respi Flashcards
RESPIRATORY EPITHELIUM
pseudostratified columnar epithelium
w/ goblet cells
will transition to simple cuboidal in bronchioles,
then to simple squamous in alveolar ducts and alveoli!
(i.e. Type I cells, fn of gas exchange)
note: the parts which come into contact w/ external envt
(e.g. part of pharynx and larynx)
= STRATIFIED SQUAMOUS epithelium
Main mucles involved in respiration
Diaphragm and chest wall muscles
- Inspiration: CONTRACT
to move down and move ribs down
=> increase intrathoracic volume - Expiration: RELAX
to allow thoracic cavity to recoil
=> decrease intrathoracic volume
thus,
inspiration = ACTIVE process
expiration = PASSIVE process
which is/are true about intrapleural pressure?
A) Intrapleural pressure is always greater than intrapulmonary pressure
B) Intrapleural pressure is always less than intrapulmonary pressure
C) Intrapleural pressure is always greater than atmospheric pressure
D) Intrapleural pressure is always less than atmospheric pressure
B) and D)
- Intrapleural < Intrapulmonary
in order to keep lungs expanded
- Intrapleural < Atmospheric
as lungs have tendency to collapse inward due to elastic recoil while chest wall has natural tendency to expand outward
-> negative pressure acts like vacuum
=> prevents lung from collapsing
relationship bet intrapulmonary pressure and atmospheric pressure during inspiration
intrapulmonary pressure < atmospheric pressure
-> pressure gradient drives air to flow INTO lungs
relationship bet intrapulmonary pressure and atmospheric pressure during expiration
intrapulmonary pressure > atmospheric pressure
-> pressure gradient drives air to flow OUT of lungs
causes of change in intrapleural pressure
increased air or fluid in pleural space
increased air = pneumothorax
increased fluid = pleural effusion (serous fluid) OR haemothorax (blood)
which sensors (and where) detect changes in O2
Peripheral chemoreceptors
in aortic and carotid bodies
senses mainly O2, but also CO2 and pH
which sensors (and where) detect changes in CO2
Central chemoreceptors
in medulla
senses mainly CO2 and pH
which drive is normally a more potent stimulator of ventilation,
hypoxic (low pO2) or hypercapnic (high pCO2)?
hypercapnic
bcos normal range of pCO2 is 35-45mmHg
and hypercapnic drive has range of 45-70mmHg
=> more sensitive
normal range of pO2 is 80-100mmHg
and hypoxic drive has range of less than 60mmHg
=> less sensitive
since chemoreceptors of pCO2 is in medulla (brain),
most powerful respiratory stimulant in healthy person is
decreased CSF pH
In what scenario will patients rely more on hypoxic drive for ventilation
COPD patients
bcos there is chronic CO2 retention
-> blood becomes chronically more acidic
-> blood buffers step in to normalise blood pH
=> less stimulation of chemoreceptors even though CO2 remains high
implications:
giving oxygen supplementation
-> reduce hypoxic drive
=> cause decreased ventilation instead of increased ventilation
definition of tidal volume (TV)
volume of air entering or exiting lungs
with EACH passive breath
definition of inspiratory reserve volume (IRV)
extra air entering lungs with maximum inspiration
definition of expiratory reserve volume (ERV)
extra air exiting lungs with maximum expiration
definition of vital capacity (VC)
total volume of air which can be moved in or out of lungs
(i.e. TV + IRV + ERV)
Which of the following is true about Functional Residual Capacity (FRC)?
A) It is the total amount of air in the lungs after normal exhalation.
B) It consists of Expiratory Reserve Volume (ERV) and Residual Volume (RV).
C) It plays a key role in preventing large fluctuations in alveolar gas composition.
D) All of the above.
D) All of the above.
FRC = ERV + RV,
and represents the volume of air left in the lungs AFTER a normal expiration
helps maintain steady oxygen and CO₂ levels.
air flow in, air flow out or both
Compliance vs Elasticity vs Airway resistance
in relationship to airflow
- Compliance
= stretchability
=> affects how easily air flows IN - Elasticity
= recoil
=> affects how easily air flows OUT - Airway resistance
= resistance to airflow
=> affects how easily air flows IN AND OUT
what is compliance affected by
- surfactant
which disperses the fluid molecules on lining of alveoli
-> decreases surface tension
=> thus helping alveoli stretch - fibrosis
- skeletal deformities
1 pathology linked to surfactant production is neonatal respiratory distress syndrome
where insufficient surfactant production
-> alveoli collapse,
esp in not fully developed lungs of premature neonates
what is airway resistance affected by
-
size of airway
(changes with bronchoconstriction and bronchodilation) - mucus accumulation
pathologies linked to this are
* asthma: bronchoconstriction + mucus overproduction
(and also airway swelling/oedema)
* drugs (anti-adrenergics, anti-cholinergics, anti-inflammatory): bronchodilation or bronchoconstriction
difference in pressure and flow in lungs
compare bet before birth/fetus vs after birth/adults
- before birth: high pressure, low flow
due to lungs being prevented from being used for gas exchange
-> constriction of pulmonary blood vessels
-> high resistance in these blood vessels
=> high pressure, low flow - after birth: low pressure, high flow
due to lungs having function of gas exchange
-> dilation of pulmonary blood vessels
-> low resistance in these blood vessels
=> low pressure, high flow
before birth,
oxygenation occurs via placenta
and blood from RV bypasses lungs via ductus arteriosus and foramen ovale
what does restrictive lung disease affect
- limit lung expansion
=> reduced compliance - since lungs now resist expansion more
=> high recoil
what does obstructive lung disease affect
- impede airflow
=> increased airway resistance
how does restrictive lung disease affect FEV1/FVC ratio
increase in FEV1/FVC
(to ≥ 0.7-0.8)
* due to air having difficulty ENTERING lungs
lung volumes are reduced (FVC decrease)
=> less air available to be exhaled in 1st second of forced exhalation too (FEV1 decrease)
* however due to high recoil
-> rapid expiration in 1s
=> FEV1 decreases less than FVC
how does obstructive lung disease affect FEV1/FVC ratio
decrease in FEV1/FVC
(to ≤ 0.7-0.8)
due to airway impedement
-> exhalation (passive process) being limited and thus slowing down
=> decreased FEV1
also have decrease in FVC
as patient cannot exhale completely
-> air being trapped
however, decrease in FEV1 > decrease in FEV1
Why is oxygen (O₂) more affected than carbon dioxide (CO₂) in many respiratory pathologies?
A) O₂ has a higher solubility in blood than CO₂
B) CO₂ has a greater solubility in blood than O₂
C) O₂ is actively transported across the alveolar membrane
D) CO₂ is not affected by ventilation-perfusion mismatches
B) CO₂ has a greater solubility in blood than O₂
thus CO2 is more efficiently removed than O2 is taken up
-> O2 levels are affected first in various pathologies
=> ventilation must be severely impaired before CO2 retention (hypercapnia) occurs
how does RATE of blood flow change during exercise
increased rate of blood flow
-> less time available for gases to diffuse and equilibrate
=> lead to exercise-induced hypoxia in intense exercise
what factors affect affinity of Hb for O2
- pH
(lower pH = decreased affinity) - temperature
(higher temp = decreased affinity) - 2,3-DPG
(increased 2,3-DPG = decreased affinity)
2,3-DPG is molecule in RBC which regulates affinity of Hb for O2
when we NEED more O2
(e.g. during exercise or at higher altitudes),
affinity of Hb for O2 should decrease,
to allow O2 to be released to tissues more easily
change in affinity due to 2,3-DPG is NOT IMMEDIATE
=> affinity of Hb for O2 will not change UPON e.g. ascending to higher altitudes
Does pO2 change in Hb disorders (e.g. anaemia)
No!
as pO2, which measures the pressure of O2 dissolved in blood
is determined by alveolar O2 conc
and is independent of amt of Hb
explain CO2 transport in human body
eqn is CO2 + H2O -> H2CO3 -> H+ + HCO3-
- CO2 diffuses from lungs/tissue to blood
- some CO2 are dissolved in blood
=> resposible for pCO2 - the rest enter RBCs
- in RBC, some will bind to proteins
e.g. Hb to form carbamino Hb - others will be converted to H2CO3 then to HCO3-
- HCO3- is then transported into blood
(while Cl- is transported into RBC to maintain electrical neutrality)
eqn is CO2 + H2O -> H2CO3 -> H+ + HCO3-
HCO3- in blood is the predominant form of CO2
definition of dead space
- ventilation ≥ perfusion
=> wasted ventilation
as air inspired does not undergo gas exchange - V/Q = infinity
definition of shunt
- perfusion ≥ ventilation
=> wasted perfusion as blood does not undergo gas exchange - V/Q = 0
example of dead space
- pulmonary embolism
as it obstructs blood flow to areas of lung that still receive ventilation
there is also physiologic dead space
<- mainly due to anatomical dead space
(i.e. air in conducting airways (e.g. nose, pharynx) where no gas exchange occurs)
examples of shunt
- atelectasis
as collapse of alveoli
-> alveoli not being ventilated but still receiving blood flow - pneumonia
as inflammation
-> fluid-filled alveoli (w/ exudate)
-> alveoli is poorly ventilated but still receiving blood flow
there is also physiologic shunts
due to bronchial circulation
<- bronchial arteries, after supplying lung tissues w/ oxygenated blood and thus now carrying deoxygenated blood,
drain into pulmonary veins(carries oxygenated blood)
Which of the following is FALSE?
A) Absence of cyanosis indicates normal SaO2
B) Hyperbaric treatment can be used to treat both decompression sickness and carbon monoxide poisoning
C) A patient with carbon monoxide poisoning is unlikely to have arterial hypoxaemia
D) For a given partial pressure, there are more CO2 molecules dissolved in blood than O2 molecules
E) Acidosis shifts the oxygen dissociation curve to the right
A) Absence of cyanosis indicates normal SaO2
absence of cyanosis can still occur w/ drop is SaO2 below normal
<- cyanosis occurs when there is EXCESS deoxygenated Hb (around SaO2 of 70-80%)
(C) is true as CO binds to Hb
=> affects Hb and does not affect PO2
also note that CO poisoning does NOT cause cyanosis
<- CO binds to Hb to form COHb which is cherry pink
separate structures into upper and lower respiratory tract
pathway of airflow:
* Nasal cavity (or oral cavity)
* Pharynx
* Epiglottis and larynx
* Trachea
* Bronchi
* Bronchioles
* Alveoli
- Upper RT: nasal cavity and pharynx
- Lower RT: trachea and below
larynx can either be upper RT or lower RT
risk factors of NPC
-
EBV infection at young age
=> patients w/ NPC often have high antibody titres to EBV - Southern Chinese descent
- Family history
=> screening recommended for people w/ 2 close family members infected
since EBV infection occurs at young age
-> long latency bet EBV infection and NPC
Symptoms of NPC
- enlarged CERVICAL lymph nodes
<- metastases - hearing loss and tinnitus
due to obstruction to eustachian tube
-> secretory otitis media
(i.e. tube blocked -> everything behind tube gets infected) - epistaxis (i.e. nosebleed)
- diplopia (i.e. double vision)
<- invasion of CN VI
- enlargement of cervical (neck) lymph nodes is PAINLESS
- other nasal-related symptoms include blocked nose and serous discharge
3 types
types of NPC
- keratinising
- non-keratinising
(differentiated or undifferentiated)
i.e. what results in higher likelihood of getting NPC
what is keratinising NPC associated with
Smoking and drinking alcohol
(rmb as keratin
-> strong (bcos in fingernails)
-> gangsters (who are strong) all smoke and drink)
what is the most common subtype of NPC
non-keratinising squamous cell carcinoma (undifferentiated)
which subtype of NPC is the most sensitive to radiotherapy
UNdifferentiated NON-keratinising type
(rmb that two Ls make a W
=> most likely to be cured)
in contrast, keratinising type is the least sensitive
(rmb that keratin is strong)
what does the screening for EBV involves
annual screening of
* EBV IgA antibody
(bcos we swab the mucosA)
* nasoendoscopy
Which of the following is the most common cause of croup?
A) Respiratory syncytial virus (RSV)
B) Haemophilus influenzae
C) Parainfluenza virus
D) Streptococcus pneumoniae
C) Parainfluenza virus
take note that (A), (B) and (C) are all common causes of acute laryngotracheobronchitis (i.e. croup)
Which of the following best describes the pathophysiology of croup?
A) Excess mucus production in the bronchi
B) Inflammation and edema of the subglottic region
C) Necrotizing infection of the epiglottis
D) Bronchoconstriction due to IgE-mediated response
B) Inflammation and edema of the subglottic region
Viral infection
-> sudden swelling of epiglottis and vocal cords
-> partial obstruction of airway
=> barking cough and stridors
stridor is a high-pitched sound heard typically during inhalation
complication of croup
choking in young children
what is 1 possible benign neoplasm
sinonasal papillomas
(a.k.a. transitional “Schneiderian” papilloma)
* defining characteristic:
HIGH recurrence, LOW malignancy
(i.e. it keeps coming back, but doesn’t become malignant and metastasise)
complication of sinusitis
sinusitis is the inflammation of the paranasal sinus linings of the maxillary, ethmoid and frontal sinuses
inflammation
-> mucosal oedema
-> bacterial infection
-> **spread to meninges*
pathogenesis of asthma
- Sensitisation to allergens
exposure to allergens stimulate APCs
-> activate naive CD4+ T cells
-> differentiate into Th2 cells
-> release key cytokines like IL-4 and IL-5
-> IL-4 promotes IgE production by B cells
-> IgE then bind to mast cells
=> mast cells are now sensitised - Mast cell activation (EARLY stage rxn)
during re-exposure, allergens cross-links IgE
-> mast cell degranulation
-> release of mediators such as histamine, leukotrienes (LTB4, LTD4) and prostaglandins
=> bronchoconstriction, mucus production
and edema due to increased vascular permeability - Eosinophilic inflammation (LATE stage rxn)
IL-5 recruits eosinophils
-> release toxic granules
=> tissue damage (destruction of epithelium)
and thus worsening inflammation
histamine release causes excess production of mucus
Structural changes due to chronic inflammation in asthma
- Airway remodeling:
<- smooth muscle hypertrophy and hyperplasia - Airway hyperresponsiveness
- Goblet cell metaplasia -> mucus overproduction
- Mucosal oedema
can also result in
* Fibrosis and scarring
-> permenant reduction in airway diameter
* (In longstanding cases) Deposition of collagen beneath bronchial epithelium
<- lung adapts to try and increase muscle strength so that it doesn’t collapse so easily
airway hyperresponsiveness = airways excessively narrowing even in response to mild triggers
What are Curschmann spirals composed of?
A) Eosinophil-derived proteins
B) Mucus from goblet cell hyperplasia
C) Collagen fibers
D) Fibrin deposits
B) Mucus from goblet cell hyperplasia
Curshmann spirals form thick mucus plugs
-> block exchange of air
and block inhaled medications
seen in sputum analysis
What causes the formation of Charcot-Leyden crystals in asthma?
A) Breakdown of eosinophils releasing Galectin-10
B) Chronic inflammation leading to fibrosis
C) Excess surfactant production in the lungs
D) Neutrophil aggregation in response to allergens
A) Breakdown of eosinophils releasing Galectin-10
its presence indicates eosinophilic inflammation
=> thus likely to be atopic (allergy) asthma
seen in sputum analysis
mediators? inflammation type? key players?
types of asthma
- allergic asthma:
IgE-mediated type 1 inflammation,
involving IL-4 and IL-13 - eosinophilic asthma:
cell-mediated type 2 inflammation,
involving IL-5, IL-4 and IL-13 - mixed asthma:
allergic asthma + eosinophilic asthma
drug classes used in asthma and COPD
- bronchodilators:
beta-2 agonists and muscarinic antagonists - anti-inflammatory:
inhaled corticosteroids (ICS)
what are the preferred bronchodilators used for asthma
beta-2 agonists
(SABAs and LABAs)
bcos bronchoconstriction (MAIN problem)
is due to inflammatory mediators
=> quick solution is to directly relax airway smooth muscle
in contrast, in COPD,
bronchoconstriction and mucus secretion
is due to increased vagal (i.e. parasympathetic) tone
=> solution is to give
parasympatholytics which = antimuscarinics
and route
which drug is given in emergency to relieve asthma attack
adrenaline (or epinephrine),
IV/SC
and route
what drug is given to relieve bronchospasm in acute asthma
n
Salbutamol (SABA)
(rmb as “SABA-tamol),
IV in emergency,
inhalation/oral otherwise
acts for 3-6 hrs
and route
what drug can be used both for maintenance (controller) and for acute relief (reliever) of asthma
Formoterol
(Fast-acting LABA),
inhalation/oral
acts for 12 hr
and route
what drug is used for long-term maintenance (controller) of asthma
Salmeterol
(slow-acting LABA),
inhalation/oral
acts for 12 hr
and route
what bronchodilator is ultra long-acting
Indacaterol
(ulta long-acting, almost like infinity, LABA),
inhalation/oral
acts for 24 hr => given once a day
used for maintenance in COPD
and LAMA NOT working
most common side effect of bronchodilators
tremor
bcos B2 agonist
-> stimulate skeletal muscles
=> tremors
by increasing cAMP
-> enhanced Na+/K+ pump activity
-> disrupts normal muscle contraction-relaxation balance
=> involuntary muscle twitching
how do bronchodilators affect K+ and glucose levels
- hypokalaemia
due to bronchodilators being B2 agonists
-> stimulate Na+/K+ pump in skeletal muscles
-> increase uptake of K+ from bloood into cells
=> decrease serum K+ levels - hyperglycaemia
via stimulation of glycogenolysis and gluceoneogenesis
and inhibition of insulin secretion (@ higher doses)
glycogenolysis = breakdown of gly…
gluconeogenesis = glu… production
hypokalaemia has same MOA as tremors
use of which drug class alone will worsen asthma
LABAs
-> downregulate B2 adrenoceptors
-> reduce effectiveness of B2 agonists as reilievers when used for bronchodilation in acute asthma attack
=> must prescribe inhaled corticosteroids together
downregulation is due to
chronic stimulation -> body desensitisation
think if the pathophysiology of asthma
MOA of bronchodilators
- airway smooth muscle relaxation
=> combat bronchoconstriction -
mast cell stabilisation
=> help with ALL effects - decrease microvascular leakiness
=> reduce oedema - increase mucociliary clearance
=> increase mucus clearance
examples of inhaled corticosteroids
- Fluticasone
- Ciclesonide
- Budesonide
side effects of ICS
- Candidiasis
- Dysphonia
both related to throat area
Which of the following ICS has the greatest risk of adrenal suppression?
A) Budesonide
B) Beclomethasone
C) Fluticasone
D) Ciclesonide
C) Fluticasone
bcos it has higher systemic bioavailability
Which of the following ICS is an example of a soft steroid?
A) Budesonide
B) Beclomethasone
C) Fluticasone
D) Ciclesonide
Soft steroid: Drugs that have localised action and are metabolised into inactive forms once absorbed systemically
D) Ciclesonide
prodrug
-> requires esterase activation in lungs
-> reduced systemic side effects
(including adrenal suppression)
why are corticosteroids administered via IV in acute asthma attack
so that they can be administered early
<- have slow onset of action
why should corticosteroids NOT be used in every situation
must strike balance bet
control of inflammatory disease
and increased risk of opportunistic infection
Examples of leukotriene pathway inhibitors
- zi-LEU-ton
- monte-LU(LEU)-kast
are LEU-kotriene pathway inhibitors
administered vis ORAL route only
side effects of leukotriene pathway inhibitors
- mood disturbances,
insomnia/vivd dreams
and suicidal thinking - Churg-Strauss syndrome:
steroid withdrawal
-> eosinophilic rebound
-> triggering vasculitis and worsening asthma and systemic symptoms
Churg-Strauss syndrome more commonly seen in Montelukast
what is another anti-inflammatory drug is used as 2nd-line treatment for severe allergic asthma
Anti-IgE antibody
= Omalizumab
side effects of Omalizumab
Omalizumab = anti-IgE antibody
sounds like O-shit ma heart hurts
=> side effectd are heart attack,
as well as blood clots and TIA
bcos heart attack can be caused by blood clots
and blood clot can also cause TIA
what is another anti-inflammatory drug is used as 2nd-line treatment for severe eosinophilic asthma
Anti-IL5 antibody
= RESLIzumab
(bcos RESLIzumab = Re5lizumab)
side effect of reslizumab
oropharyngeal pain
Cromoglicic acid is primarily used in the management of:
a) Acute asthma attacks
b) Chronic obstructive pulmonary disease (COPD)
c) Exercise-induced and mild persistent asthma
d) Status asthmaticus
c) Exercise-induced and mild persistent asthma
used prophylactically to prevent asthma symptoms
used in mild persistent asthma when patients cannot tolerate ICS
MOA:
* prevents mast cell degranulation
-> prevent release of histamine and inflammatory mediators
Adverse effects of cromoglicic acid?
A) Throat irration
B) Dry mouth
C) Cough
D) Unpleasant bitter taste
E) All of the above
E) All of the above
Cromoglicic acid
= Cough-mouth-glicic acid
=> symptoms include
* cough
* mouth related: dry mouth,
and unpleasant bitter taste in mouth
Which of the following are used as an adjunct treatment for severe acute asthma?
A) Magnesium oxide
B) Magnesium sulphate
C) Sodium sulphate
D) Calcium oxide
E) Calcium sulphate
used when 1st-line treatments (bronchodilaters and corticosteroids) are not working
B) Magnesium sulphate
has multiple beneficial effects,
including bronchodilation
(via inhibiting Ca2+ influx into smooth muscle cells)
and anti-inflammatory effects
What is the primary cause of chronic bronchitis?
A) Bacterial infection
B) Long-term exposure to irritants
C) Autoimmune response
D) Genetic mutations
B) Long-term exposure to irritants
inflammation of bronchi
-> MUCUS HYPERSECRETION
& luminal narrowing (from thickened bronchial walls)
=> airway obstruction
NEUTROPHILIC inflammation
(i.e. chronic exposure to irritants
-> activate neutrophils
-> release substances which stimulate mucus-secreting cells to secrete more mucus)
Why are patients with chronic Bronchitis known as Blue Bloaters
- Blue
due to mucus plugs
-> shunts in some lung areas (“wasted perfusion”)
-> systemic hypoxemia (i.e. blood has little O2
=> cyanosis which gives skin the blue colour - Bloaters
due to RHF
-> fluid retention
How does chronic bronchitis contribute to cor pulmonale (right heart failure)?
A) Increased systemic vascular resistance
B) Pulmonary hypertension due to hypoxic vasoconstriction
C) Left ventricular hypertrophy
D) Increased cardiac output
B) Pulmonary hypertension due to hypoxic vasoconstriction
explain hypoxic vasoconstriction
occurs in COPD
physiological response by body
where arteries to shunted lung segments constrict
-> divert blood to better-oxygenated lung segments
How does chronic bronchitis contribute to cor pulmonale (right heart failure)?
A) Increased systemic vascular resistance
B) Pulmonary hypertension due to hypoxic vasoconstriction
C) Left ventricular hypertrophy
D) Increased cardiac output
B) Pulmonary hypertension due to hypoxic vasoconstriction
chronic hypoxia
-> pulmonary vasoconstriction
-> increased pressure in those pulmonary arteries
=> strain in right heart (specifically RV)
pathogenesis of emphysema:
Irritants (e.g. cigarette smoke)
→ Triggers (…)
→ Recruited inflammatory cells release (…), including (…)
→ (…) in activity of proteases and protease inhibitors, e.g. (…)
EITHER due to (…) of proteases
OR due to (…) in anti-proteases, e.g. (…) deficiency
→ (…) of alveolar walls and thus larger but less efficient air spaces, a.k.a. (…)
& (…) of elastic recoil
irritants (e.g. cigarette smoke)
-> triggers inflammation
-> recruited inflammatory cells release inflammatory mediators (including proteases)
-> imbalance in activity of proteases and protease inhibitors (e.g. alpha-1-antitrypsin)
EITHER due to oveproduction of proteases
OR due to decrease in anti-proteases
(e.g. a1-antitrypsin deficiency)
-> breakdown of alveolar walls and thus larger but less efficient air spaces (bullae)
& loss of elastic recoil
proteases break down protein
-> in lungs, they degrade elastin,
which proides structural integrity to alveolar walls
as well as provide elasticity
is emphysema considered obstructive or restrictive lung disease
Obstructive
due to the loss of elastic recoil
-> affect exhalation
* decrease in FVC
<- patient cannot exhale completely
* large decrease in FEV1
<- exhalation (passive process) is now limited and thus slows down
* decrease in FEV1 > decrease in FVC
=> decrease in FEV1/FVC
(to ≤ 0.7-0.8)
What is the primary cause of panacinar emphysema?
A) Alpha-1-antitrypsin deficiency
B) Air pollution
C) Smoking-related irritation
D) Chronic infections
A) Alpha-1-antitrypsin deficiency
ENTIRE acinus is uniformly affected
in contrast, centrilobular emphysema is commonly associated with smoking
In which part of the lung does centrilobular emphysema primarily occur?
A) Upper lobes
B) Lower lobes
C) Central parts of the acinus
D) Distal alveolar sacs only
A) Upper lobes
centrilobular emphysema
= associated with smoking
-> smoke rises
=> more severe in upper lobes
observations in chest X-ray of patient w/ emphysema
A. barrel chest
due to loss of elastic recoil
* resulted in chest wall’s outward force
(intrinsic inelasticity and thus tendency to expand outwards) being relatively unopposed
-> ribcage expand more than normal
* also resulted in air being unable to be exhaled completely and thus being trapped
-> expansion of chest wall even more
B. flattening of hemidiaphragms
due to trapped air exerting pressure
-> forces diaphragm down
Why are patients with emPhysema known as Pink Puffers
- Pink
due to adequate oxygenation - Puffers
due to increased respiratory efforts to expel air
<- destruction of alveolar walls and loss of elastic recoil makes it hard for air to be expelled
definition of emphysema
permenant dilatation
of airspaces distal to the terminal bronchiole
w/ destruction of tissue
in absence of scarring
- permenant dilatation of airspaces distal to the terminal bronchiole
= alveoli forming bullae - destruction of tissue
= destruction of alveoli by proteases
pathogenesis of bronchiectasis:
Interference with drainage of secretions,
either via (…) of airway
or abnormality in (…) of mucus
→ accumulation of (…)
→ which are (…) and thus an ideal environment for (…)
=> recurrent and persistent (…)
→ chronic (…) inflammation
=> bronchial (…)
interference w/ drainage of secretions
* obstruction of airway
* abnormality in viscocity of mucus
(i.e. either block drainage or stop clearing system)
-> accumulation of mucus
-> which are stagnant and thus an ideal envt for infections
=> recurrent and persistent infection
-> chronic necrotising inflammation
=> bronchial dilatation
is bronchiectasis considered obstructive or restrictive lung disease
obstructive
bcos accumulated mucus clog the dilated bronchi
-> reduce airflow
hypoxemia
-> hypoxic vasoconstriction by lungs to compensate
-> pulmonary hypertension
=> cor pulmonale (i.e. RHF)
[Complication of bronchiectasis]
important symptoms of bronchiectasis
- (productive) COUGH
<- excess mucus trigger cough reflex to clear the airways - accompanied by FOUL-SMELLING sputum
<- chronic bacterial infections - often HAEMPTYSIS
due to damage of bronchial blood vessels
-> bleeding into airways
Which of the following is NOT a direct cause of ARDS?
A) Systemic sepsis
B) Severe trauma/burns
C) Inhalation of toxic fumes
A) Systemic sepsis
indirect cause that is most commonly associated with ARDS
What is the primary pathophysiologic mechanism of the acute exudative phase of ARDS?
A) Fibrosis of the alveoli
B) Damage to type II pneumocytes leading to surfactant loss
C) Vasoconstriction of pulmonary capillaries
D) Decreased mucus production in the airways
B) Damage to type II pneumocytes leading to surfactant loss
lung injury (direct or indirect)
-> activation of immune cells (e.g. neutrophils) which release cytokines into blood
-> damage to alveolar epithelium and capillary endothelium
-> results in surfactant loss,
thus increased surface tension
and thus alveolar collapse
AND increased vascular permeability,
thus fluid, proteins and inflammatory cells leak into alveoli
and form hyaline membranes
What occurs in the organizing phase of ARDS?
A) Regeneration of normal alveolar tissue
B) Resolution of pulmonary edema with complete recovery
C) Fibroblast proliferation leading to fibrosis and stiff lungs
D) Increased surfactant production
C) Fibroblast proliferation leading to fibrosis and stiff lungs
regeneration of type II alveolar lining,
then organisation of hyaline membranes w/ fibrosis
=> marked interstitial fibrosis (“honeycomb” lungs)
and NO MORE hyaline membranes
biggest COPD risk factor
age
disease usually sets in @ around 40 or older
what cell count do we use to track disease progression of COPD?
A) Eosinophil
B) Neutrophil
C) WBC
4) Platelets
A) Eosinophil
eosinophil levels is a biomarker for ICS responsiveness
=> low levels = neutrophilic-driven inflammation
-> ICS will have minimal effect on reducing exacerbations
and increase risk of infections (e.g. pneumonia)
A patient with ≥ 2 moderate COPD exacerbations in the past year but eosinophil count < 300 should receive which treatment?
A) LABA only
B) LABA + ICS
C) LABA + LAMA
D) LABA + LAMA + ICS
C) LABA + LAMA
- patient is in Grp E
bcos ≥ 2 moderate COPD exacerbations
or ≥ 1 leading to hospitalisation - but EOS < 300
-> at higher risk of infections (e.g. pneumonia)
=> CANNOT use ICS
A patient with a CAT score of 15, mMRC of 3, and no recent exacerbations should be classified under which COPD treatment group?
A) Group A
B) Group B
C) Group E
B) Group B
- both grps A and B involve
0 or 1 moderate COPD exacerbations - but grp B as
mMRC ≥ 2
and CAT ≥ 10
example of SAMA
Ipratropium
examples of LAMA
- Tiotropium
- Glycopyrronium
why are muscarinic antagonists (MA) preferred in COPD
bcos bronchoconstriction and mucus secretion in COPD
is due to increased vagal i.e. parasympathetic tone
-> antimuscarinics
= parasympatholytics
= reduce vagal tone
chronic airway irritation in COPD
-> chronic inflammation and remodeling of airways
-> persistent stimulation of vagal sensory fibers
=> increased vagal tone
3 conditions
in what conditions do we not use ICS in treatment of COPD
- Repeated pneumonia events
as using ICS
-> immmunosuppression
=> higher risk of recurrent infections - Blood eosinophils < 100 cells/μl
(relate to subset within Grp E) - History of mycobacterial infection (e.g. TB)
as using ICS
-> immmunosuppression
=> higher risk of reactivation
what kind of infections are COPD exacerbations usally triggered by
viral infections
(e.g. influenza)
thus getting viral vaccines (e.g. influenza vaccine) will help reduce exacerbations of COPD
while getting bacterial vaccines (e.g. pneumococcal vaccine) will not
what are the 2 malignant epithelial cell tumours of the lung
- small cell carcinoma
- non-small cell carcinoma
risk factors include
* cigarette smoking
* radioactive material (e.g. asbestos)
diff in treatment of
small cell lung carcinoma vs non-small cell lung carcinoma
- small cell: chemotherapy + radiotherapy
<- metastasise - non-small cell: surgery
<- less frequently metastatic
and thus less responsive to chemotherapy
histological features of small cell carcinoma (lung)
- small neoplastic cells
(“oat-like”) - w/ finely granular nuclear chromatin
(“salt and pepper”)
pepper = lighter staining cytoplasm
salt = darker staining chromatin that appear in form of dark dots
what type of non-small cell carcinoma (lung) is this
adenocarcinoma
* more commonly seen in female non-smokers
* peripherally located on lungs
what type of non-small cell carcinoma (lung) is this
squamous cell carcinoma
due to the keratin pearls
* more commonly seen in male smokers
* central centivation and necrosis seen in lungs
Why do pulmonary infarctions occur in only about 10% of PE cases?
A) The lungs have a high oxygen reserve
B) The pulmonary arteries can autoregulate to prevent infarction
C) The lungs have dual blood supply from both the pulmonary and bronchial arteries
D) The embolus is usually rapidly dissolved by fibrinolysis
C) The lungs have dual blood supply from both the pulmonary and bronchial arteries
thus when emboli blocks blood flow in pulmonary arteries,
bronchial arteries can supply lung tissue
however, if infarction DOES occur,
tissue damage and death
-> bronchial arteries STILL supplying blood to tissue
-> blood leaks into damaged tissue
=> presence of haemorrhagic wedge-shaped lesion
(lesion is due to healing leaving a scar)
What is a long-term consequence of recurrent small pulmonary emboli (PE)?
A) Pulmonary edema
B) Pulmonary hypertension
C) Pleural effusion
D) Chronic hypoventilation
B) Pulmonary hypertension
Recurrent small emboli progressively narrow the pulmonary arteries
-> increasing vascular resistance
=> pulmonary hypertension
A patient is experiencing a persistent cough with thick mucus. Which class of medication would be MOST appropriate to help them clear their airways?
A) Antitussives
B) Mast cell stabilizers
C) Expectorants
D) Antihistamines
C) Expectorants
* increases production of respiratory tract fluids
-> help liquefy and reduce viscocity of the thick mucus
=> helps to loosen and thus clear mucus from airways
* oral route
example of expectorant
guaifenesin
A patient with allergic rhinitis is experiencing a runny nose and sneezing. Which medication would be MOST appropriate?
A) Expectorants
B) Decongestants
C) Antitussives
D) Antihistamines
D) Antihistamines
- counteract the effects of histamine, which is released during allergic reactions
-> reduce symptoms like runny nose and sneezing - CNS effects, including sedation, if take 1st gen ones
don’t use mucregulators / mast cell stabilisers
as those are for more severe cases
s
If medication helps to regulate the production or viscosity of mucus, into what category does it fall?
A) Antihistamine
B) Mucoactive agent
C) Antitussive
D) Decongestant
B) Mucoactive agent
2 types:
* mucolytics
* mucokinetics
what drug class is it
Acetylcysteine reduces mucous viscosity by which mechanism?
A) Stimulating ciliary beat frequency to clear mucus
B) Increasing surfactant production in the alveoli
C) Blocking voltage-gated sodium channels to reduce local irritation
D) Breaking bonds in mucoproteins
D) Breaking bonds in mucoproteins
has free sulfhydryl group
-> opens disulfide bonds in mucoproteins
(i.e. break down mucoproteins)
=> lowers viscocity of mucus
Mucoactive agent, specifically a mucolytic
A patient with a known history of asthma is prescribed a medication to help with excessive mucus production. Which of the following medications would require the MOST caution given the patient’s medical history?
A) Bromhexine
B) Ambroxol
C) Acetylcysteine
D) Guaifenesin
C) Acetylcysteine
Mucolytics have adverse effect of bronchospasm
=> used with caution in patients with asthma
and elderly or debilitated patients w/ severe respiratory insufficiency
Mucokinetics (Bromhexine + its active metabolite Ambroxol) must also be avoided in patients with asthma
test for what
how to check if PE has occurred
levels of D-dimers
bcos clot formation involves the cross-linking of D-dimers in fibrin mesh
by Factor 13
-> breakdown of clots will increase D-dimer lvls in blood
where emboli comes from, what is the pathway it travels
pathogenesis of pulmonary embolism
DVT
-> venous emboli from lower limb
-> IVC
-> R heart
-> pulmonary arteries
which factor causes pulmonary oedema,
low oncotic pressure
OR increased hydrostatic pressure?
Increased hydrostatic pressure
* pulmonary capillaries have tight junctions that prevent fluid from easily leaking into alveoli
-> must have increased hydostatic pressure to force fluid out
* low oncotic pressure only causes oedema when there is another contributing factor,
e.g. increased hydrostatic pressure or damage to capillary barrier
does PE result in pulmonary oedema or pleural effusion
pleural effusion
* bcos embolism
-> ischemia and inflammation
-> inflammatory mediators increase permeability of pleural capillaries
=> fluid leakage into pleural cavity
* NOT pulmonary edema
bcos emboli obstructs the pulmonary arteries
-> increased pressure before the clot
and NOT in downstream capillaries
-> no direct increase in hydrostatic pressure in pulmonary capillaries
=> fluid is less likely to move into alveoli
fluid in pleural effusion = exudate
bcos inflammation
<-> fluid in pulmonary oedema = transudate
Which of the following pharmacological effects is NOT associated with bromhexine and its metabolite, ambroxol?
A) Stimulation of surfactant production
B) Increased adherence of mucus to cilia
C) Suppression of influenza virus multiplication
D) Antioxidant activity via free radical scavenging
B) Increased adherence of mucus to cilia
Mucoactives actually decrease adherence of mucus to cilia
via increasing cilia beat frequency
for (A), surfactant acts as “anti-glue”
-> prevent mucus from sticking to alveolar and bronchial walls
for (D), antioxidant activity
= protect lung tissue from oxidative damage by neutralising free radicals
other pharmacological effects include
anti-inflammatory and local anaesthetic
A patient is prescribed carbocisteine for excessive mucus production. Which of the following conditions would be a contraindication for this medication?
A) Allergic reaction to penicillin
B) Active peptic ulcer
C) Severe respiratory insufficiency
D) History of asthma
B) Active peptic ulcer
Mucoactive agents (acetylcysteine, carbocisteine) has gastrointestinal disturbance as adverse side effect,
but carbocisteine in particular is contraindicated in patients w/ peptic ulcer
types of antitussives
- opioid
- nonopioid
Which of the following best describes the mechanism of action of codeine as an antitussive?
A) It directly relaxes bronchial smooth muscle, reducing airway constriction and cough.
B) It reduces inflammation in the airways, thereby decreasing the urge to cough.
C) It acts in the central nervous system (CNS) to suppress the cough reflex.
D) It acts on peripheral sensory nerves to reduce their sensitivity to cough triggers.
C) It acts in the central nervous system (CNS) to suppress the cough reflex.
Codeine acts on cough centre in medulla (CNS)
-> alters its sensitivity
=> suppresses cough reflex
when is antitussives used
for non-productive (“dry”) coughs
Why is codeine not recommended as an antitussive for children?
A) Codeine is metabolized faster in children, leading to reduced efficacy.
B) Children are more sensitive to opioid-induced respiratory depression due to immature respiratory centers and liver development.
C) Children are more likely to become addicted to opioid antitussives compared to adults.
D) Codeine can cause severe gastrointestinal side effects in children.
B) Children are more sensitive to opioid-induced respiratory depression due to immature respiratory centers and liver development.
Not recommended for children < 18 y/o
recall! respiratory depression is an adverse effect of antitussives,
for which there is an increased risk of
* during overdose
* in patients with severe respiratory insufficiency
* when combined w/ other CNS depressants
In individuals who are CYP2D6 ultra-rapid metabolizers, what potential risk is associated with codeine use?
A) Lower risk of addiction due to rapid drug metabolism.
B) Increased risk of severe respiratory depression, even at normal doses.
C) Increased risk of gastrointestinal side effects.
D) Reduced antitussive effect due to rapid drug breakdown.
B) Increased risk of severe respiratory depression, even at normal doses.
due to faster rate of conversion of codeine to morphine, an even more potent opoid
=> greater risk of side effects, including respiratory depression
A patient has a history of opioid abuse. Which of the following antitussives would be the MOST appropriate and safest choice for this patient?
A) Codeine
B) Diphenhydramine
C) Oxycodone
D) Dextromethorphan
D) Dextromethorphan
- from greatest to lowest risk of addiction:
1. codeine
2. dextromethorphan
3. diphenhydramine (no risk at all) - from most to least effective:
1. codeine
2. dextromethorphan
3. diphenhydramine
(H1 antihistamine -> mild antitussive effects)
=> dextromethorphan used as it is the
most effective non-opoid antitussive
Which of the following is a common adverse effect associated with the use of first-generation antihistamines like diphenhydramine, particularly in elderly patients?
A) Improved cognitive function.
B) Diarrhea.
C) Increased salivation.
D) Urinary retention.
D) Urinary retention
1st-gen antihistamines have significant anticholinergic effects
-> block parasympathethic
(i.e. effects that mimic sympathethic)
=> Reduced salivation, urination, digestion, HR, etc
urinary retention is one of the more concerning anticholinergic effects in elderly
types of decongestants used
- Sympathomimetic agents
-> EITHER direct a-adrenoceptor agonists
OR indirect increase in release of adrenaline/noradrenaline
-> vasoconstriction of nasal blood vessels
=> reduce inflammation (and thus swelling)
and secretion of mucus - Nasal corticosteroids
-> reduce inflammation
=> reduce (swelling and thus) congestion
and secretion of mucus
examples of sympathomimetic agents used as decongestants
- a-adrenoceptor agonists: phenylephrine
- indirect increase in release of adrenaline/noradrenaline: pseudoephedrine
examples of nasal corticosteroids
- fluticasone
- mometasone
“mom takes care of you when you have the flu”
A patient reports experiencing a ‘rose water’ odor while using a medication for nasal congestion. Which of the following medications is most likely responsible for this?
A) Acetylcysteine.
B) Cetirizine.
C) Dextromethorphan.
D) Phenylephrine.
D) Phenylephrine
unique characteristic of phenylephrine,
an a-adrenoceptor agonist decongestant
A patient with a history of hypertension is seeking an over-the-counter medication for nasal congestion. Which of the following decongestants should be avoided?
A) Intranasal ipratropium.
B) Cetirizine.
C) Pseudoephedrine.
D) Intranasal cromoglicic acid.
C) Pseudoephedrine
- pseudoephedrine = indirect sympathomimetic nasal decongestant
- adverse effects of nasal decongestants include
CNS stimulation (e.g. restlessness, tremors, irritability)
and cardiovascular effects
(e.g. hypertension due to vasoconstriction) - these adverse effects are worse when taken through oral route
and pseudoephedrine is taken orally
note: indirect sympathomimetics like pseudoephedrine also has cardiovascular adverse effect of tachycardia
esp in relation to nasal corticosteroids
side effects of intranasal route
local mucosal dryness and irritation
A patient taking diphenhydramine for cold symptoms reports increased appetite. What receptor antagonism is most likely responsible for this side effect?
A) H1 antihistamine in CNS.
B) Cholinergic antagonism.
C) α-adrenergic antagonism.
D) 5-HT receptor antagonism.
D) 5-HT receptor antagonism
1st gen anti-histamines (e.g. diphenhydramine) also exhibit
5-HT receptor antagonism,
which has been linked to an increased appetite
A factory worker with a runny nose and nasal congestion is prescribed an intranasal decongestant. What is the MOST important instruction to give this patient regarding the duration of use for this medication?
A) Use the decongestant for as long as symptoms persist to ensure complete resolution.
B) Use the decongestant only when symptoms are severe to prevent tolerance.
C) Limit use to 5-7 days to avoid rebound congestion.
D) Alternate between different brands of decongestants to maintain effectiveness.
C) Limit use to 5-7 days to avoid rebound congestion
prolonged use of sympathomimetic agents
-> compensatory upregulation of parasympathetic nervous system
-> effects seen when sympathomimetic agents are stopped
What is the primary mechanism of action of ipratropium as a mucoregulator?
A) β2-adrenergic receptor agonism
B) Inhibition of phosphodiesterase (PDE)
C) Muscarinic receptor antagonism
D) Histamine receptor antagonism
C) Muscarinic receptor antagonism
Ipratropium
= SAMA
-> inhibits M3 muscarinic receptors
and thus its activation of submucosal glands and goblet cells
=> reduce mucus output
route: intranasal
How would you advise a patient on the administration of nasal drops and sprays?
1. (…) all the way forwards or backwards
2. Insert (…) and press pump steadily and firmly
3. Breathe through (…) gently and avoid (…) for (…) minutes in head tilted posture
- Bend all the way forwards or backwards
- Insert spray bottle nozzle and press pump steadily and firmly
- Breathe through nose gently and avoid blowing nose for 2-3 mins in head tilted posture
Which cough and cold medication is the most contraindicated in children?
Promethazine
* < 6 months: contraindicated,
* 6 months - 2 yrs: not recommended,
* ≥ 2 yrs: use (with caution)
1st gen anti-histamine,
very high risk of respiratory depression
all other cough and cold meds are
* < 6 months: not recommended
* 6 months - 2 y/o: use only when benefits > risks
* ≥ 2 y/o: use (w/ caution)
which cough and cold medication is safe to use in elderly
Guaifenesin
* expectorant
* no significant A/Es in elderly
- cough suppressants are generally not recommended
- other cough and cold meds all cause A/Es
(note: notable anticholinergic effects in elderly are
precipitation of dementia due to cognitive impairment
and contraindication in NARROW-angle glaucoma due to increased intraocular pressure)
What is the role of Annexin A1 in cromoglicic acid’s mechanism?
A) It stimulates histamine release
B) It promotes prostaglandin and leukotriene production
C) It inhibits prostaglandin and leukotriene production
D) It increases chloride channel activity
C) It inhibits prostaglandin and leukotriene production
Cromoglicic acid INCREASES annexin A1 secretion
-> annexin A1 blocks PLA2
-> prevent release of AA
-> prevent conversion of AA into inflammatory mediators, prostaglandins and leukotrienes
why should patients on guaifenesin take more water
- further reduce viscocity of mucus
- protect renal function
definition of residual volume
volume of air left in lungs AFTER maximum expiration
CANNOT be measured using spirometry since it remains in lungs AFTER maximal exhalation
how does theophylline help in treatment of asthma
2nd line bronchodilator
as it blocks adenosine receptors
-> prevent adenosine-caused bronchoconstriction and histamine release from mast cells
i.e. adjunct bronchodilator
treatment for Group A COPD
SAMA
and/or SABA
recall! criteria is
* 0 or 1 moderate exacerbations (NOT leading to hospital admission)
* CAT < 10
* mMRC 0-1
treatment for Group B COPD
LAMA
or LABA
recall! criteria is
* 0 or 1 moderate exacerbations (NOT leading to hospital admission)
* CAT ≥ 10
* mMRC ≥ 2
treatment for Group E COPD
- LAMA and LABA
- ICS if blood EOS ≥ 300
recall! criteria is
* ≥ 2 moderate exacerbations
or ≥ 1 leading to hospitalisation
adverse effects of theophylline
nausea, vomiting,
anxiety, insomnia,
tremors, arrhythmias
“theophylline = tea-ophylline
and thus cause similar symptoms to caffeine”
what antibiotic can be given to patients with COPD
used for prevention is patient has frequent bacterial exacerbations
azithromycin
-> has anti-fibrotic and airway-relaxing effects
=> prevent exacerbation
drug class: macrolide
recall!
* adverse effects include QT prolongation (ur a MF cutie (QT)!)
* contraindicated in hepatic dysfunction
used to reduce sputum viscocity and aid mucus clearance
what is the preferred mucolytic for patients with COPD
erdosteine
(thiol derivative)
compared to other mucolytics which are cysteine derivatives
(e.g. carbocisteine, acetylcysteine)
how are leukotriene pathway inhibitors administered
oral route only
“monty python chug straws
using his mouth!”
monty python = montelukast,
chug straws = churg-straws syndrome
what is the most common way to pick up cancer
paraneoplastic syndromes,
common ones are
* cushing’s
* SIADH
