Respiratory system

Question 1

describe the organization of the respiratory system:

Answer 1

upper airway ( conditioning of air ) - lower airway ( transfer of air and gas exchange)
trachea, Main bronchi, Lobular
–& segmental bronchi, nonrespiratory bronchioles , respiratory bronchioles, Alveolar ducts ( elastic fibers), alveoli

Both
lungs covered by thin
membrane , visceral pleura
and encased by another
parietal pleura (Parietal behaves like a serum )

Question 2

explain the mechanics of ventilation:

Answer 2

*
Inspiration
*
Active
*
Medulla
oblongata (Brain stem
*
Diaphragm
(1 10 cm)
*
Air flows into the alveoli until the alveolar pressure
equals to the pressure at the airway opening
*
Expiration
*
Passive
*
Elastic
recoil of the lungs
*
Forced expiration: Internal intercostal (between ribs)
and anterior abdominal muscles (core muscles)

Boyle’s
law
P1 *V 1 =P 2 *V 2
Pressure and volume are
inversely related
Work
of breathing is affected by:
*
Compliance
Distensibility
*
Elastance
Elastic recoil
*
Airway
Resistance Affected by length
and radius of tube , and viscosity of air.

Question 3

explain acid-base physiology:

Answer 3

The pulmonary system adjusts pH using carbon dioxide; upon expiration, carbon dioxide is projected into the environment. Due to carbon dioxide forming carbonic acid in the body when combining with water, the amount of carbon dioxide expired can cause pH to increase or decrease.

Question 4

describe the transport of oxygen and carbon dioxide in the blood:

Answer 4

Oxygen is carried both physically dissolved in the blood and chemically combined to hemoglobin. Carbon dioxide is carried physically dissolved in the blood, chemically combined to blood proteins as carbamino compounds, and as bicarbonate.

Question 5

explain gas exchange in the lungs:

Answer 5

Gas exchange takes place in the millions of alveoli in the lungs and the capillaries that envelop them. As shown below, inhaled oxygen moves from the alveoli to the blood in the capillaries, and carbon dioxide moves from the blood in the capillaries to the air in the alveoli.

Question 6

describe ventilation and perfusion of the lungs:

Answer 6

Ventilation (V) refers to the flow of air into and out of the alveoli, while perfusion (Q) refers to the flow of blood to alveolar capillaries

Question 7

explain the control of ventilation:

Answer 7

1.
Central controller
2.
Respiratory
muscles and innervation
3.
Strategically
placed sensors
mechanoreceptors &
chemoreceptors

Question 8

describe the pharmacology underlying regulation of musculature, blood vessels and glands of the airways

Answer 8

Anticholinergic Agents: Anticholinergic drugs, like ipratropium bromide, block the effects of acetylcholine by inhibiting M3 receptors.

Leukotriene Modifiers: Leukotrienes are lipid mediators that can stimulate mucus production and contribute to airway inflammation

antinflamatory

b- adrenergic agonists

Question 9

describe the difference between obstructive and restrictive lung diseases and provide examples of each:

Answer 9

1. Obstructive – diseases of the airways or tubes, usually cause a narrowing e.g. asthma and COPD
   narrowing = obstruction, mostly of smaller bronchi and larger bronchioles
2. Restrictive – diseases of affecting the structure of the lung tissue e.g. pulmonary fibrosis
   Difficult to fully expand the lungs

Question 10

describe the symptoms and characteristics of asthma:

Answer 10

+vasodialation

Features of asthma:
*
Bronchoconstriction
*
Bronchial hyperresponsiveness (BHR)
*
Airway inflammation
*
Airway remodelling
*
Increased mucus secretion

Question 11

discuss the biological mechanisms and triggers that cause the development of asthma, the cell types and mediators involved:

Answer 11

all types of things that cause inflamation allergies

Various cell types, including Th2 lymphocytes, eosinophils, mast cells, and macrophages, along with mediators like cytokines and histamines, play pivotal roles in the pathogenesis of asthma.

Question 12

describe the concept of asthma phenotypes:

Answer 12

allergic eosinophilic ,non - allergic eosinophilic, non eosinophilic, structural changes

TH2 in kids non TH2 in adults

Question 13

Explain the different drugs used to treat asthma and their mechanism of action:

Answer 13

Asthma treatments - categories
1. Bronchodilators (relievers)
2. Anti-inflammatory (controllers)
non-specific
specific (biological treatments

Bronchodilators
β
β2 adrenergic agonists (salbutamol, salmeterol)
Muscarinic antagonists (ipratropium, tiotropium)
Leukotriene receptor antagonists (e.g. montelukast)
Histamine receptor antagonist (e.g. loratadine)

Molecular mechanisms of corticosteroid action
1.
Diffuse across cell membrane and bind glucocorticoid
receptors
2.
This causes dissociation of chaperone proteins (
e.g.
heat shock protein 90) allowing translocation of
glucocorticoid receptor to nucleus
3.
In nucleus, glucocorticoid receptor can dimerize and
bind to glucocorticoid response elements in promoter
regions of steroid responsive genes which can switch
on (or off) gene transcription ( e.g. β 2 adrenergic
receptors)
Or
1.
GR can bind other transcription factors (
e.g. nuclear
factor κB ) as a monomer, and thereby switch off
genes activated by such transcription factors

Asthma
treatments summary
Avoidance
of trigger factors
Bronchodilators
e.g. β 2 adrenergic receptor agonists
General anti
inflammatory treatments e.g. glucocorticosteroids
Mast
cell mediator antagonists e.g. anti histamines, anti leukotrienes
Immunotherapy
allergen specific desensitisation allergen vaccination)
Biologics
e.g. anti IgE, anti IL 5, anti IL 4/13R, anti Thymic stromal lymphopoietin (TSLP)
Adrenaline
only anaphylaxis with severe asthma

Question 14

Conducting
airways:

Answer 14

*
Trachea
, bronchi , non
respiratory bronchioles
*
Contain
cartilage resilient and
smooth elastic tissue
*
Pseudostratified
columnar
epithelium ( with cilia)
*
Volume
is 150 ml (30% of
normal breath ) anatomical
dead space

*
Gel (mucus)
*
Inorganic salts, antimicrobial enzymes
(such as lysozymes), immunoglobulins
and glycoproteins.
*
Sol (airway surface/periciliary liquid)
*
Aqueous fluid containing salts.
*
Mucociliary
clearance (MCC)
*
Important for pulmonary hygiene.
*
A metachronal rhythm (wavy
movements produced by the sequential
action, like a Mexican Wave).

Question 15

Respiratory
Unit:

Answer 15

*
Respiratory
bronchioles , alveolar ducts and alveoli
*
Cuboidal
epithelium
*
Gas
exchanging unit
*
Alveoli
composed of type I and type II epithelial cells ( pneumocytes
*
~3
500 million alveoli (250 µm in diameter with a polygonal shape )
producing 70 80 m 2 surface area.
Type
I cells:
*
96
98% of surface area of the alveolus
*
Primary
site for gas exchange
*
Thin
cytoplasm , basement membrane fused with capillary
endothelium , optimal for gas exchange
Type
II cells:
*
2
4% of surface area of the alveolus
*
Small and
cuboidal
*
Can differentiate to replace damaged type I cell
*
Synthesises
pulmonary surfactant to reduce surface tension in alveolar
fluid.

Question 16

Surfactant
and surface tension( what are they )

Answer 16

*
Surface tension =
elastic like force
caused by water molecules at air liquid
interface that tends to minimise surface
area.
*
Difficult
to inflate lungs without
surfactant
*
Surfactant
= complex lipoproteins
*
Phospholipid
dipalmitoyl
phosphatidyl choline (DPPC) is the
strongest surfactant
*
Increase
compliance
*
Prevent
atelectasis at end of
expiration
*
Surfactant
replacement therapy is used
to treat preterm infants with infant
respiratory distress syndrome’ (

Question 17

Compliance

Answer 17

Normalcompliance
Low compliance- fibrosis
High compliance- emphysema

Question 18

Elastance

Answer 18

Often inversed to compliance . Tendency of a hollow organ to return to its original size when
distended .

Question 19

Airway
resistance

Answer 19

Q =Δ P *π *r^ 4/ η8L

Q is the air flow

Question 20

Two
patterns of gas flow in the airways
High

Answer 20

turbulant , parabolic
In general,
more turbulent in larger airways ,
nose , mouth , trachea , bronchi ) and more
laminar flow in smaller airways

Question 21

the 2 opposite Effects
of ANS on Airway Resistance

Answer 21

*
Activation
of parasympathetic rest and
digest ) nerves → acetylcholine → muscarinic
receptors →
*
Bronchoconstriction
*
Blood
vessel dilation
*
Glandular
secretions
*
Little
direct sympathetic fight or flight ) neural
innervation of airways , but circulating
adrenaline → β 2 receptors →
*
Bronchodilation
*
Inhibition
of glandular secretion
*
Blood
vessel constriction

Question 22

Main categories of lung disease:

Answer 22

1. Obstructive – diseases of the airways or tubes, usually cause a narrowing e.g. asthma and COPD
   narrowing = obstruction, mostly of smaller bronchi and larger bronchioles
2. Restrictive – diseases of affecting the structure of the lung tissue e.g. pulmonary fibrosis
   Difficult to fully expand the lungs
3. Pulmonary circulation disease
   diseases affecting blood vessels in the lungs e.g. pulmonary hypertension
   Caused by clotting, scarring, or inflammation of blood vessels
   Affects ability of lungs to take up O
   2 and release CO 2
4. Infections
5. Malignancies

Question 23

lung disease symptoms :

Answer 23

shortness of breath

chronic cough

phlegm

wheezing

chest tightness

respiratory infection

Question 24

Diagnosis of Lung Diseases:

Answer 24

*
Patient history
*
Physical exam. Check for wheezing, crackling,
long exhalation
*
Imaging tests
e.g. X ray or CT scan of chest or
bronchoscopy. Check for evidence of
obstructions and lung damage
Pulmonary function testing
*
Lung volume test
whole body
plethysmography. Can measure volumes
that simple spirometry can not e.g. FRC
*
Gas diffusion test. How oxygen and other
gases move from the lungs to the
bloodstream e.g. DLCO test
*
Spirometry

Question 25

Spirometry examples of obstructive and restrictive lung disease

Answer 25

obstruction : PEF down FVC normal

restriction: FVC, PEF both down

Question 26

What do you know about Restrictive Lung Disease and its causes- origins?

Answer 26

Can’t fill lungs fully as lungs restricted from expanding.
Often occurs due to conditions causing lung stiffness, muscle weakness, or
physical restriction.
Intrinsic (cause originates from issue within the lungs):
*
Pulmonary fibrosis (lung parenchyma changed to fibrotic tissue, scarring)
*
Sarcoidosis (abnormal collections of inflammatory cells form lumps known as
granulomata, contain macrophages & T cells).
*
Pneumoconiosis (interstitial lung diseases where inhalation of dust has
caused the fibrosis. Most common types are asbestosis, silicosis, and coal
miner’s lung)
Extrinsic (originate from causes outside of the lungs):
*
Obesity
*
Scoliosis (diminished lung capacity due to curvature of spine)
*
Myasthenia gravis (autoimmune
disease causing muscle weakness, can affect
respiratory muscles)
*
Pleural effusion (build
up of excess fluid between the layers of the pleura)

Question 27

differences between asthma and COPD?

Answer 27

Asthma : more intermitent airflow obstruction
improvement in airflow with bronchodialators and steroids
cellular inflamation ( with eosinophils , mast cells, T- cells , lymphocytes and neutrophils ) in more severe disease
broad inflamatory mediator response
airways remodeling

COPD: prograssively worsening airflow obstruction
often presents in 6th decate of life in patients or later
more permanent , less reversible and lessnormalization of airflow obstruction
cellular inflamation ( eosinophils, neutrophils , mast cells, macriphages ) may occur
emphysema frequently found

Question 28

COPD phenotypes

Answer 28

Chronic bronchitis, excessive mucus
Inflammation
Blue – inadequate oxygenation of blood
Ventilation/perfusion mismatch
-
Drop in ventilation, rise in CO2
Swelling (bloating) - heart failure

Emphysema
Damaged lung parenchyma
Loss of elastic recoil, air trapping, airway collapse
Inadequate ventilation, each breath less efficient due to ↓ recoil
Destruction of alveoli + capillary bed means areas of low ventilation also have poor perfusion = matched V/Q defect
Pink – elevated respiratory rate
Cachexia – weight loss, muscle wasting, disturbed energy balance

Question 29

What is asthma?

Answer 29

“ Airways that constrict
too much, too often and too easily,
resulting in impaired lung physiology
and quality of life”
Ann J.
Woolcock

Question 30

Genes in allergy and asthma:

Answer 30

*
Twin studies show genes important in development of
allergies & asthma (50% 80%)
*
Parental allergy or asthma increases
childs risk 4 5 times
*
Complex disease
not one but many genes affect overall risk, each gene
has only small effect.

Question 31

Genetic associations with
atopy and
allergic diseases ? ( antisos)

Answer 31

*
Th2 cytokines (
Chr 5q31)
*
HLA (
Chr 6)
*
T cell receptor genes (
Chr 7q, 14q)
*
FCeRIb
Chr 11q)
*
IL
4 receptor ( Chr 16)
*
ADAM
33 ( Chr 20)
*
GPRA (Chr7p)
*
PHF11 (Chr13q14)
*
DPP10, DRPR3 (Chr2q14)
*
ORMDL3

Question 32

What can be learnt from epidemiological
studies in industrialized countries?

Answer 32

*
Urban > rural
*
“West” > “East” in Europe
*
Increase particularly last 40 years
*
Increase initially among the affluent
*
Increase most obvious in children
Reasons for

Question 33

immunological mechanisms involved in allergic disease :

Answer 33

Sensitasation= allergen- antigen presenting cell- MHC class 2 protein and epitope - TH2 cell and B cell- production of antigen specific IgE-

re-exposure= mast cell degranulation - mediators - Clinical efeects

Question 34

what do you know about the release of mast cell mediators and their time frames?

Answer 34

Rapid < 10 min
Granule mediators:
Histamine
Proteases (tryptase & chymase)
Heparin etc.

Rapid ca. 15 min
Lipid mediators: Prostaglandins Leukotrienes

Delayed > 3 hours
Cytokines Chemokines Growth Factors
(TNF
 , IL 4,
IL 5, IL 13, GM CSF)

Question 35

Allergic inflammation: early phase

Answer 35

Rapid – seconds/minutes after exposureMast cell activation
Rapidly secreted mediators lead to:
Bronchocontriction
Vasodilation
Increased vascular permeability
Increased mucus production

Question 36

Allergic inflammation: late phase

Answer 36

Delayed – 4-6 hours after exposureCell recruitment from circulation:
Eosinophils (granule proteins→ epithelial damage)Neutrophils (elastase → collagen degredation)BasophilsFurther bronchoconstriction, mucous secretion, oedema

Question 37

Allergic inflammation: chronic persistent phase:

Answer 37

Repetetive or persistent exposure → chronic inflammationImmune cells take up residence in tissuesMore mast cells expressing IgE develop in tissuesChronic repair reponse (epithelial-mesenchymal trophic unit) can sustain Th2-type inflammation→ REMODELLING
Thicker ASM, thicker basement membrane, more myofibroblasts

Question 38

what is Pulmonary ventilation?

Answer 38

*
Pulmonary ventilation is
commonly referred to as
breathing (inspiration and
expiration).
*
Ventilation
(V E ) = frequency of
breath (f ) * tidal volume (
*
Ex. At rest the average breathing
frequency is 12 breaths/min
with a tidal volume of 500 ml =
6000 ml/min.

Question 39

what is Alveolar ventilation?

Answer 39

Alveolar ventilation is less than the pulmonary ventilation volume
because the last part of each inspiration remains in the conducting
airways and does not reach the alveoli.
*
Alveolar ventilation
(VA) = frequency of breath (f ) * tidal volume
(VT) physiological dead space volume (
*
Anatomical dead space is ~2mL/kg (~150 ml).
*
Ex. At rest the average breathing frequency is 12 breaths/min with
alveolar volume of 350 ml (500 150) = 4200 ml/min.

Question 40

what is perfusion?

Answer 40

How deoxygenated blood passes through the lung and becomes reoxygenated

The lung has two separate blood supplies:
*
Pulmonary circulation - Brings deoxygenated blood from right ventricle to gas-exchanging units for removal of CO2 and oxygenation before return to left atrium for distribution to rest of body (systemic circulation).
*
Bronchial circulation - Arises from aorta and provides nutrition and oxygen to the lung itself.

Question 41

what do you know about Bronchial circulation?

Answer 41

The bronchial circulation is the part of the circulatory
system that supplies nutrients and oxygen to the cells
that constitute the lungs, as well as carrying waste
products away from them.
*
~2% of the left ventricular output.
*
In the bronchial circulation, blood goes through the
following steps:
*
Bronchial arteries that carry oxygenated blood to the lungs
*
Pulmonary capillaries, where there is exchange of water,
oxygen, carbon dioxide, and many other nutrients and waste
chemical substances between blood and the tissues
*
Veins, where only a minority of the blood goes through
bronchial veins, and most of it through pulmonary veins.

Question 42

Ventilation-Perfusion Relationship

Answer 42

V/Q-ratio
*
The lung regions can be
visualized as zones based on
the degree of perfusion
(gravity
*
Under normal condition the
mean V/Q ratio is 0.8
*
Ventilation (V): 4 L/min
*
Perfusion (Q): 5 L/min
*
V/Q
ratio: 4/5 = 0.8
*
Zone 1 rarely exists i healthy
individual’s lungs
the more the Pa is in relation to PA the bigger the Perfusion and the smaller the V/Q ratio
A
lveolar (P A ), arterial (P a ) and venous pressures P v )

Question 43

what are the 4 cases of Ventilation
perfusion mismatch?

Answer 43

*
Shunt
*
Unventilated alveoli cannot
participate in gas exchange with
the pulmonary capillaries, which
remain de oxygenated.
*
Reduced ventilation
*
When ventilation is less than
perfusion, the partial pressure of
pulmonary blood carbon dioxide
increases

*
Reduced perfusion
*
The partial pressure of pulmonary
blood carbon dioxide decreases,
while the partial pressure of
oxygen increases.
*
Alveolar dead space
*
Absence of blood perfusion
produces a ventilation to
perfusion ratio equal to infinity.
*
Pulmonary embolism is a common
cause of alveolar dead space

Question 43

how does Ventilation/perfusion
lung scan (V/Q scintigraphy) work?

Answer 43

*
The V/Q ratio can be measured
with a ventilation/perfusion scan
(V/Q scan).
*
Two scans
*
1) Flow of air is measured by
inhaling a radionuclide ( ex. Xenon)
*
2) Flow of blood is measured by
i.v. injection of radioactive
technetium.
*
A gamma camera acquires
images of both phases.

Question 43

How does the lung achieve such a large surface area of blood
gas barrier inside the limited
thoracic cavity?

Answer 43

280 billion capillaries supply 3-500 million alveoli (so dense it may be considered sheet of blood)
Enormous surface area + thinness of air blood interface = efficient gas exchange

Question 44

Diffusion
How do gasses get across the blood
gas barrier?
Movements of gases across membranes?

Answer 44

*
Movement of molecules from area where that gas exerts a high partial pressure to area where it exerts lower partial pressure.
*
Dissolved blood gases equilibriate with gas concentrations of alveolar air as blood flows through pulmonary capillaries.

*
Diffusion of gas across a membrane depends on:
*
membrane area (A)
*
membrane thickness (T)
*
The gas concentrations in the two compartments (P1-P2)
*
solubility / molecular weight of the gas called the diffusion constant (D)
Fick’s law Vgas = A x D (P1-P2)/T
The amount of gas that moves across the tissue is
proportional to the area of the tissue but inversely proportional to its thickness

epithelium and film of moisture between the two

Question 45

Gas Transport , how does it work ?

Answer 45

*
Oxygen is not very soluble in plasma.
*
The amount of dissolved oxygen in arterial blood is normally 0.3 ml O2/100ml blood.
*
But actual measured concentration of oxygen in normal arterial blood is ~ 20.4ml O2/100 ml blood.
*
How does it work?

*
O2 binds hemoglobin (Hb) in red blood cells
*
Concentration of Hb is ~15g/100ml blood
*
Each gram of Hb binds 1.34 ml O2, when fully saturated.
*
O2 binding capacity = (1.34ml O2/g Hb) x (15g Hb/100ml blood) = 20.1 ml O2/100ml blood
*
Hb has positive Cooperative binding (increases affinity for oxygen
at the other sites)

Question 45

The Oxyhaemoglobin Dissociation Curve

Answer 45

*
When oxyhemoglobin dissociates and release oxygen it’s
called deoxyhemoglobin.
*
The Oxyhaemoglobin Dissociation Curve describes relationship between O2 saturation of blood (SO2) and the pressure of O2 (PO2).
*
It’s sigmoidal (and not linar) due to cooperative binding of oxygen to Hb.

PO
2 (partial pressure of oxygen):
oxygen gas dissolved in the
blood. It primarily measures the
effectiveness of the lungs in
pulling oxygen into the blood
stream from the atmosphere.
SO
2 (oxygen saturation): a
measure of how much
hemoglobin is currently bound to
oxygen compared to how much
hemoglobin remains unbound

Reduced affinity of haemoglobin for O2, enhanced dissociation (delivery to tissues)

less CO2 , higher PH, lower Temperatures lead to saturation for lower PO2

Question 46

Transport of Carbon Dioxide

Answer 46

*
7% dissolved in plasma
*
23% combined with protein (including Hb as carbaminohaemoglobin).
*
70% as bicarbonate anions (HCO3-).

CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3-
*
CO2 in blood reacts with H2O to form carbonic acid which dissociates to form H + and bicarbonate anions HCO3-
*
Catalysed by carbonic anhydrase in red blood cells
*
As HCO3- is formed, diffuses out of RBCs while Cl- diffuse in to maintain electrochemical equilibrium = chloride shift
Carbonic anhydrase
Non enzymatic dissociation

Question 47

Acid-base balance

Answer 47

Lab tests reveal that a COPD
patient has a blood pH of 7.2, elevated
arterial PCO 2 , and elevated arterial plasma bicarbonate
What is the condition?
*
Metabolic acidosis:
too much acid is produced by the body, or
too much bicarbonate is lost.
*
Metabolic alkalosis
: caused by losing too much acid from the
body, or by having too much bicarbonate.
*
Respiratory
acidosis: occurs when lung affect the body’s ability to
breathe out carbon dioxide, leading to too much acid in the body.
*
Respiratory alkalosis:
happen when there is too little carbon
dioxide in the blood due to the lungs breathing out too much
carbon dioxide.
A pH of less than 7.35 indicates acidosis and a pH greater than 7.45 indicates alkalosis.
Respiratory:
Primary issue occurs in the lung. Metabolic: Primary issue occurs cellular respiration.

Question 48

Carbon Monoxide (CO) Poisoning

Answer 48

*
Produced during combustion of petrol, propane, charcoal, natural gas and other fuels.
*
Affinity for Hb is 240x that of O2 → carboxyhaemoglobin
*
CO displaces O2 and reduces O2 carrying capacity
*
Bound CO also increases affinity of Hb for O2 preventing unloading and delivery of O2 to tissues (shifts dissociation curve to the left)
*
100% binding sites occupied by CO = death
*
Healthy - 1-2% of Hb binding sites occupied by CO
*
Increased up to 10% by cigarette smoke/pollution
*
Symptoms: headache, weakness, dizziness, nausea, vomiting,
shortness of breath, confusion, blurred vision, unconsciousness
*
Treatment of poisoning = 100% oxygen