Respiratory physiology on airway resistance

relationship between airflow, resistance and pressure difference

1. Faez Baherin MBBS
MMed (Emergency) Training Programme USM
Supervised by Dr T. Hairul

2. Outlines
•Relationship between flow, pressure and
resistance in regards to the conducting airway
•Effects of catecholamines and cholinergic
agonists on the airflow
•Effects of histamine and prostaglandins on
bronchial smooth muscles and air flow

3. Airflow, pressure and resistance
relationships
•Analogous to the relationship in
cardiovascular system whereby
1.airflow = blood flow
2. gas pressure = fluid pressure
3.resistance of airway = resistance of blood
pressure

4. Airflow, pressure and resistance
relationships
ohm’s law
•Q = airflow (ml/min or L/min)
• P = pressure gradient (mm Hg or cm H20)
•R = airway resistance (cm H20/L/sec)

5. Pressure Gradient and Airflow
•Pressure difference ( P) is the driving force for
the airflow.
•In a breathing cycle :
-Rest : alveolar pressure = atmospheric pressure,
no pressure difference, no driving force, no
airflow
-Inspiration : diaphragm contracts, increase lung
volume, decrease alveolar pressure, presence of
pressure gradient hence the airflow

6. Pressure Gradient and Airflow

7. Airway Resistance and Airflow
•Flow is inversely proportional to resistance
•Resistance determinants : Poiseuille’s Law

8. Airway Resistance and Airflow
•Airway resistance is :
-directly proportional to viscosity and length
-inversely proportional to radius to the power of 4
(powerful relationship)
•Airflow is :
-directly proportional to the pressure gradient and
radius
-inversely proportional to the viscosity and length

10. Effects of catecholamines and
cholinergic agonists on the airflow
•Bronchial smooth muscle is innervated by
parasympathetic cholinergic nerve fibers and by
sympathetic adrenergic nerve
•Sympathetic stimulation produces relaxation of
bronchial smooth muscle via stimulation of β2
receptors – increase airway diameter – decrease
resistance – increase airflow (adrenergic agonist)
•Parasympathetic stimulation produces
constriction of bronchial smooth muscle – reduce
diameter – increase resistance – decrease airflow
(cholinergic agonist)

11. Effects of catecholamines and
cholinergic agonists on the airflow
•Drugs affecting ANS are divided into 2 groups
(depending to the type of neuron involved in
the mechanism of action)
1.Cholinergic drugs - acts on the receptors that
are activated by Ach – stimulates the
parasympathetic
2.Adrenergic drugs – acts on the receptors that
are stimulated by norepinephrine and
epinephrine – stimulates the sympathetic

12. Effects of catecholamines and
cholinergic agonists on the airflow
1.Norepinephrine
•Post-ganglionic Neurotransmitter for the
sympathetic Nervous system
2.Acetylcholine
•Pre-ganglionic Neurotransmitter for both
systems
Post-ganglionic neurotransmitter for the
parasympathetic nervous system

13. Adrenergic agonists and cholinergic
agonists
Adrenergic Agonists
Albuterol
Dopamine
Epinephrine
Isoproterenol
Norepinephrine
Salmeterol
Terbutaline
Cholinergic Agonists
Bethanechol
Carbachol
Neostigmine
Physostigmine
Tacrine

14. Effects of Catecholamines on airflow
•Adrenergic neurons and receptors (stimulated by
epi/nor epi) are the sites of effect of adrenergic
drugs – catecholamines
•Adrenergic receptors – α and β
α adrenergic order of potency
Epinephrine > norepinephrine > isoproterenol
β adrenergic order of potency
Isoproterenol > epinephrine > norepinephrine

15. Cathecolamines receptors
α 1 α 2 β 1 β 2
VasoconstrictionInhibition of
norepinephrine
release
Tachycardia Vasodilation
Increased
peripheral
resistance
Inhibition of insulin
release
Increase lipolysisSlightly Decrease in
peripheral resistance
Increase in blood
pressure
Increase in
contractility of
myocardium
BRONCHODILATION
Mydriasis Increse release of
renin
Increase muscle and
liver glygogenolysis
Increased closure of
spinchter of
internal spinchter
and bladder
Relaxed uterine
smooth muscle

16. Drugs and Receptor Interaction
α 1 α 2 β 1 β 2
ADRENALINE ++ ++ +++ +++
NORAD ++++ + ++ +
DOPAMINE >10 µg/kg/min 5- 10 µg/kg/min
ISOPROTERENOL ++++ +++

17. Cholinergic agonists
•Cholinergic drugs - acts on the receptors that are
activated by Ach
•Carbachol, Bethanechol
-Synthetic esters of choline - binds directly to
cholinoreceptor - constriction of bronchial
smooth muscle
•Neostigmine
-Cholinesterase inhibitor - allow accumulation of
acetylcholine at the NMJ – prolongs effects
-constriction of bronchial smooth muscle

18. Summary for the effects of catecholamine
and cholinergic agonists on airflow
1.Catecholamine effect : isoproterenol and
epinephrine – adrenergic receptor –
sympathetic stimulation – bronchodilation –
decrease resistance
2.Cholinergic agonist : - Carbachol,
Bethanechol - cholinergic receptor –
parasympathetic stimulation –
bronchoconstriction – increase resistance

20. Histamine effect on airflow
•Histamine
-Chemical messenger that mediates a wide range of
cellular responses including allergic and inflammatory
rxn, gastric acid secretion and neurotransmissions in
parts of the brain.
-Occurs in all tissues but unevenly distributed, high
amount found in lung, skin and GI tract
-High concentration in mast cells or basophils
-Component of venoms and in secretion from insect
stings

21. Histamine effect on airflow
•Histamine exerts its actions by combining with specific
cellular histamine receptors.
•The four histamine receptors that have been
discovered in humans and animals are designated H1
through H4
•Release of histamine may be from the response to
some stimuli like cold, bacterial toxins, bee sting
venoms, allergic and trauma.

22. Histamine effect on airflow
H1 receptors effect :
Increased production of nasal and bronchial mucous
Constriction of bronchioles
Mucosal edema from increased microvascular permeability
Itching and pain – sensory nerve ending

23. Prostaglandins effect on airflow
•Any member of a group of lipid compounds that
are derived enzymatically from fatty acids and
have important functions in the human body.
•They are synthesized in the cell from the
essential fatty acids.
•Mediate a wide range of physiological functions,
such as control of blood pressure, contraction of
smooth muscle, and modulation of inflammation.
•Found in most tissues and organs and produced
by almost all nucleated cells.
•They act upon platelets, endothelium, uterine
and mast cells.

24. Prostaglandins effect on airflow
•An intermediate arachidonic acid is created from
diacylglycerol via phospholipase-A
2
, then brought to
either the cyclooxygenase pathway or the
lipoxygenase pathway to form either prostaglandin
and thromboxane or leukotriene respectively.
•The cyclooxygenase pathway produces thromboxane,
prostacyclin and prostaglandin D, E and F.
•The lipoxygenase enzyme pathway is active in
leukocytes and in macrophages and synthesizes
leukotrienes.

25. Prostaglandins effect on airflow

26. Prostaglandins effect on airflow

27. Summary
•Airflow is directly proportional to the radius and
pressure gradient, and inversely proportional to
the length and viscosity
•Catecholamine causes bronchodilation
•Cholinergic agonist causes bronchoconstriction
•Histamine causes increase in airway resistance
•Prostaglandins have dual effects
-Protacycline – bronchodilation
-PGE2 – EP 1 – bronchoconstriction
EP 2 - bronchodilation

28. Reference
•Linda S Constanzo, 4
th
Edition 2006
•Lippincott’s illustrated reviews of pharmacology, 3
rd
Edition 2006
•Previous slide presentations