Ø  PULMONARY PATHOLOGY:  CLASSIFICATION OF PULMONARY PATHOLOGY:   ROVIN → R-restrictive lung disease, O-obstructive lung disease, V-vascular lung disease, I-infectious lung disease, N-neoplastic lung disease.

o   TYPES OF RESTRICTIVE LUNG DISEASES:  PAINT → P-pleural disease (pleural fibrosis, pleural effusion, empyema, pneumothorax), A-alveolar diseases (edema-ARDS/IRDS, hemorrhage), I-inflammatory/autoImmune diseases (WG, GP), I-ILD (interstitial lung disease), I-idiopathic, N-neuromuscular (MG, phrenic nerve palsy, myopathy), T-thoracic wall diseases (kyphoscoliosis, obesity, pregnancy, ascites, and ankylosing spondylitis).

o   TYPES OF OBSTRUCTIVE LUNG DISEASES:  ABC anD E → A-asthma, B-bronchiectasis, C-chronic bronchitis, E-emphysema, and C-CF.

o   TYPES OF VASCULAR LUNG DISEASE:  Pulmonary edema, Pulmonary embolism, Pulmonary hyptertension

o   INFECTIOUS LUNG DISEASES: Viral, bacterial, fungal, parasitic

o   NEOPLASTIC LUNG DISEASES-TYPES OF LUNG CANCER:  LABS → L-large cell lung carcinoma, A-adenocarcinoma and B-bronchioloalveolar carcinoma (these 3 usually originate at the periphery), S-squamous cell lung carcinoma and S-small cell lung carcinoma (these 2 usually originate centrally).



·       The laryngotracheal diversticulum forms in the ventral wall of the foregut.

·       The tracheoesophageal septum divides the foregut into the esophagus and trachea.

·       The distal end of the laryngotracheal diverticulum enlarges to form the lung bud.

·       The lung undergo four stages of development:

The head and neck of a human embryo thirty-two days old, seen from the ventral surface. The floor of the mouth and pharynx have been removed. (Laryngo-tracheal tube labeled at lower left, second from bottom.)

By Henry Vandyke Carter - Henry Gray (1918) Anatomy of the Human Body (See "Book" section below)Bartleby.com: Gray's Anatomy, Plate 947, Public Domain, https://commons.wikimedia.org/w/index.php?curid=566892

Lungs during development, showing primitive lung buds that have not yet fully divided into mature lungs.

By Henry Vandyke Carter - Henry Gray (1918) Anatomy of the Human Body (See "Book" section below)Bartleby.com: Gray's Anatomy, Plate 949, Public Domain, https://commons.wikimedia.org/w/index.php?curid=566894


·       PLEURA: 2 membranes that enclosed a lung.

Visceral layer:  Adheres to lung surface and becomes continuous with the parietal layer at the root of the lung.
Parietal layer: Outer layer that adhere to chest wall, diaphragm, and pericardial sac.

·       LUNG:

Right lung:  Divided into 3 lobes (superior, middle, inferior) by oblique and horizontal fissure.

Left lung:  Divided into 2 lobes (superior, inferior) by an oblique fissure.  Lingula is the most inferior and anterior portion of the left superior lobe.
Root of lung:  The hilum contains a pulmonary artery (lie superiorly), the superior and inferior pulmonary veins (lie inferiorly), and the bronchus (lies posteriorly).

Detail of lung showing the pleurae

By OpenStax College - Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013., CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=30148380

The human lungs flank the heart and great vessels in the chest cavity

By Gray's Anatomy - Gray's Anatomy at http://www.bartleby.com/107/138.html, Public Domain, https://commons.wikimedia.org/w/index.php?curid=141450



A respiratory lobule, the functional unit of the lung. The alveolus, respiratory bronchiole and surrounding blood vessels can be seen.

By LadyofHats - self-made(extracted from Image:Respiratory system complete.svg) (duplicate of Image:Respiratory system complete en.svg), Public Domain, https://commons.wikimedia.org/w/index.php?curid=3222341

Gas exchange occurs in the alveolus, where venous blood exchanges carbon dioxide for oxygen.

By helix84 - en:Image:Alveoli.jpg, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=1737765



Lung volumes



o   Ventilation occurs under the control of the autonomic nervous system from the pons (apneustic center and pneumotaxic center) and the medulla (dorsal and ventral respiratory group-DRG, VRG).  Ventilation is normally CO2-driven as there are CNS receptors to monitor PaCO2 and pH of CSF, but there are no CNS mechanisms to detect pO2.

1.     Apneustic center:  Stimulates/prolongs inspiration by stimulation of the DRG in the medulla to delay the 'switch off' signal of the inspiratory ramp provided by the pneumotaxic centre of pons.

2.     Pneumotaxic center (aka pontine respiratory group-PRG):  Antagonises the apneustic center, cyclically inhibiting inspiration by limiting the burst of action potentials in the phrenic nerve, effectively decreasing the tidal volume and increasing the respiratory rate.

3.     DRG (dorsal respiratory group):  Located in the dorsomedial region of the medulla, and is composed of cells in the solitary tract nucleus.  It primarily responsible for the generation of inspiration.  DRG’s rhythm produces a respiratory rate of 12-16 breaths per minute, with inspiration lasting 2s, and expiration 3s.

4.     VRG (ventral respiratory group):  Located in the ventrolateral region of the medulla.  It contains both inspiratory and expiratory neurons. It is secondarily responsible for initiation of inspiratory activity, after the DRG.  Also, it is responsible for motor control of inspiratory and expiratory muscles during exercise.

o   Inspiration begins when neurons of the DRG (primarily) and VRG fire.   Impulses travel down the phrenic and intercostal nerves to stimulate the diaphragm and external intercostal muscles. The thoracic cavity expands and air rushes into the lungs due to the negative pressure, producing inspiration.

o   Expiration begins when these cells stop firing.  The inspiratory muscles relax, inspiration ceases, and exhalation begins.  Forced expiration is aided by contraction of the accessory expiratory muscle (e.g. internal intercostals and abdominal muscles.

PATHOLOGY:  CLASSIFICATION OF PULMONARY PATHOLOGY:   ROVIN  → R-restrictive lung disease, O-obstructive lung disease, V-vascular lung disease, I-infectious lung disease, N-neoplastic lung disease.

·       R _______________, _______________, _______________, _______________, _______________

·       O _______________, _______________, _______________, _______________, _______________

·       V _______________, _______________, _______________, _______________, _______________

·       I _______________, _______________, _______________, _______________, _______________

·       N _______________, _______________, _______________, _______________, _______________

·       RESTRICTIVE LUNG DISEASE (RLD):  Characterised by a loss of airway compliance, causing incomplete lung expansion. This change manifests as ↓ IC, and thus TLC and VC are also ↓.  In contrast to obstructive pulmonary disease (OPD), in RLD TV, ERV, FRC, RV are unchanged.  Both the FEV1 and FVC for a patient with RLD will be decreased however FEV1/FVC ratio will be normal or increased because of a disproportionately larger reduction of the FVC.

·       TYPES OF RESTRICTIVE LUNG DISEASES:  PAINT → P-pleural disease (pleural fibrosis, pleural effusion, empyema, pneumothorax), A-alveolar diseases (edema-ARDS/IRDS, hemorrhage), I-inflammatory/autoImmune diseases (WG, GP), I-ILD (interstitial lung disease), I-idiopathic, N-neuromuscular (MG, phrenic nerve palsy, myopathy), T-thoracic wall diseases (kyphoscoliosis, obesity, pregnancy, ascites, and ankylosing spondylitis).

o   P _______________, _______________, _______________, _______________, _______________

o   A _______________, _______________, _______________, _______________, _______________

o   I _______________, _______________, _______________, _______________, _______________

o   N _______________, _______________, _______________, _______________, _______________

o   T _______________, _______________, _______________, _______________, _______________

o   PLEURAL DISEASES:  Pleural effusion, Pneumothorax.

o   PLEURAL EFFUSION:  Excess fluid that accumulates in the pleural cavity, which can impair breathing by limiting the expansion of the lungs during inhalation.

Ø  PATHOPHYSIOLOGY:  Healthy individuals have < 15 ml of fluid in each pleural space. Normally, fluid enters the pleural space from the capillaries in the parietal pleura, from interstitial spaces of the lung via the visceral pleura, or from the peritoneal cavity through small holes in the diaphragm. This fluid is normally removed by lymphatics in the visceral pleura, which have the capacity to absorb 20X more fluid than is normally formed. When this capacity is overwhelmed, either through excess formation or decreased lymphatic absorption, a pleural effusion develops.  If left untreated, the fluid accumulation put pressure on the mediastinum and the trachea, effectively limiting the amount of diastolic filling of the ventricles and deviating the trachea to the unaffected side.  Four types of fluids can accumulate in the pleural space:  1) Hydrothorax:  Serous fluid 2) Hemothorax:  Blood (usually from major chest injuries, malignancy, or TB) 3) Pyothorax/empyema:  Pussy, pH < 7.2, glucose < 60 mg/dL, gram-stain positive (resulting from chest infections) 4) Chylothorax:  Milky lymph fluid with high triglycerides (resulting from rupture of the thoracic duct).

The Starling equation, which explains fluid movement across the capillary membrane that occurs as a result of filtration, can be used to describe pleural effusion:

Pleural effusions may be differentiated into transudative and exudative effusion. 

1.     TRANSUDATIVE EFFUSION:  Intact capillaries (i.e. normal Kf) lead to protein-poor fluid  with a specific gravity < 1.012, that is an ultrafiltrate of plasma.  It results from ↑ capillary hydrostatic pressure (Pc ) or ↓ capillary osmotic pressure  (πc).  Some common causes of transudative pleural effusion: CHF → C-cirrhosis (↓πc), H-heart failure (#1 cause; ↑ Pc ), F-FSGS and other nephrotic syndrome ((↓πc); and protein-losing enteropathy.

v  C _______________, _______________, _______________, _______________, _______________

v  H _______________, _______________, _______________, _______________, _______________

v  F _______________, _______________, _______________, _______________, _______________

2.     EXUDATIVE EFFUSION: Leaky cappillaries (i.e. ↑ Kf) lead to protein-rich pleural fluid with a specific gravity > 1.012.  It resutls from inflammatory damage to the capillary wall.  Some common causes of exudative pleural effusion: PIMA → P-pancreatitis, P-pulmonary embolism with infarction, I-injury (i.e. chest trauma), I-infection (e.g. pneumonia, TB), M-malignancy (e.g. lung cancer, breast cancer, lymphoma, Meig’s syndrome), A-automimmune diseases (e.g. collagen vascular diseases such as SLE, RA). 

v  P _______________, _______________, _______________, _______________, _______________

v  I _______________, _______________, _______________, _______________, _______________

v  M _______________, _______________, _______________, _______________, _______________

v  A _______________, _______________, _______________, _______________, _______________

Ø  PRESENTATION:  Possible symptoms:  CHEST PAIN → C-chest pain, C-cough, H-hypotension, E-edema, E-elevated JVP, E-egonphony, S-SOB, S-subcutataneous air, T-tachypnea, T-tachycardia, T-tracheal deviation, P-pleurisy, P-percussion dull resonance, P-pale, cool, clammy skin, A-denopathy, A-asicites, I, N-narrow pulse pressure. 

v  C hest pain________, _______________, _______________, _______________, _______________

v  H ypotension______, _______________, _______________, _______________, _______________

v  E dema Egophony__, _______________, _______________, _______________, _______________

v  S OB Subq air_____, _______________, _______________, _______________, _______________

v  T achypnea Tachycardia Tracheal deviation, _____________, _______________, _______________

v  P leurisy Percusion dull Pale,___________, _______________, _______________, _______________

v  A denopathy Ascites,______________, _______________, _______________, ______________

v  I _______________, _______________, _______________, _______________, _______________

v  N arrow pulse pressure, _______________, _______________, _______________, ______________

Diagram of fluid buildup in the pleura

By Cancer Research UK - Original email from CRUK, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=34332978

Ø  DIAGNOSTIC EVALUATION:  H&P.  CBC. BMP.  CXR:  Upright AP (blunted costophrenic angles is seen if at least 300 ml of fluid is present) & lateral decubitus position (can pick up as little as 50 ml of fluid).

Ø  Once accumulated fluid is > 500 ml, there are usually detectable clinical signs (i.e. CHEST PAIN above).  CT chest:  Effusion fluid often settles at the lowest space due to gravity; here at the back as the patient is lying under scanner.  Thoracentesis:  Pleural fluid is drawn out and evaluated for the following:

1.     Chemical composition:  Protein, lactate dehydrogenase (LDH), albumin, amylase (↑ with esophageal rupture, pancreatitis, or cancer), pH (↓ <7.2 in empyema), and glucose (↓ < 60 mg/dL with cancer, bacterial infection or RA).

2.     Gram stain and culture:  Identify possible bacterial infections

3.     Cell count and differential

4.     Cytology:  Identify cancer cells and some infective organisms

5.     Other tests:  Lipids, fungal culture, viral culture, TB markers (adenosine deaminase > 45 IU/L, INF-g > 140 pg/mL, PCR for tuberculous DNA), specific immunoglobulins

Next, pleural fluid is determined to be a transudate or an exudate base on the result of pleural fluid analysis.  A pleural effusion is exudative if it meets ≥ 1 of the following:

Pleural effusion Chest X-ray of a pleural effusion. The arrow A shows fluid layering in the right pleural cavity. The B arrow shows the normal width of the lung in the cavity

By User InvictaHOG on en.wikipediaEdited by InvictaHOG, all edits released into public domainCommons upload by Magnus Manske 13:26, 28 April 2006 (UTC) - http://www.cdc.gov/ncidod/dvbid/dengue/slideset/spanish/set1/vi/slide08.htmhttp://www.cdc.gov/ncidod/dvbid/dengue/slideset/spanish/set1/images/pleural-effusion-index.jpgOriginally from en.wikipedia; description page is (was) here, Public Domain, https://commons.wikimedia.org/w/index.php?curid=738253

CT scan of the chest showing a left-sided pleural effusion. The fluid usually settles at the lowest space due to gravity; in this case, at the back because the patient is supine.

By I, Drriad, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=2262905

Pleural fluid cytopathology specimen showing malignant mesothelioma, one cause of a pleural effusion.

By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=9416972

Ø  TREATMENT:  Treatment depends on the underlying cause. Transudative:  Treat underlying condition.  Therapeutic thoracocentesis if patient is dyspneic.  Exudative:  Treat underlying condition.  Therapeutic thoracocentesis.  Thoracostomy (chest tube):  For larger effusions. Chemical (talc, bleomycin, tetracycline/doxycycline) or surgical pleurodesis:  Considered if recurrent effusions.  Empyema:  IV antibiotics, drainage of the infected pleural fluid or surgical debridement of the pleural space may be required.

Illustration depicting a collapsed lung or Pneumothorax

By BruceBlaus. When using this image in external sources it can be cited as:Blausen.com staff (2014). "Medical gallery of Blausen Medical 2014". WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436. - Own work, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=27924395

o   PNEUMOTHORAX:  Accumulation of air or gas in the pleural cavity.

Ø  PATHOPHYSIOLOGY:  Lungs are located inside the pleural cavity.   If air enters the pleural cavity, either from the outside (open pneumothorax) or from the lung (closed pneumothorax), the positive air pressure collapses the lung and it becomes mechanically impossible for the injured person to breathe. Pneumothoraces can be classified as follows:

1.     Primary spontaneous pneumothorax:  Occur when a subpleural bleb bursts causing the lung to deflate. Usually occur in tall, thin men between 20-40 y/o without any previous history of lung disease.  

2.     Secondary spontaneous pneumothorax:  A known lung disease is present, which include TENSION → T-Tuberculosis, E-emphysema/asthma (COPD is the most common cause), N-neoplasia of the lungs, S-subclavian line placement and other I-iatrogenic cause (e.g. thoracocentesis, positive-pressure ventilation, bronchoscopy), I-infection (e.g. pneumonia, PCP), I-interstitial lung disease, O-obstructive pulmonary diseases (i.e. COPD).  Others: Cystic fibrosis, Marfan syndrome, and rare diseases that are unique to women such as catamenial pneumothorax (due to endometriosis in the chest cavity) and lymphangioleiomyomatosis (LAM).

v  T _______________, _______________, _______________, _______________, _______________

v  E _______________, _______________, _______________, _______________, _______________

v  N _______________, _______________, _______________, _______________, _______________

v  S _______________, _______________, _______________, _______________, _______________

v  I _______________, _______________, _______________, _______________, _______________

v  O _______________, _______________, _______________, _______________, _______________

v  N _______________, _______________, _______________, _______________, _______________

3.     Traumatic pneumothorax: Penetrating chest wound.  Barotrauma

4.     Tension pneumothorax: When a one-way valve is formed (e.g by a piece of tissue) that allows air to enter the pleural cavity from the lung but not to escape.   Overpressure builds up with every breath, which may lead to severe SOB as well as circulatory collapse. This condition is a medical emergency.  Tension pneumothorax can arise from any etiologies above, but most commonly form penetrating trauma, infection, CHF, and positive-pressure ventilation.

Ø  PRESENTATION:  SOB, unilateral pleuritic chest pain, dry coughs, tachypnea, reduce cardiac output (shifting of the mediastinum away from the site of the injury can obstruct the SVC and IVC resulting in reduced cardiac preload), and cyanosis.  If untreated, hypoxia may lead to loss of consciousness and coma.

A schematic drawing of a bulla and a bleb, two lung abnormalities that may rupture and lead to pneumothorax.

By Original uploader was Robertolyra at pt.wikipedia - Transferred from pt.wikipedia; transferred to Commons by User:Lijealso using CommonsHelper., Public Domain, https://commons.wikimedia.org/w/index.php?curid=5125677

Ø  DIAGNOSTIC EVALUATION:  H&P:  Diminished/absence breath sounds on auscultation, hyperresonance  to percussion, and decreased tactile fremitus are suggestive of the diagnosis. "Coin test" (2 coins when tapped on the affected side, produce a tinkling resonant sound which is audible on auscultation: May be positive.  CXR: Deep sulcus sign (i.e. low lateral costophrenic angle on the affected side) on supine film is diagnostic.  Upright film often show visceral pleural line and/or lung retraction from the chest wall. The pneumothorax is followed up with repeated X-rays.

Chest X-ray showing the features of pneumothorax

By Karthik Easvur - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=52027819

CT scan of the chest showing a pneumothorax on the person's left side (right side on the image). A chest tube is in place (small black mark on the right side of the image), the air-filled pleural cavity (black) and ribs (white) can be seen. The heart can be seen in the center.

By en:User:Clinical Cases - http://clinicalcases.blogspot.com/2004/02/tension-pneumothorax.html, CC BY-SA 2.5, https://commons.wikimedia.org/w/index.php?curid=1173906

CT with the identification of underlying lung lesion: an apical bulla on the right side.

By Robertolyra - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=37797029

Ø  TREATMENT:  O2 supplement or intubation may be needed.  Small pneumothoraces:  May reabsorb spontaneously.  Supplemental O2 may speed resolution.  Large/symptomatic or tension pneumothoraces:  Needle thoracocentesis (at 2nd intercostal space, midclavicular line) to relieve the pressure and allow the lung to reinflate.  Then when time permits, place a chest tube.  Penetrating chest wounds:  Require immediate coverage with an occlusive dressing (any airtight material, even the cellophane of a cigarette pack, can be used). A small opening (i.e. flutter valve) needs to be left open, so the air can escape while the lung reinflates.  Recurrent pneumothorax:  May require pleurodesis &/or bullectomy.  Untreated pneumothorax is an absolute contraindication of transportation by flight.


o   ARDS: (ACUTE RESPIRATORY DISTRESS SYNROME):  A severe lung disease characterized by diffuse alveolar damage leading to impaired gas exchange with concomitant systemic release of inflammatory mediators causing inflammation, hypoxemia and frequently resulting in multiple organ failure. A less severe form is called acute lung injury (ALI). 

Ø  PATHOPHYSIOLOGY:  ARDS is frequently causes by ARDS → A-aspiration of gastric content, A-acute pancreatitis, R-renal failure (i.e. uremia), D-drugs and chemicals (e.g. bleomycin, heroin overdose, chlorine inhalation, oxygen toxicity), S-shock, S-sepsis. 

v  A _______________, _______________, _______________, _______________, _______________

v  R _______________, _______________, _______________, _______________, _______________

v  D _______________, _______________, _______________, _______________, _______________

v  S _______________, _______________, _______________, _______________, _______________

      Inflammation is thought to be an important triggering mechanism.  Insult to the parenchyma (i.e. ARDS mnemomic above) results in an initial release of cytokines and other inflammatory mediators, which attracts neutrophils and T-lymphocytes into the inflamed area.  The activation of these cells causes further release of inflammatory cytokines and the formation of reactive oxygen species (ROS).   As a result, there is increased alveolar epithelium and capillary endothelium permeability, which causes leakage of protein-rich inflammatory exudate from the capillaries into alveoli with resultant hyaline membrane formation in alveolar walls. This increases the thickness of the alveolo-capillary space, increasing the distance the oxygen must diffuse to reach blood. This impairs gas exchange leading to hypoxia, increases the work of breathing, eventually induces fibrosis of the airspace.  Moreover, edema and decreased surfactant production by type II pneumocytes may cause whole alveoli to collapse, or to completely flood.  Untreated, the amount of inflammatory mediators released by the lungs in ARDS may result in a systemic inflammatory response syndrome (SIRS) or sepsis if there is lung infection with eventual evolution towards shock and/or multiple organ failure.  SUMMARY OF ARDS: ARDS → A-acute A-alveolar epithelium and capillary endothelium damage causing leakage of protein-rich fluid into the alveoli space forming hyaline membrane; it is initiated by R-release of cytokine and formation of R-ROS by neutrophils, T-cell, and endothelial cell; the D-diffuse alveolar damage lead to D-diffusion defects causing hypoxia and hypercapnea; untreated cases can lead to S-SIRS or S-shock and multiple organ failure due to the cumulative effects of inflammatory cytokines and tissue hypoxia.

v  A _______________, _______________, _______________, _______________, _______________

v  R _______________, _______________, _______________, _______________, _______________

v  D _______________, _______________, _______________, _______________, _______________

v  S _______________, _______________, _______________, _______________, _______________

Ø  PRESENTATION:  Acute onse (12-48 hours) of  SOB, tachypnea, tachycardia, fever, cyanosis, and symptoms related to the underlying cause (i.e. ARDS causes). 

Ø  DIAGNOSTIC EVALUATION:  H&P: Labored breathing with rales on auscultation.  CBC: Leukocytosis in cases of infection. BMP. ABG:  Hypoxemia, respiratory acidosis.  Pulmonary artery catheter:  Measure PCWP to rule out cardiogenic cause of pulmonary edema.  CXR:  Document bilateral alveolar infiltrates.  Criteria for ARDS diagnosis:  1) Acute onset of respiratory distress 2) Bilateral infiltrates on CXR 3) PaO2:FiO2 < 200 mmHg (< 300 mmHg the condition is considered to be a milder form called acute lung injury-ALI) 4) PCWP < 18 mmHg as obtained by pulmonary artery catheterization (if this information is unavailable, then lack of clinical evidence of left ventricular failure suffices).

Chest x-ray of patient with ARDS

By Samir 04:51, 17 September 2007 (UTC). Modified by Delldot 07:55, 28 April 2008 (UTC) - http://en.wikipedia.org/wiki/Image:Noncardiogenic_pulmonary_edema.JPG, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=3954240

Stress Index of an ARDS patient with different values of PEEP

By Appendinisapprentice - Own work, CC0, https://commons.wikimedia.org/w/index.php?curid=15805832

Micrograph of diffuse alveolar damage, the histologic correlate of ARDS. H&E stain.

By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=14967283

Ø  TREATMENT:   No standard successful therapy.  Overrall goal is to maintain acceptable gas exchange and adequate perfusion.  Mechanical ventilation:  Using low tidal volume (6 ml/kg) has been shown to reduced mortality.  Maintain oxygenation with a goal of FIO2 < 0.6, PaO2 > 60 mmHg, and SaO2 > 90%.  Inotropes: Support cardiac output.  Diuresis:  Pulmonary function and outcome are better in patients that lost weight or had wedge pressure lowered by diuresis or fluid restriction. Treatment of the underlying cause is imperative, as it tends to maintain the ARDS picture (e.g. antibiotics therapy for any infection). Corticosteroids:  Not efficacious in ARDS.

IRDS (INFANTILE RESPIRATORY DISTRESS SYNDSOME aka hyaline membrane disease):  Occur  in premature infants by developmental insufficiency of surfactant production and structural immaturity in the lungs.
Ø  EPIDEMIOLOGY:  Leading cause of death in preterm infants. Incidence: 1% of newborns. The incidence decreases with advancing gestational age, from about 50% in babies born at 26-28 weeks, to about 25% at 30-31 weeks.

Ø  PATHOPHYSIOLOGY:  Surfactants are produced in Type II pneumocytes, packaged into lamellar bodies, and extruded into the alveoli. The lamellar bodies then unfold into a complex lining of the alveoli. This layer reduces the surface tension of the fluid that lines the alveolar walls. Surface tension is responsible for approximately 2/3 of the elastic recoil forces of the alveoli. By reducing surface tension, surfactant prevents the alveoli from completely collapsing on exhalation. Microscopically, a surfactant deficient lung is characterized by collapsed alveoli alternating with hyperaerated alveoli, vascular congestion and, in time, hyaline membranes. Hyaline appear as an eosinophilic, amorphous material, lining or filling the alveolar spaces and blocking gas exchange. As a result, hypoxemia and hypercapnia ensue. 

Ø  PRESENTATION:  Present shortly after birth tachypnea, tachycardia, chest wall retractions, expiratory grunting, nostrils flaring, and cyanosis.  Later, the baby may develop and apnea and ventilatory failure (hypercapnia).  IRDS remains the most common single cause of death in the first month of life from complications including respiratory acidosis, hypoglycemia, PDA, hypotension,  chronic lung changes (i.e. bronchopulmonary dysplasia), and intracranial hemorrhage.

Ø  DIAGNOSTIC EVALUATION:  The diagnosis is made by the clinical picture and the CXR.  CXR:   Decreased lung volumes (bell-shaped chest), "ground glass" appearance (small 0.5-1 mm, discrete, uniform infiltrate, and air-bronchograms (ie the infiltrate will outline the larger airways passages which remain air-filled).

Ø  TREATMENT:  O2 therapy: Ranging from CPAP in mild cases to endotracheal tube in severe cases.  Exogenous surfactant:   Given through the breathing tube into the lungs. IVF: Stabilize the blood sugar, blood salts, and blood pressure.

Ø  PREVENTION:  Fetal lung maturity may be tested by sampling the amount of surfactant in the amniotic fluid.  If the L/S (lecithin-sphingomyelin) ratio is < 2, the fetal lungs may be surfactant deficient, and a glucocorticoid is given to speeds the production of surfactant.

o   ILD (INTERSTITIAL LUNG DISEASE aka diffuse parenchymal lung disease-DPLD:  A group of lung diseases affecting the alveolar epithelium, capillary endothelium, basement membrane, perivascular and perilymphatic tissues. Most types of ILD involve fibrosis, but this is not essential; indeed fibrosis is often a later feature.


Ø  TREATMENT:  Depends on the underlying condition as ILD encompasses many different pathological processes.  It inclues: Avoid exposure to environmental trigger.  Discontinue offending drug.  Corticosteroids and other immunosuppressants.  O2 supplement.

o   CLASSIFICATION:  I-interstitial L-lung D-disease = ILD → I-inhalation of substances (organic versus inorganic substances), I-infection (Tb, Atypical pneumonia, PCP), I-idiopathic (HIS → Hamman-Rich syndrome, IPF, Sarcoidosis), I-immune disorder (RAW PIGS → RA, AS, WG, PSS, Polymyositis, IPF, GP, SLE), L-lymphangitic carcinomatosis, D-drug (BAN O2 & R-radiation = BANOR → B-busulfan, B-bleomycin, A-antibiotic (sulfas), A-antifungals (amphotericin B), A-antiarrhythmic (amiodarone, lidocaine), A-antimetabolites (MTX)), N-nitrofurantoin, O-O2 toxicity, R-radiation.

Ø  I _______________, _______________, _______________, _______________, _______________

Ø  L _______________, _______________, _______________, _______________, _______________

Ø  D _______________, _______________, _______________, _______________, _______________

A chest X-ray demonstrating pulmonary fibrosis due to amiodarone

By James Heilman, MD - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=11110205

End-stage pulmonary fibrosis of unknown origin, taken from an autopsy in the 1980s

By http://web2.airmail.net/uthman/specimens/index.html, Public Domain, https://commons.wikimedia.org/w/index.php?curid=841015

o   INHALATION:  Pneumoconiosis (inorganic substances) and Hypersensitivity pneumonitis (organic)

o   PNEUMOCONIOSIS:  Occupational lung disease caused by the inhalation of inorganic dust. Depending on the type of dust, variants of the disease are considered. 

Ø  PATHOPHYSIOLOGY:  Result of long-term, high-concentration exposure.  Inhaled dust enters the lungs can neither be destroyed nor removed, and progressively builds up.  The particles are engulfed by resident alveolar or interstitial macrophages, which set off an inflammatory response by releasing TNF, FGF, and other cytokines. In turn, these stimulate fibroblasts to proliferate resulting in fibrosis and the formation of pulmonary lesions. Types of pneumoconiosis include: C ASBESTOSIS → C-coalworker’s pneumoconiosis, A-asbestosis, S-silicosis, BE-berylliosis, S-stanosis, T-talcosis, S-siderosis or I-iron, S-silver polisher pneumoconiosis.

CAPLAN’S SYNDROME:  Pneumoconiosis in combination with multiple pulmonary rheumatoid nodules in rheumatoid arthritis.

v  C _______________, _______________, _______________, _______________, _______________

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v  S or I ______________, ______________, ______________, ______________, _______________

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Lateral chest X-ray in asbestosis shows plaquing of the diaphragm.

By User Clinical Cases on en.wikipedia - Originally from en.wikipedia; description page is (was) here04:00, 5 March 2006 Clinical Cases 843x1024 (67110 bytes) (Source: Early Asbestosis in a Retired Pipe Fitter http://clinicalcases.blogspot.com/2004/03/early-asbestosis-in-retired-pipe.html [http://en.wikipedia.org/wiki/User:Clinical_Cases Clinical_Cases]: I made the photo myself, licensed under Creative Commons ), CC BY-SA 2.5, https://commons.wikimedia.org/w/index.php?curid=729018

A plaque caused by asbestos exposure on the diaphragmatic pleura.

By Yale Rosen from USA - Asbestosis - Fibrous pleural plaqueUploaded by CFCF, CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=31127204

Micrograph of asbestosis showing the characteristic ferruginous bodies and marked interstitial fibrosis (or scarring).

By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=7597853

Complicated silicosis.

By Gumersindorego - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=17408767

Slice of a lung affected by silicosis.

By Gabacho1ro - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=5320163

Miner's lung with silicosis and tuberculosis. .

By Museomed - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=12223787

Ø  PRESENTATION:  Usually asymptomatic initial stages despite ongoing abnormalities on CXR.  After years of exposure, lung fibrosis ensues, and signs & symptoms include:  Fatigue, fever, tachypnea, shortness of breath on exertion, severe dry cough, inspiratory crackle, chest pain, reduced chest expansion, cyanosis, cor pulmonale, and clubbing of the fingers.  

Ø  DIAGNOSTIC EVALUATION:  PFT:  Restrictive pattern.  CXR. CT.

Ø  TREATMENT:  Pulmonary damage arises gradually from years of exposure, thus is irreversible and there is no cure.  Treatment focus on alleviating the symptoms and preventing complications, and include:  Stopping further exposure.  Tobacco cessation.  Cough suppressants.  Antibiotics and antitubercular agents:  Prevent tuberculosis.  Chest physiotherapy:  Help the bronchial drainage of mucus.  O2 supplement and bronchodilators:  Facilitate breathing. Lung transplantation:  The definitive treatment.

o   HYPERSENSITIVITY PNEUMONITIS (aka extrinsic allergic alveolitis):  Inflammation of the alveoli caused by hypersensitivity to inhaled organic dusts. Sufferers are commonly exposed to the dust by their occupation or hobbies.

Ø  PATHOPHYSIOLOGY:  Deposit of antigen in the alveoli results in the formaion of antigen-antibody complex (i.e. Type III hypersensitivity).  There is early infiltration by PMNs and later by mononuclear cells and mast cells.  Granuloma formation, in a classic delayed type hypersensitivity reaction, can result.  The invoking antigen can be from various microorganism, plants, or animals:

1.     thermophylic Actinomycetes:  B-bad FAMily = BFAM → B-bagassosis (sugarcan worker’s lung), F-farmer’s lung from moldy hay, A-air conditioner’s lung, M-mushroom worker’s lung.

v  B _______________, _______________, _______________, _______________, _______________

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2.     Aspergillus species: ABPA (allergic bronchopulmonary aspergillosis, compost lung, malt worker’s lung)

3.     Mycobacterium avium: Hot tub lung

4.     Bird proteins: Bird-Breeder's Lung from exposure to feathers and bird droppings.

5.     Grain weevil dust: Grain handler’s lung.

               Of these types, Farmer's Lung and Bird-Breeder's Lung are the most common. HP affects 0.4-7% of the farming population.

Ø  PRESENTATION:  HP is categorized as acute, subacute, and chronic based on the duration of the illness.

1.     Acute:  Fever, chills, malaise, cough, chest tightness, dyspnea, and headache 4-6 hours following heavy exposure to the provoking antigen.  Symptoms resolve within 12 hours to several days upon cessation of exposure.   

2.     Subacute:  Productive cough, dyspnea, fatigue, anorexia, weight loss, and pleurisy. Symptoms are similar to the acute form of the disease, but are less severe and last longer. 

3.     Chronic:  Insidious onset of tachypnea, cough, progressive dyspnea, fatigue, and weight loss.  Clubbing (seen in 50%) and inspiratory crackles over lower lung fields often are present.   Removing exposure results in only partial improvement.

Ø  DIAGNOSTIC EVALUATION:  H&P:  History of symptoms after exposure to the allergen and clinical tests. ABG:  Hypoxemia.  ESR/CRP.  CXR:  Acute:  May be normal or show diffuse micronodular interstitial infiltrate.  Subacute: Micronodular or reticular opacities most prominent in mid-to-upper lung zones.  Chronic:  Fibrotic changes with loss of lung volume particularly affect the upper lobes. Nodular or ground-glass opacities are not present.  CT scan:  Acute:  Ground-glass opacities or diffusely increased radiodensities.  Chronic:  Features of emphysema and honeycombing. Lung biopsy:  Acute:  Poorly formed noncaseating interstitial granulomas and mononuclear cell infiltration in a peribronchial distribution with prominent giant cells.  Subacute:   Well-formed noncaseating granulomas, bronchiolitis with or without organizing pneumonia, and interstitial fibrosis.  Chronic:  Chronic interstitial inflammation and alveolar destruction with dense fibrosis. Cholesterol clefts or asteroid bodies are present within or outside granulomas.  PFTs:  Restrictive loss of lung function.

Lung biopsy of chronic hypersensitivity pneumonitis, showing mild expansion of the alveolar septa (interstitium) by lymphocytes. A multinucleated giant cell, seen within the interstitium to the right of the picture halfway down, is an important clue to the correct diagnosis.

By Mutleysmith - Taken with a microscope for educationPreviously published: No, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=25879431

High magnification micrograph of hypersensitivity pneumonitis showing granulomatous inflammation. Trichrome stain.

By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=7673365

Ø  TREATMENT:  Avoiding the provoking allergen is the best treatment is to, as chronic exposure can cause permanent damage.  Face mask:  If they cannot avoid the allergen. Corticosteroids may help to control symptoms.


o   IDIOPATHIC INTERSTITIAL LUNG DISEASE:  I-Idiopathic interstitial pneumonia, S-sarcoidosis

o   IIP (IDIOPATHIC INTERSTIAL PNEUMONIA):  A type of diffuse lung disease that affect the distal lung parenchyma causing alveolitis

Ø  EPIDEMIOLOGY:  Prevalence:  29/100,000.  M = F. Usually 40-70 y/o.

Ø  PATHOPHYSIOLOGY: The earliest common manifestation is alveolitis with accumulation of inflammatory cells within the alveolar walls and spaces.  These leukocytes distort the normal alveolar structures and release cytokines that can injure parenchymal cells and stimulate fibrosis.  The end result is an end-stage fibrotic lung in which the alveoli are replaced by cystic spaces sepatd by thick bands of connective tissue (honeycomb). 

Ø  PRESENTATION:  Progressive dyspnea, non-productive cough, tachypnea, end-inspiratory crackles, and eventually cyanosis, pulmonary hypertension with cor pulmonale and digital clubbing.

Ø  DIAGNOSTIC EVALUATION:  CXR: Diffuse infiltration by small nodules, irregular lines, or ground glass shadows.  CT chest:  Linear opacities, honeycombing.  PFTs: Restrictive pattern with ↓ TLC and diminished DLCO.  Bronchoalveolar lavage:  Rules out other causes of ILD.  Lung biopsy:  Results is used to further divide IIP into 5 HISTOLOGIC TYPES:  DURAN (the band) → D-desquamative interstial pneumonia (DIP), U-usual interstitial pneumonia (UIP aka idiopathic pulmonary fibrosis-IPF), R-respiratory bronchiolitis (RB-ILD), A-acute interstitial pneumonia (AIP aka Hamman-Rich syndrome), N-nonspecific interstitial pneumonia (NSIP).

v  D _______________, _______________, _______________, _______________, _______________

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Appearance of honeycomb change in a surgical lung biopsy at low magnification. The dilated spaces seen here are filled with mucin.

By Mutleysmith - Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=8636384

CT scan of a patient with UIP. There is interstitial thickening, architectural distortion, honeycombing (seen at base of both lungs) and bronchiectasis.

By Yale Rosen from USA - UIP (Usual interstitial pneumonia)-CT scanUploaded by CFCF, CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=31127997

A fibroblast focus in a surgical lung biopsy of UIP.   It is an area of active fibroblast proliferation within the interstitium of the lung.

By Mutleysmith - Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=8636397

Diffuse alveolar damage, the histologic correlate of acute interstitial pneumonitis, acute respiratory distress syndrome (ARDS), and transfusion related acute lung injury (TRALI),

By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=14967240

Ø  TREATMENT: There is currently no consensus on the treatment of IPF.  Corticosteroid Therapy:   Response rate depends on histologic subtypes.  Cytotoxic drugs:  Azathioprine and cyclophosphamide are second line therapy that could be used in combination with Corticosteroids



LYMPHANGITIC CARCINOMATOSIS (LC):  Diffuse infiltration and obstruction of pulmonary parenchymal lymphatic channels by tumor.
Ø  EPIDEMIOLOGY:  While microscopic interstitial tumor invasion is seen in 56% of patients with pulmonary metastases, LC is seen in only 7%.

Ø  PATHOPHYSIOLOGY:  LC occurs as a result of the initial hematogenous spread of tumor to the lungs, with subsequent invasion through the vessel wall into the pulmonary interstitium and lymphatics. The pulmonary lymphatics are located in the interstitial components of the lung.  Tumor then proliferates and easily spreads through these low-resistance channels causing interstitial edema and interstitial fibrosis secondary to a desmoplastic reaction. Metastatic adenocarcinoma accounts for 80% of cases with the most common primary sites are the breasts, lungs, colon, and stomach.

Ø  PRESENTATION:  Middle-aged patient with a known malignancy present with breathlessness. Occasionally, patients may have a dry cough or hemoptysis. Symptoms often precede radiographic abnormality.

Ø  DIAGNOSTIC EVALUATION:  Plain CXR:  May be normal or show reticular or reticulonodular opacification, often with associated septal lines (Kerley A and B lines), peribronchial cuffing, pleural effusions, and mediastinal and/or hilar lymphadenopathy.   Sensitivity of CXR in LC is only 25%.   CT chest:  Findings varies and may include irregular interlobular septal thickening and thickening of the fissures as a result of the involvement of the lymphatics concentrated in the subpleural interstitium.  Lung biopsy:  Interstitial edema, tumor cells, and interstitial fibrosis secondary to a desmoplastic reaction.

Ø  TREATMENT:  No specific therapy.  The prognosis for patients with LC is poor. Most patients survive only weeks or months.

o   DRUGS:  ILD has been associated with the following substances:  BAN O2 & R-radiation (think ban them because they cause ILD) = BANOR → B-busulfan, B-bleomycin, A-antibiotic (sulfas), A-antifungals (amphotericin B), A-antiarrhythmic (amiodarone, lidocaine), A-antimetabolites (MTX), N-nitrofurantoin, O-O2 toxicity, R-radiation.

Ø  B _______________, _______________, _______________, _______________, _______________

Ø  A _______________, _______________, _______________, _______________, _______________

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Ø  O _______________, _______________, _______________, _______________, _______________

Ø  R _______________, _______________, _______________, _______________, _______________

o   NEUROMUSCULAR DISORDERS:  Such as MG, Duchene’s Muscular Dystrophy.   SEE NEUROLOGY.

o   THORACIC WALL ABNORMALITIES:  Such as kyphoscoliosis.

•       OBSTRUCTIVE LUNG DISEASE/COPD:  Characterised by an ↑ airway resistance, shown as a spirometric ↓ of PEFR (Peak Expiratory Flow Rate) and FEV1 (Forced Expiratory Volume in 1 Second). FEV1/FVC ratio will be decreased for a COPD patient because FVC will be normal or increased.  The RV is greatly increased in COPD, thus the TLC is also increased.   Since VC (IRV + TV + ERV) remains relatively normal, this leads to the clinical sign of chest over-inflation (i.e. barrel chest, flattening of the diaphragm).  TYPES OF COPD:  ABC anD E → A-asthma, B-bronchiectasis, C-chronic bronchitis, E-emphysema, and C-CF.

A _______________, _______________, _______________, _______________, _______________
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E _______________, _______________, _______________, _______________, _______________

ASTHMA:  A chronic condition in which the airway occasionally reversibly constricts, becomes inflamed, and is lined with excessive amounts of mucus, often in response to one or more triggers. Between episodes, most patients feel well but can have mild symptoms and they may remain short of breath after exercise for longer periods of time than the unaffected individual. 

Ø  EPIDEMIOLOGY:  Usually diagnosed in childhood.  US prevalence:  > 6% of children (a 75% increase in recent decades). The rate soars to 40% among some populations of urban children. Risk factors for asthma include ATOPY → A-atopy (eczema) or A-asthma history in self or family, T-tobacco use by pregnant mothers, T-triggers exposure (e.g. URIs especially with RSV, allergens [e.g. dust mice or cockroach excreta, grass pollen, mold spores, perfumed products], medications [e.g. aspirin, β-blockers, penicillin], food [e.g.  milk, peanuts, eggs], fossil fuel smog [major reasons for the high prevalence of asthma in urban areas], exercise, hormonal change [e.g. some women experience a worsening of their asthma during pregnancy or menstruation], cold weather),  O-origin of resident (higher prevalence of asthma seen in industrialized countries, urban dwellers, Blacks/Hispanics > Whites), P-premature birth or low birth weight, Y-younger population.    

v  A _______________, _______________, _______________, _______________, _______________

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Ø  PATHOPHYSIOLOGY:  Inhaled allergens that find their way to the inner airways are ingested by APCs (antigen presenting cells), which then present the digested antigen to other immune cells, including TH0 cells (undifferentiated T cell with the potential of becoming TH1 or TH2 cell). In asthmatics, TH0  differentiation is skewed to TH2 overproduction with subsequent humoral immune system activation with eosinophil-mediated response and IgE synthesis.   These IgE coats the surface of mast cells and basophils.  Later, when an asthmatic inhales the same antigen, a classic type I (IgE) hypersenstivity reaction in 2 steps:

1.     Acute phase:  Antigens bind presensitized IgE-coated mast cells and basophils causing their degranulation and release of mediators (e.g. LT, histamines, PGs), which causes bronchospasm, edema, mucus secretion,  and leukocyte recruitment.

2.     Late phase: 6-12 hours later, recruited leukocytes (e.g. eosinophils, neutrophils, lymphocytes, monocytes) release their own set of mediators (e.g. interleukins, TNF-a), which lead to prolonged bronchspasm, edema, and eventual epithelial damage and loss.

Overtime, epithelial cells damage stimulates repair processes by releasing growth factors (GFs) such as proteases, FGF, PDGF, and IL-1.  These GFs causes collagen & glycoprotein deposition, smooth muscle and goblet cell hyperplasia, angiogenesis, myofibroblast activation in a process call “airway remodeling”.

Figure A shows the location of the lungs and airways in the body. Figure B shows a cross-section of a normal airway. Figure C shows a cross-section of an airway during asthma symptoms.

By United States-National Institute of Health: National Heart, Lung, Blood Institute - http://www.nhlbi.nih.gov/health/health-topics/topics/asthma/, Public Domain, https://commons.wikimedia.org/w/index.php?curid=24760677

Ø  PRESENTATION:  Episodic bouts (i.e. asthma attack) of dyspnea, wheezing & stridor (in the late stages of an attack, air motion may be so impaired that no wheezing may be heard), coughing, tachypnea, tachycardia, prolonged expiration, ribs retraction (due to use of accessory muscles of respiration such as external intercostals and sternocleidomastoid), pulsus paradoxus (> 10 mmHg ↓ systolic BP on inspiration), lung hyper-inflation.  In severe attack, chest pain, cyanosis, and loss of consciousness may occur.   Between attacks, patients may show no sign of the disease or has chronic respiratory impairment and exercise intolerance.  Status asthmaticus:  Severe life-threatening attacks that do not respond to standard treatments of bronchodilators and corticosteroids, and may lead to respiratory arrest and death.

Ø  DIAGNOSTIC EVALUATION:  H&P:  History of atopy or asthma. CBC: Eosinophilia.  ABG: Hypoxemia. Respiratory alkalosis from tachypnea (normalization PCO2 and quiet breathing in acute exacerbation may indicate respiratory muscle fatigue and impending respiratory failure).  CXR: Hyperinflation.  PFTs:  PEF (peak expiratory flow):  Readings are higher when patients are well and lower when the airways are constricted.  Measurements are taken at baseline and during symptomatic phases to monitor severity of disease.  Post-exercise PEF measurement is also indicated in certain cases to rule out exercise-induced asthma.  Spirometry:  Obstructive lung pattern with ↓ FEV1.  Methacholine challenge:  Allow diagnosis when patient is in between asthma attack.  Nebulized methacholine will provoke bronchoconstriction in asthmatics.    SUMMARY OF ASTHMA:  CHARCOT (as in CHARCOT-Leyden crystals) → C-charcot-Leyden crystals (crystalloid eosinophil granule debris) and C-curchsmann spirals (whorled mucus plugs) are  grossly seen in the airways; H-hyperinflated lungs are seen on CXR, microscopically H-hypertrophy of bronchial wall smooth muscle and H-hyperplasia of goblet cells are seen due to A-allergen-induced A-airway R-modeling; as a result of R-reversible C-constriction of the bronchi patients present with C-cough, C-cyanosis from O-O2-desaturation (hypoxia), T-tachypnea, and T-tachycardia.

v  C _______________, _______________, _______________, _______________, _______________

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Peak flow meters are used to measure the peak expiratory flow rate, important in both monitoring and diagnosing asthma

By Hosse 19:20, 21. Jan 2005 (CET) - Fotografiert am 20.01.2005, Public Domain, https://commons.wikimedia.org/w/index.php?curid=4876396

Obstruction of the lumen of a bronchiole by mucoid exudate, goblet cell metaplasia, and epithelial basement membrane thickening in a person with asthma.

By Yale Rosen - http://www.flickr.com/photos/pulmonary_pathology/3705143121/, CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=7621937

Ø  TREATMENT:  The most effective treatment is identifying triggers and limiting or eliminating exposure to them. Smoking cessation and avoidance of second-hand smoke is strongly encouraged.  The specific medical treatment depends on the severity of illness and the frequency of their symptoms, and includes C-control ASTHMA →  C-cromolyn (prevents mediators release by mast cells), A-albuterol (and other b2-agonist like salmeterol → ↑ cAMP → bronchodilation), S-steroids (inhibits all cytokines), T-theophylline (a methylxanthine that inhibit PDE → ↑ cAMP → bronchodilation), H-humidifed O2 (prevent hypoxia), M-muscarinic antagonist (e.g. ipratropium prevents bronchoconstriction), M-MgSO4 (for acute symptoms refractory to b-agonist), A-anti-leukotrienes (Zileuton blocks 5-lipoxygenase → ↓ leukotrienes synthesis; montelukast block leukotriene receptors).

v  C _______________, _______________, _______________, _______________, _______________

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v  A _______________, _______________, _______________, _______________, _______________

Fluticasone propionate metered dose inhaler commonly used for long-term control.

By James Heilman, MD - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=10313945

Specific treatments for asthma are broadly classified as relievers, preventers and emergency treatment.

1.     Relief medication:  Symptomatic control of episodes of wheezing and shortness of breath is generally achieved:  a) Short-acting, selective b2- agonists (albuterol, levalbuterol):  These are the first line but caution against using them too frequently as their efficacy may decline, producing refractory asthma and death b) Muscarinic antagonists (e.g. ipratropium bromide):   May take up to an hour to achieve their full effect and are not as powerful as the β2-agonists, thus are rarely used, except in patients who do not tolerate b2-agonists.)

2. Preventive medication:  a) Inhaled glucocorticoids (e.g. beclomethasone, budesonide, fluticasone):  Most widely used of the prevention medications.  Rinsing the mouth after use is recommended to reduce hoarseness of voice or oral thrush from steroids deposition in the throat b) Leukotriene modifiers (montelukast) c) Mast cell stabilizers (cromolyn) d) Long acting b-agonist (salmeterol) e) Methylxanthines (theophylline and aminophylline):  Considered if sufficient control cannot be achieved with inhaled glucocorticoids and long-acting β-agonists alone f) IgE blocker (omalizumab): Consider in severe allergic asthma that does not respond to other drugs.

3.    Emergency treatment:  a) Humidifed O2:  Alleviate the hypoxia b) Nebulized short-acting b2-agnonist (salbutamol or terbutaline) often in combination with a muscarinic antagonist (ipratropium) c) Systemic steroids (prednisone):  IV or PO d) Non-specific b-agonists (isoproterenol, metaproterenol) and MgSO4:  IV form has been trialed when other drugs have failed.  Intubation and mechanical ventilation:  For respiratory arrest.

Ø  EIA (EXERCISE-INDUCED ASTHMA):  A condition characterized by SOB induced by sustained aerobic exercise.

v  PATHOPHYSIOLOGY:  Usually occurs after several minutes of vigorous, "aerobic" activity, when normal nasal breathing must be supplemented by mouth-breathing. The resultant inhalation of air that has not been warmed and humidified by the nasal passages seems to generate increased blood flow to the linings of the bronchial tree, resulting in edema. Constriction of these vessels then follows, worsening the degree of obstruction to airflow. This sequence generates symptoms similar to those seen in other forms of asthma, but occurs without the inflammatory changes that underlie them.

v  PRESENTATION:  SOB, coughing, tachypnea, wheezing, prolonged expiratory phase, and cyanosis in extreme cases.   In most cases, resolution of an attack is followed by 1) A refractory period lasting about 1 hour during which resumption of exercise will likely produce no or mild symptoms 2) A rebound period 6-10 hours after the initial attack, in which milder symptoms often develops without precipitating exertion.

v  DIAGNOSTIC EVALUATION:  Similar to asthma work-up.  Exercise challenge:  Obtain pre- and post-exercise spirometry.  Exercise is usually running on a treadmill obtaining 90% maximum HR for 6-8 minutes.  A ≥ 15% drop of FEV1 is required for diagnosis.

v  TREATMENT:  Best treatment is avoidance of conditions predisposing to attacks.  Lengthy warm up:  May preclude medications.  Short-acting b-agonists: This is the most used medication.  It is taken ~20 minutes before exercise and last 2-3 hours. Long-acting b-agonist (salmeterol) and mast cell stabilizers (cromolyn) have also proven effective.

o   BRONCHIECTASIS:  A disease that causes localized, irreversible dilatation of part of the bronchial tree. Involved bronchi are dilated, inflamed, and easily collapsible, resulting in airflow obstruction and impaired clearance of secretions.

Ø  PATHOPHYSIOLOGY:  Associated with a wide range of disorders, but it usually results from necrotizing bacterial infections, such as infections caused by Staphylococcus, Klebsiella species, Bordetella pertussis, TB.  It is also associated with Kartagener syndrome, cystic fibrosis, Young's syndrome (a rare condition that encompasses a combination of bronchiectasis and rhinosinusitis [due to abnormally viscous pulmonary mucus like CF] and reduced fertility [due to azoospermia from functional obstruction of sperm transport at the epididymis where the sperm are found in viscous, lipid-rich fluid]), a1-antitrypsin deficiency,  primary immunodeficiencies, inflammatory bowel disease (ulcerative colitis > Crohn’s disease),  ABPA (allergic bronchopulmonary aspergillosis), and environmental exposures (e.g. aspiration of toxic gases and stomach content).  The insults intially cause dilation of the bronchial walls results in airflow obstruction and impaired clearance of secretions. The pooled sputum provides an environment conducive to the growth of infectious pathogens, and these areas of the lungs are thus very vulnerable to infection. After recurren bouts of infection, the bronchial tubes become more inelastic and dilated, creating a self-perpetuating cycle of further damage to the lungs.  

Figure A shows a cross-section of the lungs with normal airways and widened airways. Figure B shows a cross-section of a normal airway. Figure C shows a cross-section of an airway with bronchiectasis.

By National Heart Lung and Blood Institute - National Heart Lung and Blood Institute, Public Domain, https://commons.wikimedia.org/w/index.php?curid=29583169

Ø  PRESENTATION:  Usually present with recurrent pneumona with cough productive of yellow-green sputum, dyspnea, halitosis, hemoptysis, wheezes, rales.

Ø  DIAGNOSTIC EVALUATION:  H&P.  ABG: Hypoxia, hypercapnia.  CXR: Increased bronchovascular markings from peribronchial fibrosis and intrabronchial secretions.  CT chest:  Airway dilatation causing characteristic "tree-in-bud" abnormalities with ballooned cysts with definable borders at the end of the bronchus.  Sputum culture:  Identify infective organism.  Spirometry:  Obstructive pattern (↓FEV1/FVC).

Ø  TREATMENT:  Goal is to control infections and bronchial secretions, relieve airway obstruction, and prevent complications.  Antibiotics:   Prolonged use of erythromycin or quinolones to prevent.   Postural drainage and chest physiotherapy: Eliminating accumulated secretion.  Inhaled steroid (e.g. beclometasone):  Reduces airway inflammation, constriction, and sputum production help prevent progression of bronchiectasis.  Albuterol and impratropium:  May helps clear the airways and decrease inflammation.   Lobectomy or lung transplant: For severe disesease.   

Bronchiectasis, gross pathology.

By Yale Rosen - http://www.flickr.com/photos/pulmonary_pathology/3791074491/, CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=7621749

Ø  KARTAGENER SYNDROME (aka primary ciliary dyskinesia or immotile ciliary syndrome):  A rare autosomal recessive genetic disorder which causes a defect in the action of cilia lining the upper and lower respiratory tract and fallopian tube.

v  EPIDEMIOLOGY:  Incidence:  ~ 1/32,000. 

v  PATHOPHYSIOLOGY:  A genetically heterogenous disorder affecting motile cilia, which are made up of approximately 250 proteins. Structures that make up the cilia including inner and/or outer dynein arms, central apparatus, radial spokes, etc. are missing or dysfunctional and thus the cilia lacks the ability to move. Dysfunction of the cilia begins during and impacts the embryologic phase of development causing situs inversus.  Postnatally, these consequences are seen 1) Impaired ciliary function reduces mucus clearance from the lungs causing recurrent respiratory infections (e.g.  sinusitis, bronchitis, pneumonia, and otitis media 2) Impair auditory hair cell causing hearing loss 3) Defective ciliary action in the follopian tube in affected females or diminished sperm motility in affected males causing infertility 4) Impaired functioning of ventricular ependymal cilia causing chronic headaches and, rarely, hydrocephalus

Normal cilia (A) and cilia representative of Kartagener's syndrome (B).

By Filip em - Own work, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=3838971

v  PRESENTATION:  Infertility + triad of situs inversus, chronic sinusitis, and bronchiectasis.

v  TREATMENT:  Goals:  Enhance clearance of mucus and prevent respiratory infections (e.g. chest physiology), and treat bacterial superinfections (e.g. antibiotics).  Early diagnosis is crucial as treatment during childhood helps prevent the lungs being damaged or colonised by infection during this vulnerable period.   IVF techniques (in vitro fertilization):  For those wishing to have children. Lung transplant:  For severe cases.

Axial CT image showing situs inversus. The liver is normally on the right side of the body and the spleen on the left, they are switched in this patient with situs inversus.

By John S. To, MD - Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=3498398

Axial CT image showing dextrocardia with the IVC and morphologic right ventricle on the left and the left ventricle on the right.

By John S. To, MD - Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=3498394

Axial CT image showing chronic sinusitis in an individual with Kartagener syndrome.

By John S. To, MD - Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=3498399

Sagittal CT image showing "tree in bud" appearance of mucous impaction in distal small airways related to primary ciliary dyskinesia.

By John S. To, MD - Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=3498395

CT image showing dilated and thickened medium-sized airways (bronchiectasis)in a patient with Kartagener syndrome.

By John S. To, MD - Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=3498393

Oblique sagittal CT image showing lower lobe cylinidrical bronchiectasis in the same patient.

By John S. To, MD - Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=3498396

o   COPD (CHRONIC OBSTRUCTIVE PULMONARY DISEASE):  A group of diseases consisting of chronic bronchitis and emphysema, characterized by the pathological limitation of airway airflow that is not fully reversible.

Ø  EPIDEMIOLOGY:  It is most often due to tobacco smoking.  It is the 4th leading cause of death in the U.S.

Ø  PATHOPHYSIOLOGY: Differences exist between chronic bronchitis and emphysema.

On the left is a diagram of the lungs and airways with an inset showing a detailed cross-section of normal bronchioles and alveoli. On the right are lungs damaged by COPD with an inset showing a cross-section of damaged bronchioles and alveoli.

By National Heart Lung and Blood Institute - http://www.nhlbi.nih.gov/health//dci/Diseases/Copd/Copd_WhatIs.html, Public Domain, https://commons.wikimedia.org/w/index.php?curid=29752919

Ø  PATHOPHYSIOLOGY: Differences exist between chronic bronchitis and emphysema.

v  CHRONIC BRONCHITIS:   Chronic bronchitis is defined clinically as a persistent productive cough that persists for at least 3 months in 2 consecutive years.  The hallmark is hyperplasia and hypertrophy of airway goblet cells, resulting in an increase of mucus secretion which contributes to the airway obstruction.  Furthermore, there is infiltration of the airway walls with inflammatory cells, particularly neutrophils. Inflammation is followed by scarring and remodeling that thickens the walls resulting in narrowing of the small airway. Further progression leads to metaplasia and fibrosis of the lower airway. The consequence of these changes is a limitation of airflow. Chronic bronchitis patients are CO2 - retainers because of CO2 trapping behind mucus plugs despite hyperventilation. Overtime, these patients an abnormal ventilatory drive (i.e. hypoxemic drive to breath) because the chronic hypercapnia reduces the CNS respiratory center sensitivity to CO2.   This is the reason how these patients turns “blue”.

v  EMPHYSEMA:  Emphysema is defined histologically as the enlargement of the air spaces distal to the terminal bronchioles, with destruction of their walls without obvious fibrosis.   When toxins such as smoke are breathed into the lungs, the particles cause a localized inflammatory response, with resultant release of mediators (e.g., neutrophil elastase, metalloproteases) that break down alveoli wall. a1-antitrypsin (A1AT) is the primary inhibitor of elastase, thus minimizes the destructive action of one of these damaging molecules.  Emphysema occurs in a higher proportion (along with liver cirrhosis) in patients with A1AT deficiency.   Alveoli wall destruction (from loss of structural supports including elastin) results in the air space enlargement and loss of elasticity (increased compliance) of the lung tissue.   Lack of alveolar recoil during expiration leads to air trapping.  Hypercapnemia stimulates hyperventilation; since emphysema patients do not have problem with CO2-trapping as in chronic bronchitis, they maintain a normal CO2 level and adequate blood oxygen levels.  This is the reason how these patient remains “pink”.  Emphysema is further divided into 3 main types:

1.     Centriacinar: 95% of emphysema cases. Affects the bronchial tree at the level of terminal and respiratory bronchioles typically in the UPPER lungs.  Associated with smokers, chronic bronchitis, and coal workers pneumoconiosis.

2.     Panacinar: The entire acinus, from the terminal bronchioles to the alveolar ducts and alveoli, is involved typically in the LOWER lungs.  This type usually occurs in younger people, and is associated with primary a-1-antitrypsin deficiency. 

3.     Paraseptal:  Involves the alveolar ducts and sacs at the lung periphery (i.e. subpleural in location), thus often surrounded by interlobular septa.  Associated with spontaneous pneumothorax in young adults, and older patients with centrilobular emphysema.

Ø  PRESENTATION:  Differences exist between chronic bronchitis and emphysema.

v  CHRONIC BRONCHITIS:  Productive cough of yellow-green sputum, dyspnea, tachypnea, wheezing, ↑ expiratory phase of respiration, ↓ breath sounds, hemoptysis, and digital clubbing (rare and suggest additional condition such as lung cancer).   Also, these patients are usually overweight and have peripheral cyanosis from hypoxemia (i.e. blue bloater).  Cor pulmonale may occure in extreme cases due to the development of pulmonary hyptertension.

v  EMPHYSEMA: Dyspnea, pursed-lip breathing, ↓ breath sounds, expanded chest, and hyperventilation.  Emphysema patients are referred to as "pink puffers" because they may hyperventilate to maintain adequate blood oxygen levels in the early stages of the diseaes.

However, as the disease progresses, both chronic bronchitis and emphysema will results in hypoxaemia and hypercapnemia, because hyperventilation becomes inadequate to maintain high enough oxygen levels in the blood. At this time, the body compensates by vasoconstricting appropriate vessels. This leads to pulmonary hypertension, and eventually cor pulmonale. 

Ø  DIAGNOSTIC EVALUATION:  H&P.  Pulse oxygen.  ABG: ↑ PaCO2.  CBC & CRP: Rule out acute infection.  Sputum gram stain and culture: Rule out pulmonary infection.  PFT:  FEV1/FVC ratio < 0.7 that is not fully reversible after bronchodilator therapy indicates COPD.  DLCO: ↓ diffusion capacity.  CXR:  Lung hyperinflation.  Other tests: CT chest, bronchoscopy (when suspect malignancy), a1-antitrypsin deficiency.

A person blowing into a spirometer. Smaller handheld devices are available for office use.

By Jmarchn - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=26590234

Chest X-ray demonstrating severe COPD. Note the small heart size in comparison to the lungs.

By James Heilman, MD - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=11110538

A lateral chest x-ray of a person with emphysema. Note the barrel chest and flat diaphragm.

By James Heilman, MD - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=9500331

A severe case of bullous emphysema

By © Nevit Dilmen, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=17757650

Axial CT image of the lung of a person with end-stage bullous emphysema.

By James Heilman, MD - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=12236115

Very severe emphysema with lung cancer on the left (CT scan)

By James Heilman, MD - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=49082157

Lung bulla as seen on CXR in a person with severe COPD

By James Heilman, MD - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=14634317

Gross pathology of a lung showing centrilobular-type emphysema characteristic of smoking. This close-up of the fixed, cut lung surface shows multiple cavities filled with heavy black carbon deposits.

By Dr. Edwin P. Ewing, Jr. - http://phil.cdc.gov/phil_images/20040517/4/865_lores.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=825643

Micrograph showing emphysema (left – large empty spaces) and lung tissue with relative preservation of the alveoli (right)

By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=7935360

Ø  TREATMENT:  Similar for both chronic bronchitis and emphysema.

v  Acute exacerbation:  O2, b-agonists (e.g. albuterol) and muscarinic-antagonists (e.g. ipratropium), Steroids IV, and Antibiotics (e.g. amoxicillin/clavulanic acid, macrolides, 2nd and 3rd generation cephalosporins, and quinolones).  

v  Chronic therapy:  Smoking cessation and O2 supplementation are the only measures proven to slow down disease progression.  O2 supplement:  Reserved for individuals with hypoxemia (PaO2 < 55 mm Hg or a PaO2 between 55-60 mm Hg with evidence of pulmonary hypertension, cor pulmonale, or secondary erythrocytosis-hematocrit >55%). The use of low flow oxygen, no more than 1 - 2L by nasal cannula, is extremely important because in the COPD patient, control of respiration is driven mainly by the blood oxygen level rather than the carbon dioxide level, increased oxygen delivery can diminish this response and cause respiratory failure.  Vaccination:  Influenza, pneumococcus.  Other meds: Inhaled b-agonists (e.g. albuterol), muscarinic-antagonists (e.g. ipratropium), and corticosteroids.  Lung transplant.

v  SUMMARY OF CHRONIC BRONCHITIS:  BRONCHITIS à B-blue bloater, B-bronchioles are affected, R-reid index ↑ (ratio between the thickness of the mucosa secreting glands and the thickness between the epithelium and cartilage; normal < 0.4), O-obese (i.e. bloater), in final stages lungs in N-non-ventilated  areas (i.e. V/Q mismatch) there is C-constriction of pulmonary vessel leading to pulmonary H-hypertension, and as a result C-cor pulmonale; patients presents with C-cough for 3 C-consecutive month/year for ≥ 2 years, C-cracke, C-cyanosis; microscopically there is H-hyperplasia of Goblet cells and I-inflammatory cells infiltration causing T-thickend sputum, I-inflammation; S-smoking is the main etiology.

§  B ______________, ______________, _______________, _______________, _______________

§  R ______________, ______________, _______________, _______________, _______________

§  O _____________­_, _______________, ______________, _______________, _______________

§  N ______________, ______________, ______________, _______________, _______________

§  C ______________, ______________, _______________, _______________, _______________

§  H ______________, ______________, _______________, _______________, _______________

§  I ______________, ______________, _______________, _______________, _______________

§  T ______________, ______________, _______________, _______________, _______________

§  I  ______________, _______________, _______________, _______________, _______________

§  S ______________, _______________, _______________, _______________, _______________

o   CF (CYSTIC FIBROSIS aka mucoviscoidosis):    

Ø  EPIDEMIOLOGY:  The most common life-limiting autosomal recessive disease among people of European heritage.  It is mostly common in Ashkenazi Jews with a carrier rate of 1/22. US prevalence: 30,000.   M = F.  Incidence: 1/3200 births.  Most CF patients are diagnosed by 6 months of age. Life expectancy for people with CF depends largely upon access to health care.  Currently, most patient die young: many in their 20s and 30s from lung failure.

The CFTR protein is a channel protein that controls the flow of H2O and Cl- ions in and out of cells inside the lungs. When the CFTR protein is working correctly, ions freely flow in and out of the cells. However, when the CFTR protein is malfunctioning, these ions cannot flow out of the cell due to a blocked channel. This causes cystic fibrosis, characterized by the buildup of thick mucus in the lungs.

Ø  PATHOPHYSIOLOGY:  CF occurs when there is a mutation (90% due to DF508) in the CFTR gene (cystic fibrosis transmembrane conductance regulator), which codes a transmembrane protein that control the movement of chloride ions (Cl-) of the cells in the sweat glands, lungs, GI tract, and other organs.  

v  Sweat glands:  Normally CFTR allows REASORPTION of Cl- from the sweat into the cells.  Thus, CFTR mutation causes increased sweat Cl- concentration (sweat Cl- test is use for diagnosis)

v  Lungs, pancreas, and other organs: Normally CFTR allows cellular SECRETION of Cl-.  Thus, CFTR mutation leads to the intracellular trapping of negatively-charged Cl-, which electrostatically attracts Na+ into the cell.  Together Na+ and Cl- cause osmotic resorption of water from the lumen creating a thick, dehydrated mucus, which ultimately obstruct ductal outflow. 

v  PRESENTATION:  The thick, dehydarated mucus (mucovicoidosis) effects these organs R.I.P, rest in peace, (CF is serious, man) →

1.     R-respiratory tract:  Dyspnea, cough, sinusitis, nasal polyps, bronchiectasis, hymoptysis, cyanosis, and digital clubbing.  Impairs mucociliary action allowing bacteria (commonly Pseudomonas, S. aureus, and H. influenza) to colonize the lung from an early age. The mucus also encourage the development of a bacterial biofilms that are difficult for immune cells and antibiotics to penetrate. 

2.     R-reproductive system:  Infertility occurs in 97% of CF males because the vas deferens is frequently missing in these patients.  It occur less frequently with women and is often due to thickened cervical mucus or malnutrition (which disrupts ovulation and causes amenorrhea).  

3.     I-intestine: Blockage by thick feces.  Constipation. Intestinal obstruction. Intussusception. Meconium ileus:  Occurs in 10% of newborns with CF.  Rectal prolapse: More common in CF because of increased fecal volume and increased intra-abdominal pressure from coughing.

4.     P-pancreas:  Blockage of exocrine gland causing dilatation and auto-digestion by pancreatic enzymes (i.e. pancreatitis).  Exocrine dysfunction causes malabsorption syndrome (including failure to thrive in kids) and fat-soluble vitamins deficiency (Vit ADKE).  Endocrine dysfunction causes diabetes mellitus II.

5.     Liver: Plug bile canaliculi results in diffuse cirrhosis.

§  R _____________, ______________, _______________, ______________, ______________

§  I ______________, ______________, ______________, ______________, ______________

§  P _____________­_, _______________, _____________, ______________, ______________

Health problems associated with cystic fibrosis

By BruceBlaus. When using this image in external sources it can be cited as:Blausen.com staff (2014). "Medical gallery of Blausen Medical 2014". WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436. - Own work, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=27924379

Figure A shows the organs that cystic fibrosis can affect. Figure B shows a cross-section of a normal airway. Figure C shows an airway with cystic fibrosis. The widened airway is blocked by thick, sticky mucus that contains blood and bacteria.

By National Heart Lung and Blood Institute (NIH) - National Heart Lung and Blood Institute (NIH), Public Domain, https://commons.wikimedia.org/w/index.php?curid=29588226

Clubbing in the fingers of a person with cystic fibrosis

By Jerry Nick, M.D. - http://knol.google.com/k/jerry-nick-m-d/cystic-fibrosis/UtI7gr91/HU2bIw#, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=8725200

v  DIAGNOSTIC EVALUATION:  Sweat chloride test:  Apply pilocarpine to stimulate sweating, which is collected on filter paper and analyzed for chloride. Positive test if > 60 mEq/L for those < 20 y/o; > 80 mEq/L in those > 20 y/o.  Genetic testing:  For mutations in the CFTR gene.  Newborn screening: Measures for ↑ serum immunoreactive trypsinogen.  This method is not done routinely, but accounts for ~ 10% of cases.  Other test:  CBC. CXR. CT scan. Sputum Gram stain and culture. PFTs. LFTs. Blood glucose and HgbA1C.

Respiratory infections in CF varies according to age.

Green = Pseudomonas aeruginosa
Brown = Staphylococcus aureus
Blue = Haemophilus influenzae
Red = Burkholderia cepacia complex

By Ninjatacoshell - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=13345834

The location of the CFTR gene on chromosome 7

By Mucoviscidose.PNG: Mirmillonderivative work: Hazmat2 (talk) - This file was derived from  Mucoviscidose.PNG:, Copyrighted free use, https://commons.wikimedia.org/w/index.php?curid=18165360

v  SUMMARY OF CF: CFRT (name of the transmembrane channel) → C-CFRT gene on chromosome 7 is mutated, C-Cl- channel, F-F508 (the most common mutation), F-fat malabsorption causing vitamin ADKE deficiency, T-thickened feces (cause meconeum ileus, intestinal obstruction), R-respiratory system (infection is number one cause of death in CF, polyps…), R-reproductive system (infertility…)

§  C _____________, ______________, _______________, ______________, ______________

§  F ______________, ______________, ______________, ______________, ______________

§  T _____________­_, _______________, _____________, ______________, ______________

§  R _____________­_, _______________, _____________, ______________, ______________

v  TREATMENT:  The goal is to delay decline of organ function.  The most important aspect of therapy is limiting and treating the lung damage to maintain quality of life. Therapy includes ABCDEF → A-antibiotics (given whenever pneumonia is suspected for a prolonged period of time because many bacteria common in CF are resistant to multiple antibiotics), A-anti-inflammatory agent (e.g. nasal steroids), B-bronchodilators (albuterol and ipratropium are inhaled to relax the airway), C-chest physiology (dislodge sputum and encourage its expectoration), D-DNAase (breaks down DNA in the sputum, thus decreasing its viscosity), E-enzyme and nutritional replacement (pancreatic enzymes, vitamins A, D, E, and K, insulin for diabetes), F-fertility treatment (assisted reproduction technology for those wishing to have children).  Lung &/or pancreas transplant: Considered when function decline approaches a point where it threatens survival. Gene therapy is recurrenly being studied.

§  A ______________, ______________, _______________, _______________, _______________

§  B ______________, ______________, _______________, _______________, _______________

§  C _____________­_, _______________, ______________, _______________, _______________

§  D ______________, ______________, ______________, _______________, _______________

§  E ______________, ______________, _______________, _______________, _______________

§  F ______________, ______________, _______________, _______________, _______________

Intracytoplasmic sperm injection can be used to provide fertility for men with cystic fibrosis

Public Domain, https://commons.wikimedia.org/w/index.php?curid=456617

VASCULAR LUNG DISEASE:  Pulmonary edema, Pulmonary embolism, Pulmonary hyptertension

o   PULMONARY EDEMA:  Fluid accumulation in the lung interstitium (i.e. extravascular space).

Ø  PATHOPHYSIOLOGY: Pulmonary edema is either a result of inadequate functioning of the heart and circulatory system (i.e. cardiogenic) or due to direct damage to lung tissue (i.e. non-cardiogenic).  The Starling equation, which explains fluid movement across capillary membrane as a result of filtration, can be used to describe pleural edema:

PLEURAL EFFUSION = Kf  ([Pc + πi] −  [Pi − πc])

Cardiogenic causes (due to ↑ Pc from backflow of fluid into the lung capillaries): HEART → H-heart failure, H-heart attack, H-hypertensive crisis, E-excessive fluid therapy, A-arrythmias (tachy- or bradycardia), R-renal failure causing fluid overload, cardiac T-tamponde (i.e. pericardial effusion).

v  H _______________, _______________, _______________, _______________, _______________

v  E _______________, _______________, _______________, _______________, _______________

v  A _______________, _______________, _______________, _______________, _______________

v  R _______________, _______________, _______________, _______________, _______________

v  T _______________, _______________, _______________, _______________, _______________

Non-cardiogenic causes:  This form is contiguous with ARDS.

v  ↑ Kf  (capillary permeability):  Inhalation of toxic gases, Multiple blood transfusions, Severe infection (e.g. sepsis, pneumonia), Pulmonary contusion, Multitrauma, Neurogenic (e.g. subarachnoid hemorrhage), Aspiration (e.g drowning, gastric fluid), Certain medication (e.g. opiates), AVM.

v  ↓ πc (capillary osmotic pressure): Hypoalbuminemia.

v  ↓ Pi (interstitial hydrostatic pressure):   Re-expansion (i.e. post pneumonectomy or large volume thoracentesis), Reperfusion injury (i.e. postpulmonary thromboendartectomy or lung transplantation).

v  Other: HAPE (high altitude pulmonary edema):  A life-threatening condition that occurs in otherwise healthy mountaineers at altitudes above > 2,500 meters.  Epidemiology: Incidence: Occurs in < 1% of unacclimatized travelers exposed to high altitude (~4,000 m).  Currently, it is not possible to predict individual susceptibility to HAPE.  Pathophysiology:  The initial insult that causes HAPE is a shortage of O2 caused by the lower air pressure at high altitudes, which lead to:  1) Hypoxic pulmonary vasoconstriction à ↑ Pc (i.e. pulmonary hypertension) 2) Idiopathic non-inflammatory ↑ permeability of the vascular endothelium (Kf).  Treatment:  Descend to lower altitude:  At least 1000 meters as quickly as possible.  This is the most important treatment, and symptoms tend to quickly improve.  O2 supplement.  Medications: Nifedipine, acetazolamide, dexamethasone, salmeterol or sildenafil may help.

Ø  PRESENTATION:  History: Cardiovascular disease, Dyspnea, coughing pink frothy sputum (classic sign, sweating, anxiety, pallor, fluid overload (e.g. ankle pitting edema, nocturia, orthopnea, and paroxysmal nocturnal dyspnea). Physical exam:  Cyanosis, end-inspiratory crackles (characteristic for pulmonary edema), 3rd heart sound (S3 is predictive of cardiogenic pulmonary edema), and Cheyne-Stokes breathing (aka periodic breathing is characterized by oscillation of ventilation between apnea and hyperpnea, to compensate for changing serum partial pressures of O2 and CO2; it is seen with brain injury [e.g. strokes, traumatic brain injuries, brain tumors, toxic metabolic encephalopathy], CHF, and morphine administration).  Untreated, it can lead to coma and death from hypoxia.

Ø  DIAGNOSTIC EVALUATION:  CBC.  CMP:  Check electrolytes, renal function, liver function.  CRP/ESR.  Coagulation studies:  PT, aPTT.  BNP (B-type natriuretic peptide):  Check for CHF.   CXR (confirm the diagnosis):   Enlarged heart,  prominent pulmonary vessels, pleural effusions, patchy alveolar infiltrates with air bronchograms, Kerley B lines (short parallel lines at the lung periphery at right angles to the pleura representing the interlobular septa; they are most frequently observed at the lung bases).  ABG: ↓ PaO2.  Echo: May strengthen the diagnosis by identifying cardiogenic causes.  Swan-Ganz catheter:  May be used to identify left ventricular dysfunction, thus confirm cardiogenic pulmonary edema.

Pulmonary edema with small pleural effusions on both sides.

By James Heilman, MD - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=14633663

Pulmonary edema on CT-scan (coronal MPR)

 By Hellerhoff - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=12228135

X-Ray showing pulmonary oedema

By Frank Gaillard - http://images.radiopaedia.org/images/4195/5e7cfb6d90bbcf70e73493819e691a.jpg, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=14698169

Ø  TREATMENT:  Initial goal focused on maintaining adequate oxygenation, then treat the underlying cause.  O2 supplement.  Cardiogenic pulmonary edema:  Nitrates (glyceryl trinitrate) and loop diuretics (e.g. furosemide or bumetanide) are used to improve both preload and afterload.  Non-cardiogenic pulmonary edema:  Removal of the causes (e.g., treating an infection) is the most important measure.

A deep vein thrombosis as seen in the right leg is a risk factor for PE

By James Heilman, MD - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=9444797

o   PE (PULMONARY EMBOLISM):  Blockage of the pulmonary artery (or one of its branches), usually from venous thromboembolism (VTE - a venous thrombus that dislodges from its site of formation and embolizes to the arterial blood supply).  Rarer forms of pulmonary embolism results from material other than a blood clot, which include fat or bone (usually with significant trauma), air (often when diving), clumped tumor cells, and amniotic fluid (affecting mothers during childbirth).

Ø  EPIDEMIOLOGY:  Incidence: 650,000/year.  Mostly in hospitalized elderly patients, and it is the 3rd most common cause of death in hospitalized patients. Autopsy studies revealed that approximately 60% of patients who died in the hospital had PE, and the diagnosis was missed in up to 70% of the cases. F > M (especially during pregnancy and postpartum period).

Ø  PATHOPHYSIOLOGY:  ~ 95% of emboli originate from proximal leg DVTs (deep venous thrombosis) or pelvic vein thromboses. ~ 60% of DVTs will present with VTE (venous thromboembolism); however < 50% of VTE are of adequate size to cause significant symptom.   Risk factors for DVTs include Virchow's triad (often > risk factor is present):  SHE (remember the incidence of DVT is F > M or SHE > he) →

1.     S-stasis: O-obesity & I-immobility C-causes S-stasis (remember this; it is a known fact) = OICS  → O-obesity, I-immobility (e.g. long-distance air travel), C-CHF, S-surgery.

§  O ______________­, _______________, _______________, _______________, ______________

§  I _______________, _______________, _______________, _______________, ______________

§  C _______________, _______________, _______________, ______________, ______________

§  S _______________, _______________, _______________, _______________, ______________

2.     H-hypercoagulable states:  OCP (remember OCP is contraindicated in femal smokers > 35 y/o due to ↑ risk of DVT) → O-OCP (estrogen-containing), C-cancers (most commonly with pancreatic and bronchogenic carcinoma), C-coagulation disorder (e.g. P-please F-feel M-my A-ass = PFMA → P-prothrombin G20210A mutation, P-protein C or S deficiency, P-PNH-paroxymal nocturnal hemoglobinuria, P-plasminogen disorder, F-FVL, M-MTHFR mutation, A-antiphospholipid antibodies syndrome, A-antithrombin III deficiency; SEE HEMATOLOGY), P-pregnancy

§  O _______________, _______________, _______________, ______________, ______________

§  C _______________, _______________, _______________, ______________, ______________

§  P _______________, _______________, _______________, _______________, ______________

3.     E-endothelial injury:  Trauma, fracture (highest risk with femur & tibial fracture), or surgery.

Ø  PRESENTATION:  History: Dyspnea, pleuritic chest pain, cough, hemoptysis, and low-grade fever  Physical exam:  Tachypnea, rales, tachycardia, S4, cyanosis and circulatory instability (e.g. hypotension, syncope) occur in severe cases. 

Chest spiral CT scan with radiocontrast agent showing multiple filling defects both at the bifurcation ("saddle" pulmonary embolism) and in the pulmonary arteries.

By James Heilman, MD - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=14660701

A Hampton hump in a person with a right lower lobe pulmonary embolism

By James Heilman, MD - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=18848816

Segmental and subsegmental pulmonary emboli on both sides

By James Heilman, MD - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=49062942

Ø  DIAGNOSTIC EVALUATION:  Initially, the Wells score is used to predict clinical probability of a PE, and stratify the patients into 3 risk categories low, moderate, and high.  Blood tests:  CBC, CMP, D-dimer (a sensitive test for PE and normal level can exclude PE in some cases), clotting status (PT, APTT, TT), and ESR/CRP.   ABG: Respiratory alkalosis (hyperventilation), hypoxemia (PO2 < 80).  Thrombophilia work-up:  Usually done only when a second PE occurs, especially when this happens while still under anticoagulant therapy.  CXR: Usually only reveal atelectasis, but may show Westermark sign (dilation of the vasculature proximal to the embolus and collapse the vasculature distal to it creates the appearance of a sharp cut off), Hampton's hump (wedge-shaped infarct at the lung periphery with the base against the pleural surface).  Doppler US of LE:  Presence of DVT is enough to warrant anticoagulation, without requiring the V/Q or spiral CT scans because of the strong association between DVT and PE.   EKG:  Most commonly reveal sinus tachycardia, but may show signs of right heart strain-RBBB, S1Q3T3 (large S wave in lead I, a large Q wave in III and inverted T wave in III).  Echocardiography:  In massive PE, dysfunction of the right heart can be seen on echo as the McConnell sign (akinesia of the mid-free wall but normal motion of the apex).  V/Q scan:  May reveal segmental areas of mismatch. Results are reported with a designated probability of PE (low, indeterminate, high) and are interpreted on the basis of clinical suspicion.  It is used less often because of the more widespread availability of CT; however, it may be useful in patients who have an allergy to iodinated contrast or in pregnancy due to lower radiation exposure.  CT with radiocontrast:  Very sensitive for pulmonary embolism in the proximal but not the distal pulmonary arteries.  Pulmonary angiography:  The gold standard but is more invasive.

Selective pulmonary angiogram revealing clot (labeled A) causing a central obstruction in the left main pulmonary artery. ECG tracing shown at bottom.

By Aung Myat and Arif Ahsan - Percutaneous mechanical thrombectomy for the treatment of acute massive pulmonary embolism: case report. Thrombosis Journal 2007, 5:20. doi:10.1186/1477-9560-5-20, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=5595362

CT pulmonary angiography showing a "saddle embolus" at the bifurcation of the pulmonary artery and thrombus burden in the lobar branches of both main pulmonary arteries.

By Aung Myat and Arif Ahsan - Percutaneous mechanical thrombectomy for the treatment of acute massive pulmonary embolism: case report. Thrombosis Journal 2007, 5:20. doi:10.1186/1477-9560-5-20, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=5595290

Ventilation-perfusion scintigraphy
(A) After inhalation of 20 mCi of Xenon-133 gas, scintigraphic images were obtained in the posterior projection, showing uniform ventilation to lungs.
(B) After intravenous injection of 4 mCi of Technetium-99m-labeled albumin, scintigraphic images shown here in the posterior projection. This and other views showed decreased activity in multiple regions.

By Westgate EJ, FitzGerald GA - Pulmonary Embolism in a Woman Taking Oral Contraceptives and Valdecoxib. PLoS Medicine Vol. 2, No. 7, e197. doi:10.1371/journal.pmed.0020197, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=5594243

Electrocardiogram of a person with pulmonary embolism, showing sinus tachycardia of approximately 100 beats per minute, large S wave in Lead I, moderate Q wave in Lead III, inverted T wave in Lead III, and inverted T waves in leads V1 and V3.

By R.W.Koster - http://en.ecgpedia.org/index.php?title=Pulmonary_Embolism, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=52912341

Large saddle embolus seen in the pulmonary artery (white arrows).

By Bakerstmd - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=39263792

Ø  TREATMENT:  O2 and analgesia. Anticoagulant therapy (mainstay of treatment):  Heparin (100 U/kg bolus then 15-18 U/kg/hr continous infustion) or LMWH (low molecular weight heparin) is administered initially.  Continue heparin for at least 5 days with overlapping therapeutic dose of warfarin for 2-3 days.  Pregnant women are often maintained on LMWH to avoid the known teratogenic effects of warfarin.  Warfarin:  Instituted once heparin dose is therapeutic.  INR is maintained between 2.0 and 3.0.  Warfarin is continued for 3-6 months or lifelong if there have been previous DVTs or PEs.  IVC filter:  Indicated if anticoagulant therapy is contraindicated and/or ineffective (i.e. recurrent emboli while anticoagulated).  Thrombolysis: Indicated only in severe cases.  Surgery:  Pulmonary thrombectomy is not recommended because of poor long-term outcomes.  DVT prophylaxis (indicated for bedridden medical patients and surgical patients): Low-dose subcutaneous heparain (require PTT monitor), LMWH, pneumatic compression devices, early ambulation.

Inferior vena cava filter.

By BozMo at the English language Wikipedia, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=14853313

o   PULMONARY HYPERTENSION:  Increase in blood pressure in the pulmonary vasculature (i.e. pulmonary artery, pulmonary vein, or pulmonary capillaries).  In rare cases, it could be idiopathic (primary).  In the majority of cases, it is secondary to a known trigger (e.g. chemical, connective tissue disorder, dietary agent).


1.     H-hypoxemia-associated:  e.g. COPD, ILD, Sleep-disorder breathing, chronic exposure to high altitude.  Pathogenesis:  Low levels of oxygen cause vasoconstriction of pulmonary arteries.

2.     A-arterial (pulmonary artery hypertension-PAH):  PAH is further subdivided into IPAH (idiopathic pulmonary arterial hypertension), FPAH (familial pulmonary arterial hypertension), and APAH) associated-with pulmonary artery hypertension).  Will discuss more below!

3.     V-venous (pulmonary venous hypertension):  This is the #1 cause of pulmonary hypertension and is due to left sided heart disease.  Pathogenesis: LV failure leads to pooling of blood in the lungs → pulmonary edema and pleural effusion.

4.     E-embolic disease:  e.g. thrombus, tumor, foreign material, schistosomiasis.  Pathogenesis:  Emboli block the vasculature causing ↑ resistant to pulmonary blood flow.

5.     M-miscellaneous:  e.g. sarcoidosis, histiocytosis X, LAM, compression of pulmonary vessels by tumor/fibrosing mediastinitis.

v  H _______________, _______________, _______________, ______________, ______________

v  A _______________, _______________, _______________, ______________, ______________

v  V _______________, _______________, _______________, ______________, ______________

v  E _______________, _______________, _______________, ______________, ______________

v  M _______________, _______________, _______________, ______________, ______________

In this section, we will concentrate on pulmonary arterial hypertension (PAH).

Ø  EPIDEMIOLOGY:  Incidence: 2-3/million/year for IPAH (idiopathic pulmonary hypertension).     However, the incidence is up to 60% in CREST syndrome patient, 14% of SLE patient, and 2% of patients with portal hypertension or HIV.  Of note, for patient who ingested diet pills such as Fen-Phen, the incidence is 1%. 

Ø  PATHOPHYSIOLOGY:  IPAH and FPAH have been linked to mutations in the BMPR2 gene, which encodes a receptor for bone morphogenetic proteins. While APAH can occurs as a consequence of autoimmune disease (e.g. CREST, SLE), portal hypertension, HIV, and use of the diet pill Fen-Phen.  Whatever the initial cause, PAH involves the vasoconstriction of arterial blood vessels. Over time, the affected blood vessels become fibrosed, and intimal and medial hypertrophy develop.  The resultant elevation of pulmonary vascular resistance increases the workload of the heart, causing thickening and enlargement of the right ventricle, and eventual right heart failure. Since blood flowing through the lungs decreases, the left side of the heart also receives less blood. Therefore it becomes harder to supply sufficient oxygen to the rest of the body, especially during physical activity. 

Molecular pathway of vasodilation mediated by nitric oxide

By BQmUB2012010 - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=22800790

Ø  PRESENTATION:  History:  Gradual onset of SOB, chest pain, fatigue, non-productive cough, fainting or syncope, peripheral edema, and hemoptysis (rarely).   Physical exam:  wide split S2 with loud P2, S3, systolic murmur (evidence of tricuspid insufficiency is consistent with pulmonary hypertension), parasternal heave, JVD, pedal edema, ascites, hepatojugular reflux, and digital clubbing.

Ø  DIAGNOSTIC EVALUATION:  ABG:  Hypoxemia. LFTs.  HIV test.  ANA: Test for autoimmune disease.  PFTs.  ECG:  May reveal sinus tachycardia, inverted T, RV strain, RVH.  CXR: Enlarged heart. If right pulmonary artery larger than the thumb this is indicative of PAH.  V/Q scan:  Rule chronic thromboembolic pulmonary hypertension.  CT chest: If interstitial lung disease is suspected.   Lung biopsy:   Indicated if interstitial lung disease is suspected. But lung biopsies are fraught with risks of bleeding due to the high intrapulmonary blood pressure.  Pressure measurenment with Swan-Ganz catheter (right heart catheterization provides the most definite assessment):  ↑ pulmonary arterial pressure (pulmonary hypertension is present when mean pulmonary artery pressure is > 25 mm Hg at rest or 30 mm Hg with exercise; normal value is 12–16 mm Hg), ↑ right atrial pressure, and ↓ cardiac output.  "Six-minute walk test" and blood BNP level:   Use to follow progress of pulmonary hypertension.

Tricuspid regurgitation

By CardioNetworks: Secretariat - CardioNetworks: E00572.jpgAMC Echolab, AMC, The Netherlands, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=24732305

Pulmonary artery catheter

By derivative work: Tariq Abdulla (talk)Pulmonary_artery_catheter_german.jpg: User:Chikumaya, modifizert von PhilippNPulmonary_arterial_catheter.svg: User:Chikumaya - Pulmonary_artery_catheter_german.jpgThis is a retouched picture, which means that it has been digitally altered from its original version. Modifications: Translated to English. The original can be viewed here: Pulmonary arterial catheter.svg. Modifications made by Paint., CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=4282351

Phonocardiogram and jugular venous pulse tracing from a middle-aged man with pulmonary hypertension caused by cardiomyopathy. The jugular venous pulse tracing demonstrates a prominent a wave without a c or v wave being observed. The phonocardiograms (fourth left interspace and cardiac apex) show a murmur of tricuspid insufficiency and ventricular and atrial gallops.

By Butterworth Publishers - http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=cm&part=A622&rendertype=figure&id=A633, Copyrighted free use, https://commons.wikimedia.org/w/index.php?curid=8101277

Pulmonary artery hypertension and emphysema as seen on a CT scan with contrast

By James Heilman, MD - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=49147244

Micrograph showing pulmonary hypertensive arteriopathy with marked thickening of the tunica intima and tunica media.

By Yale Rosen from USA - Pulmonary hypertensive arteriopathyUploaded by CFCF, CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=31128156

Cor pulmonale

By Yale Rosen from USA - Heart - cor pulmonale- right ventricular hypertrophyUploaded by CFCF, CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=31128151

Ø  TREATMENT:  Treat the underlying disorders.  A number of agents has been introduced that deal specifically with the abnormal proliferation and contraction of the vascular smooth muscle cells of the pulmonary arteries. These agents provide short-term symptomatic relief, but do not offer mortality benefit or prolonging the time to progression. 

v  PDE-5(phosphodiesterase type 5) inhibitors:  Sildenafil (Revatio) was FDA approved for the treatment of PAH in 2005.

v  Prostaglandins:  Prostacyclin (PG-I2) is considered the most effective treatment for PAH and comes in many forms.  Epoprostenol (Flolan®) is given via continuous infusion that requires a semi-permanent central venous catheter, which can cause sepsis and thrombosis.  Iloprost (Ventavis®) is the inhalation form.

v  Endothelin receptor antagonists:  Bosentan (Tracleer®) was approved in 2001.

Surgery:  Lung transplant:  Indicated in severe cases.  Pulmonary thromboendarterectomy: Indicated for chronic thromboembolic pulmonary hypertension.  Atrial septostomy:  Creates a communication between the right and left atria; it relieves right ventricular pressure, but at the cost of lower oxygen levels in blood.

o    INFECTIOUS LUNGS DISEASE (PNEUMONIA):  Usually described as lung parenchyma/alveolar inflammation and abnormal alveolar filling with fluid.

Ø  EPIDEMIOLOGY:  6th leading cause of death in the US.  Mortality occurs most commonly in the very young and the elderly.  Individuals with underlying illnesses such as Alzheimer's disease, CF, emphysema, tobacco smoking, alcoholism, immune system problems are at increased risk for pneumonia.

Ø  PATHOPHYSIOLOGY:  Pneumonia can be caused by microorganisms (most common), irritants, idiopathic (SEE ILD). When pneumonias are grouped this way, infectious causes are the most common type.  The microorganisms that cause pneumonia include virus, bacteria, fungi, and parasites.  In general, microorganisms enter the lung when airborne droplets are inhaled.  Once in the lungs, they cause cell death either through direct damage or apoptosis. In the subsequent immune respondse to the microorganism, leukocytes-derived cytokines inflict further damage to the pulmonary interstitium allowing fluid to leak into the alveoli.  Cell destruction and fluid-filled alveoli interrupt normal oxygen transportation.

Pneumonia fills the lung's alveoli with fluid, hindering oxygenation. The alveolus on the left is normal, whereas the one on the right is full of fluid from pneumonia.

Public Domain, https://commons.wikimedia.org/w/index.php?curid=6424578

1.     VIRAL PNEUMONIA:  Usually triggers a lymphocytic immune response.  It also make the body more susceptible to bacterial infections, thus bacterial pneumonia often complicates viral pneumonia.  Common viral etiology: AIR (remember these dudes are airborne) → A-adenovirus, I-influenze virus, R-RSV (respiratory syncitial virus).  Rare causes includes: CMV, HSV, VZV.

v  A _______________, _______________, _______________, ______________, ______________

v  I _______________, _______________, _______________, ______________, ______________

v  R _______________, _______________, _______________, ______________, ______________

2.     BACTERIAL PNEUMONIA:  Usually triggers a neutrophilic immune response.  Many bacteria live in parts of the upper respiratory tract (URT) such as the nose, mouth and sinuses, and can easily be inhaled into the alveoli. Common bacterial etiology: 

3.     FUNGAL PNEUMONIA:  Uncommon, but  may occur in immunocompromised individuals (e.g. AIDS, immunosuppresive drugs, or other medical problems).  Common fungal etiology: Histoplasma capsulatum (Mississippi River basin), Coccidioides immitis (southwestern US), Cryptococcus neoformans &  Pneumocystis jiroveci (AIDS patients), and Blastomyces.

4.     PARASITIC PNEUMONIA:  Usually an eosinophilic immune response.  These parasites typically enter the body through the skin or by being swallowed.  Common parasitic etiology:  Toxoplasma gondii, Strongyloides stercoralis, and Ascariasis lumbricoid.


1.     Pathological classification:

v  Lobar pneumonia: Involves a single lobe.  Most commony (95%) due to Streptococcus pneumonia.  CXR: Consolidation.  Histology:  Intra-alveolar exudate. 4 stages of progression: Congestion (predominates 1st 24 hours), Red hepatization (neutrophic infiltration with accumulation of fibrinous exudate, RBCs, and bacteria), Gray hepatization (RBCs disntegrated, while the fibrinous exudate persists), Resolution (normal structure stored).

v  Bronchopneumonia: Involve the bronchioles and the adjacent alveoli.  Caused by S. aureus, S. pneumonia, H. influenza, P. aeruginosa.  CXR: Diffuse, patchy infiltrate.

v  Interstitial pneumonia:  Involves areas in between the alveoli.  Most likely caused by virus or atypical bacteria.  CXR: Streaky interstitial infiltrates without alveolar compromise.

2.     Clinical classification

v  Community-Acquired Pneumonia (CAP is the most common type):  Infectious pneumonia in a person who has not recently been hospitalized.  It is usually caused by Streptococcus pneumoniae (#1), Haemophilus influenzae, and the so-called walking pneumonia (the less severe atypical bacteria and the viruses). Gram-negative bacteria cause CAP in certain at-risk populations (e.g. Klebsiella in alcoholics).

v  Hospital-acquired pneumonia (aka nosocomial pneumonia):  Acquired during or after hospitalization for another illness or procedure with onset at least 72 hrs after admission. Prevalence: Up to 5% of hospitalized patient. It is associated with resistant bacteria such as MRSA, and gram-negative bacteria (e.g. Pseudomonas, Enterobacter).

Ø  PRESENTATION:  History:  Fever, shaking chills, rigors, cough producing greenish or yellow sputum, SOB, pleuritic chest pain, a sharp or stabbing pain, hemoptysis, headaches, anorexia, fatigue, N/V, myalgia, and arthralgia.  Other potential symptoms:  Abdominal pain and diarrhea (occur with Legionella); weight loss and night sweats (may occur with TB, PCP).  Physical exam:  Tachypnea, tachycardia, crackles, signs of consolidation (e.g. increase tactile fremitus, bronchial breath sounds, egophony [patient says “e”, doc hears “a”), dullness to percussion), and cyanosis in severe cases.

Main symptoms of infectious pneumonia

By Mikael Häggström.When using this image in external works, it may be cited as:Häggström, Mikael (2014). "Medical gallery of Mikael Häggström 2014". WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.008. ISSN 2002-4436. Public Domain.orBy Mikael Häggström, used with permission. - All used images are in public domain., Public Domain, https://commons.wikimedia.org/w/index.php?curid=5781948

Ø  DIAGNOSTIC EVALUATION:  ABG: Check for hypoxemia. CBC:  Leukocytosis. BMP:  Hyponatremia (may be due to pneumonia induced SIADH or Legionella infection) and check renal function.  UA.  Blood culture: Should be collected from those requiring hospitalization.  Serum serology:  Can check for present of Mycoplasma, Legionella and Chlamydia antigen.  Respiratory secretions:  Can check for presence of viruses (AIR → A-adenovirus, I-influenza, R-RSV).  CXR (AP and lateral): Can reveal areas of opacity (consolidation) or streaky infiltrate, pleural effusion, and possibly masses.  Chest CT:  Sometimes used as it is more sensitive than plain x-ray.  Sputum gram-stain and cultures:  Aid in determining the exact etiologic cause and guide antibiotic therapy.   DIAGOSTIC LABS INDICATIVE OF BAD PROGNOSIS: CHOW (imagine the bacteria CHOW-ing down your Lung-lunch) → C-creatinine > 1.2 or BUN > 20, H-hematocrit < 30 or H-Hgb < 9, O-O2 < 60 (PaO2) or PaCO2 > 50, W-WBC < 4 or > 30

§  C _______________, _______________, _______________, ______________, ______________

§  H _______________, _______________, _______________, ______________, ______________

§  O _______________, _______________, _______________, ______________, ______________

§  W _______________, _______________, _______________, ______________, ______________

A chest X-ray showing a very prominent wedge-shape area of airspace consolidation in the right lung characteristic of bacterial pneumonia.

By James Heilman, MD - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=8602703

Right middle lobe pneumonia in a child as seen on plain X ray

By James Heilman, MD - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=49213117

CT of the chest demonstrating right-side pneumonia

By James Heilman, MD - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=8602750

Ø  TREATMENT: Uncomplicated CAP: Outpatient oral antibiotics X 7-10 days, rest, and fluids. Complicated CAP (e.g. severe disease [unstable vitals, hypoxemia], comorbidity [alcoholism, COPD, diabetes, immunosupression], homelessness, etc.):  Hospitalize with IV antibiotics, O2 supplement.  Empiric antibiotic treatment is usually started awaiting bacterial culture and sensitivity results. 

Antibiotic choice:  Depends on the nature of the pneumonia, the most common microorganisms causing pneumonia in the local geographic area, and the immune status and underlying health of the individual. In North America, where the "atypical" are becoming more common, macrolides (azithromycin, clarithromycin) have become the first-line treatment.

Vaccination: Pneumococcal (booster q5-7 yrs): For patients >65 y/o, and those with chronic illnesses, alcoholism, CSF leaks, or asplenia. Influenzae: Given annually to the same individuals who receive the pneumococcal vaccine.

Viral pneumonia:   Treatments are available for selected virues and are beneficial only if started within 48 hours of symptoms onset. Influenza A (other the then the H5N1 strains aka bird flu):  Rimantadine or amantadine.  Influenza B: Oseltamivir or zanamivir. There are no known effective treatments for viral pneumonias caused by the SARS coronavirus, adenovirus, hantavirus, or parainfluenza virus.

Ø  COMPLICATION:  More frequently with bacterial than viral pneumonia. The most important complications include: Respiratory failure (including ARDS), Sepsis (when microorganisms enter the bloodstream and the immune system responds by secreting cytokines), Pleural effusion (including empyema), and lung A-abscess (especially with A-aspiration pneumonia).


Ø  EPIDEMIOLOGY:  Lung cancer is the most common cause of cancer death and the second most common cancer in terms of both incidence (after breast cancer in female, and prostate cancer in male).  It is most likely to develop in smokers > 50 y/o.  Among male smokers, the lifetime risk of developing lung cancer is 17.2%. Among female smokers, the risk is 11.6%.Although the rate of men dying from lung cancer is declining in western countries, it is actually increasing for women due to the increased takeup of smoking by this group.

Ø  PATHOPHYSIOLOGY:  80-90% of lung cancer occur in smokers.  Cigarette smoke contains > 60 known carcinogens (e.g. nitrosamine, benzopyrene), and nicotine depresses the immune response to malignant growths. Carcinogens cause lung cancer by activation of oncogenes (e.g. K-ras proto-oncogenes mutation occur in 20-30% of non-small cell lung cancer) or inactivation of tumor suppressor genes-TSG (e.g. p53 mutation is common in small cell lung cancer).  The major determinant of lung cancer development is the pack-year (# of pack per day X # of year). If a person stops smoking, this chance steadily decreases as damage to the lungs is repaired and contaminant particles are gradually removed. Other known causes of lung cancers:  Radon gas (#2 cause of lung cancer after smoking):  A colorless and odorless gas generated by the breakdown of radioactive radium found in the earth's crust.  It ionizes genetic material, causing mutations that sometimes turn cancerous. Radon gas levels vary by locality and the composition of the underlying soil and rocks.  Asbestos:  Function synergistically with tobacco smoking in the formation of lung cancer.  It also causes cancer of the pleura (mesothelioma).  Viruses:  HPV, JC virus, simian virus 40 (SV40), BK virus and CMV may affect the cell cycle and inhibit apoptosis, and have been associated with lung cancer viruses.

Risk of death from lung cancer is strongly correlated with smoking

By Delphi234 - Own work, CC0, https://commons.wikimedia.org/w/index.php?curid=50623639

Graph showing how a general increase in sales of tobacco products in the USA in the first four decades of the 20th century (cigarettes per person per year) led to a corresponding rapid increase in the rate of lung cancer during the 1930s, '40s and '50s (lung cancer deaths per 100,000 male population per year)

By Sakurambo - Vectorized version of Image:Cancer smoking lung cancer correlation from NIH.png, originally published on the nih.gov website. The source page has been deleted, but an archived copy is still accessible.Own work, created in Adobe Illustrator, Public Domain, https://commons.wikimedia.org/w/index.php?curid=2564250

Pie chart showing incidences of non-small cell lung cancers as compared to small cell carcinoma shown at right, with fractions of smokers versus non-smokers shown for each type.

By Mikael Häggström.When using this image in external works, it may be cited as:Häggström, Mikael (2014). "Medical gallery of Mikael Häggström 2014". WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.008. ISSN 2002-4436. Public Domain.orBy Mikael Häggström, used with permission. - Own work, CC0, https://commons.wikimedia.org/w/index.php?curid=15469615

Ø  CLASSIFICATION:  Lung cancers are divied into 2 categories based on the size and appearance of the malignant cells on histology.  This classification has important implications for clinical management and prognosis of the disease. 

v  Non-small cell lung carcinoma (NSCLC):  ~ 80% of all lung cancers.  4 main sub-types grouped together because their prognosis and management are similar: LABS →

1.     L-large cell lung carcinoma (10.7% of lung cancers):  A fast-growing form that develops near the surface (periphery) of the lung. It is often poorly differentiated and tends to metastasize early.  Histology:  It is sort of a wastebasket category for NSCLC which show neither glandular nor squamous features. Those large cell carcinomas with clear cytoplasm are termed "clear cell" carcinomas, those with very large cells are termed "giant cell" carcinomas, and the rest are simply called "undifferentiated large cell" carcinomas.

2.     A-adenocarcinoma (29.4% of lung cancers): Originates in the peripheral lung tissue.  It is the most common bronchogenic carcinoma in women.  Most cases are smoking-related, but a minority arises from pre-existing scars (scar cancers).  Histology:  Glandular formations of neoplastic cells within large amount of dense fibrous scar tissue.

3.     B-bronchioloalveolar carcinoma (BAC):  Currently known as adenocarcinoma in-situ.  Originates in peripheral lung tissue from bronchiolar and alveolar elements (e.g. bronchiolar-lining epithelium, Clara cells, or type II pneumocytes). BAC is NOT smoking related.  The tumor is often multifocal.  Histology:  Well-differentiated columnar cells (which, depending upon the cell of origin, may or may not produce mucin) which spread along the alveolar septa, without either thickening or destroying them.

4.     S-squamous cell lung carcinoma (31.1% of lung cancers):  Originates in a central bronchus. It is the most common form of bronchogenic carcinoma in men.  Well-differentiated squamous cell lung cancers often grow more slowly than other cancer types, thus reaches a very large size, with central cavitation and necrosis (outgrow its blood supply).  Histology:  Anaplastic squamous cells with with characteristic intercellular bridges.  There is also stromal keratinization and keratin pearl formation. 

v  Small cell lung carcinoma (SCLC):  Account for ~17% of all lung cancers.  It tends to arise in the central bronchus.  It is the most rapidly progressive of the bronchogenic carcinomas, and the patient may die of metastatic disease while the primary is still small.  Histology: Small, round, blue tumor cells of neuroendocrine origin with dense cytoplasmic neurosecretory granules (which give this an endocrine/paraneoplastic syndrome association).   

v  SUMMARY OF TYPES OF LUNG CANCER:  LABS → L-large cell lung carcinoma, A-adenocarcinoma and B-bronchioloalveolar carcinoma (these 3 usually originate at the periphery), S-squamous cell lung carcinoma and S-small cell lung carcinoma (these 2 usually originate centrally).

§  L _______________, _______________, _______________, ______________, ______________

§  A _______________, _______________, _______________, ______________, ______________

§  B _______________, _______________, _______________, ______________, ______________

§  S _______________, _______________, _______________, ______________, ______________

LOWER RESPIRATORY TRACT: LARGE CELL CARCINOMA This large cell carcinoma at autopsy shows a large multilobulated tumor adjacent to the hilum. A metastatically involved lymph node is present next to the bronchus.

By The Armed Forces Institute of Pathology (AFIP) - PEIR Digital Library (Pathology image database). Image# 408026. Image and description are from the AFIP Atlas of Tumor Pathology., Public Domain, https://commons.wikimedia.org/w/index.php?curid=4336342

LARGE CELL CARCINOMA The corresponding surgical resection shows neoplastic cells with abundant pale eosinophilic cytoplasm and a surrounding infiltrate of inflammatory cells

By The Armed Forces Institute of Pathology (AFIP) - PEIR Digital Library (Pathology image database). Image# 408049.  https://commons.wikimedia.org/w/index.php?curid=4357018

A gross pathological specimen of a pulmonary adenocarcinoma, removed in a lobectomy.

By The Armed Forces Institute of Pathology (AFIP) - PEIR Digital Library (Pathology image database). Image# 407826. Image and description are from the AFIP Atlas of Tumor Pathology. Declaration of PEIR: https://commons.wikimedia.org/w/index.php?curid=4336300

LARGE CELL CARCINOMA The corresponding surgical resection shows neoplastic cells with abundant pale eosinophilic cytoplasm and a surrounding infiltrate of inflammatory cells

By The Armed Forces Institute of Pathology (AFIP) - PEIR Digital Library (Pathology image database). Image# 408049.  https://commons.wikimedia.org/w/index.php?curid=4357018

LOWER RESPIRATORY TRACT: NONMUCINOUS BRONCHIOLOALVEOLAR CARCINOMA A histologic section shows a proliferation of atypical cells along the alveolar walls (A).

By The Armed Forces Institute of Pathology (AFIP) - PEIR Digital Library (Pathology image database). Image# 407906. https://commons.wikimedia.org/w/index.php?curid=4356941

Histopathological image representing bronchiolo-alveolar carcinoma of the lung with mucin production.

By No machine-readable author provided. KGH assumed (based on copyright claims). - No machine-readable source provided. Own work assumed (based on copyright claims)., CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=504085

Micrograph of a small-cell carcinoma of the lung showing cells with nuclear moulding, minimal amount of cytoplasm and stippled chromatin. FNA specimen.

By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=9520233

Histopathologic image of small-cell carcinoma of the lung. CT-guided core needle biopsy.

By No machine-readable author provided. KGH assumed (based on copyright claims). - No machine-readable source provided. Own work assumed (based on copyright claims)., CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=513941

Ø  PRESENTATION:  History: Dyspnea, chronic coughing, chest pain, cachexia, anorexia, fatigue, hemoptysis, recurrent pneumonia (from accumulation of secretions behind blockage), dysphagia, dysphonia.  Physical exam:  Wheezes, digital clubbing, axillary &/or supraclavicular adenopathy.  Patient may also present with these complications: P-pulmonary SHAME →

v  P-pancoast’s tumor (PANcoast = PAN → P-ulmonary tumor at A-pex compressing N-nerve (recurrent laryngeal nerve → hoarseness; cervical sympathetic plexus à Horner’s syndrome); it could also compress the brachiocephalic vein & subclavian artery; P-pleural effusion (usually bloody).

v  S-skin disorders (acanthosis nigricans, erythema gyratum repens), S-SVC syndrome (SVC → SVC compression causing S-swelling of the face, V-venous dilatation in the head and neck, C-cyanosis).

v  H-horner’s syndrome (damage to the cervical sympathetic plexus → PAM → P-ptosis, A-anhidrosis, M-miosis), H-hematologic disorder (DATE → D-DIC, A-anemia, T-thrombocytosis, E-eosinophilia)

v  A-atelectasis, A-autoimmune disorder (dermatomyositis, Lambert-Eaton syndrome)

v  M-metastasis (bone mets → bone pain, spinal cord compression; liver mets; brain mets)

v  E-endocrine (SCLC → ACTH, ADH; Squamous cell lung cancer → PTHrP; Large cell lung cancer → gynecomastia), E-eaton-lambert syndrome (muscle weakness due to auto-antibodies presynaptic calcium channels located in neuromuscular junction → ↓ release of acetylcholine).

v  P _______________, _______________, _______________, ______________, ______________

v  S _______________, _______________, _______________, ______________, ______________

v  H _______________, _______________, _______________, ______________, ______________

v  A _______________, _______________, _______________, ______________, ______________

v  M _______________, _______________, _______________, ______________, ______________

v  E _______________, _______________, _______________, ______________, ______________

Ø  DIAGNOSTIC EVALUATION:  CBC.  BMP: May reveal hypercalcemia (due to PTHrP).  CXR (1st step if a patient reports symptoms suggestive of lung cancer):  May reveal an obvious mass, widening of the mediastinum (suggestive of spread to lymph nodes there), atelectasis (collapse), consolidation (pneumonia), or pleural effusion.  Bronchoscopy: Obtain tissue samples for diagnsis.  CT scan:  May show a mass.  Lung biopsy:  May be done under CT-guided needle biopsy or more invasive means such as mediastinoscopy or open thoracotomy.  PET scan:  Determine whether tumor is localised and amenable to surgery or has metastasized.  PFTs:  Assess whether patient have adequate pulmonary reserve to be operated on.  STAGING:  SCLC → Limited (confined to one half of the chest) or Extensive (everything else).  NSCLC → Base on TNM system NSCLC is staged from IA to IV.

A chest X-ray showing a tumor in the lung (marked by arrow)

By James Heilman, MD - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=18076961

CT scan showing a cancerous tumor in the left lung

By Lange123 at the German language Wikipedia, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=2110754

Internal radiotherapy for lung cancer given via the airway.

By Cancer Research UK - Original email from CRUK, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=34333518

Ø  TREATMENT:  Depends on the cancer's specific cell type, how far it has spread, and the patient's performance status.

v  SCLC: Non-resectable as surgery has influence on survivival.  Usually highly responsive to chemotherapy initially (even extensive disease have 90% response rate), but frequently recur resistant to both chemo and radiation therapy.

1.     Limited:  Chemotherapy (cisplatin, etoposide) plus radiation. Then, administer prophylactic cranial radiation after complete remission is achieved.

2.     Extensive: Palliative chemo or radiation therapy.


1.     Stage I, II, and resectable Stage IIIA:  Surgical resection with (e.g. wedge resection, segmentectomy, lobectomy, or pneumectomy) with neo-adjuvant and adjuvant chemotherapy (e.g. cisplatinum, etoposide).

2.     Non-resectable Stage IIIB and Stage IV:  Palliative chemo and radiation therapy. 

v  Pancoast’s tumor:  Neoadjuvant chemo or radiation therapy followed by surgery

v  SVC syndrome:  Usually not emergency.  Treat with standard chemo &/or radiation therapy.  Consider intraluminal metal stents

v  Bone metastasis with spinal cord compression:  Dexamethasone to ↓ inflammation, then radiation therapy.  Consider neurosurgery if radioresistant tumor.

No airway obstruction during sleep

By Drcamachoent - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=40522465

SLEEP APNEA:  Asleep disorder characterized by pauses in breathing during sleep (apneas) that occur repeatedly throughout sleep.

·       EPIDEMIOLOGY:  Obstructive sleep apnea (OSA) is the most common category of sleep apnea. Prevalence of OSA: 3-7%.  M > F.

·       PATHOPHYSIOLOGY:  There are three distinct forms of sleep apnea: COM → C-central, O-obstructive, M-mixed.

o   C _______________, _______________, _______________, ______________, ______________

o   O _______________, _______________, _______________, ______________, ______________

o   M _______________, _______________, _______________, ______________, ______________


1.     C-CENTRAL SLEEP APNEA (CSA):  Brain's respiratory control centers are imbalanced during sleep, thus the central respiratory drive is absent, and the brain does not respond to changing blood levels of the respiratory gases (remember CO2 is the primary trigger of respiration).  There is no effort made to breathe during apneic episode (no chest or abdominal movements, no struggling).  CSA can be caused by:  Central respiratory depressant (alcohol, opiates, barbiturates, benzodiazepines, and many other tranquilizers),  premature infants with immature brains and reflex systems (e.g SIDS is theorized to be attributable to sleep apnea and caffeine has been found to help reduce apnea in preterm infants), Congenital Central Hypoventilation Syndrome aka Ondine’s curse (a rare, inborn condition involves the PHOX2B gene, which guides maturation of the autonomic nervous system; its loss-of-function mutations lead to the failure of the brain to effectively control breathing during sleep and a pattern of recognizable facial abnormalities; it is now treated with tracheotomies and mechanical ventilation on respirators while sleeping or a diaphragmatic pacemaker), CHF (at risk for Cheyne-Stokes respiration, which is a form of central sleep apnea recurrent episodes of apnea alternating with episodes hyperpnea).

2.     O-OBSTRUCTIVE SLEEP APNEA:  The human upper airway is composed of walls of soft tissue, which ordinarily relaxes and, in some individuals, collapses during sleep leading to obstruction of the airway, during which respiratory efforts continue.  Individuals with decreased muscle tone (e.g. hypothyroidism), increased soft tissue around the airway (e.g., due to obesity), and anatomic abnormalities that narrow the airway (e.g. nasal obstruction, macroglossia, micrognathia, acromegaly) are at high risk for obstructive sleep apnea.    

3.     M-MIXED SLEEP APNEA (MSA):  Show features of both CSA and OSA.  It has been described under two conditions:  1) Occur after severe, longstanding OSA:   It is proposed that the loss of central respiratory drive is secondary to OSA-induced cor pulmonale, which leads to acid-base and CO2 feedback malfunctions 2) Occur during CPAP titration for OSA:   Limited and secondary to sleep fragmentation during the titration process.

DIFFERENTIAL DIAGNOSIS OF SLEEP APNEA: S-sleep APNEA = S APNEA → S-sepsis, S-seizure disorders, S-sedatives use, A-alcohol use, A-anatomic abnormalities, P-pneumonia, N-neurological damage/defect, E-electrolytes abnormalities, E-endocrine (e.g. hypothyroidism, acromegaly), A-arrythmia.

o   S _______________, _______________, _______________, ______________, ______________

o   A _______________, _______________, _______________, ______________, ______________

o   P _______________, _______________, _______________, ______________, ______________

o   N _______________, _______________, _______________, ______________, ______________

o   E _______________, _______________, _______________, ______________, ______________

o   A _______________, _______________, _______________, ______________, ______________

Screenshot of a PSG system showing an obstructive apnea.

By NascarEd - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=24509002

Airway obstruction during sleep with OSA

By Drcamachoent - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=40522463

Screenshot of a PSG system showing a central apnea.

By NascarEd - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=24601932

·       PRESENTATION:  History:  Daytime sleepiness and fatigue,  morning headache, impaired concentration, loud snoring, deep gasping or choking during sleep.  Physical exam:  Hypertension (a sequela of OSA), tachypnea and cyanosis (from hypoxemia, hypercapnia).  Complications:  Pulmonary hypertension (hypoxia causes pulmonary vascular constriction), cor pulmonale, myocardial infarction, and stroke.   

DIAGNOSTIC EVALUATION:  Polysomnography consisting of these parameters 1) EEG (encephalogram): Record the different stages of sleep (1, 2, 3, 4, REM, and Wakefulness), seizures activity 2) EOG (electrooculogram):  Measure actitivity of the eye to determine when sleep and REM sleep occurs 3) EMG (electromyogram):  Measure muscle tension in the body to determine when sleep occurs as well as REM sleep, as well as to monitor for Periodic Limb Movement Disorder 4) EKG (Electrokardiogram):  Rule out underlying heart pathology 5) Pressure transducers: Measure nasal and oral airflow, and rate of respiration 6) Belts:  Measure respiratory effort as these belts expand and contract upon breathing effort 7) Pulse ox:  Determine changes in blood oxygen levels that often occur with sleep apnea and other respiratory problems. STANDARD DEFINITION: 1) Apneic event:  ≥ 10 seconds interval between breaths, with either a neurological arousal (≥ 3 seconds shift in EEG frequency) or blood oxygen desaturation ≥ 3-4%  or both 2) Clinically significant sleep apnea:  ≥ 5 events/hour of sleep time 3) Hypopneas: 50% ↓ air flow for > 10 s, followed by a 4% desaturation, &/or arousal. The Apnea- Hypopnea Index (AHI) is expressed as the number of apneas and hypopneas per hour of sleep.
Home oximetry:  May be adequate and easier to obtain than formal polysomnography in patients who are at high likelihood of having OSA.  High probability patients were indentified by Epworth Sleepiness Scale (ESS) of  ≥ 10 and a Sleep Apnea Clinical Score (SACS) ≥ 15. 

Person using a CPAP mask, covering only nose

By Michael Symonds - Eigenanfertigung (Aufnahme ist übrigens nicht gestellt.), CC BY-SA 2.0 de, https://commons.wikimedia.org/w/index.php?curid=6078536

CPAP machine with two models of full face masks

By Zboralski - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=28930739

Uvulopalatopharyngoplasty. A) pre-operative, B) original UPPP, C) modified UPPP, and D) minimal UPPP.

By Drcamachoent - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=38852585

• TREATMENT: Lifestyle: Weight loss, smoking cessation, sleeping at a 30º angle or sideway, avoid central nervous system depressants (alcohol, sedatives), O2 therapy: CPAP is the most common treatment for sleep apnea. Oral Appliance Therapy (OAT): Custom made mouthpiece that shifs the lower jaw forward which opens up the airway. Surgery: Tonsillectomy, adenoidectomy. Treat associated condition: Hypertension: Acetazolamide is recommended as it lower blood pH and encourage respiration. GERD: PPI. Hypothyroidism: L-thyroxine.

Grand Canyon National Park, Arizona, USA