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Faez Baherin MBBS
MMed (Emergency) Training Programme USM
        Supervised by Dr T. Hairul
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
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
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)
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
Pressure Gradient and Airflow
Airway Resistance and Airflow
• Flow is inversely proportional to resistance
• Resistance determinants : Poiseuille’s Law
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
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)
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
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
Adrenergic agonists and cholinergic
               agonists
Adrenergic Agonists   Cholinergic Agonists

Albuterol             Bethanechol

Dopamine              Carbachol

Epinephrine           Neostigmine

Isoproterenol         Physostigmine

Norepinephrine        Tacrine

Salmeterol

Terbutaline
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
Cathecolamines receptors
        α1                      α2                     β1                    β2

Vasoconstriction       Inhibition of           Tachycardia          Vasodilation
                       norepinephrine
                       release
Increased              Inhibition of insulin   Increase lipolysis   Slightly Decrease in
peripheral             release                                      peripheral resistance
resistance
Increase in blood                              Increase in          BRONCHODILATION
pressure                                       contractility of
                                               myocardium
Mydriasis                                      Increse release of   Increase muscle and
                                               renin                liver glygogenolysis
Increased closure of                                                Relaxed uterine
spinchter of                                                        smooth muscle
internal spinchter
and bladder
Drugs and Receptor Interaction
                    α1          α2        β1           β2

ADRENALINE          ++          ++       +++           +++

NORAD              ++++         +         ++            +

DOPAMINE        >10 µg/kg/min        5- 10 µg/kg/min


ISOPROTERENOL                            ++++          +++
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
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
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
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.
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
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.
Prostaglandins effect on airflow
• An intermediate arachidonic acid is created from
  diacylglycerol via phospholipase-A2, 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.
Prostaglandins effect on airflow
Prostaglandins effect on airflow
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
Reference
•   Linda S Constanzo, 4th Edition 2006
•   Lippincott’s illustrated reviews of pharmacology, 3rd Edition 2006
•   Previous slide presentations

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Respiratory physiology on airway resistance

  • 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
  • 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
  • 9.
  • 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 Cholinergic Agonists Albuterol Bethanechol Dopamine Carbachol Epinephrine Neostigmine Isoproterenol Physostigmine Norepinephrine Tacrine Salmeterol Terbutaline
  • 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 α1 α2 β1 β2 Vasoconstriction Inhibition of Tachycardia Vasodilation norepinephrine release Increased Inhibition of insulin Increase lipolysis Slightly Decrease in peripheral release peripheral resistance resistance Increase in blood Increase in BRONCHODILATION pressure contractility of myocardium Mydriasis Increse release of Increase muscle and renin liver glygogenolysis Increased closure of Relaxed uterine spinchter of smooth muscle internal spinchter and bladder
  • 16. Drugs and Receptor Interaction α1 α2 β1 β2 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
  • 19.
  • 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-A2, 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.
  • 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, 4th Edition 2006 • Lippincott’s illustrated reviews of pharmacology, 3rd Edition 2006 • Previous slide presentations