increased use of NIV, and Increased length of stay
NIV indication in COPD exacerbation
Hypercapnic respiratory failure
Consider early when RR >30 and blood pH <7.35
BODE Index
Better predicts: Mortality, hospitalization, survival post LVRS)
◊ BMI ◊ Obstruction ◊ Dyspnea (MMRC)
-Exercise (6MWD)
SABA
- Salbutamol
Terbutaline
SAMA
Ipratropium
LABA
- Indacaterol
- Formoterol
Salmeterol
LAMA
- Tiotropium
- Umeclidinium
Glycopyrronium
ICS
- Fluticasone
- Ciclesonide
- Budesonide
Beclometasone
Kalydeco/Ivacaftor
For G551D mutation in CF
Ivacaftor isCFTR potentiator
Lumacaftor/Ivacaftor
CTFR corrector and potentiator
For homozygous Phe508del
Endothelin receptor antagonists
Bosentan
Phosphodiesterase inhibitors
Tadalifil
Prostanoids
Iloprost
