2. Embriologi
Tunas paru terbentuk pada usia ± 4 minggu.
Dibentuk dari suatu divertikulum pada dinding
ventral usus depan, yang meluas ke arah kaudal
(divertikulum respiratorium=tunas paru).
Mula‐mula tunas paru mempunyai hubungan terbuka
dengan usus depan, selanjutnya terpisah menjadi
bagian dorsal yaitu esofagus dan bagian ventral yaitu
trakea dan tunas paru.
4. Saat pemisahan dengan usus depan, tunas paru
membentuk trakea dan tunas bronkialis.
Pada awal minggu ke‐5 masing‐masing tunas
membesar membentuk bronkus utama kiri dan
kanan.
Bronkus utama kiri membentuk dua cabang sekunder
dan kanan membentuk tiga cabang sekunder→kiri
dua lobus dan kanan tiga lobus.
5. Tunas paru berkembang terus menembus ke dalam rongga
selom (kanalis perikardioperitonealis).
Akhirnya kanalis perikardioperitonealis terpisah dengan rongga
peritoneum dan perikardium masing‐masing oleh lipatan
pleuroperitoneal dan lipatan pleuroperikardial→ Tersisa rongga
pleura primitif→ berkembang menjadi pleura visceralis
(mesoderm) dan pleura parietalis (mesoderm somatik).
Perkembangan selanjutnya bronkus sekunder terus bercabang
secara dikotomi, → membentuk 10 bronkus tersier (segmental)
di kanan dan 8 di kiri.
Akhir bulan ke‐6 terbentuk ± 17 generasi anak cabang.
Pasca lahir terbentuk 6 anak cabang tambahan.
Saat lahir bifurcatio trakea akan terletak berhadapan dengan
V.thoracalis ke‐4.
6.
7. Pematangan paru
Sampai bulan ke‐7 prenatal bronkioli terus bercabang menjadi
saluran yang lebih banyak dan lebih kecil (tahap kanalikular),
dan suplai darah terus meningkat.
Pernapasan dapat berlangsung jika beberapa sel bronkiolus
respiratorius berbentuk kubus berubah menjadi sel gepeng yang
tipis.
Sel tersebut berhubungan dengan banyak kapiler darah dan
getah bening, ruang‐ruang di sekitarnya dikenal sebagai sakus
terminalis(alveoli primitif).
Selama bulan ke‐7 telah terdapat banyak kapiler yang menjamin
pertukaran gas sehingga janin prematur dapat bertahan hidup.
Selama dua bulan prenatal dan beberapa tahun pasca lahir
jumlah sakus terminalis terus meningkat.
8. Terdapat dua jenis sel epitel : Sel epitel alveoli tipe I
dan sel epitel alveoli tipe II.
Sel epitel alveoli tipe I, membentuk sawar darah‐udara
dengan endotel.
Sel epitel alveoli tipe II menghasilkan surfaktan
(berkembang pada akhir bulan ke‐6), suatu cairan
kaya fosfolipid dan mampu menurunkan tegangan
permukaan pada antarmuka udara‐alveolus.
Sebelum lahir paru mengandung kadar klorida tinggi,
sedikit protein, sedikit lendir dari bronkus dan
surfaktan.
9. Saat lahir, pernapasan dimulai, sebagian besar cairan
paru cepat diserap oleh kapiler darah dan getah bening
dan sejumlah kecil mungkin dikeluarkan melalui
trakea dan bronkus selama proses kelahiran.
Ketika cairan diserap di sakus alveolaris, surfaktan
mengendap sebagai lapisan fosfolipid tipis pada
selaput sel alveoli.
Tanpa ada surfaktan, alveoli akan menguncup selama
ekspirasi (atelektasis)
Alveoli akan terus dibentuk selama 10 tahun pertama
kehidupan setelah lahir.
10.
11.
12. Korelasi klinik
Kelainan pemisahan esofagus dan trakea oleh septum
esofagotrakealis mengakibatkan atresia esofagus dengan
atau tanpa fistula trakeoesofagealis.
Surfaktan sangat penting untuk mempertahankan hidup
pada bayi prematur.
Jika jumlah surfaktan tidak cukup→tegangan membran
permukaan udara‐air menjadi tinggi, resiko alveoli kolaps
saat ekspirasi sangat besar→Sindroma Gawat
Pernapasan(RDS).
Pada keadaan ini alveoli akan kolaps dan mengandung
banyak membran hialin dan badan‐badan
lamelar→Penyakit Membran Hialin ( 20 % dari semua
kematian bayi baru lahir).
13. Bagaimana membedakan bayi meninggal sebelum
lahir dan meninggal sesudah lahir, ditinjau dari
parunya?
16. Organization and Functions of the
Respiratory System
Consists of an upper respiratory tract (nose to larynx) and
a lower respiratory tract ( trachea onwards) .
Conducting portion transports air.
- includes the nose, nasal cavity, pharynx, larynx,
trachea, and progressively smaller airways, from the
primary bronchi to the terminal bronchioles
Respiratory portion carries out gas exchange.
- composed of small airways called respiratory
bronchioles and alveolar ducts as well as air sacs called
alveoli
17.
18. Respiratory System Functions
1. supplies the body with oxygen and disposes of
carbon dioxide
2. filters inspired air
3. produces sound
4. contains receptors for smell
5. rids the body of some excess water and heat
6. helps regulate blood pH
19. Breathing
Breathing (pulmonary ventilation). consists of
two cyclic phases:
inhalation, also called inspiration - draws
gases into the lungs.
exhalation, also called expiration - forces
gases out of the lungs.
20. Upper Respiratory Tract
Composed of the nose and nasal cavity,
paranasal sinuses, pharynx (throat), larynx.
All part of the conducting portion of the
respiratory system.
21. Respiratory mucosa
A layer of pseudostratified ciliated
columnar epithelial cells that secrete
mucus
Found in nose, sinuses, pharynx, larynx and
trachea
Mucus can trap contaminants
Cilia move mucus up towards mouth
22.
23. Nose
Internal nares - opening to exterior
External nares opening to pharynx
Nasal conchae - folds in the mucous
membrane that increase air turbulence and
ensures that most air contacts the mucous
membranes
24. Nose
rich supply of capillaries warm the inspired air
olfactory mucosa – mucous membranes that contain
smell receptors
respiratory mucosa – pseudostratified ciliated
columnar epithelium containing goblet cells that
secrete mucus which traps inhaled particles,
lysozyme kills bacteria and lymphocytes and
IgA antibodies that protect against bacteria
28. Nose
provides and airway for respiration
• moistens and warms entering air
• filters and cleans inspired air
• resonating chamber for speech
detects odors in the air stream
rhinoplasty: surgery to change shape of external nose
29. Paranasal Sinuses
Four bones of the skull contain paired air spaces
called the paranasal sinuses - frontal,
ethmoidal, sphenoidal, maxillary
Decrease skull bone weight
Warm, moisten and filter incoming air
Add resonance to voice.
Communicate with the nasal cavity by ducts.
Lined by pseudostratified ciliated columnar
epithelium.
31. Pharynx
Common space used by both the respiratory
and digestive systems.
Commonly called the throat.
Originates posterior to the nasal and oral
cavities and extends inferiorly near the level of
the bifurcation of the larynx and esophagus.
Common pathway for both air and food.
32. Pharynx
Walls are lined by a mucosa and contain skeletal
muscles that are primarily used for swallowing.
Flexible lateral walls are distensible in order to
force swallowed food into the esophagus.
Partitioned into three adjoining regions:
Nasopharynx
Oropharynx
laryngopharynx
33.
34. Nasopharynx
Superior-most region of the pharynx. Covered with
pseudostratified ciliated columnar epithelium.
Located directly posterior to the nasal cavity and superior
to the soft palate, which separates the oral cavity.
Normally, only air passes through.
Material from the oral cavity and oropharynx is typically
blocked from entering the nasopharynx by the uvula of
soft palate, which elevates when we swallow.
In the lateral walls of the nasopharynx, paired
auditory/eustachian tubes connect the nasopharynx to
the middle ear.
Posterior nasopharynx wall also houses a single
pharyngeal tonsil (commonly called the adenoids).
35.
36. Oropharynx
The middle pharyngeal region.
Immediately posterior to the oral cavity.
Bounded by the edge of the soft palate superiorly and the hyoid
bone inferiorly.
Common respiratory and digestive pathway through which both
air and swallowed food and drink pass.
Contains nonkeratinized stratified squamous epithelim.
Lymphatic organs here provide the first line of defense against
ingested or inhaled foreign materials. Palatine tonsils are on
the lateral wall between the arches, and the lingual tonsils are
at the base of the tongue.
37.
38. Laryngopharynx
Inferior, narrowed region of the pharynx.
Extends inferiorly from the hyoid bone to the
larynx and esophagus.
Terminates at the superior border of the
esophagus and the epiglottis of the larynx.
Lined with a nonkeratinized stratified
squamous epithelium.
Permits passage of both food and air.
39. Lower Respiratory Tract
Conducting airways (trachea, bronchi, up to
terminal bronchioles).
Respiratory portion of the respiratory system
(respiratory bronchioles, alveolar ducts, and
alveoli).
40. Larynx
Voice box is a short, somewhat cylindrical airway
ends in the trachea.
Prevents swallowed materials from entering the
lower respiratory tract.
Conducts air into the lower respiratory tract.
Produces sounds.
Supported by a framework of nine pieces of
cartilage (three individual pieces and three
cartilage pairs) that are held in place by
ligaments and muscles.
41.
42.
43. Larynx
Nine c-rings of cartilage form the framework of the
larynx
thyroid cartilage – (1) Adam’s apple, hyaline,
anterior attachment of vocal folds, testosterone
increases size after puberty
cricoid cartilage – (1) ring-shaped, hyaline
arytenoid cartilages – (2) hyaline, posterior
attachment of vocal folds, hyaline
cuneiform cartilages - (2) hyaline
corniculate cartilages - (2) hyaline
epiglottis – (1) elastic cartilage
44. Larynx
Muscular walls aid in voice production and the
swallowing reflex
Glottis – the superior opening of the larynx
Epiglottis – prevents food and drink from entering
airway when swallowing
pseudostratified ciliated columnar epithelium
45.
46. Sound Production
Inferior ligaments are called the vocal folds.
- are true vocal cords because they produce sound
when air passes between them
Superior ligaments are called the vestibular folds.
- are false vocal cords because they have no
function in sound production, but protect the vocal
folds.
The tension, length, and position of the vocal folds
determine the quality of the sound.
47. Sound production
Intermittent release of exhaled air through the vocal
folds
Loudness – depends on the force with which air is
exhaled through the cords
Pharynx, oral cavity, nasal cavity, paranasal sinuses
act as resonating chambers that add quality to the
sound
Muscles of the face, tongue, and lips help with
enunciation of words
51. Trachea
A flexible tube also called windpipe.
Extends through the mediastinum and lies anterior to
the esophagus and inferior to the larynx.
Anterior and lateral walls of the trachea supported by 15
to 20 C-shaped tracheal cartilages.
Cartilage rings reinforce and provide rigidity to the
tracheal wall to ensure that the trachea remains open at
all times
Posterior part of tube lined by trachealis muscle
Lined by ciliated pseudostratified columnar
epithelium.
52.
53. Trachea
At the level of the sternal angle, the trachea
bifurcates into two smaller tubes, called the
right and left primary bronchi.
Each primary bronchus projects laterally toward
each lung.
The most inferior tracheal cartilage separates
the primary bronchi at their origin and forms an
internal ridge called the carina.
54.
55. Bronchial tree
A highly branched system of air-conducting passages
that originate from the left and right primary bronchi.
Progressively branch into narrower tubes as they
diverge throughout the lungs before terminating in
terminal bronchioles.
Incomplete rings of hyaline cartilage support
the walls of the primary bronchi to ensure that they
remain open.
Right primary bronchus is shorter, wider, and more
vertically oriented than the left primary bronchus.
Foreign particles are more likely to lodge in the right
primary bronchus.
56. Bronchial tree
The primary bronchi enter the hilus
of each lung together with the
pulmonary vessels, lymphatic
vessels, and nerves.
Each primary bronchus branches
into several secondary bronchi
(or lobar bronchi).
The left lung has two secondary
bronchi.The right lung has three
secondary bronchi.
They further divide into tertiary
bronchi.
Each tertiary bronchus is called a
segmental bronchus because it
supplies a part of the lung called a
bronchopulmonary segment.
57. Bronchial Tree
Secondary bronchi tertiary bronchi bronchioles
terminal bronchioles
with successive branching amount of cartilage decreases and
amount of smooth muscle increases, this allows for variation
in airway diameter
during exertion and when sympathetic division active
bronchodilation
mediators of allergic reactions like histamine
bronchoconstriction
epithelium gradually changes from ciliated pseudostratified
columnar epithelium to simple cuboidal epithelium in
terminal bronchioles
59. Conduction vs. Respiratory
zones
Most of the tubing in the lungs makes up conduction
zone
Consists of nasal cavity to terminal bronchioles
The respiratory zone is where gas is exchanged
Consists of alveoli, alveolar sacs, alveolar ducts and
respiratory bronchioles
60. Respiratory Bronchioles, Alveolar
Ducts, and Alveoli
Lungs contain small saccular outpocketings called
alveoli.
They have a thin wall specialized to promote diffusion
of gases between the alveolus and the blood in the
pulmonary capillaries.
Gas exchange can take place in the respiratory
bronchioles and alveolar ducts as well as in the
alveoli, each lung contains approximately 300 to 400
million alveoli.
The spongy nature of the lung is due to the packing
of millions of alveoli together.
61. Respiratory Membrane
squamous cells of alveoli .
basement membrane of alveoli.
basement membrane of capillaries
simple squamous cells of capillaries
about .5 μ in thickness
62. Cells in Alveolus
Type I cells : simple squamous cells forming lining
Type II cells : or septal cells secrete surfactant
Alveolar macrophages
63.
64.
65. Gross Anatomy of the Lungs
Each lung has a conical shape. Its wide, concave base
rests upon the muscular diaphragm.
Its superior region called the apex projects superiorly to
a point that is slightly superior and posterior to the
clavicle.
Both lungs are bordered by the thoracic wall anteriorly,
laterally, and posteriorly, and supported by the rib cage.
Toward the midline, the lungs are separated from each
other by the mediastinum.
The relatively broad, rounded surface in contact with the
thoracic wall is called the costal surface of the lung.
66.
67. Lungs
Left lung
divided into 2 lobes by
oblique fissure
smaller than the right
lung
cardiac notch
accommodates the
heart
68. Right
divided into 3 lobes
by oblique and
horizontal fissure
located more
superiorly in the
body due to liver on
right side
69. Pleura and Pleural Cavities
The outer surface of each lung and the
adjacent internal thoracic wall are lined by a
serous membrane called pleura.
The outer surface of each lung is tightly
covered by the visceral pleura.
while the internal thoracic walls, the lateral
surfaces of the mediastinum, and the superior
surface of the diaphragm are lined by the
parietal pleura.
The parietal and visceral pleural layers are
continuous at the hilus of each lung.
70. Pleural Cavities
The potential space between the serous
membrane layers is a pleural cavity.
The pleural membranes produce a thin, serous
pleural fluid that circulates in the pleural cavity
and acts as a lubricant, ensuring minimal friction
during breathing.
Pleural effusion – pleuritis with too much fluid
71.
72. Blood supply of Lungs
pulmonary circulation -
bronchial circulation – bronchial arteries supply
oxygenated blood to lungs, bronchial veins carry
away deoxygenated blood from lung tissue
superior vena cava
Response of two systems to hypoxia –
pulmonary vessels undergo vasoconstriction
bronchial vessels like all other systemic vessels
undergo vasodilation
73. Respiratory events
Pulmonary ventilation = exchange of gases
between lungs and atmosphere
External respiration = exchange of gases between
alveoli and pulmonary capillaries
Internal respiration = exchange of gases between
systemic capillaries and tissue cells
74. Two phases of pulmonary ventilation
Inspiration, or inhalation - a very active process that
requires input of energy.The diaphragm, contracts,
moving downward and flattening, when stimulated by
phrenic nerves.
Expiration, or exhalation - a passive process that
takes advantage of the recoil properties of elastic
fiber. ･The diaphragm relaxes.The elasticity of the
lungs and the thoracic cage allows them to return to
their normal size and shape.
75. Muscles that ASSIST with respiration
The scalenes help increase thoracic cavity dimensions
by elevating the first and second ribs during forced
inhalation.
The ribs elevate upon contraction of the external
intercostals, thereby increasing the transverse
dimensions of the thoracic cavity during inhalation.
Contraction of the internal intercostals depresses the
ribs, but this only occurs during forced exhalation.
Normal exhalation requires no active muscular effort.
76. Muscles that ASSIST with respiration
Other accessory muscles assist with respiratory
activities.
The pectoralis minor, serratus anterior,
and sternocleidomastoid help with forced
inhalation,
while the abdominal muscles(external and
internal obliques, transversus abdominis,
and rectus abdominis) assist in active
exhalation.
77. Ventilation Control by Respiratory
Centers of the Brain
The trachea, bronchial tree, and lungs are
innervated by the autonomic nervous
system.
The autonomic nerve fibers that innervate the
heart also send branches to the respiratory
structures.
The involuntary, rhythmic activities that deliver
and remove respiratory gases are regulated in
the brainstem within the reticular formation
through both the medulla oblongata and
pons.
78. Respiratory Values
A normal adult averages 12 breathes per minute =
respiratory rate(RR)
Respiratory volumes – determined by using a
spirometer
81. Introduction
Non respiratory function of the respiratory
system
- provides a route for water loss and heat
elimination
- enhances venous return
- contributes to the maintenance of normal
acid-base balance
- enables speech,singing, and other
vocalization
- defends againts inhaled foreign matter
83. Respiration
- internal respiration; intra cellular
metabolic processes carried out
within the mitochondria, which use
O2 and produce CO2
84. - external respiration; encompresses 4
steps;
1. air is alternately moved in and out of
the lungs so that exchange of air can occur
between atmosphere and the alveoli
ventilation
2. O2 and CO2 are exchanged between air
in the alveoli and blood within the pulmonary
capillaries diffusion
3. O2 and CO2 are transported by the
blood between the lungs and tissues
4. exchange of O2 and CO2 takes place
between the tissues and the blood by the
process of diffusion across the sistemic
capillaries
85.
86.
87.
88.
89.
90. The alveolar walls consist of a single
layer of flattened Type I alveolar cells
(thin and wall forming)
Type II alveolar cells secrete
pulmonary surfactant, a
phospholipoprotein complex that
faciitates lung expansion
Defensive alveolar macrophages are
present within the lumen of alveoli
91. Minute pores of Kohn exist in the walls
between adjacent alveoli permits
airflow between adjoining alveoli
collateral ventilation
92. Lungs
Right lung 3 lobes
Left lung 2 lobes
No muscle within alveoli walls to
cause them to inflate and deflate
during brething process
The only muscle within the lungs is
the smooth muscle in the walls of the
arteriols and bronchioles
93. Lungs
Changes in the lung volume are
brought about through changes in the
dimension of the thorax cavity
The rib cage provides bony protection
for the lungs and the heart
Rib cage formed by 12 pairs of curved
ribs which join the sternum anteriorly
and the thoracic vertebrae
(backbone) posteriorly
94. Diaphragm is a large dome-shaped
sheet of scletal muscle forms the floor
of thoracic cavity
95. Pleural sac
pleural sac separates each lung from
thoracic wall and other surrounding
structures
- pleura visceral cover the lungs’
surface
- pleura parietal lines the
1.mediastinum
2.superior face of diaphragm
3.inner thoracic wall
96. Pleural sac
The interior of the pleural sac is
known as pleural cavity
The surfaces of the pleura secrete a
thin intra pleural fluid, which
lubricates the pleural surfaces as they
slide past each other during
respiratory movements
97. RESPIRATORY MECHANICS
Air flows in and out of the lungs by
moving down alternately reversing
pressure gradients established
between the alveoli and the
atmosphere by cyclical respiratory
musle activity
98. Three different pressure consideration
are important in ventilation
1. atmospheric (barometric)
pressure is the pressure exerted by
the weight of the air in the atmosphere
on objects on earth’s surface. At sea
level = 760 mmhg, and diminishes
with increasing altitude above sea level
as the column of air above earth’s
surface correspondingly decreases
99. 2. intra alveolar pressure (intrapulmonary)
pressure within alveoly
3. intrapleural pressure the pressure within
the pleural sac = intrathoracic pressure, it is
pressure exerted outside the lungs within the
thoracic cavity.
usually less than atmospheric pressure
averaging 756 mmhg at rest
756 mmhg is sometimes referred to as
pressure of -4 mmhg (just negative when
compared with the normal atmosphere
pressure)
100. The negative intra pleural pressure is
due to;
1. surface tension of alveolar fluid
2. elasticity of lungs
3. elasticity of thoracic wall
101. Intra pleural pressure does not
equilibrate with atmosphere or intra
pulmolmonary pressure because
there is no direct communication
between the pleural and either
atmosphere or the lungs
102. Intra pleural fluid’s cohesiveness and
transmural pressure gradient ( the
net outward pressure differential )
hold the thoracic wall and lungs in
close apposition, streching the lungs
to fill the thorax cavity
103. The transmural pressure gradient and
intra pleural fluid’s cohesiveness
prevent the thoracic wall and the
lungs pulling away from each other
except to the slightest degree
104. Normally, air does not enter the
pleural cavity, because there is no
communication between the cavity and
either atmosphere or alveoli
If the lungs punctured (by a stab
wound or broken rib) air flows down its
pressure gradient from higher
atmospheric pressure and rushes into
the pleural space pneumothorax
105. Intra pleural and intra alveolar are now
equilibrated with atmospheric
pressure, so transmural pressure
gradient no longer exists, with no force
present to stretch the lungs collapses
The intra pleural fluid’s cohesiveness
can not hold the lungs and thoracic
wall in apposition in the absence of the
transmural pressure gradient
106.
107. Air flows down a pressure gradient
During inspiration intra alveolar
pressure< atmospheric pressure
During expiration intra alveolar
pressure> atmospheric pressure
Intra alveolar pressure can be changed
by altering the volume of the lungs, in
accordance with Boyle’s law
108. Boyle’s law states that at any
constant temperature, the pressure
exerted by a gas varies inversely with
the volume of the gas
109.
110.
111.
112. Respiratory muscles
Respiratory muscles that accomplish
breathing do not act directly on the
lungs to change their volume, instead
change the volume of the thoracic
cavity causing a corresponding
change in lung volume because the
thoracic wall and lungs are linked
together
113.
114. Diaphragm innervated by nervus
phrenicus
M.intercostalis ext innervated by
nervus intercostalis
During inspiration diaphragm and
m.intercostalis ext contract on
stimulation of this nerves
115. When diaphragm contact it descend
downward, enlarging the volume of
thoracic cavity by increasing its
vertical dimension
When m. intercostalis ext contract its
fibers run downward and forward
between adjacent ribs enlarging the
thoracic cavity in both lateral and
anteroposterior dimensions
116.
117. At the end of inspiration the
inspiratory muscles relax
Diaphragm assume its original dome
shaped position
The elevated rib cage falls because of
gravity when m. intercostalis ext
relax
The chest wall and stretch lungs
recoil because of their elastic
properties
118.
119.
120. Deeper inspiration can be
accompished by contracting the
diphragm and m.intercostalis ext.
more forcefully and by bringing the
accessory inspiratory muscles into
play to further enlarge thorax cavity
121. During quite breathing, expiration is
normally a passive process, because
it is accomplished by elastic recoil of
the lungs on the relaxation of
inspiratory muscles
To produce such a forced, active
expiration expiratory muscles must
contract to further reduce the volume
of the thoracic cavity and lungs
122. During forcefull expiration the
intrapleural pressure exceed the
atmopheric pressure, but the lungs
do not collapse because the intra
alveolar pressure also increased
correspondingly, a transmural
pressure gradient still exists
123. Airway resistance influences airflow
rates
F=∆ P
R
F = airflow rate
∆ P= difference between atmopheric and
inra alveolar pressure (pressure
gradient)
R = resistance of airway, determined by
their radii
124. The primary determinant of
resistance to airflow is the radius of
the conducting airways
The airways normally offer such low
resistance that only very small
pressure gradient of 1-2 mmHg need
be created to achieve adequate rates
of airflow in and out of the lungs
125. Normally modest adjustment in
airway size can be accomplished by
autonomic nerv. Syst. Regulation to
suit the body’s need
Parasympathetic stimulation
promotes bronchiolar smooth muscle
contraction, which increases airway
resistance by producing
bronchoconstriction
126. Sympathetic stimulation and to a
greater extent its associated hormone
epinephrine, bring about
bronchodilation
Airway resistance is abnormally increased
with chronic obstructive pulmonary
disease such as;
- chronic obstuctive pulmonary disease
(COPD)
- chronic bronchitis
- asthma
-emphysema
127. During the respiratory cycle, the lung
alternately expand during inspiration
and recoil during expiration
Two interrelated concepts are involved
in pulmonary elasticity;
- elastic recoil refers to how
readily the lungs rebound after having
been stretched
128. - compliance refers to how much
effort required to stretch or distend
the lungs is a measure of
magnitude of change in lung volume
accomplished by a given change in
the transmural pressure gradient
130. Alveolar surface tension displayed by
the thin liquid film that lines each
alveolus
At an air-water interface, the water
molecules at the surface are more
strongly attached to other
surrounding water molecules than to
the air above the surface.
131. The tremendous surface tension of
pure water is normally counteracted by
pulmonary surfactan, a complex
mixture of lipids and proteins
Pulmonary surfactan intersperses
between the water molecules in the
fluid lining the alveoli and lowers the
alveolar surface tension, because the
cohesive force between a water
molecule and a pulmonary surfactan
molecule is very low
132. By lowering the alveolar surface
tension, pulmonary surfactan
provides two benefits;
1. increases pulmonary compliance
2. reduces the lung’s tendency to
recoil
One of the important factors to maintain
the stability of the alveoli
133. According to the law of La Place, the
magnitude of the inward directed
collapsing pressure is directly
proportional to the surface tension
and inversely proportional to the
radius of the bubble
134. P= 2T
r
P = inward directed collapsing pressure
T = surface tension
r = radius of bubble
135. A second factor that contributes to
alveolar stability is the
interdependence among neighboring
alveoli
If an alveolus starts to collapse, the
surrounding alveoli are stretched as
their walls are pulled in the direction of
the caving in alveolus, in turn these
neighbouring alveoli, by recoiling in
resistance to being stretched exert
expanding forces on the collapsing
alveolus and therby help keep it open
136. Normally only 3% of the total energy
is used for quiet breathing
The work of breathing may be
increased in four different situations;
1. when pulmonary compliance is
decreased
2. when airway resistance is increased
3. when elastic recoil is decreased
4. when there is a need for increased
ventilation
137. The changes in lung volume can be measured
using a spirometer
Lung volumes and capacities;
- tidal volume (TV) the volume of
air entering or leaving the lungs
during a single breath= 500 ml
- inspiratory reserve volume (IRV)
the extra volume of air that can be
maximally inspired over and above
the typical resting tidal volume=
3000 ml
138. Inspiratory capacity (IC) the max
volume of air that can be inspired at
the end of a normal quiet expiration
(IC= IRV+TV)= 3500 ml
Expiratory reserve volume (ERV) the
extra volume of air that can be actively
expired by Maximal contraction of the
expiratory muscles beyond that
normally passive expired at the end of
a typical resting tidal volume= 1000ml
139. Residual volume(RV) the minimum
volume of air remaining in the lungs
even after a maximal expiration=
1200 ml
Functional residual capacity(FRC)
the volume of air in the lungs at he
end of a normal passive expiration
(FRC= ERV+RV)= 2200 ml
140. Vital capacity (VC) the maximum
volume of air that can be moved our
during a single breath following a
maximal inspiration (VC=
IRV+TV+ERV) the VC represents the
maximum volume change possible
within the lungs= 4500 ml
Total lung capacity (TLC) the
maximum volume of air that the lungs
can hold (TLC= VC+RV)= 5700 ml
141. Forced expiratory volume in one
second (FEV1) the volume of air
that can be expired during the first
second of expiration in a VC
determination
usually, FEV1 is about 80% of VC
144. Normal Dead Space Volume. The
normal dead space air in a young
adult man is about 150 milliliters,This
increases slightly with age.
The volume of all the space of the
respiratory system other than the
alveoli and their other closely related
gas exchange areas; this space is
called the anatomic dead space.
145. Any ventilated alveoli that do not
participate in gas exchange with blood
are considered alveolar dead space
Physiologic Dead Space this is the
total dead space in the lung system
the anatomic dead space plus alveolar
dead space.
146. Pulmonary ventilation=
tidal volume x respiratory rate
Alveolar ventilation per minute is the
total volume of new air entering the
alveoli and adjacent gas exchange
areas each minute
Alveolar ventilation=
(tidal volume- dead space volume)x
resp rate
147. GAS EXCHANGE
Gas exchange at both the pulmonary
capillary and the tissue capillary
levels involves simple passive
diffusion of O2 and CO2 down partial
pressure gradients
No active transport exist for these
gases
148. gas exchange between the alveolar
air and the pulmonary blood occurs
through the membranes of all the
terminal portions of the lungs
All these membranes are collectively
known as the respiratory membrane=
pulmonary membrane
149. the following different layers of the
respiratory membrane:
1. A layer of fluid lining the alveolus and
containing surfactant that reduces the
surface tension of the alveolar fluid
2. The alveolar epithelium composed of thin
epithelial cells
3. An epithelial basement membrane
4. A thin interstitial space between the
alveolar epithelium and the capillary
membrane
5. A capillary basement membrane that in
many places fuses with the alveolar epithelial
basement membrane
6. The capillary endothelial membrane
150. the overall thickness of the
respiratory membrane in some areas
is as little as 0.2 micrometer, and it
averages about 0.6 micrometer
151.
152.
153.
154.
155.
156.
157.
158. According to Fick’s law of diffusion;
the diffusion rate of a gas through a
sheet of tissue also depends on the
surface area and thickness of the
membrane through which the gas is
diffusing and on the diffusion coeficient
of the particular gas
Factors are relatively constant under
resting situation
159. During exercise ;
1. the surface area available for exchange
can be physiologically increased to
enhance the rate of gas transport
2. When the pulmonary blood pressure is
raised by increased cardiac output, many
of previously closed pulmonary capillaries
are forced open increases surface area
of blood available for exchange
160. 3. the alveolar membranes are
stretched further than normal
because of the larger tidal volumes
(deeper breathing)
161. Ventilation-perfussion ratio
Two factors determine the PO2 and the
PCO2 in the alveoli:
(1) the rate of alveolar ventilation and
(2) the rate of transfer of oxygen and
carbon dioxide through the respiratory
membrane.
It made the assumption that all the alveoli
are ventilated equally, and that blood flow
through the alveolar capillaries is the same
for each alveolus.
162. However, even normally to some extent, and
especially in many lung diseases, some areas
of the lungs are well ventilated but have
almost no blood flow, whereas other areas
may have excellent blood flow but little or no
ventilation.
a highly quantitative concept has been
developed to help us understand respiratory
exchange when there is imbalance between
alveolar ventilation and alveolar blood flow.
This concept is called the ventilation-
perfusion ratio.
163. the ventilation-perfusion ratio is expressed
as Va/Q
Va (alveolar ventilation)
Q (blood flow)
When Va is normal and Q also normal the
ventilation perfusion ratio is also said to be
normal resting situation= 0.8 l/mnt
When there is both normal alveolar ventilation
and normal alveolar capillary blood flow
(normal alveolar perfusion), exchange of
oxygen and carbon dioxide through the
respiratory membrane is nearly optimal,
165. When the ventilation(Va) is zero, yet
there is still perfusion (Q) of the
alveolus, the Va/Q is zero
Or, at the other extreme, when there
is adequate ventilation (Va) but zero
perfusion(Q), the ratio Va/Q is infinity.
At a ratio of either zero or infinity,
there is no exchange of gases through
the respiratory membrane of the
affected alveoli
166. When Va/Q is equal to zero the air in
the alveolus comes to equilibrium with
the blood oxygen and carbon dioxide
because these gases diffuse between
the blood and the alveolar air.
Because the blood that perfuses the
capillaries is venous blood returning to
the lungs from the systemic
circulation, it is the gases in this blood
with which the alveolar gases
equilibrate.
167. The effect on the alveolar gas partial
pressures when Va/Q equals infinity is
entirely different from the effect when Va/Q
equals zero because now there is no capillary
blood flow to carry oxygen away or to bring
carbon dioxide to the alveoli.
Therefore, instead of the alveolar gases
coming to equilibrium with the venous blood,
the alveolar air becomes equal to the
humidified inspired air. That is, the air that is
inspired loses no oxygen to the blood and
gains no carbon dioxide from the blood.
168. Whenever Va/Q is below normal,
there is inadequate ventilation to
provide the oxygen needed to fully
oxygenate the blood flowing through
the alveolar capillaries.
A certain fraction of the venous blood
passing through the pulmonary
capillaries does not become
oxygenated. This fraction is called
shunted blood.
169. The total quantitative amount of
shunted blood per minute is called
the physiologic shunt. This
physiologic shunt is measured in
clinical pulmonary function
laboratories by analyzing the
concentration of oxygen in both
mixed venous blood and arterial
blood (along with simultaneous
measurement of cardiac output)
170. the physiologic shunt can be calculated by the following
equation:
Qps = CiO2 - CaO2
Qt CiO2 - CvO2
Qps is the physiologic shunt blood flow perminute
Qt is cardiac output per minute
CiO2 is the concentration of oxygen in the arterial
blood if there is an “ideal” ventilation-perfusion ratio
CaO2 is the measured concentration of oxygen in the
arterial blood
and CvO2 is the measured concentration of oxygen in
the mixed venous blood.
171. The greater the physiologic
shunt, the greater the amount of
blood that fails to be oxygenated
as it passes through the lungs.
172. In a normal person at the top of the
lung,Va/Q is as much as 2.5 times as great
as the ideal value, which causes a moderate
degree of physiologic dead space in this area
of the lung.
in the bottom of the lung, there is slightly
too little ventilation in relation to blood
flow,with Va/Q as low as 0.6 times the ideal
value. In this area, a small fraction of the
blood fails to become normally oxygenated,
and this represents a physiologic shunt.
173. inequalities of ventilation and
perfusion decrease slightly the lung’s
effectiveness for exchanging oxygen
and carbon dioxide.
during exercise, blood flow to the
upper part of the lung increases
markedly, so that far less physiologic
dead space occurs, and the
effectiveness of gas exchange now
approaches optimum.
174. O2 transport
Once oxygen has diffused from the
alveoli into the pulmonary blood, it is
transported to the peripheral tissue
capillaries almost entirely in
combination with hemoglobin.
the transport of oxygen and carbon
dioxide by the blood depends on both
diffusion and the flow of blood.
175. Normally, about 97 per cent of the
oxygen transported from the lungs to
the tissues is carried in chemical
combination with hemoglobin in the
red blood cells.
The remaining 3 per cent is
transported in the dissolved state in
the water of the plasma and blood
cells.
176. Maximum Amount of Oxygen That Can Combine
with the
Hemoglobin of the Blood.
On average, the 15 grams of
hemoglobin in 100 milliliters of blood
can combine with a total of almost
exactly 20 milliliters of oxygen if the
hemoglobin is 100 per cent saturated.
This is usually expressed as 20
volumes percent.
177. the oxygen molecule combines
loosely and reversibly with the heme
portion of hemoglobin.When PO2 is
high, as in the pulmonary capillaries,
oxygen binds with the hemoglobin,
but when PO2 is low, as in the tissue
capillaries, oxygen is released from
the hemoglobin.
179. the oxygen-hemoglobin dissociation
curve, which demonstrates a
progressive increase in the
percentage of hemoglobin bound with
oxygen as blood Po2 increases, which
is called the per cent saturation of
hemoglobin.
180. a number of factors can displace the
dissociation curve in one direction or
the other;
1. when the blood becomes slightly
acidic, with the pH decreasing from the
normal value of 7.4 to 7.2, the
oxygen-hemoglobin dissociation curve
shifts, on average, about 15 per cent
to the right.
Conversely, an increase in pH from the
normal 7.4 to 7.6 shifts the curve a
similar amount to the left.
181. 2. changes carbon dioxide
concentration
3. changes blood temperature
4. changes 2,3-biphosphoglycerate
(BPG),a metabolically important
phosphate compound present in the
blood in different concentrations
under different metabolic
conditions.(increased in hypoxic
condition O2 released)
182.
183.
184. Carbon monoxide combines with
hemoglobin at the same point on the
hemoglobin molecule as does oxygen
it can therefore displace oxygen from
the hemoglobin, thereby decreasing
the oxygen carrying capacity of
blood.
it binds with about 250 times as
much tenacity as oxygen
185. CO2 transport
the amount of carbon dioxide in the
blood has a lot to do with the acid-
base
balance of the body fluids
An average of 4 milliliters of carbon
dioxide is transported from the
tissues to the lungs in each 100
milliliters of blood.
186. To begin the process of carbon dioxide
transport, carbon dioxide diffuses out of the
tissue cells in the dissolved molecular carbon
dioxide form.
The dissolved carbon dioxide in the blood
reacts with water to form carbonic acid (70
per cent) catalized by carbonic anhidrase
enzyme
the reaction occurs so rapidly in the red
blood cells
187. In another fraction of a second, the
carbonic acid formed in the red cells
(H2CO3) dissociates into hydrogen
and bicarbonate ions (H+ and HCO3–
)
Most of the hydrogen ions then
combine with the hemoglobin in the
red blood cells, because the
hemoglobin protein is a powerful
acid-base buffer.
188. In turn, many of the bicarbonate ions diffuse from the
red cells into the plasma, while chloride ions diffuse
into the red cells to take their place.
This is made possible by the presence of a special
bicarbonate-chloride carrier protein in the red cell
membrane that shuttles these two ions in opposite
directions at rapid velocities. Thus, the chloride
content of venous red blood cells is greater than that
of arterial red cells, a phenomenon called the chloride
shift.
189. In addition to reacting with water, carbon
dioxide reacts directly with amine radicals
of the hemoglobin molecule to form the
compound carbaminohemoglobin
(CO2Hb) 23%
This combination of carbon dioxide and
hemoglobin is a reversible reaction that
occurs with a loose bond, so that the
carbon dioxide is easily released into the
alveoli, where the Pco2 is lower than in the
pulmonary capillaries 7%
190. A small amount of carbon dioxide also
reacts in the same way with the
plasma proteins in the tissue
capillaries.
This is much less significant for the
transport of carbon dioxide because
the quantity of these proteins in the
blood is only one fourth as great as
the quantity of hemoglobin.
191. the Bohr effect; increase in carbon
dioxide in the blood causes oxygen to
be displaced from the hemoglobin an
important factor in increasing oxygen
transport
binding of oxygen with hemoglobin
tends to displace carbon dioxide from
the blood. the Haldane effect
important factor in increasing CO2
transport
192. REGULATION OF RESPIRATION
respiratory center is composed of
several groups of neurons located
bilaterally in the medulla oblongata
and pons of the brain stem
193. It is divided into three major collections of
neurons:
(1) a dorsal respiratory group (inspiratory
center), located in the dorsal portion of the
medulla, which mainly causes inspiration
(2) a ventral respiratory group (expiratory
center), located in the ventrolateral part of
the medulla, which mainly causes expiration
(3) the pneumotaxic center,located dorsally in
the superior portion of the pons, which mainly
controls rate and depth of breathing.
The dorsal respiratory group of neurons plays the
most fundamental role in the control of
respiration.
194. The dorsal respiratory group of neurons are
located within the nucleus of the tractus
solitarius
The nucleus of the tractus solitarius is the
sensory termination of both the vagal and
the glossopharyngeal nerves, which
transmit sensory signals into the
respiratory center from
(1) peripheral chemoreceptors
(2) baroreceptors, and
(3) several types of receptors in the lungs.
195. The basic rhythm of respiration is generated mainly in
the dorsal respiratory group of neurons.
The nervous signal that is transmitted to the
inspiratory muscles, mainly the diaphragm in normal
respiration, it begins weakly and increases steadily in
a ramp manner for about 2 seconds. Then it ceases
abruptly for approximately the next 3 seconds, which
turns off the excitation of the diaphragm and allows
elastic recoil of the lungs and the chest wall to cause
expiration.
196. the inspiratory signal is a ramp signal
it causes a steady increase in the
volume of the lungs during inspiration
197. There are two qualities of the inspiratory ramp that
are controlled, as follows:
1. Control of the rate of increase of the ramp signal,
so that during heavy respiration, the ramp increases
rapidly and therefore fills the lungs rapidly.
2. Control of the limiting point at which the ramp
suddenly ceases. This is the usual method for
controlling the rate of respiration; that is, the earlier
the ramp ceases, the shorter the duration of
inspiration. This also shortens the duration of
expiration. Thus, the frequency of respiration is
increased.
198. A pneumotaxic center, located
dorsally in the nucleus parabrachialis
of the upper pons, transmits signals
to the inspiratory area.
effect of this center is to control the
“switch-off” point of the inspiratory
ramp, thus controlling the duration of
the filling phase of the lung cycle.
199. When the pneumotaxic signal is
strong, inspiration might last for as
little as 0.5 second, thus filling the
lungs only slightly; when the
pneumotaxic signal is weak,
inspiration might continue for 5 or
more seconds, thus filling the lungs
with a great excess of air.
200. The function of the pneumotaxic
center is primarily to limit inspiration.
This has a secondary effect of
increasing the rate of breathing,
because limitation of inspiration also
shortens expiration and the entire
period of each respiration.
201. ventral respiratory group of neurons,
found in the nucleus ambiguus
rostrally and the nucleus
retroambiguus caudally.
202. The function of this neuronal group;
1. The neurons of the ventral respiratory
group remain almost totally inactive during
normal quiet respiration.
2. There is no evidence that the ventral
respiratory neurons participate in the basic
rhythmical oscillation that controls
respiration.
3. the ventral respiratory area contributes
extra respiratory drive
4. especially important in providing the
powerful expiratory signals to the abdominal
muscles during very heavy expiration.
203. Hearing Breur Reflex
Most important, located in the
muscular portions of the walls of the
bronchi and bronchioles throughout
the lungs are stretch receptors that
transmit signals through the vagi into
the dorsal respiratory group of
neurons when the lungs become
overstretched.
204. when the lungs become overly inflated, the
stretch receptors activate an appropriate
feedback response that “switches off” the
inspiratory ramp and thus stops further
inspiration Hering-Breuer inflation reflex.
is not activated until the tidal volume
increases to more than three times normal
(greater than about 1.5 liters per breath).
205. The ultimate goal of respiration is to
maintain proper concentrations of
oxygen, carbon dioxide, and
hydrogen ions in the tissues.
Excess carbon dioxide or excess
hydrogen ions in the blood mainly act
directly on the respiratory center
206. Oxygen, in contrast, does not have a
significant direct effect on the
respiratory center of the brain in
controlling respiration. Instead, it acts
almost entirely on peripheral
chemoreceptors located in the carotid
and aortic bodies, and these in turn
transmit appropriate nervous signals
to the respiratory center for control of
respiration.
207.
208.
209.
210. Arterial PO2 is monitored by
peripheral chemoreceptors
The arterial PO2 must fall below 60
mmhg before the peripheral chem.
Respond by sending afferent impulses
to inspiratory centers increasing
ventilation
211. Central chemoreceptors sensitive to
changes in CO2 induced H+
concentration in the brain
extracellular fluid (ECF)
212.
213. Changes in arterial H+ concentration
cannot influence the central
chemoreceptors, because H+ cannot
cross the blood brain barrier the
peripheral chem. Are highly
responsive to the fluctuation in
contrast to their unsensitiveness to
arterial PCO2 and PO2 until it falls
below 60 mmhg
214.
215.
216.
217.
218.
219.
220.
221.
222. Bronkiektasis kelainan anatomik dilatasi
bronkus yang kronik dan menetap.
Bronkus yang terkena biasanya berukuran sedang
(generasi 4-9).
Karakteristik bronkiektasis yaitu kerusakan dari
dinding bronkus, pembuluh darah, jaringan elastis
dan komponen otot-otot polos
223. Penyebab bronkiektasis yang pasti belum
diketahui, namun banyak faktor yang
dapat mengakibatkan terjadinya
bronkiektasis :
1. Acquired Bronchiectasis
2. Congenital Bronchiectasis
224. ACQUIRED BRONCHIECTASIS
1. FAKTOR OBSTRUKSI
Sebagian besar cabang bronkus yang kecil
Akibat aspirasi mukus masuk ke dalam lumen
bronkus yang menyebabkan kolaps bagian distal.
Keadaan ini menyebabkan tekanan intraluminer
proksimal dilatasi bronkus.
Bila terjadi infeksi pada bronkus yang mengalami dilatasi ini
serta terjadi destruksi dinding bronkus, maka akan terjadi
dilatasi bronkus yang permanen.
225. Obstruksi dapat disebabkan :
Aspirasi benda asing
Mucous plaque
Bronchogenic carcinoma
Pembesaran KGB di hilus yang menyebabkan
bronkiektasis pada distal bronkus.
Kondisi yang telah disebutkan diatas
menyebabkan gangguan mekanisme mucociliary
cleareance dan gangguan ini akan menyebabkan
berkembangnya infeksi bakteri
226. 2. INFEKSI PARU BERULANG
(Recurrent Pulmonary Infection)
Infeksi saluran nafas akut misalnya
bronkopneumonie destruksi jaringan
peribronkhial penarikan dinding bronkhus
dilatasi bronkhus
227. Bronkiektasis pada umumnya dijumpai pada
individu yang mempunyai recurrent dan infeksi
saluran pernapasan bawah dalam jangka waktu
lama
Seperti anak-anak ; penderita bronkopneumonia
akibat komplikasi sekunder seperti cacar,
measle, influenza yang akan menderita
bronkiektasis pada usia dewasa
228. 3. Inhalasi dan Aspirasi
Bronkiektasis pada umumnya dijumpai
akibat inhalasi oleh gas ammoniak atau
teraspirasi cairan lambung.
230. MANIFESTASI KLINIS
Batuk kronis yang produktif terutama pagi hari,
sputum banyak, sepanjang hari (wet
bronchiectasis). Batuk kering kadang disertai
hemoptisis dry bronchiectasis
Sputum putih dan kadang-kadang warna kuning
infeksi berat 400 - 500 cc/hari .
Batuk darah 50 -70% kasus masif.
Demam berulang
Nyeri dada
Sesak napas
Akut eksaserbasi
231. PEMERIKSAAN FISIS
Suara pernapasan : - bronkial
- ekspirasi memanjang
Suara tambahan ronki basah / ronki kering
Clubbing finger
Kasus berat gagal napas
232. 1. Sumbatan bronkus (Bronchial obstruction)
o Tumor endobronkial
o Bronkolitiasis dan gangguan inflamasi seperti
tuberkulosis dan aspirasi benda asing.
2. Infeksi
o Infeksi paru nekrotik yang tidak diobati
o Disebabkan oleh Klebsiella, Staphylococcus, M.
tuberculosis, M.non tuberkulosis, Mycoplasma
pneumoniae, dll.
KONDISI-KONDISI YANG BERHUBUNGAN
DENGAN BRONKIEKTASIS
233. 3. Inflamasi
Ulserasi asam lambung aspirasi bronkiektasis
4. Aspergilosis Bronkopulmoner Alergi
o Ditandai dengan bronkospasme, bronkiektasis dan
sekret yang mengandung aspergillosis
o Reaksi hypersensitif thd antigen yang terhirup di
trakeobronkhial.
o Bronkiektasis terjadi akibat sumbatan sekret yang
mengandung hipa dan aspergilus.
KONDISI-KONDISI YANG BERHUBUNGAN
DENGAN BRONKIEKTASIS
234. 5. Defisiensi Imun
o Terjadi pada penderita defisiensi imun
kongenital maupun didapat.
o Limfosit B yang abnormal.
o Hipogammaglobulinemia kongenital atau
didapat penurunan hilangnya IgG.
6. Defisiensi Alfa-1 Antitripsin
KONDISI-KONDISI YANG BERHUBUNGAN
DENGAN BRONKIEKTASIS
235. 7. Diskinesia Silia Primer
Sindroma kartagener ( dextrocardia, bronkiektasis
, sinusitis syndrome)
8. Fibrosis Kistik
Gangguan transportasi klorida penumpukan
klorida dlm sel sel kering sekret kental
membatu iritasi kronik infeksi berulang
KONDISI-KONDISI YANG BERHUBUNGAN
DENGAN BRONKIEKTASIS
236. Klasifikasi Reid tahun 1950 membagi
bronkiektasis atas 3 tipe :
1. SILINDRIK
2. VARIKOSA
3. KISTIK ATAU SAKULAR
KLASIFIKASI GAMBARAN RADIOLOGIS
237. Gambaran foto toraks bisa normal
Corakan bronkovaskuler bertambah
Atelektasis
Struktur cincin (ringlike structure)
Dilatasi dan penebalan saluran napas (tram lines)
Mucus plugging finger in glove
Diagnosa pasti : bronkografi masukkan zat
kontras ke saluran nafas ( Daonosil, Lipiodol )
GAMBARAN RADIOLOGIS
239. 1. SILINDRIK
Seringkali dihubungkan dengan kerusakan parenkim
paru, terdapat penambahan diameter bronkus bersifat
reguler, lumen distal bronkus tidak begitu melebar
2. VARIKOSA
Pelebaran bronkus lebih lebar dari bentuk silindrik dan
bersifat irregular. Gambaran garis irregular dan distal
bronkus yang mengembang adalah gambaran khas
pada bentuk varikosa.
240. 3. SAKULER / KISTIK
Dilatasi bronkus sangat progresif ke perifer, bronkus.
Pelebaran bronkus ini terlihat sebagai balon, kelainan ini
biasanya terjadi bronkus yang besar, pada bronkus
generasi ke 4.
247. Sputum 3 lapisan : lapisan atas jernih
,lapisan tengah serous dan lapis bawah keruh
( pus dan cellular debris).
Sebaiknya sputum diambil dari aspirasi
transtrakeal pulasan gram, biakan serta
uji resistensi.
Umumnya dijumpai H. influenza
P. aeruginosa
249. 1. Antibiotika
Diberi bila terjadi perubahan sifat sputum dari
mukoid purulen
Sesuai dengan hasil uji resistensi
2. Bronkodilator
Beta agonist, antikolinergik atau teofilin
Diberi pada pasien dengan gambaran
bronkitis kronis dan obstruksi jalan nafas.
1. PEMBERIAN OBAT-OBATAN
250. 3. Mukolitik dan Ekspektoran
Mengencerkan sekret
Merangsang sekresi dahak dari saluran napas
4.Steroid Inhalasi
Terbukti dalam mengurangi produksi sputum
Menurunkan angka eksaserbasi.
PEMBERIAN OBAT-OBATAN..
251. Mengeluarkan sekret dalam saluran napas
memperbaiki fungsi paru
Cara : latihan napas dan drainase postural
Posisi drainase postural tergantung dari lokasi
segmen yang terkena
2. FISIOTERAPI
252. Pengobatan konservatif yang adekuat
tetap ada keluhan.
Infeksi berulang
Batuk darah berulang masif
Operasi : segmentektomi, lobektomi
atau pneumonektomi.
Transplantasi paru
3. PEMBEDAHAN
259. SOAL UKDI
Laki-laki berusia 67 tahun datang ke RS dengan
keluhan utama batuk berdahak. Hal ini dialami Os sejak
4 hari yang lalu. T 37,5 C. Pada foto thoraks, didapati
gambaran Honey Bee dan air fluid level pada segmen
inferior paru. Diagnosanya adalah?
A. Pneumonia
B. Bronkiektasis
C. Bronkitis
D. Bronkitis kronik
E. TB milier
260.
261. Chronic Recurrent Cough and
Childhood Asthma
Helmi Lubis
Ridwan M. Daulay
Wisman Dalimunthe
Rini S. Daulay 1
262. Definition of cough
a sudden explosive expiratory maneuver
that tends to clear materials from the
airways and prevent aspiration of food or
fluid
2
264. Cough Model Reflex
Voluntary control
of cough
Placebo effect
Exogenous opioids
Endogenous
opioids
Cough control
centre
Respiratory area of brainstem
+ve -ve
Cerebral cortex
Vagus nerve
Sensation of
irritation
Airway irritation Respiratory muscles
COUGH 4
Widdicombe J. Cough. Blackwell publishing 2003; 20
265. Cough Reflex Arc
Vagal nerve
Trigeminal, Facial
Hippoglosus nerve, etc
Diaphragm;
Intercostal,
Abdominal & lumbal
muscles
Respiratory tract muscles
Muscles involve in
respiration
Cough center Efferent Efector
Muscle,
Larynx, trachea,
and bronchus
Afferent
Vagal nerve
branch
Distributed evenly
in medulla near by
the respiratory
center:
Under the higher
control center
Receptor
Larynx
Trachea
Bronchus
Ear
Gastric
Nose
Sinus paranasal
Trigeminal nerve
Nerve Phrenicus,
Intercostal &
lumbaris
Pharynx
Glossopharyngeal
nerve
Pericardium
diaphragm
Nerve phrenicus
5
Chang AB. Cough 2003;7:1-15.
266. How do we cough ?
Inspiratory ExpiratoryCompressive
Deep inspiration
(150-200% tidal
volume)
Maximal dilation of
tracheo-bronchial tree
Glottic closure 0.2’
Contraction of
thoracic & abdminal
muscles vs fixed
diaphragm
Intrathoracic
pressure
Expiratory muscles
contraction
Sudden glottic
opening
Explosive release of
intrathoracic air
Cloutier MM: Cough, in : Loughlin GM ed Resp dis in children, 1994
Inspiratory muscles contraction
267. 7
Figure 1. Diagrammatic representation of the changes of the following variables during
a representative cough: flow rate, volume, subglottic pressure and sound level.
McCool FD. Chest 2006;129:48S-53S.
1 2 3
0
10
20
30
40
50
cmH2O
L/s
0.0
Air
volume
Subglottic
pressure
Flow rates
1.0
2.0
3.0
4.0
5.0
6.0
positive
Flow phase
Min flow
phase
Negative
Flow phase
Inspiratory
phase
glottis
closure
Expiratory phase
(explosive)
Sound
Mechanism of Cough
268. 8
IPS(IDAI): Chronic Recurrent Cough or
(Batuk Kronik Berulang / BKB)
Chronic: > 2 weeks AND/OR
Recurrent: > 3 episodes in 3 months
BKB is not a final diagnosis, but lead to
a group of diseases with the same
manifestation
277. Asthma medication, function category
Reliever
• To relieve / reduce
symptoms and/
attack
• As needed use
• Bronchodilators
• 2-agonist,
xanthenes, systemic
steroid
• Oral, inhalation,
injection
Controller
• To control / prevent
symptoms and/
attack
• Long term use
• Anti-inflammations
• Inhaled steroid, ALTR
• Oral, inhalation,
• For FEA & PA, not for
IEA
278. Acute asthma management
Asthma attack / symptoms present:
– First line therapy
• 2 agonist
• Ipratropium bromide
Chronic asthma (long term management):
– First line therapy
• Inhaled steroid
• Long-acting 2 agonist (LABA)
285. Estimation of severity of asthma attack
Sign/
Symptom
Mild Moderate Severe Imminent
respiratory
arrest
Activities
(infant)
Walking
(loudly cried)
Talking
(weak cried)
Rest
(stop eating)
Talking Complete
sentences
Phrasesor or
partial
sentences
Single words
or short
phrases
Position Can lie
down
Prefer to seat Tripod-like
sitting
positions
Alertness Maybe agitated Usually
agitated
Usually
agitated
Confused
Cyanotic Absent Absent Present
Wheezing Moderate,
end of eksp.
Loud, eksp. +
insp.
Audible Difficult/ can’t
be heard
Breathing
difficulties
Minimal Moderate Severe
286. Acessory
Muscle of
respiration
Usually not Usually yes Yes Paradoxical
movement
Retraction No intercostal
to mild
retraction
Moderate +,
tracheosterna
l retraction
Deep +, +,
nassal flaring
Decrease/
none
Respiratory
rate
Tachypnea Tachypnea Tachypnea Decreasing
Pulse rate Normal Tachycardia Tachycardia Bradicardia
Pulsus
paradoxus
Absent
(<10 mmHg)
Present
10-20 mmHg
Present
>20 mmHg
absent
(Fatique resp.
muscle)
PEF / FEV1
- pre-b.dilat.
- post-b.dilat
(% predictive-
>60%
>80%
value/ % good
40-60%
60-80%
-value)
<40%
<60%
SaO2 >95% 91-95% <90%
PaO2 Normal >60 mmHg <60 mmHg
PaCO2 <45 mmHg <45 mmHg >45 mmHg
287. Algorithms asthma attack
Clinic/ ER
Rate attack severity
First management
• 2-agonist nebulization (neb) 3x, 20’ interval
• 3rd neb + anticholinergic
Moderate attack
(neb 2-3x,
partially response)
• Give O2
• Reevaluate moderate
One day care (ODC)
• IV line
Mild attack
(neb 1x,
good response
• Hold out 1-2 hours,
may go home
• Attack reappear
moderate attack
Severe attack
(neb 3x,
bad/ no response)
• O2 since beginning
• IV line
• Chest X ray
• Reevaluate→severe
→hospitalized
288. One Day Care (ODC)
• O2 continued
• gGve oral steroid
• Neb every 2 hrs
• Improve in 8-12 hrs,
stable may go home
• No improve within 12 hrs,
hospitalized
Hospital Room
• O2 continued
• Overcome dehidration
and acidosis
• IV steroid every
6-8 hrs
• Neb every 1-2 hrs
• IV aminophylline, initial-
maintenance
• Improve neb every 4-6hrs
• Stable within 24 hrs,
may go home
• No improvement,
impending resp failure -
PICU
May go home
• Give 2-agonist
(inhalation / oral)
• Patient with
controller, continued
• Viral ARI as trigger
steroid oral may given
• Visit outpatient clinic
in 24 hours
Note:
• severe attack from beginning, directly neb with
ipratropium
• neb can be replaced by adrenalin sc 0.01 ml/kgBw/x,
max 0.3ml/x
• O2 2-4L/mnt from the start, including during neb
289. Goals of management for
asthma attack
• Relieve the symptoms quickly and
precisely
• Reduce hypocxemic
• Lung function, back to normal
• After attack: reevaluation
292. Severe Attack
• No/ bad response after nebulization
• Oxygen
• Parenteral, rehidration, acidosis
correction
• Steroid IV
• lnitial Aminophylline IV,
then the maintenance
• Nebulization
• Chest X-ray
• Good: May Go Home
• No/ bad response: Intensive Care
293. Oxygen
• Must be given in severe attack
• In severe attack, hypocxemic
294. Nebulization (severe attack)
• β2 agonist and ipratropium bromide vs
β2 agonist alone better result:
– Decreased of hospitalization rate
– Decreased of symptom scoring
– Improve lung functions
– Drugs duration of action, longer
295. Combination of salbutamol and ipratropium bromide
• The use of ipratropium alone, more inferior then 2 agonist
slow onset of action
• Combination use with 2 agonist:
– Onset of action, faster
– Prolong effect bronchodilatation
masih kontroversi
Watson, 1988 : if large airway is involved
Rubin, 1996 : not routine in the beginning
of attack
296. ß2 agonist + ipratropium bromide
• Not acceptable yet for
-Mild asthma attack
-Moderate asthma attack
• Already acceptable
- Severe asthma attack
297. IVFD
• Redehidration
– Drink less due to breathing difficulties
– vomiting
• Acid-base and electrolyte correction
• Give parenteral medication
299. Aminophylline
• Initial, 6-8 mg/kgBW/IV for 10-20 minutes
• Maintenance, 0,5-1 mg/kgBW/hours
• Need aminophylline plasma level
monitoring
• Be careful, narrow margin of safety
300. Use of other medication
• Adrenaline, there is maximal dose, effect
on and
• Salbutamol SC, have to be careful
• MgSO4, no signiffican
• Steroid inhaler, very high dose
(1600-2000 g)
• Antibiotic, not use
• Mucolitic, not suggest for severe attack
302. Classification of disease
Clinical parameter ,
And lung function
Infrequent episodic
asthma
Persistent asthma
Frequent episodic
asthma
Freq of attacks < 1x /month Daily> 1x /month
Duration of attacks < 1 week Daily>1 week
Between episodes No symptoms
Frequent nocturnal
symptoms
Symptoms (+)
Sleep and activity Normal AffectMay affect
Physical exam Normal AbnormalMay affect
Controller No need Steroid/combinationSteroid/combination
Lung function
(No attacks)
PEF/FEV1 >80%
PEF/FEV1 <60%
Variability 20-30%
PEF/FEV1 60-80%
Variability (attacks) >15% > 50%> 30%
42
303. Evolving treatment options
1975
1980
1985
1990 1995
2000
Large use of
short-acting
ß2-agonists
“Fear” of
short-acting
ß2-agonists
Single
inhaler therapy
(Symbicort®)
ICS treatment
introduced
1972
Adding
LAßA to ICS therapy
Kips et al, AJRCCM 2000
Pauwels et al, NEJM 1997
Greening et al, Lancet 1992
Bronchospasm Inflammation Remodelling
43
304. Goal of asthma management
• Minimal (ideally no) chronic symptoms
• Minimal (infrequent) exacerbations
• No emergency visits
• Minimal (ideally no) use of as needed ß2-
agonist
• No limitations on activities (exercise)
• (Near) Normal lung function
• Minimal (or no) adverse effects from medicine44
314. Infrequent episodic asthma
• No daily medication
• Treatment of exacerbations depend on
severity of attacks
• -2 agonist as needed
54
315. Frequent episodic and persistent
asthma
• Controller medications: every day
• Corticosteroid with or without any drugs
• Combination with LABA, TSR, ALT
• Gradual reduction if stable in 6-8 weeks
55
317. Long-term placebo-controlled trial of ketotifen in the
management of preschool children with asthma
Loftus BG, Price JF
J Allergy Clin Immunol 1987; 79:350-5
The results suggest that:
“Ketotifen has no place in the management
of young children with frequent asthma”
57
318. Inhaled disodium cromoglycate (DSCG) as
maintenance therapy in children with asthma:
a systematic review.
Tasche MJA, Uijen JHJ, Bernsen RMD, de Jongste JC, van der Wouden JC.
Thorax 2000; 55:913-20
“Insufficient evidence that DSCG has a
beneficial effect as maintenance treatment
in children with asthma”
58
319. Low dose steroid
Medium dose
steroid
Low dose
steroid + LABA
Low dose
steroid + ALTR
Low dose
steroid +TSR
High dose
steroid
Medium dose
steroid + LABA
Medium dose
steroid + ALTR
Medium dose
steroid + TSR
ORAL
STEROID
Longterm
management
59
320. Corticosteroids
• The most effective anti-inflammatory
medications
• Improving lung function
• Airway hiperresponsiveness:
• Reducing symptoms
• Frequency and severity of
exacerbations:
• Improving quality of life
60
326. CS + LABA Vs CS double dose
• Increases in PEF and FEV1
• Similar improvements in asthma
symptoms
• Similar in use of rescue medications
• Similar adverse event
• Similar in sputum markers of airway
inflammation Am J Respir Crit Care Med 2000; 161:996-1001
Eur Respir J 2001; 18:262-8
Pediatr Pulmonol 2002; 34:342-50 66
328. Corticosteroids and LABA improves quality
of life of school-age children with asthma
*p<0.01 vs baseline
†p<0.05 vs placeboIncreased
functional status
Decreased
functional status
MeanFSIIR
score
Mahajan et al. Pediatr Asthma Allergy Immunol 1998
0
Chronically
ill children
Well children
80
90
100
0 12
Time (weeks)
84
Placebo
Salmeterol 50 µg bid
*
*
*
*
*
207 children, 57% receiving inhaled corticosteroids
FSIIR, functional status IIR
† †
68
330. Positive impact of inhalation therapy
• Quality of life
• Quality of therapy
• Quality of life
• Quality of therapy
INHALATION
ORAL
Patient
FamilyFinancial
• To another doctor
• Go abroad
(Low performance
of Indonesian
pediatricians )
Stable asthma
Patient Get Patient
-
70
332. Pharmacology of
Asthma
AZL & YSP
Dept. Pharmacology & Therapeutic,
School of Medicine
Universitas Sumatera Utara
Mei 2008, KBK, Respirasi, FK USU, Medan
334. Pathologic Findings
• Bronchoconstriction
• Hyperinflation of the
lungs
• Hyperplasia of the
smooth muscle
surrounding the bronchial
and bronchiolar walls
• Thickening of the
basement membrane
• Mucosal edema
DesJardin, T, Burton, G: Clinical Manifestations and Assessment of Respiratory Disease. St. Louis, Mosby, 1995
338. General Goals of Asthma Therapy
• Relief airways tightening / bronchoconstriction
immediately.
• Education of asthma management.
• Prevent chronic symptoms and asthma
exacerbations during the day and night
• Maintain normal activity levels
• Have normal or near-normal lung function
• Have no or minimal side effects while receiving
optimal medications
345. -Agonists
• Mechanism of Action -relax smooth muscle
within the airways, causing bronchodilation.
• Short Acting
– Salbutamol (Various Brands)
– Levalbuterol (Xopenex)
– Biltolterol (Tornalate)
– Pirbuterol (Maxair)
– Isoproternol (Medihaler-Iso)
– Metaproternol (Alupent)
– Terbutaline (Brethaire)
• Long Acting
– Salmeterol (Serevent)
– Formoterol (Foradil)
346. Classification of agonists
Beta Agonists
Short acting
Generic name Duration of action 2-selectivity
Salbutamol 4-6 h +++
Levalbuterol 8 h +++
Metaproterenol 4-6 h ++
Isoproterenol 3-4 h ++
Epinephrine 2-3 h -
Long acting
Salmeterol 12+ h +++
Formoterol 12+ h +++
2 agonists were developed through substitutions in the catecholamine structure of norepinephrine
(NE). NE differs from epinephrine in the terminal amine group, and modification at this site confers
beta receptor selectivity; further substitutions have resulted in 2 selectivity. The selectivity of 2
agonists is obviously dose dependent. Inhalation of the drug aids selectivity since it delivers small
doses to the airways and minimizes systemic exposure. agonists are generally divided into short
(4-6 h) and long (>12 h) acting agents.
347. Beta-2 Adrenergic Agonists –
Short acting agents
• Mode of administration
– Inhaled/Parenteral
• Modes of action
– Relax airway smooth muscle
– Enhance mucociliary clearance
– Decrease vascular permeability
– May modulate mediator release from mast
cells and basophils
348. • Role in therapy
– Medication of choice for treatment of acute
exacerbations of asthma and useful in the
pretreatment of exercise-induced
bronchospasm (EIB)
– Used to control episodic bronchoconstriction
• Increased used – or even daily use of these agents
is a warning of deterioration of asthma and
indicates the need to institute or to intensify regular
anti-inflammatory therapy.
Beta-2 Adrenergic Agonists –
Short acting agents
349. Side Effects
• Tremor
• Papitations and tachycardia
• Headache
• Insomnia
• Rise in blood pressure
• Nervousness
• Dizziness
• Nausea
Beta-2 Adrenergic Agonists –
Short acting agents
350. Salbutamol
• Mainstay of Therapy for Many Years
• Characteristics
– Dosing –every 4-6 hours
– Dosage Forms
• MDI (HFA), Unit Dose Vials for Nebulizers, Oral
Solutions, Oral Tablets
– Advantages- quick action, “rescue therapy”
– Side Effects/Problems
• The most common side effects are heart
palpitations, irregular, rapid heartbeat, anxiety, and
increased blood pressure.
352. Anticholinergic Bronchodilators
• Mode of administration
– Inhaled
• Mechanisms of action
– Block the effects of acetylcholine released from
cholinergic nerves in the airways (i.e., reduce intrinsic
vagal cholinergic tone to the airways).
– Block reflex bronchoconstriction caused by inhaled
irritants
– They do not diminish the early and late allergic
reactions and have no effect on airway inflammation.
– Less potent bronchodilators than inhaled beta-2
agonists, and in general, have a slower onset of
action (30-60 min to maximum action).
353. Anticholinergic Bronchodilators
• Role in therapy
– Additive effect when nebulized together with a
rapid-acting beta-2 agonist for exacerbations
of asthma
– It is recognized that Ipratropium can be used
an alternative bronchodilator for patients who
experience adverse effects such as
tachycardia, arrhythmias, and tremors from
beta-2 agonists.
• Side effects
– Dryness of the mouth and bitter taste
357. Inhaled Glucocorticoids
• Mechanisms of action
– Reduces pathologic signs of airway
inflammation mediated in part by inhibition of
production of inflammatory cytokines
– Airway hyperresponsiveness continues to
improve with prolonged treatment
• Role in therapy
– Most effective anti-inflammatory medication
for the treatment of asthma
358. Inhaled Glucocorticoids
• Side effects
– Local adverse effects include oropharyngeal
candidiasis, dysphonia, and occasional coughing from
upper airway irritation.
– Because there is some systemic absorption, the risks
of systemic adverse effects will depend on the dose
and potency of the Glucocorticoids as well as its
bioavailability, absorption in the gut, metabolism by
the liver, and the half-life of its systemically absorbed
fraction.
• Contraindication:
– hypersensitivity, nasal infection and haemorrhage,
candidiasis orofaring, and patient with recurrent
epistaxis.
360. Systemic Glucocorticoids
• Mode of administration
– Oral
– Parenteral
• Mechanisms of action
– Same as for inhaled Glucocorticoids however
systemic Glucocorticoids may reach different
target cells than inhaled drugs
• Role in therapy
– Long-term oral Glucocorticoids therapy (daily
or alternate-day) may be required to control
severe persistent asthma.
361. Systemic Glucocorticoids
side effects
– Osteoporosis
– Arterial hypertension
– Diabetes
– Hypothalamic-pituitary
axis suppression
– Cataracts
– Glaucoma
– Obesity
– Skin thinning leading
to cutaneous striae
– Easy bruising
– Muscle weakness
– Fatal herpes virus
infections have been
reported among
patients who are
exposed to these
viruses when they are
taking systemic
Glucocorticoids
363. • Modes of administration
– Inhaled
– Oral
• Mechanisms of action
– Same as short-acting beta-2 agonists
– Effects persists for at least 12 hours
Adrenergic Bronchodilators –
Long-Acting Agents
364. • Role in therapy
– Long-acting inhaled beta-2 agonists should be
considered when standard introductory doses of
inhaled Glucocorticoids fail to achieve control of
asthma before raising the dose of inhaled
Glucocorticoids.
– Because long-term treatment with these agents does
not appear to influence the persistent inflammatory
changes in asthma, this therapy should be combined
with inhaled Glucocorticoids
• Fluticosone propionate – salmeterol and bedesonide-
formoterol inhalers (Advair®)
Adrenergic Bronchodilators –
Long-Acting Agents
365. • Side effects
– Inhaled beta-2 agonists cause fewer systemic
adverse effect (e.g., cardiovascular
stimulation, skeletal muscle tremors, and
hypokalemia) than oral therapy particularly if
the oral regimen includes theophylline.
Adrenergic Bronchodilators –
Long-Acting Agents
366. Salmeterol
• Dosing - every 12 hours
• Dosage Forms
– MDI, Discus (powder), combination with steroid
• Advantages
– long acting, less tolerance to effects than
salbutamol- decreases need to increase
corticosteroid dose
• Side Effects/Problems
– Slow onset of effect
– Headache, tremor, palpitations, and
nervousness are the most frequent side
effects.
367. Formoterol
• Dosing every 12 hours
• Dosage Forms –aerosolized powder
– Similar to Spinhaler (drug in gelatin capsule)
• Advantages
– has both a rapid-onset bronchodilator is long-
acting but not as a rescue medicine
• Side Effects/Problems
– The most common side effects are headache,
palpitations, and tremor.
– Less common side effects include agitation,
restlessness, sleep disturbance, muscle
cramps, and increased heart rate
369. Methylxanthines
• Mode of administration
– Oral or Parenteral
• Mechanisms of action
– The bronchodilator effect may be related to phosphodiesterase
inhibition (>10mg/L);
– anti-inflammatory effect is due to an unknown mechanism and
may occur at lower concentrations (5-10mg/L).
• This latter mechanism may involve the inhibition of cell surface
receptors for adenosine, which modulate adenylyl cyclase activity
(contraction of isolated smooth muscle and to provoke histamine
release from mast cells.
– Most studies show little or no effect on airway
hyperresponsiveness
• Role in therapy
– Sustained release theophylline is effective in controlling asthma
symptoms and improving lung function (i.e., nocturnal symptoms;
may be used as an add-on therapy to low or high doses of
glucocorticoids)
370. Methylxanthines
• Side effects (serum concentrations > 15µg/mL)*
– Gastrointestinal symptoms – nausea, vomiting
– CNS – Seizures
– Cardiovascular – tachycardia, arrhythmias
– Pulmonary – stimulation of the respiratory
center
*Monitoring theophylline levels is advised when high-dose
therapy (>10mg/kg body weight is used or when a
patient develops an adverse effect on the usual dosage
371. Mast Cell Stabilizing Agents
• Mechanism of Action:
– inhibit the activation of mast cells within the airway, thereby
preventing release of mediators that provoke asthma symptoms.
– alter the function of delayed chloride channels in the cell
membrane
– considered by some as a type of NSAID.
• Used for preventing asthma attack
• Advantages:
– As the prophylaxis of asthma attack caused by allergen,
exercise, aspirin, and working.
– Used for long term medication
• Disadvantages:
– Using dosage four times a day
– Expensive
– Less effectivity than inhaled corticosteroid
– side effects: throat iritation, cough, dry mouth, and bad taste of
tongue.
372. Cromolyn & Nedocromil
–Dosing QID
–Dosage Forms – MDI or
Nebulized solution (Cromolyn)
–Advantages - alternative to
steroids/-agonists
–Side Effects/Problems
• Daily dosing required (works
prophylactically)
• Cromolyn (throat irritation or
dryness, wheezing, nausea,
coughing, and a bad taste in the
mouth).
• Nedocromil (bad taste, nausea,
abdominal pain, and vomiting).
373. Leukotriene modifiers
Zafirlukast, Montelukast, and Zileuton
• A relatively new class of
anti-asthma drugs that
include
– cysteinyl leukotriene 1
(CysL T1) receptor
antagonists
• (montelukast, zafirlukast)
and
– 5-lipoxeygenase inhibitor
• (zileuton)
374. Leukotriene modifiers
• Mode of administration
– Oral
– Using dosage four times a day (Zileuton)
• Mechanism of action
– Receptor antagonists block the CysLT1
receptors on airway smooth muscle and thus
inhibit the effects of cysteinyl leukotrienes that
are release from mast cells and eosinophils
– 5-lipoxygenase inhibitors block synthesis of
leukotrienes.
375. Leukotriene modifiers
• Role in therapy
– These agents have a small and variable
bronchodilator effect, reduce symptoms,
improve lung function, and reduce asthma
exacerbations.
– Effect of these drugs is less than that of low-
doses of inhaled glucocorticoids. There is
evidence that the use of these drugs as an
add-on may reduce the dose of inhaled
glucocorticoid required by patients with
moderate to severe asthma.
• Note that leukotriene modifiers are less effective than long-
acting inhaled beta-2 agonists as an add-on therapy.
376. Leukotriene modifiers
• Side effects
– These drugs are usually well tolerated, and
few if any class-related effects have been
recognized.
• Zileuton has been associated with liver toxicity and
monitoring liver test is recommended
• There are several reports of Churg-Strauss
syndrome associated with the leukotriene modifier
therapy (typically associated with a reduction of
systemic glucocorticoids)
• Contraindication:
patients with coronary heart disease, and
cardiac arrhythmias.
377. IgE Antibody
Omalizumab
• Used as intravenous or intramuscular anti-asthma.
• diminishing the production of IgE through effects on
interleukin 4 or on IgE itself have been evaluated
– Soluble recombinant IL-4 receptor that can be delivered by
aerosol
– Recombinant human monoclonal antibody that forms
complexes with free IgE (rhuMAb or omalizumab blocks the
interaction of IgE with mast cells and basophils.
• Attenuates the early-phase and late phase airway obstruction
response to allergen and suppressed the accumulation of
eosinophils in the airways
• Advantages:
- Decreasing the degrees of asthma
- Reducing the used of corticosteroid
- Repaired nasal symptoms for patients
with allergic rhinitis.
• Disadvantage:
→ very expensive
382. Is there an advantage to
using a nebulizer, as
opposed to an MDI, for
delivery of medications
for the treatment of
asthma?
383. Studies comparing Nebulizers
to MDIs with Spacers
• Chou KJ, et al. Metered-Dose Inhalers with
Spacers vs Nebulizers for Pediatric Asthma.
Arch Ped Adol Med 149:201-5,1995.
• Nebulized beta-agonist therapy had been the
standard of care for patients with acute asthma
exacerbations. Several studies in adults,
however, have found metered dose inhaler
(MDI) administration to be as effective.
• Use of the MDI instead of nebulizer
administration would be economically
beneficial and easier for both patients and
clinicians.
386. Clin Exp Allergy. 29 Suppl 3:98-104,1999.
• Effectiveness of H1 antagonists in
adults with “seasonal” asthma
387. • Conclusions of Analyses
• severe persistent asthma
– no significant clinical effect
• moderate persistent asthma
– clinical benefits of H1 antagonists are apparent but
require higher-than-usual doses and are not worth the
risk to patient
• mild seasonal asthma and allergic rhinitis
coexistant
– significant improvement in asthma symptoms at usual
dosing
Clin Exp Allergy. 29 Suppl 3:98-104,1999.
