All About Respiratory

Respiratory System
Fakultas Kedokteran
Universitas Pelita Harapan
Author:
Kevin
Vice Executive Board of Academic Division
Member of SECRET Training Division
Member of HMFK Logistic Division
Mentor Faculty of Medicine Universitas Pelita Harapan

All About Respiratory System Kevin - 00000008132
Respiratory System
WEEK OBJECTIVES – Week 1
1. Describe the embryological development of the lung and the diaphragm.
2. Describe the structure anatomy of the lung, the pleura, the relational between chest wall, the
thorax and the mediastinum, lungs and their lobes, the vascular system of the thorax, the vagus
and the phrenic nerves, structure of diaphragm, lymphatic system of the lung.
3. Describe the pressure differences in the chest wall, diaphragm, pleura and airways.
4. Classify two main disorders in the lung.
5. Classify the type and management of pneumothorax.
6. Describe the function of chest tube
7. Explain about lung oedema
Describe the embryological development of the lung and the diaphragm

Formation of the Lung Buds
When the embryo is app 4 weeks old, the lung bud /

respiratory diverticulum appears as an outgrowth from the
ventral wall of the foregut. The appearance and the location of
the lung bud depends on the increase in retinoic acid (RA)
produced by adjacent mesoderm.TBX4 which is upregulated by
an increase in RA promotes formation of the lung bud from the
endoderm of the gut tube. Therefore, the epithelium of the
internal lining of the larynx, trachea, bronchi, and lungs are
endodermal origin. While cartilaginous, muscular, and
connective tissue components of the trachea and lungs are
derived from splanchnic mesoderm.
Initially, the lung bud is in open communication with the

foregut. When the diverticulum expands caudally, however,
two longitudinal ridges, the tracheoesophageal ridges,
separate it from the foregut. Subsequently, when these ridges
fuse to form the tracheoesophageal septum, the foregut is
divided into a dorsal portion, the esophagus, and a ventral
portion, the trachea and lung buds. The respiratory
primordium maintains its communication with the pharynx
through the laryngeal orifice
Universitas Pelita Harapan | WEEK OBJECTIVES – Week 1 1

Larynx
Larynx originate from endoderm.

4th and 6th are mesenchyme cells that will form cartilages and muscles.
Rapid proliferation of these mesenchyme cells causes the laryngeal orifices to changes in
appearance to a T-shaped opening.
Mesenchyme of the 2 arches will transform into the thyroid, cricoid, and arytenoid cartilages.
Then, laryngeal epithelium also proliferates rapidly and temporarily occluded the lumen.
Vacuolization and recanalization produce a pair of lateral recesses, the laryngeal ventricles.
These recesses are bounded by folds of tissue that differentiate into the false and true vocal
cords.

Musculature of the larynx is derived from mesenchyme of the 4th and 6th pharyngeal arches
and all laryngeal muscles are innervated by branches of the 10th cranial nerve (the vagus
nerve) :
o The superior laryngeal nerve innervates derivatives of the 4th pharyngeal arch
o The recurrent laryngeal nerve innervates derivatives of the 6th pharyngeal arch.
Trachea, Bronchi, and Lungs
Lung bud forms the trachea and 2 lateral outpocketings, the bronchial buds.
At the 5th week, each of these buds enlarges to form right and left main bronchi.
o The right then forms 3 secondary bronchi
o The left then forms 2 secondary bronchi
o Secondary bronchi divide repeatedly in a dichotomous fashion.
Forming 10 tertiary (segmental) bronchi in the right lung
Forming 8 tertiary (segmental) bronchi in the left
Creating the bronchopulmonary segments of the adult lung.
o By the end of the 6th month app 17 generations of subdivisions have formed
o Before the bronchial tree reaches its final shaped, an additional six divisions form
during postnatal life.
Branching is regulated by
epithelial-mesenchymal
interactions between the
endoderm of the lung buds and
splanchnic mesoderm that
surrounds them.
By the time of birth, bifurcation
of the trachea is opposite the
fourth thoracic vertebra.

Growth in caudal and lateral directions, the lung buds expand into the body cavity
The spaces for the lungs, the
pericardioperitoneal canals are narrow and
gradually filled by the expanding lung buds.
Ultimately, the pleuroperitoneal and
pleuropericardial folds separate the
pericardioperitoneal canals from the peritoneal
and pericardial cavities respectively.
The remaining spaces form the primitive pleural
cavities.
The mesoderm which covers the outside of the
lung, develops into the visceral pleura.
The somatic mesoderm layer, converting the
body wall from the inside, becomes the parietal
pleura.
The space between them called pleural cavity.
Maturation of the Lungs
Up to the seventh prenatal month, the bronchioles divide continuously into more and smaller
canals (canalicular phase) and the vascular supply increases steadily. Terminal bronchioles divide to
form respiratory bronchioles and each of these divides into three to six alveolar ducts. The ducts end in
terminal sacs (primitive alveoli) that are surrounded by flat alveolar cells in close contact with
neighboring capillaries. By the end of the seventh month, sufficient numbers of mature alveolar sacs and
capillaries are present to guarantee adequate gas exchange, and the premature infant is able to survive.

During the last 2 months of prenatal life and for several years thereafter, the number of
terminal sacs increases steadily. In addition, cells lining the sacs, known as type I alveolar epithelial
cells, become thinner, so that surrounding capillaries protrude into the alveolar sacs. This intimate
contact between epithelial and endothelial cells makes up the blood–air barrier. Mature alveoli are not
present before birth. In addition to endothelial cells and flat alveolar epithelial cells, another cell type
develops at the end of the sixth month. These cells, type II alveolar epithelial cells, produce surfactant,
a phospholipid-rich fluid capable of lowering surface tension at the air–alveolar interface.
Amount of surfactant increases during the last 2 weeks before birth.

During the 34th week of gestation, some of this phospholipid enters the amniotic fluid and acts
on macrophages in the amniotic cavity, these macrophages migrate across the chorion into the

uterus where they begin to produce immune system proteins, including interleukin-1β results in
increased production of prostaglandins that cause uterine contractions and initiating labor and
birth.
Fetal breathing movements begin before birth and cause aspiration of amniotic fluid, this is
important for stimulating lung development and conditioning respiratory muscles, thus most of
the lung fluid is rapidly resorbed by the blood and lymph capillaries, and a small amount is
probably expelled via the trachea and bronchi during delivery.
When the fluid is resorbed from the alveolar sacs, surfactant remains deposited so that when air
entering alveoli during the first breath, the surfactant coat prevents development of an air-
water (blood) interface with high surface tension.
Although the alveoli increase somewhat in size, growth of the lungs after birth is primarily due
to an increase in the number of respiratory bronchioles and alveoli.
During birth, 1-6th of alveoli has been formed and the remaining alveoli are formed during the
first 10 years of postnatal life.
Describe the structure anatomy of the lung, the pleura, the relational between
chest wall, the thorax and the mediastinum, lungs and their lobes, the vascular
system of the thorax, the vagus and the phrenic nerves, structure of
diaphragm, lymphatic system of the lung
Cek lab manual anatomi click here
LUNG VOLUMES AND CAPACITIES
Basically, a spirometer consists of an air-filled drum floating in a water-filled chamber. As the person
breathes air in and out of the drum through a tube connecting the mouth to the air chamber, the drum
rises and falls in the water chamber. This rise and fall can be recorded as a spirogram, which is calibrated
to volume changes. The pen records inspiration as an upward deflection and expiration as a downward
deflection.

This is a hypothetical example of a spirogram in a healthy young adult male. Generally, the values are
lower for females. The following lung volumes and lung capacities (a lung capacity is the sum of two or
more lung volumes) can be determined.
Tidal volume (TV). The volume of air entering or leaving the lungs during a single breath.
Average value under resting conditions = 500 ml.
Inspiratory reserve volume (IRV). The extra volume of air that can be maximally inspired over
and above the typical resting tidal volume. The IRV is accomplished by maximal contraction of
the diaphragm, external intercostal muscles, and accessory inspiratory muscles. Average value =
3000 ml.
Inspiratory capacity (IC). The maximum volume of air that can be inspired at the end of a normal
quiet expiration (IC = IRV + TV). Average value = 3500 ml.
Expiratory reserve volume (ERV). The extra volume of air that can be actively expired by
maximally contracting the expiratory muscles beyond that normally passively expired at the end
of a typical resting tidal volume. Average value = 1000 ml.

Residual volume (RV). The minimum volume of air remaining in the lungs even after a maximal
expiration. Average value = 1200 ml. The residual volume cannot be measured directly with a
spirometer, because this volume of air does not move into and out of the lungs. It can be
determined indirectly, however, through gas-dilution techniques involving inspiration of a
known quantity of a harmless tracer gas such as helium.
Functional residual capacity (FRC). The volume of air in the lungs at the end of a normal passive
expiration (FRC = ERV + RV). Average value = 2200 ml.
Vital capacity (VC). The maximum volume of air that can be moved out during a single breath
following a maximal inspiration. The subject first inspires maximally, then expires maximally (VC
= IRV + TV + ERV). The VC represents the maximum volume change possible within the lungs. It
is rarely used, because the maximal muscle contractions involved become exhausting, but it is
useful in ascertaining the functional capacity of the lungs. Average value = 4500 ml.
Total lung capacity (TLC). The maximum volume of air that the lungs can hold (TLC = VC + RV).
Average value = 5700 ml.
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; that is,
normally 80% of the air that can be forcibly expired from maximally inflated lungs can be
expired within one second. This measurement indicates the maximal airflow rate that is possible
from the lungs.
Describe the pressure differences in the chest wall, diaphragm, pleura and
airways
There are different pressures included in the process of ventilation:
Atmospheric (Barometric) pressure.

At sea level it equals to 760 mmHg and diminishes with increasing altitude above sea level as the
layer air above earth’s surface correspondingly decreases in thickness.
Intra-alveolar pressure / intrapulmonary pressure
pressure within the alveoli and air quickly flows down its pressure gradient any time intra-
alveolar pressure differs from atmospheric pressure.
Intrapleural pressure / intrathoracic pressure
pressure within the pleural sac and is usually less than atmospheric pressure, averaging 756
mmHg. Intrapleural pressure does not equilibrate with atmospheric or intra-alveolar pressure,
because there is no direct communication between the pleural cavity and either the atmosphere
or the lungs.
The lungs and thoracic wall are held in close apposition by intrapleural fluid’s cohesiveness and a
transmural pressure gradient.
Intra-alveolar pressure (760 mmHg) is greater than the intrapleural pressure (756 mmHg) and so
greater pressure is pushing outward than is pushing inward, therefore pushes out the lungs,
stretching or distending them.

The lungs follow the movement of the chest wall.

Similar transmural gradient exists across the thoracic wall and the atmospheric pressure that is
pushing inward on the thoracic wall is greater than the intrapleural pressure pushing outward
on this same wall, so the chest wall tends to be squeezed in or compressed compared to what it
would be in an unrestricted state.
The intrapleural pressure is subatmospheris because:
1. Due to the lung’s elasticity, it tends to pull inward away from the thoracic wall as they are
stretched to fill the larger thoracic cavity.
2. The compressed thoracic wall tends to move outward away from the lungs.
3. These structures are prevented from separated away by the fluid’s cohesiveness and transmural
pressure gradient except to the slightest degree.
4. Slight expansion of the pleural cavity is sufficient to drop the intrapleural pressure to
subatmospheric level of 756 mmHg.
5. Therefore, a vacuum exists in the infinitesimal space in the slightly expanded pleural cavity not
occupied by intrapleural fluid, producing a small drop in intrapleural pressure below
atmospheric pressure.
Classify two main disorders in the lung

Obstructive lung disease
COPD
Asthma
Bronchiectasis
CF

Characteristics
‘Obstructive pattern’ on PFT’s – see below
Disease mechanisms affect the bronchi and bronchioles, usually in a diffuse pattern across the
whole lung
Obstructive pattern lung disease
Reduced FVC (<80% of normal)
Reduced FEV1:FVC ratio (<70%)
Reduced peak flow
Restrictive Lung Disease
Pulmonary fibrosis
This is caused by disease in the interstitium of the lung – and this is usually an increase in the amount
of tissue in the interstitium of the lung.
The lung x-ray will show increased density of the lung tissue
The lung will be stiff with reduced compliance
Restrictive pattern of lung disease
Reduced FVC
Reduced FEV1

Normal FEV1:FVC ratio
Normal PEFR
Causes of restrictive lung disease
The underlying mechanism is usually fibrosis of the lung. As the normal lung tissue is destroyed it is
replaced by scar tissue, which is interspersed with pockets of air. This often leads the lung to have
a honeycomb like appearance on x-ray.
The main symptoms are SOB and cough.
Common causes
Asbestosis
Radiation fibrosis
Drugs – common ones include amiodarone (anti-arrhythmic) and methotrexate (anti-folate and
anti-metabolite drug – used in cancer and auto-immune diseases)
Rheumatoid arthritis
ARDS – acute respiratory distress syndrome
this is an acute onset syndrome, which present with shortness of breath, bilateral
infiltrates on the CXR and may occur within 48 hours of an acute illness
Mixed Pattern of Disease
Remember also you could see somebody who has both restrictive and obstructive disease – in which
case they would have a mixed pattern of disease:

Classify the type and management of pneumothorax

Types of pneumothorax:
Primary spontaneous pneumothorax

usually occurs in young people and without any lungs problems. It is very rare for this type of
pneumothorax causes tension pneumothorax. It is associated with a higher risk in tall man and is
smoking.
Secondary spontaneous pneumothorax
this type of pneumothorax usually has an underlying pulmonary disease, which is why the
symptoms are usually more severe. Sometimes people with the disease develop hypoxia and
hypercapnia which cause the patient to be confused and coma.
The diseases that can increase the risk of pneumothorax are:
o Disease of the airway : COPD, acute asthma, cystic fibrosis
o Lung infection : Pneumonia, Tuberculosis, necrotizing pneumonia interstitial lung
disease
o Sarcoidosis, idiopathic lung fibrosis, histiocytosis, lymphangioleiomyomatosis (LAM)
connective tissue
o Disease : RA, ankylosing spondylitis, polimyocytosis and dermatomyocytosis, systemic
sclerotic, Marfan syndrome, and Ehlers-Danlos syndrome
o Cancer : lung cancer, sarcoma in the lungs
o Catamenial (interrelated with the menstrual cycle) : endometriosis in the chest
Trauma Pneumothorax
this is a pneumothorax caused by a hole in the chest like shot wound or stabbed wound. This
problem also found in people using the mechanic ventilator.
Tension Pneumothorax
If severe hypoxia occurred even with oxygen therapy, drop of blood pressure or confusion, then
it is considered as an emergency case. This type of pneumothorax also can occurs in people with
mechanic ventilator.
Treatment:

In patient without SOB and no underlying pulmonary disease, the pneumothorax is usually small
and it doesn’t need any treatment since it will gone by itself. But, it is still needed to be checked
by x-ray to ensure repair and this is legal only in pneumothorax <1 cm and limited symptoms.
Water Seal Drainage (WSD)
o Indications:
Pneumothorax
Pleural Effusion
Chylothorax
Empyema
Hemothorax
Hydrothorax
Describe the function of chest tube

A chest tube is a hollow, flexible tube placed into the chest. It acts as a drain.
Chest tubes drain blood, fluid, or air from around your lungs. This allows your lungs to fully
expand.
The tube is placed between your ribs and into the space between the inner lining and the outer
lining of your chest cavity. This is called the pleural space.
Underwater seal bottle
An example is shown below.
The underwater drainage bottle.
The underwater seal bottle is the most important element in pleural drainage. It is essentially an
extension of the chest tube underwater; a low-resistance, one-way valve for the evacuation of pleural
contents.
The underwater seal is a conduit for the expulsion of air and fluid from the chest against minimal
resistance. When intrapleural pressure rises (eg, expiration, coughing), air is forced out of the lungs
through the mouth, and free contents of the pleural space are forced out through the chest tube and
into the underwater seal drainage bottle.[5]

The underwater seal is also an anti-reflux valve. Re-entry of air into the pleural space when intrapleural
pressures become negative (eg, inspiration), is blocked by the underwater seal. Water can be drawn up
the tube only to the height equal to the negative intrathoracic pressure (usually up to -20 cm of water).
Therefore, the apparatus must be kept far enough below the patient to prevent water from being
sucked up into the chest (100 cm is sufficient).[5] The water in this tube is referred to as the "column" of
water; it reflects the changes in intrathoracic pressure with each inspiration and expiration.
The end of the tube in the underwater seal bottle must remain covered with water at all times. When a
broad-based bottle (eg, Tudor-Edwards) and a narrow tube are used, elevation of the water column in
the tube lowers the level in the reservoir by only a very small amount, keeping the seal intact.
The end of the tube must not be kept too far below the surface of water because the resistance to
expulsion of air from the chest is equal to the length of tubing that is underwater. Keeping the tip of the
tube 2-3 cm below the surface of water should be enough to act as a constant valve.[6, 2]
The whole system is placed erect, 100 cm below the level of the patient’s chest. This placement aids
gravity drainage of chest contents into the bottle and prevents reentry of fluid into the chest during the
upward swing of the fluid in the tube during inspiration.[7, 8]
Trap bottle
The trap bottle.
When excessive fluid drains from the chest, the level of fluid in the underwater seal is raised. This
increases resistance to further outflow of fluid from the chest.
To decrease this resistance, a trap bottle is introduced between the chest tube and the underwater seal.
The trap bottle collects the fluid draining out of the chest, while the air passes on to the second bottle.
This keeps the underwater seal at a constant level.[9]

Suction regulator bottle
The suction bottle.
Suction hastens the expansion of the lung. Another bottle is needed to introduce suction regulation to
this system.
The suction regulator bottle has a 3-hole stopcock. Short tubes are passed through 2 of the holes. One
short tube connects to the underwater seal bottle’s vent tube and the other short tube connects to the
suction source. An atmospheric vent runs through the 3rd hole, passing below the level of water in this
bottle.
When suction is applied, air is drawn down the atmospheric vent in this bottle, equal to the pressure
inside the bottle that is decreased by the vacuum. Under stronger vacuum, airflow through the
atmospheric vent commences, and air bubbles through the water in the bottle, but the level of suction
in the bottle remains the same.
This constant level of low pressure suction is now transmitted to the underwater seal bottle and then
into the pleural cavity, thus aiding evacuation of contents there, allowing a quicker reexpansion of the
underlying lung. The maximum force of suction is determined by the depth of the atmospheric vent
underwater in the suction regulation bottle.[2]
To obtain a suction of -20 cm of water, set the tip of the tube 20 cm below the surface of the fluid. Now,
increase the vacuum gradually until air bubbles gently and constantly through the atmospheric vent in
the water during both phases of respiration. A constant pressure of -20 cm of water is now transmitted
to the underwater seal and on to the chest drain.
Explain about lung oedema

I. Cardiogenic
Pathophysiology: Caused by rapid transudation of fluid into lungs secondary to increased pulmonary
wedge pressure without time for compensation of pulmonary bed. Increased wedge pressure translates
to increased pulmonary venous pressure and elevated microvascular pressure, leading to transudation
of fluid (Starling’s forces at work!). Can occur at wedge pressures as low as 18mmHg or not until
>25mmHg if chronic condition has resulted in increased lymphatic drainage capacity.
Etiology:
A. Heart muscle:
1. Systolic dysfunction: Most common cause of pulmonary edema. Can be due to CAD, HTN,valvular
disease, idiopathic dilated cardiomyopathy, toxins, hypothyroidism, viral myocarditis. If condition is
somewhat chronic, volume overload is exacerbated by reninangiotensin system upregulation due to
decreased forward flow.
2. Diastolic dysfunction: Increase in ventricular stiffness impairs filling leading to proximal pressure rise.
Causes include hypertrophic and restrictive cardiomyopathies, ischemia, HTN crises. B. Valvular
problems:
1. Mitral stenosis: usually due to rheumatic heart disease.
2. Aortic stenosis: causes pulmonary edema by requiring elevated LVED filling which translates to
high pulmonary pressures and cardiac ischemia due to impaired diastolic coronary artery filling.
3. Aortic regurgitation: acutely can be seen in infective endocarditis or aortic dissection.
C. Other:
1. Renal artery stenosis: In some cases, pulmonary edema has been the presenting sign of RAS!
2. Atrial myxoma, intracardiac thrombus impeding left atrial outflow track, congenital membrane in
left atrium (cor triatriatum).
Diagnosis:
a). HISTORY and physical exam
b). ECG: Can see ischemic changes consistent with CAD. Can also see negative T waves, global T
wave inversions, and marked QT interval prolongation unrelated to ischemia that resolve within 1-7
days.
c). Echocardiogram
Treatment
1. Supplemental oxygen
2. Diuretics: lasix or other loop diuretics. Dosage should be at least 40mg IV but often higher doses
needed, especially if patient is already on diuretics at home. Peak diuresis in 30minutes. Furosemide
initally causes venodilation prior to onset of diuresis. In chronic CHF can occasionally see transient

arteriolar vasoconstriction and increased blood pressure due to increase in plasma renin and
norepinephrine levels.
3. Morphine: give 2-5 mg over 3 minutes and repeat in 15 minutes if necessary. Decreases patient
anxiety and work of breathing, thereby limiting sympathetic outflow and aiding in arteriolar and
venous dilatation.
4. Vasodilators: nitroglycerin or nitroprusside. Nitroprusside especially helpful for HTN emergency,

acute aortic or mitral regurgitation, acute ventricular septal wall defect.
5. Position: sit patient upright
6. Positive pressure ventilation: decreases venous return and increases pressure gradient between
LV and extrathoracic arteries. To be used with caution as one study showed increased incidence of
deterioration requiring intubation when compared with high dose nitrate group.
II. Noncardiogenic
Definition: Radiographic evidence of alveolar fluid accumulation without elevated pulmonary capillary
wedge pressure.
Pathophysiology: Alveolar-capillary membrane becomes damaged and leaky, resulting in movement of

proteins and water into interstitial space. Note: hypoalbuminemia does NOT cause pulmonary edema.
Etiologies:
A. ARDS (acute respiratory distress syndrome): Multiple etiologies, including sepsis, DIC, inhaled toxins,
radiation pneumonia, inhalation of high oxygen concentrations, severe trauma (thoracic or otherwise).
Often occurs within first 2 hours of inciting event but can occur 1-3 days later. Xray shows bilateral
alveolar filling pattern. Treat underlying cause. High frequency, low volume ventilation with diuresis
proven to be beneficial.
B. Reexpansion pulmonary edema: can occur after reexpansion of pneumothorax or following removal
of large amounts of pleural fluid (>1.0-1.5 L). Can see within 1 hr in 64%. Ongoing for 24-48hr but sx can
last up to 5 days. Pathophysiology unknown but worse in patients with chronic collapse. Supportive
treatment. Mortality has been reported as high as 20%.
C. High altitude pulmonary edema: etiology unclear but thought due to unequal pulmonary
vasoconstriction and overperfusion of remaining vessels. Support patient and move to lower altitudes.
D. Narcotic overdose: From overdose of heroin or methadone. Usually occurs within 2 hours of
injection. Pathophysiology unknown but believed due to direct toxicity, hypoxia, hyperventilation, or
cerebral edema. Supportive measure for patient are indicated.
E. Pulmonary embolism: Treatment aimed at anticoagulation and supportive measures. ***Pulmonary

edema can be confused with diffuse alveolar hemorrhage or lymphangitic spread of cancer. Not all cases

of diffuse alveolar hemorrhage present with hemoptysis, but clues to diagnosis may be in unexplained
hematocrit drop. Lymphangitic spread of tumors most often seen with lymphoma or acute leukemia,
but solid tumors can behave this way. ***
Diagnosis:
a). HISTORY and physical exam
b). ABG can be helpful.
III. Neurogenic
Presentation: hypoxia, tachypnea, diffuse rales, frothy sputum or hemoptysis in setting of neurologic
disorders or procedures. Occurs within minutes to hours of severe CNS insult. Can be confused with
aspiration pneumonitis/pneumonia. Common CNS injuries: epileptic seizures, head injury, cerebral
hemorrhage(subarachnoid or intracerebral). In head injuries, pulmonary edema is seen with elevated
intracranial pressures.
Pathophysiology: likely due to sympathetic activation causing pulmonary venoconstriction and increased
vascular permeability.
Treatment: Supportive measures. Usually resolves within 48-72 hours. Some have tried alpha adrenergic
blockers such as phentolamine but no trials done with this yet.


1. Describe the causes of hypoxemia.
2. Describe the diffusion process of oxygen and carbon dioxide across the alveolar capillary
membrane.
3. Describe pathological feature of specific infection due to Mycobacterium tuberculosis.
4. Describe the special supportive examinations (serological test) for diagnosing tuberculosis.
5. Describe and distinguish the active lesion and the inactive lesion of TB from imaging.
6. Distinguish and describe the pathogenesis of primer tuberculosis (TB) and post primer TB.
7. Describe the principle of Mantoux test.
Describe the causes of hypoxemia

Hypoxemia : reduced oxygenation of arterial blood (reduced PaO2), is caused by respiratory alterations,
whereas hypoxia : reduced oxygenation of cells in tissues, may be caused by alterations of other systems
as well. Although hypoxemia can lead to tissue hypoxia, tissue hypoxia can result from other
abnormalities, such as low cardiac output or cyanide poisoning.
Hypoxemia causes
Mechanism Common Clinical Causes

Decrease in inspired oxygen High altitude
(decreased FiO2) Low oxygen level of gas mixture
Enclosed breathing spaces (suffocation)
Hypoventilation of the Lack of neurologic stimulation of the respiratory center (oversedation,
alveoli drug overdose, neurologic damage)
Defects in chest wall mechanics (neuromascular disease, trauma, chest
deformity, air trapping)
Large airway obstruction (laryngospasm, foreign body aspiration,
neoplasm)
Increased work of breathing ( emphysema, severe asthma)
Ventilation-perfusion Asthma
mismatch Chronic Bronchitis
Pneumonia
Acute respiratory distress syndrome
Atelectasis
Pulmonary Embolism
Alveolocapillary diffusion Edema
abnormality Fibrosis
Emphysema
Decreased pulmonary Intracardiac defects
capillary perfusion Intrapulmonary arteriovenous malformations
Problems with one or more of the major mechanism of oxygenation can cause hypoxemia:
1. Oxygen delivery to the alveoli

a) Oxygen content of the inspired air (FiO2)

b) Amount of alveolar minute ventilation (tidal volume x respiratory rate)

Hypoventilation leads to increase in PACO2 and a decrease in PAO2
2. Ventilation of the alveoli
3. Diffusion of oxygen from the alveoli into the blood
a) Balance between alveolar ventilation and perfusion (V/Q mismatch)
b) Diffusion of oxygen across the alveolocapillary membrane
4. Perfusion of pulmonary capillaries
O2 saturation: PO2:
Severe : <75% Severe : <40

Moderate : 75 – 89% Moderate : 40 – 59
Mild : 90 – 94% Mild : 60 – 79
Describe the diffusion process of oxygen and carbon dioxide across the
alveolar capillary membrane
1) Blood acts as a transport system for O2 and CO2 between the lungs and the tissues, with the
tissue cells extracting O2 from the blood and eliminating CO2 into it.
2) Gases move down partial pressure gradient
3) Atmospheric air is a mixture of gases; total atmospheric pressure 760 mmHg
a) 79% Nitrogen (N2) 600 mmHg
b) 21% Oxygen (O2) 160 mmHg
c) Negligible percentages of CO2, H20 vapor, other gases and pollutants 0.23 mmHg
4) A difference between the capillary blood and the surrounding structures is known as a partial
pressure gradient
5) Alveolar air is not of the same composition as inspired atmospheric air, 2 reasons:
a) Atmospheric air enters the respiratory passages; exposure to the moist airways
saturates it with H2O. Like any other gas, water vapor exerts a partial pressure.
Humidification of inspired air in effect “dilutes” the partial pressure of the inspired gas
by 47 mmHg because the sum of the partial pressure must total the atmospheric
pressure of 760 mmHg.
PH2O = 47 mmHg, PN2 = 563 mmHg, PO2 = 150 mmHg.
b) Alveolar PO2 is also lower than atmospheric PO2 because fresh inspired air is mixed with
large volume of old air that remained in the lungs at the end of the preceding
expiration.
c) Average alveolar PO2 is 100 mmHg compared to the atmospheric PO2 of 160 mmHg
6) Logically, alveolar PO2 would increase during inspiration with the arrival of fresh air and would
decrease during expiration, but only small fluctuations occur, the 2 reasons:
a) Only a small proportion of the total alveolar air is exchanged with each breath, high-PO2
air is quickly mixed with larger volume of retained alveolar air, which has a lower PO2.
Thus, the O2 in the inspired air can only slightly elevate the level of the total alveolar PO2.

b) Yet this slight elevation is diminished by passive diffusion of O2 down it pressure

gradient from alveoli into the blood. The O2 arriving in the alveoli in the newly inspired
air simply replaces the O2 diffusing out of the alveoli into the pulmonary capillaries.
7) Similar situation exists in reverse for CO2, which is continuously produced by the body as a
metabolic waste product and constantly added to the blood, in the pulmonary capillaries, CO2
diffuses down its partial pressure gradient from the body during expiration. As with O2, alveolar
PCO2 remains fairly constant throughout the respiratory cycle but lower value of 40 mmHg.
8. Blood entering pulmonary capillaries is systemic venous blood pumped to the lungs through the
pulmonary arteries. This blood is relatively low in O2 with a PO2 of 40 mmHg, and is relatively
high in CO2 with a PCO2 of 46 mmHg. So that O2 will diffuse to the blood while CO2 will diffuse to
the alveolus.
9. After leaving the lungs, the blood now has a PO2 of 100 mmHg and a PCO2 of 40 mmHg.

10. The extra O2 (40 mmHg) carried in the blood beyond that normally given up to the tissues
represents an immediately available O2 reserve that can be tapped by the tissue cell whenever
their O2 demands increase.
11. The CO2 remaining in the blood even after passage through the lungs plays an important role in
the acid-base balance of the body because CO2 generates carbonic acid, arterial PCO2 is
important in driving respiration.
12. When the tissues metabolize more actively, PO2 even lower than 40 mmHg and when this blood
returns to the lungs, a larger than normal PO2 gradient exists between the newly entering blood
and the alveolar air. Therefore, more O2 diffuses from the alveoli into the blood down the larger
partial pressure gradient before blood PO2 equals alveolar PO2. This additional transfer of O2 into
the blood replaces the increased amount of O2 consumed, so O2 uptake matches O2 use even
when O2 consumption increases. Ventilation is stimulated to that O2 enters the alveoli more
rapidly from the atmosphere to replace the O2 diffusing into the blood.
Factors other than partial pressure gradient influence the rate of gas transfer:
Effect of surface area on gas exchange

o Exercise increased cardiac output open the previously closed capillaries which is
the normally low pressure of the pulmonary circulation is inadequate to keep all the
capillaries open
o Emphysema decreased surface area
Effect of thickness on gas exchange
As the thickness increases, the rate of gas transfer decreases because a gas takes longer to
diffuse through the greater thickness
o Pulmonary edema
o Pulmonary fibrosis
o Pneumonia
The diffusion constant for CO2 is 20 times that of O2 because CO2 is much more soluble in body tissues
than O2 is. The rate of CO2 diffusion across the respiratory membranes is therefore 20 times more rapid
than that of O2 for a given partial pressure gradient. Normally, approximately equal amounts of O2 and
CO2 are exchanged. The time the blood spends in transit in the pulmonary capillaries is decreased as
pulmonary blood flow increases with the greater cardiac output that accompanies exercise. Even when
less time is available for exchange, blood PO2 and PCO2 are normally able to equilibrate with alveolar
levels because of the lung’s diffusion reserves.
Describe pathological feature of specific infection due to Mycobacterium

tuberculosis
Microscopically, the inflammation produced with TB infection is granulomatous, with epithelioid
macrophages and Langhans giant cells along with lymphocytes, plasma cells, maybe a few PMN's,
fibroblasts with collagen, and characteristic caseous necrosis in the center. The inflammatory response
is mediated by a type IV hypersensitivity reaction. This can be utilized as a basis for diagnosis by a TB
skin test. An acid fast stain (Ziehl-Neelsen or Kinyoun's acid fast stains) will show the organisms as
slender red rods. An auramine stain of the organisms as viewed under fluorescence microscopy will be
easier to screen and more organisms will be apparent. The most common specimen screened is sputum,
but the histologic stains can also be performed on tissues or other body fluids. Culture of sputum or
tissues or other body fluids can be done to determine drug sensitivities.
Describe the special supportive examinations (serological test) for diagnosing

tuberculosis
1. Enzyme Linked Immunosorbent Assay (ELISA)
Mendeteksi respons humoral berupa proses antigen-antibodi yang terjadi. Masalah dalam teknik ini
adalah kemungkinan antibody menetap dalam waktu yang cukup lama.
2. ICT (Immunochromatographic Tuberculosis)
uji serologi untuk mendeteksi antibody M. tuberculosis dalam serum. Uji ini merupakan uji
diagnostic Tb yang menggunakan 5 antigen spesifik yang berasal dari membrane sitoplasma M.
tuberculosis, 5 antigen tersebut diendapkan dalam bentuk 4 garis melintang dengan membrane
immunokromatografik (2 antigen di antaranya digabung dalam 1 garis). Apabila serum mengandung
antibody IgG terhadap M. tuberculosis, maka antibody akan berikatan dengan antigen dan
membentuk garis berwarna merah muda. Dinyatakan positif bila setelah 15 menit terbentuk garis
control dan minimal 1 dari 4 garis antigen pada membrane.
3. Mycodot
Mendeteksi antibody antimikobakterial dalam tubuh manusia. Menggunakan antigen
lipoarabinomannan (LAM) yang direkatkan pada suatu alat yang berbentuk sisir plastic. Sisir plastic
ini kemudian dicelupkan ke dalam serum pasien, bila di dalamm serum tersebut terdapat antibody
spesifik anti LAM dalam jumlah yang memadai sesuai dengan aktivitas penyakit, maka akan timbul
perubahan warna pada sisir.
4. Uji peroksidase anti peroksidase (PAP)
mendeteksi reaksi serologi yang terjadi namun perlu hati-hati karena banyak variable yang
mempengaruhi kadar antibody yang terdeteksi
5. Uji serologi yang baru / IgG TB
pemeriksaan dengan cara mendeteksi antibody IgG dengan antigen spesifik untuk Mycobacterium
tebuerculosis dan lebih sering digunakan untuk mendiagnosa TB extraparu, tetapi tidak cukup baik
untuk mendiagnosa TB pada anak. Sensitivitas dan spesifisitas nya dapat ditingkatkan dengan uji IgG
berdasarkan antigen mikobakterial rekombinan seperti 38kDa dan 16kDa dan kombinasi lainnya.
Describe and distinguish the active lesion and the inactive lesion of TB from
imaging
Gambaran lesi TB aktif:
Bayangan berawan/nodular di segmen apikal dan posterior lobus atas paru dan segmen superior
lobus bawah
Kaviti, Bayangan bercak milier
Efusi pleura unilateral (sering) atau bilateral (jarang)

Gambaran lesi TB inaktif:
Fibrotik pada segmen apikal dan atau posterior lobus
Kalsifikasi
Kompleks ranke
Fibrotoraks
Luluh paru
Distinguish and describe the pathogenesis of primer tuberculosis (TB) and

post primer TB
Primary Healing Reduced

Exposure Infection Late Host
(TB Reactivation Immunity
nt :
Local
Progression Secondary
Infection
(TB
Disseminated New
Disease Exposure
(Reinfection)
Tuberkulosis Primer
Tuberkulosis yang masuk melalui saluran napas akan bersarang di jaringan paru sehingga akan terbentuk
suatu sarang pneumoni, yang disebut sarang primer atau afek primer. Sarang primer ini mungkin timbul
di bagian mana saja dalam paru, berbeda dengan sarang reaktivasi.

TB Multiply Gohn Local Regional

enters in lungs focus lymphangi Lympadenitis
airway tis
Kompleks Primer
Spread Heal with Heal w/o

marks marks
Perkontinuitatum Bronkogen Hematogen/Limfogen
Recovery Death
Dari sarang primer akan kelihatan peradangan saluran getah bening menuju hilus (limfangitis local).
Peradangan tersebut diikuti oleh pembesaran kelenjar getah bening di hilus (limfadenitis regional). Afek
primer bersama-sama dengan limfangitis regional dikenal sebagai kompleks primer. Kompleks primer ini
akan mengalami salah satu nasib sebagai berikut:
1. Sembuh dengan tidak meninggalkan cacat sama sekali (restitution ad integrum)

2. Sembuh dengan meninggalkan sedikit bekas (antara lain sarang Ghon, garis fibrotic, sarang
perkapuran di hilus)
3. Menyebar dengan cara:
a. Perkontinuatum
menyebar ke sekitarnya misalnya epituberkulosis, dimana pada penekanan bronkus
yang disebabkan oleh pembesaran kelenjar hilus yang menyebabkan obstruksi lobus
medius yang akhirnya mengakibatkan atelektasi dan bakteri tuberculosis menjalar
sepanjang bronkus yang tersumbat ini ke lobus yang atelectasis dan menimbulkan
peradangan.
b. Bronkogen
ke paru sebelahnya atau tertelan
c. Hematogen dan limfogen
berkaitan dengan daya tahan tubuh, jumlah dan virulensi kuman. Sarang yang
ditimbulkan dapat sembuh secara spontan, akan tetapi bila tidak terdapat imuniti yang
adekuat, penyebaran ini akan menimbulkan keadaan cukup gawat seperti tuberculosis
milier, meningitis tuberculosis, typhobacillosis landouzy. Penyebaran ini juga dapat
menimbulkan tuberculosis pada alat tubuh lainnya, misalnya tulang, ginjal, anak ginjal,
genitalia dan sebagainya. Komplikasi dan penyebaran ini mungkin berakhir dengan:

i. Sembuh dengan meninggalkan sekuele (misalnya pertumbuhan terbelakang

pada anak setelah mendapat ensefalomeningitis, tuberkuloma)
ii. Meninggal
Tuberkulosis PostPrimer
Tuberkulosis postprimer akan muncul bertahun-tahun kemudian setelah tuberculosis primer, biasanya
terjadi pada uusia 15-40 tahun. Tuberkulosis postprimer memppunyai nama yang bermacam-macam
yaitu tuberculosis benruk dewasa, localized tuberculosis, tuberculosis menahun, dan sebagainya.
Tuberkulosis postprimer dimulai dengan sarang dini, yang umumnya terletak di segmen apical lobus
superior maupun lobus inferior. Sarang dini ini awalnya berbentuk suatu sarang pneumoni kecil. Sarang
pneumoni ini akan mengikuti salah satu jalan sebagai berikut:
1. Diresorpsi kembali dengan sembuh tanpa meninggalkan cacat

2. Sarang tersebut akan meluas dan segera terjadi proses penyembuhan dengan penyebukan
jaringan fibrosis. Selanjutnya akan terjadi pengapuran dan akan sembuh dalam bentuk
perkapuran. Sarang tersebut dapat menjadi aktif kemblai dengan membentuk jaringan keju dan
menimbulkan kaviti bila jaringan keju dibatukkan keluar;.
3. Sarang pneumoni meluas, membentuk jaringan keju (karingan kaseosa). Kaviti akan muncul
dengan dibatukannya jaringan keju keluar. Kaviti awalnya berdinding tipis, kemudian dindingnya
akan menjadi tebal (kaviti sklerotik). Kaviti tersebut akan menjadi:
a. Meluas kembali dan menimbulkan sarang pneumoni baru.
b. Memadat dan membungkus diri (enkapsulasi), dan disebut tuberkuloma. Tuberkuloma
dapat mengapur dan menyembuh, tetapi mungkin pula aktif kembali, mencair lagi dan
menjadi kaviti lagi
c. Bersih dan menyembuh yang disebut open helaed cavity, atau kaviti menyembuh
dengan membungkus diri dan akhirnya mengecil. Kemungkinan berakhir sebagai kaviti
yang terbungkus dan menciut sehingga kelihatan seperti bintang (stellate shaped)
Describe the principle of Mantoux test

Skin testing for tuberculosis is useful in countries where the incidence of tuberculosis is low, and the
health care system works well to detect and treat new cases. In countries where BCG vaccination has
been widely used, the TB skin test is not useful, because persons vaccinated with BCG will have a
positive skin test.
The TB skin test is based upon the type 4 hypersensitivity reaction. If a previous TB infection has
occurred, then there are sensitized lymphocytes that can react to another encounter with antigens from
TB organisms. For the TB skin test, a measured amount (the intermediate strength of 5 tuberculin units,
used in North America) of tuberculin purified protein derivative (PPD) is injected intracutaneously to
form a small wheal, typically on the forearm. In 48 to 72 hours, a positive reaction is marked by an area
of red induration that can be measured by gentle palpation (redness from itching and scratching doesn't
count). Reactions over 10 mm in size are considered positive in non-immunocompromised persons.
Repeated testing may increase the size of the reaction (induration), but repeated TB skin testing will not
lead to a positive test in a person not infected by TB. Anergy, or absence of PPD reactivity in persons
infected with TB, can occur in immunocompromised persons, or it may even occur in persons newly
infected with TB, or in persons with miliary TB.
An induration of 5 or more millimeters is considered positive in

HIV-infected persons
A recent contact of a person with TB disease
Persons with fibrotic changes on chest radiograph consistent with prior TB
Patients with organ transplants
Persons who are immunosuppressed for other reasons (e.g., taking the equivalent of >15
mg/day of prednisone for 1 month or longer, taking TNF- antagonists)
An induration of 10 or more millimeters is considered positive in

Recent immigrants (< 5 years) from high-prevalence countries
Injection drug users
Residents and employees of high-risk congregate settings
Mycobacteriology laboratory personnel
Persons with clinical conditions that place them at high risk
Children < 4 years of age
Infants, children, and adolescents exposed to adults in high-risk categories

An induration of 15 or more millimeters is considered positive in any person, including persons

with no known risk factors for TB. However, targeted skin testing programs should only be conducted
among high-risk groups.
Efek Samping OAT

1. Isoniazid (INH)
Efek samping yang berat pada obat ini adalah hepatitis sehingga timbul ikterik, sehingga
pemberian OAT harus dihentikan dan pengobatan sesuai TB pada keadaan khusus. Efek samping
yang ringan dapat berupa kesemuta, tanda-tanda keracunan syaraf tepi, rasa terbakar di kaki
dan nyeri otot yang dapat dikurangi dengan pemberian piridoksin dengan dosis 100 mg perhari
atau dengan vitamin B komples. Kelainan lain adalah syndrome pellagra (menyerupai defisiensi
piridoksin)
2. Rifampicin
Efek yang berat:
o Hepatitis imbas obat atau ikterik
o Purpura, anemia hemolitik yang akut, syok dan gagal ginjal
o Sindrom respirasi yang ditandai dengan sesak napas
Dapat menyebabkan air seni, keringat, air mata dan air liur berwarna merah
Efek yang ringan:
o Sindrom flu berupa demam, menggigil, dan nyeri tulang
o Sindrom perut berupa sakit perut, mual, tidak nafsu makan, muntah kadang-
kadang diare
o Sindrom kulit seperti gatal” kemerahan
3. Pirazinamid
Efek samping utama : hepatitis imbas obat
Nyeri sendi (beri aspirin)
Serangan arthritis gout
Demam, mual, kemerahan dan reaksi kulit yang lain
4. Etambutol
Gangguan penglihatan berupa berkurangnya ketajaman, buta warna untuk warna
merah dan hijau, dapat kembali sendiri setelah beberapa minggu dan sebaiknya tidak
diberikan pada anak karena resiko kerusakan okuler sulit untuk dideteksi.
5. Streptomisin
Kerusakan syaraf ke-8 berkaitan dengan keseimbangan dan pendengaran
o Resiko tersebut dapat meningkat seiring peningkatan dosis
o Meningkat juga pada pasien dengan gangguan fungsi ekskresi ginjal
Telinga mendenging (tinnitus)
Pusing
Kehilangan keseimbangan
Dapat dihilangkan dengan menghentikan pengobatan atau menurunkan dosis 0.25 gr.

Demam yang timbul tiba-tiba disertai sakit kepala

Muntah
Eritema pada kulit
Dapat menembus sawar plasenta sehingga tidak diberikan pada ibu hamil karena dapat
merusak syaraf pendengaran janin.
Pemeriksaan mikroskopik:
Mikroskopik biasa : pewarnaan Ziehl-Nielsen

Mikroskopik fluoresens: pewarnaan auramin-rhodamin (khususnya untuk screening)
lnterpretasi hasil pemeriksaan dahak dari 3 kali pemeriksaan ialah bila :
3 kali positif atau 2 kali positif, 1 kali negatif ® BTA positif

1 kali positif, 2 kali negatif ® ulang BTA 3 kali, kemudian
o bila 1 kali positif, 2 kali negatif ® BTA positif
o bila 3 kali negatif ® BTA negatif

Interpretasi pemeriksaan mikroskopis dibaca dengan skala IUATLD (rekomendasi WHO).
Skala IUATLD (International Union Against Tuberculosis and Lung Disease) :
Tidak ditemukan BTA dalam 100 lapang pandang, disebut negative

Ditemukan 1-9 BTA dalam 100 lapang pandang, ditulis jumlah kuman yang ditemukan
Ditemukan 10-99 BTA dalam 100 lapang pandang disebut + (1+)
Ditemukan 1-10 BTA dalam 1 lapang pandang, disebut ++ (2+)
Ditemukan >10 BTA dalam 1 lapang pandang, disebut +++ (3+)


1. List the major air pollutants and the factors which influences deposition of pollutants within the
respiratory system (particles, ozone, oxides of nitrogen, sulfur oxides, environmental tobacco
smoke, radon, organic dusts, metal fumes)
2. List the sources of exposure to pollutants in the work place.
3. Describe the macroscopic and microscopic pathology of the major types of lung and pleural
cancers- squamous, adenocarcinoma, large cell, small cell carcinoma and pleural mesothelioma.
4. Recognize the clinical and therapeutic implications of Small Cell Carcinoma (SCC) and NonSmall
Cell Carcinoma (NSCC).
5. Describe the clinical procedures to get cells and tissues for the diagnosis of lung cancer.
6. List some of pneumoconiosis which will develop lung cancer.
7. Distinguish lung tumor and mediastinum tumor.
8. Describe the principles of chest radiography, computed tomography, magnetic resonance
imaging and positron emission tomography.
9. Describe how important the cigarette smoke causing lung cancer.
10. Describe the indication of oxygen therapy.
List the major air pollutants and the factors which influences deposition of
pollutants within the respiratory system
Pollutant Sources Effects
Ozone is not created directly,

but is formed when nitrogen Ozone near the ground can
Ozone. A gas that can be found in
oxides and volatile organic cause a number of health
two places. Near the ground (the
compounds mix in sunlight. That problems. Ozone can lead to
troposphere), it is a major part of
is why ozone is mostly found in more frequent asthma attacks in
smog. The harmful ozone in the
the summer. Nitrogen oxides people who have asthma and
lower atmosphere should not be
come from burning gasoline, can cause sore throats, coughs,
confused with the protective layer of
coal, or other fossil fuels. There and breathing difficulty. It may
ozone in the upper atmosphere
are many types of volatile even lead to premature death.
(stratosphere), which screens out
organic compounds, and they Ozone can also hurt plants and
harmful ultraviolet rays.
come from sources ranging from crops.
factories to trees.
Carbon monoxide is released Carbon monoxide makes it hard

when engines burn fossil fuels. for body parts to get the oxygen
Emissions are higher when they need to run correctly.
engines are not tuned properly, Exposure to carbon monoxide
Carbon monoxide. A gas that
and when fuel is not completely makes people feel dizzy and
comes from the burning of fossil
burned. Cars emit a lot of the tired and gives them
fuels, mostly in cars. It cannot be
carbon monoxide found headaches. In high
seen or smelled.
outdoors. Furnaces and heaters concentrations it is fatal. Elderly
in the home can emit high people with heart disease are
concentrations of carbon hospitalized more often when
monoxide, too, if they are not they are exposed to higher

properly maintained. amounts of carbon monoxide.
High levels of nitrogen dioxide

Nitrogen dioxide mostly comes
exposure can give people
from power plants and cars.
coughs and can make them feel
Nitrogen dioxide is formed in two
short of breath. People who are
Nitrogen dioxide. A reddish-brown ways—when nitrogen in the fuel
exposed to nitrogen dioxide for
gas that comes from the burning of is burned, or when nitrogen in
a long time have a higher
fossil fuels. It has a strong smell at the air reacts with oxygen at
chance of getting respiratory
high levels. very high temperatures. Nitrogen
infections. Nitrogen dioxide
dioxide can also react in the
reacts in the atmosphere to form
atmosphere to form ozone, acid
acid rain, which can harm plants
rain, and particles.
and animals.
Particulate matter can be divided

into two types—coarse particles Particulate matter that is small
Particulate matter. Solid or liquid
and fine particles. Coarse enough can enter the lungs and
matter that is suspended in the air.
particles are formed from cause health problems. Some of
To remain in the air, particles
sources like road dust, sea these problems include more
usually must be less than 0.1-mm
spray, and construction. Fine frequent asthma attacks,
wide and can be as small as
particles are formed when fuel is respiratory problems, and
0.00005 mm.
burned in automobiles and premature death.
power plants.
Sulfur dioxide exposure can

Sulfur dioxide mostly comes affect people who have asthma
from the burning of coal or oil in or emphysema by making it
Sulfur dioxide. A corrosive gas that power plants. It also comes from more difficult for them to
cannot be seen or smelled at low factories that make chemicals, breathe. It can also irritate
levels but can have a “rotten egg” paper, or fuel. Like nitrogen people's eyes, noses, and
smell at high levels. dioxide, sulfur dioxide reacts in throats. Sulfur dioxide can harm
the atmosphere to form acid rain trees and crops, damage
and particles. buildings, and make it harder for
people to see long distances.
Outside, lead comes from cars

in areas where unleaded
High amounts of lead can be
gasoline is not used. Lead can
dangerous for small children
also come from power plants
Lead. A blue-gray metal that is very and can lead to lower IQs and
and other industrial sources.
toxic and is found in a number of kidney problems. For adults,
Inside, lead paint is an important
forms and locations. exposure to lead can increase
source of lead, especially in
the chance of having heart
houses where paint is peeling.
attacks or strokes.
Lead in old pipes can also be a
source of lead in drinking water.
Each toxic air pollutant comes Toxic air pollutants can cause
Toxic air pollutants. A large
from a slightly different source, cancer. Some toxic air
number of chemicals that are known
but many are created in pollutants can also cause birth
or suspected to cause cancer. Some
chemical plants or are emitted defects. Other effects depend
important pollutants in this category
when fossil fuels are burned. on the pollutant, but can include
include arsenic, asbestos, benzene,
Some toxic air pollutants, like skin and eye irritation and
and dioxin.
asbestos and formaldehyde, can breathing problems.

be found in building materials

and can lead to indoor air
problems. Many toxic air
pollutants can also enter the
food and water supplies.
CFCs are used in air If the ozone in the stratosphere

Stratospheric ozone
conditioners and refrigerators, is destroyed, people are
depleters. Chemicals that can
since they work well as coolants. exposed to more radiation from
destroy the ozone in the
They can also be found in the sun (ultraviolet radiation).
stratosphere. These chemicals
aerosol cans and fire This can lead to skin cancer and
include chlorofluorocarbons (CFCs),
extinguishers. Other eye problems. Higher ultraviolet
halons, and other compounds that
stratospheric ozone depleters radiation can also harm plants
include chlorine or bromine.
are used as solvents in industry. and animals.
Carbon dioxide is the most

The greenhouse effect can lead
important greenhouse gas. It
Greenhouse gases. Gases that to changes in the climate of the
comes from the burning of fossil
stay in the air for a long time and planet. Some of these changes
fuels in cars, power plants,
warm up the planet by trapping might include more temperature
houses, and industry. Methane
sunlight. This is called the extremes, higher sea levels,
is released during the
“greenhouse effect” because the changes in forest composition,
processing of fossil fuels, and
gases act like the glass in a and damage to land near the
also comes from natural sources
greenhouse. Some of the important coast. Human health might be
like cows and rice paddies.
greenhouse gases are carbon affected by diseases that are
Nitrous oxide comes from
dioxide, methane, and nitrous oxide. related to temperature or by
industrial sources and decaying
damage to land and water.
plants.
Inhalation is the most important route of exposure in the workplace. When particles are in the air, there
is the chance that you will inhale them. How far the particle gets in the air passages of the respiratory
system, and what it does when it is deposited, depends on the size, shape, and density of the particulate
material. The "what happens" also depends on the chemical and toxic properties of the material.
Particles are deposited in the lungs by one of four different ways: interception, impaction,
sedimentation, and diffusion.
Interception: A particle is intercepted or deposited when it travels so close to a surface of the airway
passages that an edge of the particle touches the surface. This method of deposition is most important
for fibres such as asbestos. The fibre length determines where the particle will be intercepted. For
example: fibres with a diameter of 1 micrometre (µm) and a length of 200 µm would be deposited in the
bronchial tree.
Impaction: When particles are suspended in air, they have a tendency to travel along their original path.
When there is a bend in the airway system, for example, many particles do not turn with the air but
rather impact or stick to a surface in the particles' original path. The likelihood of impaction depends on
the air velocity and the particle mass. Typically, most particles greater than 10 µm (aerodynamic
diameter) are deposited in the nose or throat and cannot penetrate the lower tissues of the respiratory
tract. Aerodynamic diameter is the diameter of a spherical particle that has the same settling velocity as
another particle regardless of its shape, size or density. Using aerodynamic diameters allows

occupational hygiene specialists to compare particles of different sizes, shapes and densities in terms of
how they will settle out of the air flow stream.
Sedimentation: As particles travel through air, gravitational forces and air resistance eventually
overcome their buoyancy (the tendency for the particle to stay up). The result is that the particles will
settle on a surface of the lung. This type of deposition is most common in the bronchi, and the
bronchioles. Sedimentation is not an important factor when the aerodynamic diameter of the particle is
less than 0.5 µm.
Diffusion: The random motion of particles is similar to gas molecules in the air when particles are
smaller than 0.5 µm. When particles are in random motion, they deposit on the lung walls mostly by
chance. This movement is also known as the "Brownian motion". The smaller the particle size, the more
vigorous the movement is. Diffusion is the most important mechanism for deposition in the small
airways and alveoli. Very fine particles 001 µm or smaller are also trapped in the upper airway.
Penyakit saluran napas akibat inhalasi debu dipengaruhi oleh :
Faktor debu : kimiawi,bentuk,ukuran partikel, daya larut,konsentrasi dan lama paparan

o > 0,1 -10 mikron : mudah dihirup
o > 5 -10 mikron : tertahan di saluran napas atas
o > 3 – 5 mikron : tertahan di saluran napas tengah
o > 1 – 3 mikron : paling berbahaya krn tertahan dan tertimbun di saluran napas kecil
o < 1 mikron : tidak mudah mengendap
o 0,1 – 0,5 mikron : dengan gerak Brown
Faktor individu : mekanisme pertahanan paru
o Anatomi saluran napas
o Refleks batuk
o Refleks bersin
o Sistem mukosilier
o Sistem fagositosis/makrofag alveolar
Coal Worker Pneumoconiosis
The spectrum of lung findings in coal workers is wide, ranging from asymptomatic anthracosis, in which
pigment accumulates without a perceptible cellular reaction, to simple coal worker’s pneumoconiosis
(CWP), in which accumulations of macrophages occur with little to no pulmonary dysfunction, to
complicated CWP or progressive massive fibrosis (PMF), in which fibrosis is extensive and lung function
is compromised.
Pulmonary anthracosis is the most innocuous coalinduced pulmonary lesion in coal miners and also is
commonly seen in all urban dwellers and tobacco smokers. Inhaled carbon pigment is engulfed by
alveolar or interstitial macrophages, which then accumulate in the connective tissue along the
lymphatics, including the pleural lymphatics, or in lymph nodes.

Simple CWP is characterized by coal macules and the somewhat larger coal nodule. The coal macule
consists of dust-laden macrophages; in addition, the nodule contains small amounts of collagen fibers
arrayed in a delicate network. Although these lesions are scattered throughout the lung, the upper lobes
and upper zones of the lower lobes are more heavily involved. In due course, centrilobular emphysema
can occur. Functionally significant emphysema is more common in the United Kingdom and Europe,
probably because the coal rank is higher than in the United States.
Complicated CWP (PMF) occurs on a background of simple CWP by coalescence of coal nodules and
generally requires many years to develop. It is characterized by usually multiple, intensely blackened
scars larger than 2 cm, sometimes up to 10 cm in greatest diameter. On microscopic examination the
lesions are seen to consist of dense collagen and pigment.
Silicosis
Silicosis is currently the most prevalent chronic occupational disease in the world. It is caused by
inhalation of crystalline silica, mostly in occupational settings. Workers in several occupations but
especially those involved in sandblasting and hard-rock mining are at particular risk. Silica occurs in both
crystalline and amorphous forms, but crystalline forms (including quartz, cristobalite, and tridymite) are
by far the most toxic and fibrogenic. Of these, quartz is most commonly implicated in silicosis. After
inhalation the particles interact with epithelial cells and macrophages. Ingested silica particles cause
activation and release of mediators by pulmonary macrophages, including IL-1, TNF, fibronectin, lipid
mediators, oxygen-derived free radicals, and fibrogenic cytokines. Especially compelling is the evidence
incriminating TNF, since anti-TNF monoclonal antibodies can block lung fibrosis in mice that are given
silica intratracheally. When mixed with other minerals, quartz has been observed to have a reduced
fibrogenic effect. This phenomenon is of practical importance, because quartz in the workplace is rarely
pure. Thus, miners of the iron-containing ore hematite may have more quartz in their lungs than some
quartz-exposed workers and yet have relatively mild lung disease, because the hematite provides a
protective effect.
Silicotic nodules are characterized grossly in their early stages by tiny, barely palpable, discrete, pale-to-
blackened (if coal dust is also present) nodules in the upper zones of the lungs (Fig. 12–19).
Microscopically, the silicotic nodule demonstrates concentrically arranged hyalinized collagen fibers
surrounding an amorphous center. The “whorled” appearance of the collagen fibers is quite distinctive
for silicosis (Fig. 12–20). Examination of the nodules by polarized microscopy reveals weakly
birefringent silica particles, primarily in the center of the nodules. As the disease progresses, the
individual nodules may coalesce into hard, collagenous scars, with eventual progression to PMF. The
intervening lung parenchyma may be compressed or overexpanded, and a honeycomb pattern may
develop. Fibrotic lesions may also occur in the hilar lymph nodes and pleura. Sometimes, thin sheets of
calcification occur in the lymph nodes and are appreciated radiographically as “eggshell” calcification
(e.g., calcium surrounding a zone lacking calcification).
Most patients do not develop shortness of breath until late in the course, after PMF is present. At this
time, the disease may be progressive, even if the person is no longer exposed. Many patients with PMF

develop pulmonary hypertension and cor pulmonale, as a result of chronic hypoxia-induced

vasoconstriction and parenchymal destruction. The disease is slow to kill, but impaired pulmonary
function may severely limit activity. Silicosis is associated with an increased susceptibility to tuberculosis.
It is postulated that silicosis results in a depression of cell-mediated immunity, and crystalline silica may
inhibit the ability of pulmonary macrophages to kill phagocytosed mycobacteria. Nodules of
silicotuberculosis often contain a central zone of caseation. The relationship between silica and lung
cancer has been a contentious issue; crystalline silica from occupational sources is carcinogenic in
humans.
Asbestos
On the basis of epidemiologic studies, occupational exposure to asbestos is linked to (1) parenchymal
interstitial fibrosis (asbestosis); (2) localized fibrous plaques or, rarely, diffuse fibrosis in the pleura; (3)
pleural effusions; (4) lung carcinomas; (5) malignant pleural and peritoneal mesotheliomas; and (6)
laryngeal carcinoma.
PATHOGENESIS
Concentration, size, shape, and solubility of the different forms of asbestos dictate whether inhalation
of the material will cause disease. There are two distinct forms of asbestos: serpentine, in which the
fiber is curly and flexible, and amphibole, in which the fiber is straight, stiff, and brittle. Several subtypes
of curly and straight asbestos fibers are recognized. The serpentine chrysotile accounts for most of the
asbestos used in industry. Amphiboles, even though less prevalent, are more pathogenic than the
serpentine chrysotile, but both types can produce asbestosis, lung cancer, and mesothelioma. The
greater pathogenicity of straight and stiff amphiboles is apparently related to their structure. The
serpentine chrysotiles, with their more flexible, curled structure, are likely to become impacted in the
upper respiratory passages and removed by the mucociliary elevator. Those that are trapped in the
lungs are gradually leached from the tissues, because they are more soluble than amphiboles. The
straight, stiff amphiboles, in contrast, align themselves in the airstream and are hence delivered deeper
into the lungs, where they may penetrate epithelial cells to reach the interstitium. Despite these
differences, both asbestos forms are fibrogenic, and increasing exposure to either is associated with a
higher incidence of all asbestos-related diseases. Asbestosis, like other pneumoconioses, causes fibrosis
by a process involving interaction of particulates with lung macrophages.
In addition to cellular and fibrotic lung reactions, asbestos probably also functions as both a tumor
initiator and a promoter. Some of the oncogenic effects of asbestos on the mesothelium are mediated
by reactive free radicals generated by asbestos fibers, which preferentially localize in the distal lung
close to the mesothelial layer. However, potentially toxic chemicals adsorbed onto the asbestos fibers
undoubtedly contribute to the pathogenicity of the fibers. For example, the adsorption of carcinogens
in tobacco smoke onto asbestos fibers may well be important to the remarkable synergy between
tobacco smoking and the development of lung carcinoma in asbestos workers.
MORPHOLOGY

Asbestosis is marked by diffuse pulmonary interstitial

fibrosis. These changes are indistinguishable from UIP,
except for the presence of asbestos bodies, which are
seen as golden brown, fusiform or beaded rods with a
translucent center. They consist of asbestos fibers coated
with an iron-containing proteinaceous material (Fig. 12–
21). Asbestos bodies apparently are formed when
macrophages attempt to phagocytose asbestos fibers; the
iron is derived from phagocyte ferritin. Asbestos bodies
sometimes can be found in the lungs of normal persons, but usually in much lower concentrations and
without an accompanying interstitial fibrosis.
In contrast with CWP and silicosis, asbestosis begins in the lower lobes and subpleurally, but the middle
and upper lobes of the lungs become affected as fibrosis progresses. Contraction of the fibrous tissue
distorts the normal architecture, creating enlarged air spaces enclosed within thick fibrous walls. In this
way the affected regions become honeycombed. Simultaneously, fibrosis develops in the visceral pleura,
causing adhesions between the lungs and the chest wall. The scarring may trap and narrow pulmonary
arteries and arterioles, causing pulmonary hypertension and cor pulmonale.
Pleural plaques are the most common manifestation of asbestos exposure and are well-circumscribed
plaques of dense collagen (Fig. 12–22), often containing calcium. They develop most frequently on the
anterior and posterolateral aspects of the parietal pleura and over the domes of the diaphragm. They
do not contain asbestos bodies, and only rarely do they occur in persons with no history or evidence of
asbestos exposure. Uncommonly, asbestos exposure induces pleural effusion or diffuse pleural fibrosis.
List the sources of exposure to pollutants in the work place

Many substances found in the workplace can cause breathing problems or lung damage. Some of them
include the following:
Dust from such things as wood, cotton, coal, asbestos, silica and talc. Dust from cereal grains,
coffee, pesticides, drug or enzyme powders, metals and fiberglass can also hurt your lungs.
Fumes from metals that are heated and cooled quickly. This process results in fine, solid
particles being carried in the air. Examples of jobs that involve exposure to fumes from metals
and other substances that are heated and cooled quickly include welding, smelting, furnace
work, pottery making, plastics manufacture and rubber operations.
Smoke from burning organic materials. Smoke can contain a variety of particles, gases and
vapors, depending on what substance is being burned. Firefighters are at an increased risk.
Gases such as formaldehyde, ammonia, chlorine, sulfur dioxide, ozone and nitrogen oxides.
These are associated with jobs where chemical reactions occur and in jobs with high heat
operations, such as welding, brazing, smelting, oven drying and furnace work.

Vapors, which are a form of gas given off by all liquids. Vapors, such as those given off by
solvents, usually irritate the nose and throat first, before they affect the lungs.
Mists or sprays from paints, lacquers (such as varnish), hair spray, pesticides, cleaning products,
acids, oils and solvents (such as turpentine).
Describe the macroscopic and microscopic pathology of the major types of

lung and pleural cancers- squamous, adenocarcinoma, large cell, small cell
carcinoma and pleural mesothelioma
Squamous cell carcinoma
is a malignant epithelial tumor which originates in
epidermis, squamous mucosa or areas of squamous
metaplasia. In skin, tumor cells destroy the basement
membrane and form sheets or compact masses which
invade the subjacent connective tissue (dermis).
In well differentiated carcinomas, tumor cells are
pleomorphic/atypical, but resembling normal
keratinocytes from prickle layer (large, polygonal,
with abundant eosinophilic (pink) cytoplasm and
central nucleus). Their disposal tends to be similar to
that of normal epidermis: immature/basal cells at the periphery, becoming more mature to the centre
of the tumor masses. Tumor cells transform into keratinized squames and form round nodules with
concentric, laminated layers, called "cell nests" or"epithelial/keratinous pearls". The surrounding stroma
is reduced and contains inflammatory infiltrate (lymphocytes).Poorly differentiated squamous
carcinomas contain more pleomorphic cells and no keratinization. (H&E, ob. x10)
Adenocarcinoma
Adenocarcinoma is a malignant neoplasm with glandular differentiation, pneumocyte

phenotype or mucin production
Lung carcinomas are mainly divided into two groups: nonsmall cell (NSCC) and small cell
carcinoma (SCC)
Adenocarcinoma is a type of NSCC arising from the bronchi, bronchioles and alveolar cells with
or without mucin production
o WHO subdivides into mucinous and non-mucinous variants (WHO: WHO Classification
of Tumours of the Lung, Pleura, Thymus and Heart, 4th Edition, 2015)
Adenocarcinoma represents the most common type of lung cancer in females, nonsmokers and
younger males

Based on the new classification, invasive adenocarcinomas with multiple different patterns
should no longer be classified as "mixed adenocarcinoma" and each subtype has to be assessed
and reported semiquantitatively (in 5% increments)
Adenocarcinomas should be classified by the predominant pattern of growth: for example,

tumors displaying largely papillary structures should be classified as "adenocarcinoma papillary
predominant" (J Thorac Oncol 2011;6:244, Pathol Int 2005;55:619, Eur J Cardiothorac Surg
2015 Mar 11 [Epub ahead of print])
Different histologic subtypes in lung adenocarcinomas include lepidic, acinar, papillary,

micropapillary and solid subtypes
o Lepidic pattern is composed of neoplastic cells lining the alveolar lining with no
architectural disruption/complexity, and no lymphovascular or pleural invasion
o Acinar pattern is characterized by glandular formation
o Papillary pattern displays true fibrovascular cores lined by tumor cells replacing the
alveolar lining
o Micropapillary pattern is composed of ill defined projection / tufting with no

fibrovascular cores
Psammoma bodies may be present in papillary and micropapillary variants (Am

J Surg Pathol 1997;21:43, J Thorac Oncol 2011;6:244)
o Solid pattern is defined as solid sheets and nests of tumor
Different histologic subtypes have prognostic significance; lepidic has best prognosis,
micropapillary and solid patterns have more aggressive behavior
Adenocarcinoma in situ: either (a) 3 cm or less or (b) with pure lepidic pattern but no features of
invasion; "bronchioloalveolar carcinoma" is no longer used
o Nearly 100% disease free survival following complete surgical resection (J Thorac Oncol
2011;6:244)
MInimally invasive adenocarcinoma: solitary tumors measuring 3 cm or less with predominantly

lepidic pattern and 5 mm or less invasion in any greatest dimension and in any one focus
Tumors are classified as invasive if they have any of the following features:
o Histologic patterns other than lepidic
o Infiltrating tumor with desmoplastic reaction
o Lymphovascular or pleural invasion

o Necrosis
LARGE CELL CARCINOMA
Gross description
=========================================================================
● Usually peripheral lung; spherical tumor with well-defined borders and bulging, fleshy, homogenous
gray-white cut surface
● No anthracosis
● Frequently involves thoracic wall
Micro description
=========================================================================
● Large polygonal cells and anaplastic cells growing in solid nests without obvious squamous or
glandular differentiation
● Moderately abundant cytoplasm, well defined cell borders, vesicular nuclei, prominent nucleoli

Nondiagnostic immunohistochemical phenotypes of large cell carcinoma (LCC). A–H, A case of LCC
showing basaloid features on H&E-stained slides and with the following immunophenotype: TTF-1–,
CK5+, CK7+, p63+, p40+/–, DSC3–, napsin A– (A, H&E, ×400; B, TTF-1, ×400; C, CK5, ×400; D, CK7,
×400; E, p63, ×400; F, p40, ×400; G, DSC3, ×400; H, napsin A, ×400).I–P, A case of LCC with clear cell
features and the following nondiagnostic immunophenotype: TTF-1–, CK5+, CK7+, p63–, p40–, DSC3–,
napsin A– (I, H&E, ×400; J, TTF-1, ×400; K, CK5, ×400; L, CK7, ×400; M, p63, ×400; N, p40, ×400; O, DSC3,
×400; P, napsin A, ×400).
SMALL CELL CARCINOMA ALSO CALLED OAT CELL CARCINOMA
Gross description
=========================================================================
● Usually central/hilar
● White-tan, soft, friable, extensive necrosis
● Peripheral nodules have fairly well-defined border and fleshy cut surface
Micro description
=========================================================================

● Sheets, ribbons, clusters, rosettes or peripheral pallisading of small to medium sized (2-4x neutrophils)
round/oval cells with minimal cytoplasm, salt and pepper chromatin without prominent clumps,
hyperchromatic, indistinct nucleoli, nuclear molding, smudging, frequent mitotic figures
● Azzopardi phenomena (basophilic nuclear chromatin spreading to wall of blood vessels), indistinct cell
borders
● Stroma is scanty, vascular, delicate
● No glands, replacement of epithelium is less common than subepithelial growth
● Necrosis and apoptotic debris are common
● More cytoplasm is present in cells in metastases or resections than in small biopsies
● May have larger cells with similar morphology, small mixtures of squamous cell carcinoma or
adenocarcinoma (Am J Surg Pathol 2002;26:1184)
● Rarely scattered giant cells, prominent nucleoli
Typical case of small cell carcinoma. Scattergrams show the population of malignant cells to be
CD56+CD45− (A) and cytokeratin+ (B). The arrows denote the malignant population. Cells have
condensed stippled nuclear chromatin and exhibit nuclear molding (C) (hematoxylin-eosin, original

magnification ×200). Immunostains show positivity for AE1/AE3 (D), CD56 (E), and neuron-specific
enolase (F) (all original magnifications ×200)
Mesothelioma
=========================================================================
Malignant mesothelioma arises from mesothelial lining of pleura, peritoneum, pericardium and
tunica vaginalis - pleural mesothelioma is the most common of these
Etiology
=========================================================================
Smoking is not a risk factor
Risk factors include :
1. Asbestos exposure:
Usually a prolonged latency period
Studies do not show a linear dose-reponse relationship between asbestos

exposure and malignant mesothelioma
The role of amphibole (crocidolite) asbestos is well established
Crocidolite is a much more potent carcinogen than chrysotile (serpentine form);

it accounts for 95% of asbestos used, and so is the main cause of malignant
mesothelioma
2. Radiation
3. Erionite: very carcinogenic mineral fiber used in gravel roads
4. SV40 virus (association is not clear)
Clinical features
=========================================================================
Progressive shortness of breath
Chest pain, possibly unilateral
Cough, fever, malaise, myalgia and weight loss (American Cancer Society)
Micro description
=========================================================================
Three broad histopathological features (see below):

o Epithelioid: includes tubulopapillary, deciduoid, clear cell, and small cell types
o Sarcomatoid: desmoplastic and lymphohistiocytoid types
o Biphasic / mixed
Stromal or fat invasion is helpful in diagnosis
Figure 9.
Cytokeratin immunostain demonstrates infiltration of cytokeratin-positive mesothelioma cells

infiltrating into adipose tissue in a case of early diffuse malignant mesothelioma (original magnification
×300).
Figure 10. Vacuoles in the midst of mesothelial cells create the false impression of invasion into the
adipose tissue in this example of “fake fat” in organizing pleuritis (hematoxylin-eosin, original
magnification ×300).

Figure 11. Bland necrosis consists of a “clean,” ischemic necrosis in the upper left of this sarcomatoid
diffuse malignant mesothelioma (hematoxylin-eosin, original magnification ×300).
Figure 12. The malignant cells in this well-differentiated, solid diffuse malignant mesothelioma have
features of mesothelial cells, including relatively round nuclei, prominent nucleoli, abundant cytoplasm,
and distinct cell borders (hematoxylin-eosin, original magnification ×300).
Figure 13. Papillae with fibrovascular cores lined by malignant cells that cytologically resemble
mesothelial cells are seen in this tubulopapillary diffuse malignant mesothelioma (hematoxylin-eosin,
original magnification ×300).
Figure 14. Malignant cells that cytologically resemble mesothelial cells line lumens in this case of acinar
diffuse malignant mesothelioma (hematoxylin-eosin, original magnification ×300).
Recognize the clinical and therapeutic implications of Small Cell Carcinoma

(SCC) and Non-Small Cell Carcinoma (NSCC)

Most common symptom of lung cancer are cough and hemoptysis which is frequently patients dismiss
their symptom as routine complications of smoking.
Tumors in large airways (squamous cell carcinoma and small cell carcinoma) may also have problems
related to bronchial obstruction, such as pneumonia behind the obstruction or shortness of breath
secondary to occlusion of a major bronchus.
In contrast, with tumors that arise in the periphery of the lung ( adenocarcinomas and large cell
carcinomas) patients ten to not having symptoms related to bronchial involvement and their lesions are
often found on chest radiograph obtained for unrelated purposes.
All types of advanced lung cancers, constitutional symptoms such as malaise, anorexia, and weight loss
occur frequently but are nonspecific.
When the tumors involve the pleural surface, patients may have chest pain, and often pleuritic in
nature, or dyspnea resulting from substantial accumulation of pleural fluid.
Often affect the adjacent structures such as the heart and esophagus, either by direct invasion or
external compression by the tumor and results in pericardial effusion, cardiac dysrhythmias, and
dysphagia.
Potential clinical problems:
1. Symptoms of endobronchial tumor: cough, hemoptysis

2. Problems of bronchial obstruction: postobstructive pneumonia, dyspnea

3. Pleural involvement: chest pain, pleural effusion, dyspnea
4. Involvement of adjacent structures: heart, esophagus
5. Complications of mediastinal involvement phrenic or recurrent laryngeal nerve paralysis,
superior vena cava obstruction
6. Distant metastases: brain, bone, or bone marrow, liver, adrenals. Small cell carcinoma is the
most likely to generate metastases, while squamous cell carcinoma is the least likely.
7. Ectopic hormone production: ACTH, ADH, parathyroid hormone-related peptide
8. Other paraneoplastic syndromes: neurologic, clubbing, hypertrophic osteoarthropathy
9. Nonspesific systemic effects: anorexia, weight loss
Three major forms of treatment for lung cancer are surgery, radiation therapy, chemotherapy, and
combination modalities of therapy.
1. Surgery is the treatment of choice for localized tumors.

2. If the tumor has extended directly to the pleura or adjacent tissue usually unresectable.
Similarly with patients whose cancer has spread to mediastinal node or chest wall involvement,
combining surgery with radiation therapy or chemotherapy has been a promising approach.
3. If metastases to distant tissues or organs have occurred, surgery almost invariably is not an
appropriate form of therapy. The choices are no treatment, chemotherapy or radiotherapy
Describe the clinical procedures to get cells and tissues for the diagnosis of
lung cancer
A lung biopsy removes a small piece of lung tissue which can be looked at under a microscope.
The biopsy can be done in four ways. The method used depends on where the sample will be taken from
and your overall health.
Bronchoscopic biopsy. This type of biopsy uses a lighted instrument (bronchoscope) inserted
through the mouth or nose and into the airway to remove a lung tissue sample. This method
may be used if an infectious disease is suspected, if the abnormal lung tissue is located next to
the breathing tubes (bronchi), or before trying more invasive methods, such as an open lung
biopsy.
Needle biopsy. A needle biopsy uses a long needle inserted through the chest wall to remove a
sample of lung tissue. This method is used if the abnormal lung tissue is located close to the
chest wall. Acomputed tomography (CT) scan, an ultrasound, or fluoroscopy are usually used to
guide the needle to the abnormal tissue.
Open biopsy. An open biopsy uses surgery to make a cut (incision) between the ribs and remove
a sample of lung tissue. An open biopsy is usually done when the other methods of lung biopsy
have not been successful, cannot be used, or when a larger piece of lung tissue is needed for a
diagnosis.

Video-assisted thoracoscopic surgery (VATS). VATS uses a scope (called a thoracoscope) passed
through a small incision in the chest to remove a sample of lung tissue.
Pemeriksaan khusus (versi PDPI)
Bronskoskopi Biopsi transtorakal (Transthoracic

Biopsi aspirasi jarum biopsy, TTB)
Transbronchial needle aspiration Aspirasi jarum halus
(TBNA) Biopsi lain
Transbronchial lung biopsy (TBLB) Torakoskopi medik
Transthoracic needle aspiration (TTNA) Sitologi sputum
List some of pneumoconiosis which will develop lung cancer

Most occupational lung cancer is asbestos which can cause mesothelioma which has a poor prognosis.
Non-smoking related risk factors include occupational exposure to:
Asbestos Second Hand Smoke

Chromium Outdoor Air Pollutants
Arsenic Previous Lung Disease
Cadmium Radon Exposure
Silica Dietary Factors
Nickel
Distinguish lung tumor and mediastinum tumor

Mediastinum tumor is less likely to cause hemoptysis.
What is a Mediastinal Tumor?
Normal, healthy cells grow and divide to form new cells as your body needs them. They die when they
grow old or become damaged, and they are replaced with new cells. Sometimes, new cells form when
your body does not need them, and old or damaged cells do not die when they should. The buildup of
extra cells often forms a mass of tissue called a growth or tumor. Tumor cells can be malignant, meaning
cancerous, or benign, meaning non-cancerous.
The mediastinum is the part of your chest cavity that separates your lungs. Your heart, aorta (your
body's largest artery), esophagus, thymus (one of your glands), trachea, lymph nodes, and nerves are
contained within the mediastinum, which is bordered by your breastbone (sternum) in front, your spine
in back, and your lungs on either side. Mediastinal tumors are growths that form in this area. They can
be cancerous (malignant) or non-cancerous (benign). Because some mediastinal tumors tend to grow in
specific areas of the mediastinum, physicians often divide it into three sections:
Anterior (front)

Middle
Posterior (back)
There are different types of mediastinal tumors based on the types of cells from which the tumor grows.
The main types of mediastinal tumors are:
Thymoma, which is a tumor of the thymus gland. The thymus gland is part of the lymphatic
system and is located behind your breastbone.
Thymic carcinoma (also called C thymoma), which is a rare type of cancer of the thymus gland.
Germ cell, which is a tumor that forms from embryologically immature cells. Although germ cell
tumors can form anywhere in your body, they rarely form outside the sex organs. When they
do, they frequently form in the mediastinum, and can be either benign or malignant.
Lymphoma, which is cancer that begins in the cells of the immune system; it is grouped into two
categories, Hodgkin's lymphoma or non-Hodgkin's lymphoma
Neurogenic tumors, which are tumors that begin in cells that make up your nervous system.
Typically they are non-cancerous in adults. These are located in the posterior (back) of the
mediastinum, which is an area in your chest behind the breastbone that contains the heart,
aorta, trachea, and thymus.
What are the Symptoms?
About 40 percent of people with mediastinal tumors experience no symptoms at all. Most mediastinal
tumors are discovered during a test for another reason. When symptoms occur, however, they often
result from compression of the surrounding structures and may include:
Cough Hoarseness
Shortness of breath Unexplained weight loss
Chest pain Lymphadenopathy (swollen or tender

lymph nodes)
Fever
Wheezing
Chills
Stridor (high-pitched, noisy breathing
Night sweats that can signal an obstruction in your
Coughing up blood respiratory tract, especially the trachea
or larynx [voice box])
What Causes Mediastinal Tumors?
The cause of mediastinal tumors is often unknown. Although the cause may be unknown, certain kinds
of mediastinal tumors may be associated with other conditions. For example, thymoma can be
associated with other conditions, such as myasthenia gravis, polymyositis, lupus erythematosus,
rheumatoid arthritis, and thyroiditis.
Describe the principles of chest radiography, computed tomography, magnetic

resonance imaging and positron emission tomography
X-ray CT – (X-ray computed tomography) uses ionising radiation, source is external to the body. In some
cases, contrast agents are injected. Anatomical images MRI (Magnetic resonance imaging) – uses
magnetic fields and radiofrequency pulses to produce anatomical images. In some cases, contrast agents
are injected.
The chest x-ray is the most commonly performed diagnostic x-ray examination. A chest x-ray produces
images of the heart, lungs, airways, blood vessels and the bones of the spine and chest.
An x-ray (radiograph) is a noninvasive medical test that helps physicians diagnose and treat medical
conditions. Imaging with x-rays involves exposing a part of the body to a small dose of ionizing
radiation to produce pictures of the inside of the body. X-rays are the oldest and most frequently used
form of medical imaging.
A chest computed tomography (to-MOG-ra-fee) scan, or chest CT scan, is a painless, noninvasive test. It
creates precise pictures of the structures in your chest, such as your lungs. "Noninvasive" means that no
surgery is done and no instruments are inserted into your body.
A chest CT scan is a type of x ray. However, a CT scan's pictures show more detail than pictures from a
standard chest x ray.
Like other x-ray tests, chest CT scans use a form of energy called ionizing radiation. This energy helps
create pictures of the inside of your chest.
Doctors use chest CT scans to:
Show the size, shape, and position of your lungs and other structures in your chest.
Follow up on abnormal findings from standard chest x rays.
Find the cause of lung symptoms, such as shortness of breath or chest pain.
Find out whether you have a lung problem, such as a tumor, excess fluid around the lungs, or
a pulmonary embolism (a blood clot in the lungs). The test also is used to check for other
conditions, such as tuberculosis (tu-ber-kyu-LO-sis), emphysema (em-fi-SE-ma),
and pneumonia (nu-MO-ne-ah).
The chest CT scanning machine takes many pictures, called slices, of the lungs and the inside of the
chest. A computer processes these pictures; they can be viewed on a screen or printed on film. The
computer also can stack the pictures to create a very detailed, three-dimensional (3D) model of organs.

Sometimes, a substance called contrast dye is injected into a vein in your arm for the CT scan. This
substance highlights areas in your chest, which helps create clearer images.
A chest MRI (magnetic resonance imaging) scan is an imaging test that uses powerful magnetic fields
and radio waves to create pictures of the chest (thoracic area). It does not use radiation (x-rays).
A chest MRI provides detailed pictures of tissues within the chest area.
A chest MRI may be done to:
Provide an alternative to angiography, or avoid repeated exposure to radiation
Clarify findings from earlier x-rays or CT scans
Diagnose abnormal growths in the chest
Evaluate blood flow
Show lymph nodes and blood vessels
Show the structures of the chest from many angles
See if cancer in the chest has spread to other areas of the body (this is called staging -- it helps
guide future treatment and follow-up, and gives you an idea of what to expect in the future)
Detect tumors
A lung positron emission tomography (PET) scan is an imaging test. It uses a radioactive substance
(called a tracer) to look for disease in the lungs such as lung cancer.
Unlike magnetic resonance imaging (MRI) and computed tomography (CT) scans, which reveal the
structure of the lungs, a PET scan shows how well the lungs and their tissues are working.
This test may be done to:
Help diagnose lung cancer
See if lung cancer has spread to other areas of the body
Help determine if a growth in the lungs (seen on a CT scan) is cancerous or not
Determine how well cancer treatment is working
Describe how important the cigarette smoke causing lung cancer

Cigarette smoking is the leading cause of lung cancer, accounting for about 85% of lung cancers.
Risk for lung cancer increases with the duration, intensity and depth of smoke inhalation.
Second-hand (passive) smoking also causes lung cancer, but is less strongly associated
compared to active smoking.
Cigarettes contain multiple carcinogens (more than 60) that have been shown to induce cancers
in laboratory settings.
J Natl Cancer Inst. 2004 Jan 21;96(2):99-106.
o Polycyclic aromatic hydrocarbons (PAH) such as benzo[α]pyrene produce mutations in

the p53 gene. G to T transversion within the p53 gene is a molecular signature of lung
tumours caused by tobacco mutagens.
o N-nitroso compounds are a major group of chemicals found in tobacco smoke, several
of which are potent animal carcinogens.
Nicotine: causes addiction to cigarette smoking and is also a promoter for carcinogenesis.
o Sympathetic/parasympathetic activation: nicotine binds to and activates nicotinic

cholinergic receptors, which are located on both sympathetic and parasympathetic
postganglionic neurons. The endogenous ligand for this receptor
is acetylcholine(nicotine is not naturally found in humans). Therefore, smoking
stimulates both sympathetic (increased heart rate, blood pressure) and parasympathetic
(intestinal motility, relaxation) systems, releasing a whole range of hormones and
neurotransmitters into the circulation.
o Addiction: nicotine causes dopamine release from the nucleus accumbens, mediating
reward and addiction
o Carcinogen: nicotine does not initiate carcinogenesis, but it does promote initiated cells
by nicotinic cholinergic receptor signalling in the lungs. Nicotine has been shown to
inhibit apoptosis, proliferate cells, and cause angiogenesis in lung tumours.
Distribution of carcinogens: Cigar and pipe tobacco smoking produces relatively large particles
that only reach the upper airways, unlike cigarette smoking, which produces fine particles that
reaches the distal airways. Thus, cancer risk is lower with cigar and pipe smoking. The addition
of anti-irritants (e.g. menthol) to cigarettes allows deeper inhalation and a more rapid rise in
serum nicotine levels, increasing the addictiveness of cigarettes.
Smoking cessation: smokers at all ages can benefit from the cessation of smoking; however, the
risk still remains elevated compared to never smokers.

Describe the indication of oxygen therapy

The indications for home oxygen therapy are based on the original NOTT and MRC oxygen trials but for
Medicare requirements include:
Group I Requires annual recertification
A resting arterial blood gas oxygen content equal to or below 55 mmhg or
A resting or ambulatory oxygen saturation of 88% or below that is correctable with oxygen
therapy
Group II Requires recertification and testing within 90 Days
A resting arterial blood gas oxygen content of 56-59 mmHg or
A resting oxygen saturation of 89%.
Additionally Group II requirements include:
o Dependent edema suggesting congestive heart failure or
o Pulmonary hypertension or cor pulmonale, demonstrated by echocardiogram or ekg (p

wave >3 mm in standard lead II, III, or AVF or
o Erthrocythemia with HCT >56%


1. Describe the 4 main forms of obstructive lung disease (Asthma, COPD, bronchiectasis,
bronchiolitis obliterans); include epidemiology, risk factor, and natural history.
2. Describe the concept of ventilation-perfusion relationship.
3. Describe the pathology, immunology and pulmonary function abnormalities of asthma and
COPD.
4. Describe the cellular mechanisms which are play role in asthma and COPD.
5. Differentiating asthma and COPD from patient’s history, physical examination findings and
pulmonary function test.
6. Distinguish the main principle of treatment between asthma and COPD.
7. Describe the use of oxygen therapy in obstructive lung disease, the role of assisted ventilation
and the complication of respiratory support devices.
8. Distinguish radiologic imaging between asthma and COPD.
9. Describe the group of drugs used to treat obstructive airways disorders, their mechanisms of
action and the rational in treatment approach for different obstructive.
10. Explain about cor pulmonale.
Describe the 4 main forms of obstructive lung disease

Asthma
Asthma is defined as “a chronic disorder of the airways that involves a complex interaction of
airway obstruction, bronchial hyperresponsiveness and an underlying inflammation.” 33 Many cells and
cellular elements contribute to the inflammatory response including mast cells, eosinophils, neutrophils,
T lymphocytes, macrophages, and damaged epithelial cells (especially in sudden onset, fatal
exacerbations, occupational asthma, and individuals who smoke). In susceptible individuals, this
inflammation causes recurrent episodes of coughing (particularly at night or early in the morning),
wheezing, breathlessness, and chest tightness. These episodes are usually associated with widespread
but variable airflow obstruction that is often reversible either spontaneously or with treatment.
Inflammation resulting in hyperresponsiveness of the airways is the major pathologic feature of
asthma. Airway epithelial cell irritation combined with exposure to antigens initiates both an innate and
an adaptive immune response (see Chapter 8). In sensitized individuals, allergen exposure leads to
activation of T-helper cells. These cells release what are called T-helper 2 cytokines, especially IL-4, IL-5,
IL-8, and IL-13. IL-4 stimulates B-cell activation, proliferation, and production of antigen-specific IgE. IgE
causes mast cell degranulation with the release of a large number of inflammatory mediators, such as
histamine, prostaglandins, and leukotrienes. IL-5 stimulates the activation, migration, and proliferation
of eosinophils, which cause direct tissue injury and release toxic neuropeptides that contribute to
increased bronchial hyperresponsiveness, fibroblast proliferation, and airway scarring.33,47 IL-8
activates polymorphonucleocytes that contribute to a more exaggerated inflammatory response. IL-13
impairs mucociliary clearance, enhances fibroblast secretion, and contributes to bronchoconstriction.
The resulting inflammatory process produces bronchial smooth muscle spasm, vascular congestion,
increased vascular permeability, edema formation, production of thick tenacious mucus, impaired
mucociliary function, thickening of airway walls, and increased contractile response of bronchial smooth
muscle. Other inflammatory cytokines, such as TNF and IL-1, have been found to alter muscarinic
receptor function, leading to increased levels of acetylcholine, which cause bronchial smooth muscle
contraction and mucus secretion. These changes, combined with the epithelial cell damage caused by
eosinophil infiltration, produce acute airway hyperreponsiveness and obstruction.
Airway obstruction increases resistance to airflow and decreases flow rates, especially
expiratory flow. Impaired expiration causes air trapping, hyperinflation distal to obstructions, altered
pulmonary mechanics, and increased work of breathing. Changes in resistance to airflow are not
uniform throughout the lungs and the distribution of inspired air is uneven, with more air flowing to the
less resistant portions. Continued air trapping increases intrapleural and alveolar gas pressures and
causes decreased perfusion of the alveoli. Increased alveolar gas pressure, decreased ventilation, and
decreased perfusion lead to variable and uneven ventilationperfusion relationships within different lung
segments. Hyperventilation is triggered by lung receptors responding to increased lung volume and
obstruction. The result is early hypoxemia without CO2 retention. Hypoxemia further increases
hyperventilation through stimulation of the respiratory center, causing Paco2 to decrease and pH to
increase (respiratory alkalosis). As the obstruction becomes more severe, the number of alveoli being
inadequately ventilated and perfused increases. As air trapping in the lungs because of obstruction of
expiratory airflow progresses, the lungs and thorax become hyperexpanded putting the respiratory
muscles at a mechanical disadvantage. This leads to CO2 retention and respiratory acidosis. Respiratory
acidosis signals respiratory failure.
Chronic Obstructive Pulmonary Disease
Chronic obstructive pulmonary disease (COPD) has been defined as pathologic lung changes consistent
with emphysema or chronic bronchitis. A recent consensus report defines COPD as a “preventable and
treatable disease with some significant extrapulmonary effects that may contribute to the severity in
individual patients. Its pulmonary component is characterized by airflow limitation that is not fully
reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory
response of the lung to noxious particles or gases. COPD is primarily caused by cigarette smoke, and
active as well as passive smoking have been implicated. Other risks include occupational exposures,
indoor and outdoor air pollution, and history of severe childhood respiratory infections. Genetic
susceptibilities have been identified, including polymorphisms of genes that code for TNF, surfactant,
proteases, and antiproteases. Gender differences in the genes that code for the breakdown and removal
of cigarette smoke metabolites may explain the increased susceptibility of women smokers to COPD and
lung cancer. An inherited mutation in the α1-antitrypsin gene results in the development of COPD at an
early age, even in nonsmokers.
Chronic bronchitis is defined as hypersecretion of mucus and chronic productive cough that continues
for at least 3 months of the year (usually the winter months) for at least 2 consecutive years. Incidence
is increased in smokers (up to 20-fold) and even more so in workers exposed to air pollution. It is a
major health problem for older adults. Repeated infections are common.
Emphysema is abnormal permanent enlargement of gas exchange airways (acini) accompanied by
destruction of alveolar walls without obvious fibrosis. The major mechanism of airflow limitation in
emphysema is loss of elastic recoil. Some degree of emphysema is considered normal in older adults but
results in a slow and predictable decline in lung function with aging. When it occurs earlier in life,

however, it is usually secondary to cigarette smoking or indoor and outdoor air pollution, although it
may be primary emphysema in rare cases.
Bronchiolitis click here
Describe the concept of ventilation-perfusion relationship

Click here
Describe the pathology, immunology and pulmonary function abnormalities of

asthma and COPD
Click Here

Describe the cellular mechanisms which are play role in asthma and COPD
Mast cells are notable for expression of the high-affinity IgE receptor, FcεRI. IgE molecules are
constitutively bound to these receptors on the surface of mast cells. Upon encountering an allergen, the
antigen-specific IgE molecules are bound with allergen and the subsequent cross-linking of FcεRI
receptors activates mast cells. There is the immediate release of preformed mediators including
histamine and tryptase. In some mast cells, TNF-α (tumor necrosis factor-α and VEGF (vascular
endothelial growth factor) may also be among the preformed mediators. This is followed by the
synthesis of leukotrienes (primarily LTC4), prostaglandins (primarily PGD2), and cytokines, which all
contribute to the inflammatory milieu as discussed below.
Basophils are also derived from CD34+ hematopoietic stem cells via the myeloid lineage;
however, in contrast to mast cells, these cells are typically found in the peripheral circulation. Basophils
share some commonfeatureswith mast cells in the expression of FcεRI and tryptase; however, both are
expressed at much lower levels than the mast cells. In addition, basophils are also capable of an
immediate release of histamine upon activation. It is currently thought that mast cell activation is
involved in immediate allergic inflammation, whereas basophils are involved in the late-phase response.
Upon exposure to allergen, eosinophils are actively recruited into the airway predominantly by
chemokines such as eotaxins. The migration of eosinophils to the airway is dependent on extravasation
of peripheral blood eosinophils. This process is highly regulated and occurs via interaction between
adhesion molecules on the endothelium (e.g., VCAM-1) and eosinophils (e.g., VLA-4).
Upon entry into the airway, eosinophils are able to release numerous mediators including granule
proteins, leukotrienes (primarilyLTC4), prostaglandins, and cytokines. The role of eosinophils may be in
the development of the chronic changes associated with asthma. Thus, the role of eosinophils in acute
exacerbations of asthma remains unclear
Primary (azurophilic) and secondary (specific) granules contain various antimicrobial enzymes,
neutral proteases, and acid hydrolases. Neutrophils, in contrast to eosinophils, are natural residents of
the lung, particularly the lung parenchyma. Airway neutrophilia can be observed in response to viral

infections, during nocturnal exacerbations of asthma, and in the BAL fluid of allergic asthmatics 4 hours,
but not 24 hours, after inhaled allergen challenge. Neutrophils contain or synthesize a number of
molecules with the potential to damage airway tissue and, perhaps more importantly, to act as
chemotactic factors or mediators for other inflammatory cells.
T cells are thought to be a prominent source of cytokines in the asthmatic inflammatory

response. In asthma, an increase in activated T cells is observed in the airway. Furthermore, increased
numbers of activated BAL T cells have been correlated with increased bronchial responsiveness and
numbers of eosinophils. These observations suggest that T cells may play a critical role is the
pathogenesis of asthma by regulating or orchestrating the inflammatory response.
It follows that Th2 cells, by virtue of their associated cytokines, can specifically enhance allergic
inflammation with promotion of IgE synthesis and eosinophil activation and accumulation. It has been
proposed that allergic inflammation represents the predominant activation of Th2 cells and release of
their proinflammatory cytokines. In accord with this notion, cells in the BAL fluid from patients with
asthma have shown increased mRNA expression for both IL-4 and IL-5. This and other observations
suggest that Th2 cells and their associated cytokines play a major role in orchestrating the inflammatory
response in the asthmatic airway, in particular its IgE production (IL-4, IL-13), eosinophilia (IL-5), mucus
secretion (IL-13), and airway hyperresponsiveness (IL-13).
Macrophage and dendritic cells are phagocytic cells capable of presenting antigen to T cells.
Alveolar macrophages are present in abundance within the airway of normal and asthmatic patients and
are known to play a critical role in the clearing of microbes from the airway. There are also suggestions
that alveolar macrophages can suppress allergic inflammation in the airway by the secretion of Th1
cytokines, including IL-12, IL-18, and IFN-γ .
The dendritic cells are present in the lung in an immature form, either adjacent to epithelial cells or in
the interstitium. These immature dendritic cells encounter antigen and migrate to a local lymph node,
where they mature, characterized by increased expression of MHC class II molecules and B7
costimulatory molecules. The plasmacytoid dendritic cells can then induce tolerance, possibly by
inducing T regulatory cells or by providing inhibitory costimulatory signaling via PDL-1 (programmed
death ligand-1). In contrast, myeloid dendritic cells are thought to be important both for the initial
sensitization with allergen as well as for enhancing the inflammation upon repeat exposure to allergen.
Interestingly, repeated exposure to antigen may bypass the requirement for dendritic cells to migrate to
a lymph node.
Bronchospasm remains an important component of asthma, particularly acute asthma. Despite

this long-standing recognition, the details of airway smoothmuscle function, both in normal and
asthmatic persons, are still under investigation.
Epithelial cells also participate in inflammation with the release of several molecular mediators,
including cytokines, chemokines, and lipid mediators. Furthermore, epithelial cells are capable of
producing endothelins, which are a family of three related peptides with potent bronchoconstrictor
activity. Some of the stimuli for endothelin secretion include IL-1, IL-6, IL-8, TNF-α, TGF-β and LPS
(lipopolysaccharide). Endothelin secretion is inhibited by IFN-γ and glucocorticoid treatment.

In asthma, goblet cell hyperplasia and increased mucus production are typically observed. The increased
numbers of goblet cells are derived from the proliferation and differentiation of epithelial cells. In
asthma, several cytokine signaling pathways, including IL-9 and IL-13, induce goblet cell hyperplasia and
increased secretion of mucin into the airway. The clinical sequelae are mucus plugging and obstruction.
Pada PPOK sel yang berperan antara lain:
Neutrofil : meningkat dalam sputum perokok. Peningkatan neutrophil pada PPOK sesuai dengan
beratnya penyakit. Keduanya mungkin berhubungan dengan hipersekresi dan pelepasan
protease.
Makrofag : meningkatkan mediator inflamasi dan protease pada pasien PPOK sebagai respons
terhadap asap rokok dan menunjukkan fagositosis yang tidak sempurna.
Limfosit T : sel CD4+ dan CD8+ meningkat pada dinding saluran napas dan parenkim paru
dengan peningkatan CD8+ lebih besar dari CD4+. Peningkatan sel T CD8+ (Tcl) dan sel Th1 yang
mensekresikan interferon-gamma dan mengekspresikan reseptor kemokin CXCR3, mungkin
merupakan sel sitotoksik untuk sel-sel alveolar yang berkontribusi terhadap kerusakan alveolar.
Limfosit B : meningkat dalam saluran napas perifer dan folikel limfoid sebagai respons terhadap
kolonisasi kuman dan infeksi saluran napas
Eosinofil : meningkat di dalam sputum dan dinding saluran napas selama eksaserbasi
Sel epitel : mungkin diaktifkan oleh asap rokok sehingga menghasilkan mediator inflamasi
Differentiating asthma and COPD from patient’s history, physical examination

findings and pulmonary function test
Distinguish the main principle of treatment between asthma and COPD

Click Here
Describe the use of oxygen therapy in obstructive lung disease, the role of
assisted ventilation and the complication of respiratory support devices
-
Distinguish radiologic imaging between asthma and COPD

Asthma
Plain films can be normal in upto 75% of patients with asthma.
Reported features with asthma include:
pulmonary hyperinflation
bronchial wall thickening: peribronchial cuffing (non specific finding but may be present in ~48%
of cases with asthma 1)
pulmonary oedema (rare): pulmonary oedema due to asthma (usually occurs with acute
asthma)

Severity classification
The global initiative for chronic obstructive lung disease (GOLD) staging system is a commonly used
severity staging system based on air flow limitation. According to this, there are 4 key stages:
stage I: mild, FEV1 > 80% of normal
stage II: moderate, FEV1 = 50-79% of normal
stage III: severe, FEV1 = 30-49% of normal
stage IV: very severe, FEV1 <30% of normal or <50% of normal with presence of chronic
respiratory failure present
The FEV1:FVC ratio should be <0.70 for all stages. The GOLD staging system may be insensitive in early
stage
Findings of chronic bronchitis on chest radiography are nonspecific and include

increased bronchovascular markings and cardiomegaly. Emphysema manifests as lung
hyperinflation with flattened hemidiaphragms, a small heart, and possible bullous changes. On the
lateral radiograph, a "barrel chest" with widened anterior-posterior diameter may be visualized. The
"saber-sheath trachea" sign refers to marked coronal narrowing of the intrathoracic trachea (frontal
view) with concomitant sagittal widening (lateral view).
Describe the group of drugs used to treat obstructive airways disorders, their
mechanisms of action and the rational in treatment approach for different
obstructive
Click Here
Explain about cor pulmonale

Cor pulmonale is secondary to pulmonary artery hypertension and consists of right ventricular
enlargement (hypertrophy, dilation, or both).
PATHOPHYSIOLOGY
Cor pulmonale develops as pulmonary artery hypertension creates chronic pressure overload in the
right ventricle similar to that created in the left ventricle by systemic hypertension. (Systemic
hypertension is discussed in Chapter 30.) Pressure overload increases the work of the right ventricle and
causes hypertrophy of the normally thin-walled heart muscle. Acute hypoxemia, such as might occur
with pneumonia, can exaggerate pulmonary hypertension and dilate the ventricle as well. Right
ventricular filling pressures are normal until failure occurs. The right ventricle usually fails when
pulmonary artery pressure equals systemic blood pressure.
CLINICAL MANIFESTATIONS
The clinical manifestations of cor pulmonale may be obscured by primary respiratory disease and appear
only during exercise testing. The heart appears normal at rest, but with exercise, cardiac output falls.

The electrocardiogram shows right ventricular hypertrophy. Chest pain is common. The pulmonary
component of the second heart sound, which represents closure of the pulmonic valve, may be
accentuated, and a pulmonic valve murmur also may be present. Tricuspid valve murmur may
accompany the development of right ventricular failure. Peripheral edema, hepatic congestion, and
jugular venous distention often may be detected.
EVALUATION AND TREATMENT

Diagnosis is made on the basis of physical examination, radiologic examination, and electrocardiogram
or echocardiogram, or both. The goal of treatment for cor pulmonale is to decrease the workload of the
right ventricle by lowering pulmonary artery pressure. Treatment is the same as for pulmonary artery
hypertension, and its success depends on reversal of the underlying lung disease.


1. Describe the responses of lung to microbials, fungi, parasites and viral.
2. Describe and recognize the all microbials, fungi and parasites which may cause infection in the
lung.
3. Describe and explain the pulmonary blood flow.
4. Describe the pathological features of pneumonia and Acute Respiratory Distress Syndrome
(ARDS).
5. Review the imaging diagnostic algorithm for diffuse lung disease including pattern of
abnormality, distribution of abnormality correlated with physical findings.
Describe the responses of lung to microbials, fungi, parasites and viral

In healthy individuals, pathogens that reach the lungs are expelled or held in check by mechanisms of
self-defense. If a microorganism gets past the upper airway defense mechanisms, such as the cough
reflex and mucociliary clearance, the next line of defense is the airway epithelial cell. Airway epithelial
cells can recognize some pathogens directly (e.g., P. aeruginosa and S. aureus). However, the most
important guardian cell of the lower respiratory tract is the alveolar macrophage. This phagocyte can
recognize pathogens through its pattern-recognition receptors (e.g., Toll-like receptors) which then
activates both innate and adaptive immune responses.86 Release of TNF-α and IL-1 from macrophages
contributes to widespread inflammation in the lung with recruitment of polymorphonuclear neutrophils
(PMNs). PMNs migrate from the capillaries of the lungs into the alveoli. PMNs are critical phagocytes
that kill microbes through the formation of phagolysosomes filled with degredative enzymes,
antimicrobial proteins, and toxic oxygen radicals.
Neutrophils have also been found to extrude a meshwork of proteins called a neutrophil extracellular
trap (NET) that can capture and kill bacteria that have not yet been phagocytosed. Unfortunately many
pathogens, such as the pneumococcus, can release a DNase that cleaves the NET and thus escape PMN
defense. In addition to activating PMNs, macrophages also present infectious antigens to the adaptive
immune system activating T cells and B cells with the induction of cellular and humoral immunity. The
release of inflammatory mediators and immune complexes can damage bronchial mucous membranes
and alveolocapillary membranes, causing the acini and terminal bronchioles to fill with infectious debris
and exudate. In addition, some microorganisms release toxins from their cell walls that can cause
further lung damage. The accumulation of exudate in the acinus leads to dyspnea and to V/Q
mismatching and hypoxemia.

S. pneumoniae microorganisms initiate innate and adaptive immune responses. The immune response
includes complement activation and the production of antibodies, which are crucial for opsonizing the
encapsulated bacterium. Rapid lysis of pneumococcal bacteria (as occurs with antibiotic treatment)
results in the release of intracellular bacterial proteins that can be toxic. The best known of these
proteins is pneumolysin, which is cytotoxic to virtually every cell in the lung and is partially responsible
for the worsening in clinical symptoms sometimes seen in individuals immediately after they begin
antibiotic treatment. Inflammatory cytokines and cells are released that cause alveolar edema.73 Edema
creates a medium for the multiplication of bacteria and aids in the spread of infection into adjacent
portions of the lung. The involved lobe undergoes consolidation (solidification of the tissue caused by
filling with exudate). A stage of red hepatization follows in which alveoli fill with blood cells, fibrin,
edematous fluid, and pneumococci, giving lung tissue a red appearance. This passes into the stage of
gray hepatization, in which affected tissues become gray because of fibrin deposition over the pleural
surfaces and the presence of fibrin and leukocytes (neutrophils) in the consolidated alveoli, where
phagocytosis is rapidly taking place. With resolution, increasing numbers of macrophages appear in the
alveolar spaces, the neutrophils degenerate, and the fibrin threads and remaining bacteria are digested
by macrophages and removed by lymphatic vessels. Usually infection is limited to one or two lobes.
Viral pneumonia is usually mild and self-limiting, but it can set the stage for a secondary bacterial
infection (especially by S. aureus microorganisms) by providing an ideal environment for bacterial
growth and by damaging ciliated epithelial cells, which normally prevent pathogens from reaching the

lower airways. Viral pneumonia can be a primary infection (e.g., influenza pneumonia) or a complication
of another viral illness (e.g., chickenpox, measles). The virus not only destroys the ciliated epithelial cells
but also invades the goblet cells and bronchial mucous glands. Sloughing of destroyed bronchial
epithelium occurs throughout the respiratory tract, preventing mucociliary clearance. Bronchial walls
become edematous and infiltrated with leukocytes. Some forms of viral pneumonia can progress to
severe systemic illness with many complications and a high morbidity and mortality. Severe viral
pneumonia can include common types of influenza which can be fatal, especially in older adults. Other
severe viral infections are considered opportunistic infections, such as cytomegalovirus pneumonia in
immunocompromised individuals. New or atypical forms of viral infection, such as influenza A (H1N1)
virus, avian influenza and the virus that causes the severe acute respiratory syndrome (SARS), are
affecting previously healthy populations and pose a considerable threat for pandemics.
Describe and recognize the all microbials, fungi and parasites which may
cause infection in the lung
CAP HCAP/HAP/VAP Immunocompromised
Individuals
Streptococcus pneumoniae Pseudomonas aeruginosa Pneumocystis jiroveci
Haemophilus influenza Staphylococcus aureus (including Mycobacterium tuberculosis
Staphylococcus aureus methicillin resistant strains) Atypical mycobacteria
Mycoplasma pneumoniae Klebsiella pneumoniae Respiratory viruses
Chlamydia pneumoniae Enterobacter species Protozoa
Moraxella catarrhalis Parasites
Legionella pneumophila
Influenza
Rhinovirus
Coronavirus
Describe and explain the pulmonary blood flow

Pulmonary circulation is the movement of blood from
the heart to the lungs for oxygenation, then back to the
heart again . Oxygen-depleted blood from the body
leaves the systemic circulation when it enters the
right atrium through the superior and inferior venae
cavae. The blood is then pumped through the tricuspid
valve into the right ventricle. From the right ventricle,
blood is pumped through the pulmonary valve and into
the pulmonary artery. The pulmonary artery splits into
the right and left pulmonary arteries and travel to each
lung. At the lungs, the blood travels through capillary beds on the alveoli where respiration occurs ,
removing carbon dioxide and adding oxygen to the blood. The alveoli are air sacs in the lungs that
provide the surface for gas exchange during respiration. The oxygenated blood then leaves the lungs
through pulmonary veins, which returns it to the left atrium, completing the pulmonary circuit. Once
entering the left heart, the blood flows through the bicuspid valve into the left ventricle. From the left

ventricle, the blood is pumped through the aortic valve into the aorta to travel through systemic
circulation, delivering oxygenated blood to the body before returning again to the pulmonary
circulation.
Source: Boundless. “Systemic and Pulmonary Circulation.” Boundless Anatomy and Physiology.
Boundless, 21 Jul. 2015. Retrieved 09 Dec. 2015
from https://www.boundless.com/physiology/textbooks/boundless-anatomy-and-physiology-
textbook/the-cardiovascular-system-18/circulation-and-heart-valves-173/systemic-and-pulmonary-
circulation-872-1153/
Describe the pathological features of pneumonia and Acute Respiratory

Distress Syndrome (ARDS)
All disorders that result in ARDS cause acute injuri to the alveolocapillary membrane producing massive
pulmonary inflammation, increased capillary permeability, severe pulmonary edema, shunting, V/Q
mismatch, and hypoxemia. The alveolocapillary injury can occur directly, as with the aspiration of highly
acidic gastric contents or the inhalation of toxic gases; or indirectly, as from circulating inflammatory
mediators released in response to systemic disorders, such as sepsis and trauma. Lung inflammation and
injury damages the alveolar epithelium and the vascular endothelium. ARDS is often referred to as non-
cardiogenic pulmonary edema characterized by 3 phases:
Exudative (Inflammatory) Phase (Within 72 hours)

Lung injury activated neutrophils, platelets, macrophages, lung epithelial, and
endothelial cells, and uncontrolled inflammation. Inflammatory mediators include complement,
cytokines, arachnidonic acid metabolites, platelet-activating factor, reactive oxygen species, and
other mediators (specifically tumor necrosis factor [TNF], interleukin-1 [IL-1], and IL-6).
Activated complement factors and platelet aggregation result in intravascular microthrombus
formation and further damage to lung capillaries.
The role of neutrophils is central to the development of ARDS. Activated neutrophils
release a battery of inflammatory mediators, among them proteolytic enzymes, oxygen-free
radicals (superoxide radicals, hydrogen peroxide, hydroxyl radicals), arachidonic acid
metabolites (prostaglandins, thromboxanes, leukotrienes), and platelet-activating factor. These
mediators cause extensive damage of the alveolocapillary membrane and greatly increase
capillary membrane permeability.
Increased capillary permeability, a hallmark of ARDS, allows fluids, proteins, and blood
cells to leak from the capillary bed into the pulmonary interstitium and alveoli. The resulting
pulmonary edema and hemorrhage severely reduce lung compliance and impair alveolar
ventilation.
Mediators released by neutrophils, and to a certain extent by macrophages, also cause
pulmonary vasoconstriction. Pulmonary hypertension occurs early in the course of the disease
secondary to vasoconstriction and to vascular occlusion by aggregated neutrophils,
macrophages, and platelets. Because vasoconstriction occurs more in some vascular beds than

others, blood flow to selected areas of the lungs is decreased, resulting in V/Q mismatching.
Lung inflammation and injury damages the alveolar epithelium and the vascular
endothelium. Surfactant is inactivated, and its production by type II alveolar cells is impaired as
alveoli and respiratory bronchioles fill with fluid or collapse. The lungs become less compliant,
resulting in increased work of breathing and decreased minute ventilation and hypercapnia.
Proliferative Phase (4 to 21 days)
Within 1 to 3 weeks after the initial lung injury, there is resolution of the pulmonary edema and
proliferation of type II pneumocytes, fibroblast, and myofibroblast. The intra-alveolar
hemorrhagic exudate becomes a cellular granulation tissue appearing as hyaline membranes
and there is progressive hypoxemia.
Fibrotic Phase (14 to 21 days)

About 2 to 3 weeks after the initial injury, remodeling and fibrosis occur. The fibrosis

progressively obliterates the alveoli, respiratory bronchioles and interstitium, leading to a

decrease in functional residual capacity (FCR) and continuing V/Q mismatch with severe right to
left shunt. The result of this overwhelming inflammatory response by the lungs is acute
respiratory failure.
The same chemical mediators responsible for the alveolocapillary damage of ARDS often cause
inflammation, endothelial damage, and capillary permeability throughout the body, resulting in
the systemic inflammatory response syndrome (SIRS), SIRS then leads to multiple organ
dysfuntion syndrome (MODS). In fact, death may not be caused by respiratory failure alone, but
by MODS associated with ARDS.
Review the imaging diagnostic algorithm for diffuse lung disease including
pattern of abnormality, distribution of abnormality correlated with physical
findings
-

References
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William & Wilkins.
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McGraw-Hill Medical.

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Respiratory System

Member of SECRET Training Division

Member of HMFK Logistic Division

Mentor Faculty of Medicine Universitas Pelita Harapan

Describe the embryological development of the lung and the diaphragm

When the embryo is app 4 weeks old, the lung bud /

Initially, the lung bud is in open communication with the

Universitas Pelita Harapan | WEEK OBJECTIVES – Week 1 1

Larynx originate from endoderm.

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Trachea, Bronchi, and Lungs

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Maturation of the Lungs

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Amount of surfactant increases during the last 2 weeks before birth.

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LUNG VOLUMES AND CAPACITIES

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Atmospheric (Barometric) pressure.

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The lungs follow the movement of the chest wall.

The intrapleural pressure is subatmospheris because:

Classify two main disorders in the lung

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‘Obstructive pattern’ on PFT’s – see below

Obstructive pattern lung disease

Reduced FVC (<80% of normal)

Reduced FEV1:FVC ratio (<70%)

Reduced peak flow

Restrictive Lung Disease

The lung will be stiff with reduced compliance

Restrictive pattern of lung disease

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Normal FEV1:FVC ratio

Causes of restrictive lung disease

The main symptoms are SOB and cough.

ARDS – acute respiratory distress syndrome

Mixed Pattern of Disease

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Classify the type and management of pneumothorax

Primary spontaneous pneumothorax

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Describe the function of chest tube

Underwater seal bottle

An example is shown below.

The underwater drainage bottle.

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An example is shown below.

The trap bottle.

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Suction regulator bottle

An example is shown below.

The suction bottle.

Explain about lung oedema

1. Mitral stenosis: usually due to rheumatic heart disease.

3. Aortic regurgitation: acutely can be seen in infective endocarditis or aortic dissection.

a). HISTORY and physical exam

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4. Vasodilators: nitroglycerin or nitroprusside. Nitroprusside especially helpful for HTN emergency,

5. Position: sit patient upright

Pathophysiology: Alveolar-capillary membrane becomes damaged and leaky, resulting in movement of

E. Pulmonary embolism: Treatment aimed at anticoagulation and supportive measures. ***Pulmonary

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