Ikhlas Muhammad Jenie

Physiology Department
FKIK UMY
 Cough is the commonest single symptomp
presented to GP

Cough can grouped into acute and chronic,

that both can range from trivial conditions to
life-threatening illnesses
 Cough in general practice can mean a
problem that is:
Acute & serious
Non-acute but serious
Self-limiting
Persistent or recurring disease
 Infections
Viral -- > respiratory syncytial virus (RSV)
Bacterial superinfections
Mycoplasma or fungal
Physical & chemical
Cold, smoke
Cardiac failure
Dry cough relief with diuretics
Allergic
Night cough
Medications
ACE inhibitors
Beta blocker
Inhalation medications
 Acute and chronic non-asthmathic cough
Postnasal drip syndrome
Asthma (cough variant asthma)
Gastro-esophageal reflux
Chronic bronchitis
Angiotensin-converting enzyme inhibitors
(ACE inhibitors)
 Others:
Pharyngitis
Pulmonary congestion
Pulmonary tuberculosis
Intrathoracal malignancies
Pleural effusion
Pleurisy
 Trachea has cartilago ring (5/6 of its
diameter) to prevent it from collapse

However, starting from bronchus, the

cartilago becomes less

Bronchiolus has no cartilago (smooth muscles

only)

It creates the airway resistance

 Normal values
measured by the body plethysmograph
Airway resistance = 0.05-1.5 cm H20/L/sec (adults)

Sources of airway resistance

Nasal passage
Mouth
Glottis
Branching tubes
1. Constriction of bronchial smooth muscle
2. Mucosal congestion or inflammation
3. Edema of bronchiolar tissues
4. Plugging of the lumen by mucus, edema
fluid, exudate or foreign bodies
5. Cohesion of mucosal surfaces by surface
tension forces
6. Infiltration, compression or fibrosis of
bronchioles
7. Collapse or kinking of bronchioles due to
loss of the pull of alveolar elastic fibers of
bronchiolar walls or to loss of structural,
supporting tissues of the bronchial walls
1. Respiratory movement (passive or active)
2. The secretion from the bronchial glands
3. The ciliary activity of the epithelium lining
the trachea and bronchi
4. The cough reflex
 Physical factors
Nervous regulation
Chemical factors
 Airway resistance becomes less as the lung
volume is increased

1 = FVC
R

Coughing
 Sympathetic nerve impulses relax smooth
muscle of the airways

Parasympathetic impulses constrict airway

smooth muscle
 Lungs have a few of sympathetic nerve fiber
but contain much of parasympathetic ones
(vagus nerves)

It secretes neurotransmitter Ach

(acetylcholine)

Contriction of bronchiolus
 Secretion of Ach from parasympathetic
nerves in the airway was stimulated by:
Iritation of airway tract (infection, dust,
smoke, gases)
Microemboli (in pulmonary artery)
 Some drugs & chemicals affect bronchiolar
smooth muscle by stimulating autonomic
ganglia but some have direct action

Isopropylarterenol, epinephrine, norepinephrine

stimulate receptor sites of sympathetic
postganglionic fibers bronchodilation

Acetylcholine stimulates parasympathetic receptor sites

bronchoconstriction
 Medulla adrenal gland

Epinephrine (adrenaline)

adrenergic receptor

Smooth muscle of bronchiolus

Dilatation of bronchiolus
 Alergy, iritation, infection

Mast cells

Histamine, SRSA

Constriction of bronchiolus
 Central nervous
system

Afferent fibers Efferent fibers

Receptor Effector

Reflex arc
 Cough receptors are found in :
Trachea
Main carina
Branching points of large airways
More distal smaller airways
Pharynx

Laryngeal and tracheobronchial receptors

respond to both mechanical and chemical
stimuli (acid, heat, and capsaicin-like
compounds which activate type 1 vallinoid
{capsaicin} receptor)
 In addition cough receptors are found also in:
The external auditory canals
Eardrums
Paranasal sinuses
Pharynx
Diaphragm
Pleura
Pericardium
Stomach

Probably mechanical receptors only, which

can be stimulated by touch or displacement
 The airway epithelium contains sensory nerve
fibers, which can be seen under the electron
microscope and studied by immuno-
fluorescent techniques.
Most of these nerves lie in the basal region of
the epithelium, deep to the tight junction
between the epithelial cells.
 The nerves branch to mucus secreting glands,
blood vessels, airway smooth muscle, and
autonomic ganglia.
The nerves also send process up towards the
lumen and mucosa, often with splayed
terminals.
The extensive plexus stained for substance P
(SP) and calcitonin gene-related peptide
(CGRP).
 Rapidly adapting pulmonary stretch receptors
(RAR-PSR)
Slowly adapting pulmonary stretch receptors
(SAR-PSR)
Pulmonary & bronchial C-fibers receptors
 Terminate within or beneath epithelium of
intrapulmonary airways
Conduction velocity 4-18 m/s
The firing, after it increased, decreases
within 1 sec.
Sensitive to lung collapse and/or lung
deflation (dynamic lund compliance)
 Active t/out respiratory cycle, become more
active as the rate of and volume of lung
inflation increases (are activated by dynamic
forces accompanying lung inflation and
deflation)
Activated by stimuli that evoke brochospasm
or obstruction resulting from mucus
secretion and edema t/ parasympathetic fib.
Indirectly activated by chemical substances
such as histamine, capsaicin, substance P and
bradykinin t/ local end0organ effect
 SARs are highly sensitive to mechanical
forces put on the lung during breathing
SAR activity increases during inspiration
and peaks just prior to the initiation of
expiration
SARs are thought to be involved in the
Hering-Breuer reflex (terminates inspiration
and initiates expiration when the lungs are
adequately inflated)
The firing once it develops decays very
slowly over time.
 SAR facilitate coughing by a central cough
network via activation of brainstem second-
order neurons of the SAR reflex pathway
 A rich network of small, unmyelinated
axons (C fibers) innervate receptors in
either:
the conducting airways (bronchial) or
the alveoli (pulmonary) (J receptors or
juxtacapillary receptors)
These receptors are sensitive to chemical
stimuli.
 Directly activated by bradykinin and capsaicin
PGE2 , adrenaline, adenosine -- >
bronchodilators -- > inhibits RARs activation
but sensitize C-fibers to capsaicin and
bradykinin t/ direct effect on their peripheral
nerve terminals
C-fibers may synthesize neuropeptides
C-fibers generally quiescent t/out respiratory
cycle but are activated by chemical stimuli
 Reflex responses evoked by C-fiber activation
include:
Increased airway parasympathetic nerve activity
Chemoreflex:
Apnea (followed by rapid shallow breathing)
Bradycardia
Hypotension
 Pharynx -- > the afferent fibers of the
glossopharyngeal nerve (the IXth cranial
nerve)
Larynx, trachea, and larger bronch -- >
afferent fibers of the vagus (the xth cranial
nerve) [and also through n.laryngeus
superior]

The nucleus of tractus solitarius (NTS)

 Medulla oblongata (brain stem) near the
respiratory center
Receptors in MO:
Opioid receptors
5-hydroxytryptamine receptors (5HT1A)
GABA receptors
NMDA antagonist
(N-methyl-D-asparate)
 Impulses from the cough center travel via the
vagus, phrenic, and spinal motor nerves to
diaphragm, abdominal wall and muscles
The descending fibers arising from NTS to the
spinal primary motor neurons and
n.laryngeus recurrence
 The nucleus retroambigualis, by phrenic and
other spinal motor nerves, sends impulses to
the inspiratory and expiratory muscles
The nucleus ambiguus, by the laryngeal
branches of the vagus to the larynx
 Laryngeal muscles
Diaphragm
The intercostal muscles
The abdominal muscles
 The air is inspired (2.5 L)
The epiglottis is closed, and the vocal cords
shut tightly to entrap the air within the lungs
The abdominal muscle contract forcefully,
pushing against the diaphragm, while other
expiratory muscle contract forcefully the
pressure in the lungs > 100 mmHg
 The vocal cords and epiglottis suddenly
opened widely, so that the air under pressure
in the lungs explodes outward (velocity 75
100 miles/ hour)
The rapidly moving air usually carries with it
any foreign matter that is present in the
bronchi or trachea
 Deep inspiration
Glottis is closed
Forced expiratory effort against
the closed glottis
Raised intrathoracic & intraabdominal
pressure
Glottis is suddenly opened
A drop in intralaryngeal pressure
Increased air flow (axial & radial)
Brief violent rush of air out of trachea
(800 km/h)
Phases of cough
 Inspiratory phase:
Inhalation, which generates the volume necessary
for an effective cough
Compression phase:
Closure of the larynx combined with contraction
of muscles of chest wall, diaphragm, and
abdominal wall result in a rapid rise in
intrathoracic pressure
 Expiratory phase:
The glottis opens, resulting in high expiratory
airflow and the coughing sound.
Large airway compression occurs.
The high flows dislodge mucus from the airways
and allow removal from the tracheobronchial tree
 The axon reflex set up by irritation of the
nerve terminals in the epithelium and mucosa
(antidromic).
Their activation will release sensory
neuropeptides (tachykinins) -- > neurogenic
inflammation
P substance
Neurokinin A (NKA)
CGRP
 Vasodilatation
Plasma exudation
Edema
Epithelial damage
Submucosal gland secretion
Smooth muscle contraction
COUGH
 Watery viscoelastic secretion in the bronchi of
respiratory tract (tracheobronchial secretion)
Depth 5um
Produced by:
Submucosal glands
Goblet cells
Stimulated by:
Neural -- > Parasympathetic nerves (acetylcholine)
Local -- > Irritant (cigarette smoking, ammonia)
Structural representation of the tracheobronchial wall
 Two phases:
Gel
semisolid, sticky
outer most layer
Sol
thin
Inner most layer
 Composition
Gel
95% water
1% ash
1% CH
1% protein
Glycoprotein:
Threonine, serine
Cyctein
0,025% DNA
Electrolytes: sodium (211 mEq/L), potassium (17), calcium
(3), chloride (157)
Sol
Salivary amylase, lysozyme, lactoferrin, albumin,
sialoglycoprotein, salivary alpha, beta and gamma globulin