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Respiratory System:
Embryology
Bronchopulmonary Segment of lung tissue supplied by a segmental (tertiary) bronchus, a branch of
segment pulmonary artery and a branch of bronchial artery (run together through the
center part of the segment). Tributaries of pulmonary vein are found on the
periphery (between two adjacent segments). Surgeons can resect diseased lung
tissue along bronchopulmonary segments rather than remove the entire lobe.
Congenital a large opaque area in the right upper lobe due
bronchogenic cyst to a fluid-filled cyst

Aeration at birth Is the replacement of lung liquid with air in the newborn’s lungs. In the
fetal state, the functional residual capacity (FRC) of the lung is filled with liquid
secreted by fetal lung epithelium via Cl–transport using CFTR (cystic fibrosis
transmembrane protein). At birth, lung liquid is eliminated by a reduction in lung
liquid secretion via Na+ transport by type II pneumocytes and resorption into
pulmonary capillaries (major route) and lymphatics (minor route). Lungs of a
stillborn baby will sink when placed in water because they contain fluid rather than
air

Neonatal Surfactant is stored and transported to the cell surface by lamellar bodies
respiratory distress (organelles containing parallel stacks of membrane lamellae).
syndrome It is normally released by exocytosis into the alveolar spaces, where the lamellar
contents unravel and spread along the alveolar lining. As it degrades; surfactant is
recycled back into the same type Il pneumocytes by endocytosis for reprocessing.

Anatomy and Histology:

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Physiology:
Lung volumes Function of FCR:
Breathing is cyclic, while blood flow through the pulmonary capillary bed is continuous.
During the respiratory cycle, there are short periods of apneas at the end of inspiration and
expiration when there is no ventilation but there is continuous blood flow. Without the FRC
acting as a buffer for continued gas exchange during apneic periods, these conditions would
in effect create an intrapulmonary shunt, inducing deoxygenated blood from the pulmonary
capillaries to empty into the pulmonary veins.
Ventilation Dead space: regions of respiratory system that contain air but are not exchanging O2 and CO2
with blood
Anatomic dead space: (conducting zone, ends at the level of terminal bronchioles)
At the end of expiration, the anatomic dead space is filled with air originating in the alveoli or
respiratory zone.
At the end of inspiration the anatomic dead space is filled with room air.
The presence of an atomic dead space implies in order to get fresh air into the alveoli one must
always take a tidal volume larger than the volume of anatomic dead space.

Alveolar dead space: alveoli containing air but without blood in the surrounding capillaries (e.g.,
pulmonary embolism )
Physiologic dead space = anatomic dead space + alveolar dead space
Lung mechanics Alveolar compliance decreases as lung volume
increases.

Cardiovascular changes During inspiration:

during respiration ↓ IPP → ↑ transpulmonary preesure across vasculature → expanding the great veins and the
RA → ↓ intravascular pressure → ↑ pressure grdient driving venous return to the heart → ↑
systemic VR and right ventricular output → splitting of S2 (delayed closure of pulmonary
valves).
↑ volume of blood in the pulmonary circuit → ↑ pulmonary vascular resistance (PVR).
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Pooling of blood in the lungs → ↓ blood flow to LA and LV → ↓COP and BP (mainly sysytolic )
↓ BP → ↓ Baroreceptor firing → ↓vagal outflow→ Slight ↑ in HR ( respiratory suinus
arrhythmia)
During expiration: → the reverse occurs
Valsalva maneuver: forced expiration against closed glottis → creates positive IPP →
compresses the great veins of the chest →↓ VR

Positive-pressure Assisted Cotrol Mode Ventillation (ACMV): respiratory cycle initiated by patient or
ventilation automatically if no signal is detected withi specified time window. Expiration is not assisted
(passive recoil )
Positive End-Expiratory Pressure (PEEP): useful in treating hypoxemia of ARDS
Continuous Positive airway Pressure (CPAP): by mask not tube – treating OSA

Airway resistance
Lung compliance
Most of airway resistance is implicated by primary and secondary bronchi.
As the lung volume increases, airway resistance decreases (due to ↑ in transpulmnary pressure
and radial traction effect by the small airways)
A represents respiratory distress syndrome (a
greater change in intrapleural pressure is required
to inflate the lungs )
B represents atelectasis
(once the alveoli collapse it is difficult to reinflate
them )

Pulmonary function tests PFTs measure both flow (FEV1) and volume (FVC)D
Alveolar- blood gas Factors affecting alveolar PCO2: metabolic CO2 production and alveolar ventilation
exchange Factors affecting alveolar O2 : atmospheric pressure (↑ in hyberbaric chamber, ↓ in high
altitude) – oxygen concentration in inspired air – alveolar PCO2 (change in alveolar PCO2 causes
change in alveolar PO2 in opposite directions )
Factors affecting Alveolar-blood gas transfer: membrane surface area – membrane thickness
– partial pressure gradient – diffusion constant of the gas (ie, solubility)
Because CO2 is extremly soluble gas, it diffuses across the lung membranes faster than oxygen
even though it has small gradient.
Supplemental oxygen rises oxygen gradient to overcome diffusion problem.
Diffusion capacity of the lung is an index of the overall surface area and membrane thickness.
It is measured as the uptake of CO from the alveolar air to the blood.
Transport of oxygen The amount of oxygen dissolved in the blood determines PO2 and amount of oxygen bound to
Hb – maximal hyperventilation increases PO2 to 130 mmHg (0.4 % volume ).
Effect of CO on Oxygen-Hb dissociation curve:
Causes left shift → ↑ the affinity of Hb to oxygen
Causes downward shift → ↓ oxygen content
Neural regulation of Central chemoreceptor: the main drive of ventilation undernormal conditions. Stimulaions →
alveolar ventilation ↑ ventiation. Stimulated by cerebrospinal fluid H+ and CO2 ( the stimulatory effect of CO2
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may be due to local production of H+ from CO2.

Peripheral receptor: (carotid and aortic bodies)
two different receptors: H+ /
CO2 receptors:
PO2 receptors: ( PO2 not oxygen content )
They monitor dissolved oxygen not oxygen on Hb.
Normal CO2 drive to brath is suppressed in COPD
patients, and by narcotics and general
anesthetics.
Central respirator center : Medullary center

Abnormal breathing Apneustic breathing: prolonged inspirations alternating with a short period of
pattern expiration. This pattern is attributed to the loss of the normal balance between
vagal input and the pons-medullary interactions. Lesions in patients with apneustic
breathing are usually found in the caudal pons.
Cheyne-Stokes breathing: periodic type of breathing which has cycles of gradually
increasing depth and frequency followed by a gradual decrease in depth and frequency
between periods of apnea. It may result from midbrain lesions or congestive heart failure.
Bitot’s breathing: irregular periods of apnea alternating with periods in which several
breathings of identical depth are taken. Seen in patients with↑ ICT and certain midbrain
lesions.
Ventilation /perfusion As V•a/Q falls, PO2 falls and
mismatch PCO2 rises. The extreme is a
shunt.
As V•a/Q rises, PO2 rises and
PCO2 falls. The extreme is
alveolar dead space.

Hypoxic vasoconstriction This is a clinically important phenomenon that is unique to the pulmonary circulation.
Whenever there is a decrease in alveolar PO2, a local vasoconstriction
of pulmonary blood vessels is produced. The result is a lowering of blood flow
through that lung unit and a redistribution of blood to better-ventilated units.
Hypoxemia Causes:
1- Hypoventilation → ↑ Alveolar PCO2→ ↓ alveolar PO2 → ↓arterial PO2 Hypoxiemia
can be relieved by increasing supplemental oxygen ( CO2 remains elevated because
ventilation is not changed), normal A-a gradient
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,end-tidal air reflects the systemic arterial compartment. Causes include: narcotics,
general anasthetics, COPD, guillian-Barre syndrome, Lambert-Eaton syndrome and
Myasthenia gravis.
2- Diffusion impairment (↓ surface area and/or ↑ thickness of lung membranes),
supplementa oxygen can relieve hypoxemia, ↑ A-a gradient, end-tidal air does not
reflect systemic arterial blood, ↓ DLCO. Causes include: pulmonary fibrosis,
sarcoidosis, Pulmonary Edema.
3- Ventilation-Perfusion mismatch ( ↓ V•a/Q), supplemental oxygen corrects
hypoxemia, ↑ A-a gradient, end-tidal air does not reflect systemic arterial blood.
Causes include: sever obstruction (status asthmaticus, cystic fibrosis, and
anaphylaxis), infection (pneumonia), partial airway occlusion (foreign body, mucus
plug).
4- Intrapulmonary shunts (systemic venous blood is delivered to the left side of the
heart without exchanging oxygen and carbon dioxide with the alveoli), supplemental
oxygen cannot correct hypoxemia, ↑ A-a gradient, end-tidal air does not reflect
systemic arterial blood. Causes include: atelectatic lung regions (pneumothorax,
ARDS), complete airway occlusion (mucus plug, foreign body) and right-to-left shunts
caused by congenital heart defects.
Pathology:
Nasopharyngeal Associated with EBV infections.
carcinoma Pleomorphic keratin-positive epithelial cells (poorly differentiated SCC) in a back ground of
lymphocytes.
Involvement of cervical lymph nodes.
Angiofibroma Benign tumour of nasal mucosa.
Composed of large blood vessels and fibrous tissue
Seen in adolescent males
Present with profuse epistaxis
Larynx Vocal cord nodule (singer’s nodule):
Arises on true vocal cords, usually bilateral, due to excessive use of voice, comosed of
degenerative (myxoid) connective tissue, presents with hoarseness, resolves with resting of voice
Laryngeal papilloma:
Due to HPV 6 and 11 infection, single in adults and multiple in childern
Laryngeal carcinoma:
SCC- alcohol and tobacco are risk factors
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Atelectasis Alveolar collapse, which can be due to multiple

etiologies:
Obstructive—airway obstruction prevents new air from
reaching distal airways, old air is resorbed (eg, foreign
body, mucous plug, tumor)
Compressive—external compression on lung decreases
lung volumes (eg, space-occupying lesion, pleural
effusion)
Contraction (cicatrization)—scarring of lung parenchyma
that distorts alveoli (eg, sarcoidosis)
Adhesive—due to lack of surfactant (eg, NRDS in
premature babies).

An obstructive lesion in a mainstem bronchus can

prevent ventilation of an entire lung, leading to
obstructive atelectasis and complete lung collapse.
Characteristic findings on chest x-ray include
unilateral
pulmonary opacification and deviation of the
mediastinum toward the opacified lung.

Acute White-out on CXR

respiratory Three phases of ARDS:
distress • Exudative phase: Inflammatory cytokines (eg, tumor
syndrome necrosis factor, IL-I IL-6) activate the pulmonary
endothelium and recruit neutrophils to the lung tissue,
which release Inflammatory mediators Resultant
endothelial damage leads to Increased capillary
permeability and leakage of protein-rich fluid into the
alveolar space. Organization of the edema and cellular
debris leads to the formation of hyaline membranes.
• Proliferative phase: One to two weeks later; endothelial cells, pneumocytes, and fibroblasts
proliferate in attempts to repair the damaged lung; collagen is deposited and scarring may occur.
Edema is reabsorbed.
• Fibrotic phase:
In a minority of patients, excessive collagen deposition leads to irreversible pulmonary fibrosis
and pulmonary hypertension.
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Restrictive lung Idiopathic pulmonary fibrosis:

diseases Etiology: cyclical lung injury; TGF-β from injured
pneumocytes induces fibrosis
Clinically: progressive dyspnea and cough
CT scan: at first → subpleural patches.
Later on → diffuse fibrosis ( honey-comb appearance)
Treatment: lung transplantation.

Idiopathic pulmonary fibrosis is characterized by patchy

interstitial inflammation intermixed with areas of dense
fibrosis and normal lung, focal fibroblastic proliferation, and a honeycomb pattern most
prominent in the periphery. Repetitive injury and disordered healing are implicated as potential
causes; lung injury results in focal loss of type 1 pneumocytes and hyperplasia of type 2
pneumocytes.

Hypersensitivity pneumonia:
BAL→ ↑ level of CD8+ T-cell
↑ circulating eosinophils ( not BAL fluid eosinophils)
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Sarcoidosis: Hypercalcemia is a common feature of sarcoidosis, and even patients with normal serum calcium
levels may have increased urinary excretion of calcium; suggesting abnormal calcium metabolism.
1-alpha hydroxylase expression in activated macrophages in the lung and lymph nodes causes
PTH-independent production of 1, 25-dihydroxvitamin D. This leads to increased intestinal
absorption of calcium and subsequent hypercalcemia.

Most patients develop liver involvement, which typically manifests as asymptomatic

hepatomegaly with mild liver function test abnormalities Liver biopsy frequently demonstrates
scattered noncaseating granulomas

Asteroid bodies: stellate inclusions seen within giant cells of the granuloma
Schaumann bodies: Laminated calcium concretions

Pneumoconiosis Silicosis:
Silicosis is characterized by dyspnea and productive cough occurring years after inhalational
exposure to crystalline silica Histologically, it is characterized by birefringent silicate particles
within dense, whorled collagenous nodules surrounded by dust-laden macrophages.
Radiography typically demonstrates numerous small rounded nodules predominant in the
upper lobes; calcification of the rim of hilar nodes (eggshell calcification) may also be seen.
Asbestosis:
Major clinical manifestations:
Pleural disease includes pleural effusions and pleural plaques. Pleural plaques are a hallmark
of asbestos exposure that typically affect the parietal pleura along the lower lungs and
diaphragm. The plaques are composed of discrete circumscribed areas of dense collagen that
frequently become calcified.
Asbestosis is characterized by progressive pulmonary fibrosis that is most predominant in the
lower lobes and by the presence of asbestos bodies (golden-brown beaded rods with
translucent centers).
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Bronchogenic carcinoma is the most common malignancy associated with asbestos exposure
Smoking and asbestos exposure have a synergistic effect on the development of lung
carcinoma; Increasing the risk from 6-fold in nonsmoking patients with asbestos exposure to
60-fold in asbestos-exposed patients who smoke regularly.
Malignant mesothelioma is a rare malignancy of the pleura for which asbestos is the only
known environmental risk factor. It is less common than bronchogenic carcinoma in asbestos-
exposed patients. However; mesothelioma is more specific for heavy asbestos exposure.
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Pulmonary The risk of venous thromboembolism (ie, pulmonary embolism or deep vein thrombosis) in
embolism hospitalized patients can be greatly reduced with the administration of prophylactic anticoagulation;
usually with low molecular-weight heparin (enoxaparin).

Ventilation-perfusion (V/Q) scans use radiotracers to compare the ventilation and blood perfusion of
each area of the lung V/Q mismatch with perfusion defects are often Indicative of a pulmonary
embolism; which are most commonly caused by deep vein thrombosis in the lower extremities that
embolizes to the pulmonary vasculature.

CXR of PE: Usually present with normal CXR, characteristic findings include Westermark sign (area of
lucency due to decreased perfusion) or Hampton’s hump ( wedge-shaped opacity occurs near the
pleura)

Fat embolism syndrome:

The clinical triad of acute-onset neurologic abnormalities, hypoxemia, and petechiae in a patient with
traumatic bone fracture is strongly suggestive of fat embolism syndrome (FES). This condition most
commonly occurs 24-72 hours following long-bone and/or pelvic fracture.
Pathophysiologically, the traumatic event dislodges fat globules from the bone marrow and allows
them to enter disrupted marrow venules; where they can then traverse the systemic veins and
deposit in pulmonary microvessels. The pulmonary capillary occlusion impairs gas exchange and
induces hypoxemia; release of free fatty acids from the fat globules also causes local toxic injury to
the endothelium, potentially leading to acute respiratory distress syndrome. Some fat globules escape
the lungs via precapillary arteriovenous shunts that open due to increased pulmonary artery pressure.
This phenomenon appears to be responsible for the fat emboli—associated microvascular occlusion
that can occur within the CNS, manifesting with confusion and neurologic impairment; and in the
dermal capillaries, resulting in erythrocyte extravasation and a petechial rash. Thrombocytopenia may
also occur due to platelet adherence and aggregation to circulating fat globules.
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Chronic obstructive pulmonary diseased

Asthma Common triggers of asthma

Inhaled allergens (Animal dander, Dust mites & cockroaches, Pollens & molds )
Respiratory irritants (Cigarette smoke & air pollutants, Perfumes)
Medications (Aspirin/NSAlDs , Nonselective beta blockers )
Other (Upper respiratory infection, Exercise & cold dry air, Gastroesophageal reflux disease)

Intermittent respiratory symptoms in a patient with a normal chest x-ray, sputum eosinophils, and
reduced FEV1 suggest asthma.
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Pneumonia
Aspiration Predisposing conditions for aspiration pneumonia
pneumonia Altered consciousness impairing cough reflex/glottic closure (eg, dementia, drug intoxication)
Dysphagia due to neurologic deficits (eg, stroke, neurodegenerative disease)
Upper gastrointestinal tract disorders (eg, GERD)
Mechanical compromise of aspiration defenses (eg, nasogastric & endotracheal tubes)
Protracted vomiting
Large-volume tube feedings in recumbent position

The superior regions of the lower lobes and posterior regions of the upper lobes are the most dependent
locations in the lungs of supine individuals. Infiltrates in these locations revealed on chest x-ray are further
evidence of aspiration pneumonia

Anaerobic bacteria (Peptostreptococcus, Bacteroides, Prevotella, Fusobacterium) are the dominant

organisms in the oral cavity and may be isolated from cultures from patients with aspiration pneumonia
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Tuberculosis Mycobacterium tuberculosis is a facultative intracellular, acid-fast bacillus that is acquired by

inhalation. Replication within the alveoli leads to phagocytosis by alveolar macrophages. Macrophages
are Initially unable to destroy the pathogen due to microbial adaptations that inhibit the formation of
an effective phagolysosome. After a few weeks of infection, antigen presenting cells (eg, infected
macrophages and dendritic cells) in the draining lymph nodes display mycobacterial antigens to naive
CD4 T lymphocytes, which subsequently differentiate into T helper type 1 (THI) cells that secrete
interferon-gamma.
Interferon-gamma activates macrophages leading to the formation of fully acidified phagolysosomes
capable of destroying intracellular mycobacteria. Activated macrophages also differentiate into
epithelioid histiocytes and multinucleated giant cells, which surround extracellular mycobacteria within
granulomas. The release of proteases, nitric oxide, and reactive oxygen species by these cells helps
contain the infection However, these compounds also cause extensive collateral tissue damage and can
result in the formation of cavitary lung lesions.
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Lung tumors
Pulmonary The most common benign lung tumor is a hamartoma (also called pulmonary chondroma).
hamartoma Hamartomas usually present as incidental findings on chest x-ray with the appearance of a well-
defined coin lesion with "popcorn calcifications". A hamartoma is an excessive growth of a tissue type
native to the organ of involvement. The lung is the most common location. Lung hamartomas often
contain islands of mature hyaline cartilage; fat, smooth muscle and clefts lined by respiratory
epithelium.
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Extra UW BAL fluid ↑ eosinophils seen in eosinophilic pneumonia and tropical pulmonary eosinophilia.
notes
Elastase is a neutral protease contained in macrophage lysosomes and in the azurophilic (primary)
granules of neutrophils. Normally, elastase released from alveolar macrophages and infiltrating
neutrophils is balanced by the presence of serum and tissue protease inhibitors Neutrophil elastase is
inhibited by serum alpha-I antitrypsin, and macrophage elastase is inhibited by tissue inhibitors of
metalloproteinases. Neutrophil and macrophage elastases can also degrade each other's (but not their
own) inhibitors; augmenting their destructive capacity when both proteases are present. Excess
protease activity is a major contributor to the development of both centracinar and panacinar
emphysema.

Histoplasma capsulatum replicates within macrophages and often spreads from the lungs through the
pulmonary lymphatics to the reticuloendothelial system (eg, spleen, liver). Most healthy individuals
quickly contain the infection within granulomas and do not become ill. a minority develop self-limited
pneumonia. Overtime, the granulomas at the initial sites of infection calcify and may be seen
incidentally on radiographic imaging.
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Second-hand smoking:
Risks of secondhand smoke exposure:

Prematurity, low birth weight

Sudden infant death syndrome
Middle ear disease (eg, otitis media)
Asthma
Respiratory tract infections (eg, bronchitis, pneumonia)

Secondhand smoke (SHS) has numerous adverse effects on nearly every organ system. The level of
tobacco in the fetus of a mother who smokes is the same as that of an active smoker. Maternal
tobacco use impairs fetal oxygenation; alters fetal development and response, and exposes the fetus
to multiple toxins (eg; nicotine, carbon monoxide, ammonia). As a result; detrimental outcomes
include abnormal placentation (eg, Previa, abruption); prematurity, perinatal mortality and
significantly reduced birth weight.
One of the most dangerous effects of SHS exposure (pre- and postnatal) is the increased risk of sudden
infant death syndrome (SIDS). SIDS refers to the unexpected death of a seemingly healthy infant during
sleep. Up to half of all SIDS cases are due to SHS exposure, likely due to impaired arousal and abnormal
cardiovascular responses to stimuli. SHS also increases the risk of recurrent otitis media, asthma, and
other respiratory tract illnesses (eg, pneumonia) in children. Parents who smoke outside the home
should be counseled on cessation as chemicals from cigarette smoke are adsorbed and retained by
clothing; skin, and hair and therefore pose a risk to children.
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Intestinal Atresia occurs when the lumen of the intestines is completely occluded, whereas stenosis occurs
atresia and when the lumen of the intestines is narrowed. The causes of these conditions seem to be both
stenosis failed recanalization and/or an ischemic intrauterine event (“vascular accident”).

1. Type I atresia is characterized by a membranous septum or

diaphragm of mucosa and submucosa that obstructs the lumen.
2. Type II atresia is characterized by two blind bowel ends
connected by a fibrous cord with an intact mesentery.
3. Type IIIa atresia is characterized by two blind bowel ends
separated by a gap in the mesentery.
4. Type IIIb atresia (“apple peel” atresia) is characterized by a
bowel segment (distal to the atresia) that is shortened, coiled
around a mesentery remnant, and lacking a blood supply from
the superior mesentery artery (blood supply to this bowel
segment is via collateral circulation
5. Type IV atresia is characterized by multiple atresia
throughout the bowel having the appearance of a “string of
sausages.” Proximal atresias are associated clinically with
polyhydramnios and bilious vomiting early after birth. Distal
atresias are associated clinically with normal amniotic fluid,
abdominal distention, later vomiting, and failure to pass
meconium.
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Transplant Hyperacute graft rejection:

rejection
Widespread thrombosis of graft vessels
leads to ischemia and necrosis.

Acute graft rejection:

This is a form of acute renal transplant
rejection known as acute cellular
tubulointerstitial rejection because most of
the inflammation is in the interstitium. The
glomerulus seen here is normal, but the
tubules are infiltrated by many lymphocytes
at the upper right.

Chronic graft rejection:

The renal arteries with chronic vascular
rejection are markedly thickened and
fibrotic. There is interstitial fibrosis and
chronic inflammation. Such chronic
rejection usually occurs slowly over several
months to years following transplantation.
This form of rejection, unlike acute cellular
rejection, is difficult to treat.
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