Biomedicine Review of the Respiratory System

Felix Hernandez, M.D.

Facts about the Respiratory System

• 1. open-ended and in direct contact with the environment

– Allows for a high number of URI

• 2. exposed to many allergens inhaled in air

– Allows for a high number of immunologic diseases

• 3. Inhaled air contains pollutants, airborne particles, and gases that may cause disease

• 4. The heart and the lungs for a functional unit

– Pathology in one leads to pathology in the other

• 5. inhaled air contains many potential carcinogens

Locating Findings on the Chest

To locate findings around the circumference of the chest, imagine a series of vertical lines

Lungs, Fissures, and Lobes

Each lung is divided roughly in half by an oblique (major) fissure

The right lung is further divided by the horizontal (minor) fissure

These fissures divide the lungs into lobes

The right lung is divided into upper, middle, and lower lobes

The left lung is divided into upper and lower lobes

The Trachea and Major Bronchi

The trachea bifurcates into its mainstem bronchi at the levels of the sternal angle anteriorly and the T4 spinous process posteriorly

The Pleurae

The pleurae are serous membranes that cover the outer surface of each lung (visceral pleura), and also the inner rib cage and upper surface of the diaphragm (parietal pleura)

Figure 17-4: Branching of the airways

Inspiration:Inspiration:

Contraction of diaphragm / intercostal muscles Contraction of diaphragm / intercostal muscles

Expansion of thorax Expansion of thorax expansion of lungs expansion of lungs

Pressure in lungs Pressure in lungs ↓↓

Air inflowAir inflow

Expiration:Expiration:

Relaxation of muscles Relaxation of muscles

Thorax / lung recoil back Thorax / lung recoil back

Pressure in lungs Pressure in lungs ↑↑

Air outflowAir outflow

Hypothalamus (emotions / pain)Hypothalamus (emotions / pain)

Cortex (voluntary control)Cortex (voluntary control)

Chemoreceptors:Chemoreceptors:

Central (in medulla oblongata): responds to COCentral (in medulla oblongata): responds to CO2 2 ↑↑

COCO22 passes blood brain barrier passes blood brain barrier

COCO2 2 + H+ H22OO HH22COCO33 HH++ + HCO + HCO33--

HH++ stimulates receptors stimulates receptors breathing depth breathing depth ↑↑ + rate + rate ↑↑

Peripheral (in aortic / carotid bodies): Peripheral (in aortic / carotid bodies):

responds when Oresponds when O2 2 < 60 mm Hg < 60 mm Hg increase ventilation increase ventilation

Responds to pH Responds to pH ↓↓ increase ventilation increase ventilation

Marieb, Human Anatomy & Physiology, 7th edition

Diaphragm & rib cage are pumps for inspiration

Alveolar surface exchanges O2 & CO2 with blood

The gasses in air act independently & move down a pressure gradient

Airway resistance can limit ventilation efficiency

Typically ventilation matches blood perfusion via local regulators of vasodilation & bronchodilation

URI Etiology• Recognized as common colds

• Acute inflammation of the nose, sinuses, throat or larynx

• Most are caused by viruses

– Most commonly influenza virus, parainfluenza virus, and rhinovirus

• Predisposing factors include physical exhaustion, old age, and general poor health

URI Clinical Presentation

• Rhinorrhea

• Throat pain, discomfort in swallowing, sneezing and a hacking cough

• Lasts from a few days to 1 to 2 weeks

• Heal spontaneously

• Signs of purulent discharge indicates a bacterial superinfection

Drugs:Drugs:

Budesonide (Rhinocort)Budesonide (Rhinocort)

Triamcinolone (Nasacort)Triamcinolone (Nasacort)

Fluticasone (Flonase)Fluticasone (Flonase)

Mometasone (Nasonex)Mometasone (Nasonex)

MOA: inhibit inflammatory cells in the nasal MOA: inhibit inflammatory cells in the nasal mucosa thus reducing the symptoms of mucosa thus reducing the symptoms of rhinitisrhinitis

Side effects: may increase the risk of thrush Side effects: may increase the risk of thrush and prevent healing of damaged nasal and prevent healing of damaged nasal mucosamucosa

Intranasal SteroidsIntranasal Steroids

Lobar Pneumonia

Figure 8-07B

Widespread/diffuse alveolar pneumonia

Common Causes of Pneumonia

• Bacteria- 75% of cases

– Streptococcus pneumoniae #1

• Viruses

– influenza virus

• Fungi

– Pneumocystis carinii

• Bacteria-like organisms

– Mycoplasma pneumoniae

Bronchopneumonia

• Bacterial invasion of the bronchial mucosa

• PMN move into the lumen of the airways and starts an inflammatory response

• The inflammation spreads form the bronchi into the adjacent alveoli

– Lobular single lobules

– Lobar large portions of entire lobes

• Intra-alveolar exudate accumulates and replaces the air causing the lung parenchyma to become consolidated

Bronchopneumonia

Figure 8-07A

Limited to the segmental bronchi and surrounding lung parenchyma

Interstitial Pneumonia

• Inflammation primarily affects the alveolar septa and does not result in exudation of PMNs into the alveolar lumen

• Caused by viruses or M. pneumoniae that attach to the surface of respiratory epithelial cells

• Cause cell necrosis and induce an infiltrate in the alveolar septa

Interstitial Pneumonia

Figure 8-07C

Diffuse and bilateral

Infection caused by Mycoplasma pneumiae or viruses

Clinical Features of Pneumonia

• Systemic signs of infection—fever, chills, prostration

• Local signs of irritation—cough

• Airway obstruction—shortness of breath (dyspnea), rapid breathing (tachypnea)

• Inflammation and tissue destruction—expectoration of rusty sputum, hemoptysis

Amoxicillin

DOC for: empiric therapy in otitis media, sinusitis and pneumonia

Side Effects: Diarrhea

2nd generation Cephs

moderate gram + and gram - coverage

Vancomycin

MOA: prevents transfer of cell wall precursors from plasma membrane to cell wall

Clinical Use: DOC for penicillin or methicilliin resistant staph and strep

Side Effects: thrombophlebitis, Red Man Syndrome

Common Antibiotics Used to Treat Pneumonia

Erythromycin

MOA: Inhibits protein synthesis

DOC for Mycoplasma pneumonia

Common Antibiotics Used to Treat Pneumonia

Pulmonary Tuberculosis• Key feature is the formation of granulomas which

are composed of lymphocytes, macs and giant cells.

– The central portion of the granuloma is necrotic and consists of caseous necrosis

• Primary infection

– Hasn’t been exposed and results in localized lung inflammation

• The lession is called the Ghon complex and it consists of granulomas in the lung parenchyma and enlarged regional lymph nodes.

• 95% of the times the complex heals spontaneously and undergoes calcification

Pulmonary Tuberculosis

• Secondary infection

– Develops as a result of reactivation of a dormant primary infection or reinfection

• most are due to reactivation

– Bacteria spread to the apex of the lung and cause a granulomatous lobular pneumonia

– Confluent granulomas can form cavities which become a source of hemoptysis

Ghon Complex

Figure 8-10

Isoniazid

MOA: inhibits mycolic acid synthesis in the wall

Side Effects: peripheral neuropathies (prevent with treatment with pyridoxine)

Rifampin

MOA: stopping bacterial RNA synthesis

Side Effects: urine and sweat turn red

Pyrazinamide

Side Effects: hepatitis, hyperuricemia with gouty arthritis.

Ethambutol

MOA: inhibits mycolic acid synthesis in bacterial cell wall

Drugs Used to TreatTuberculosis

Chronic Obstructive Pulmonary Disease

• A group of diseases characterized by chronic airway obstruction

• Includes the following diseases:

– Chronic bronchitis

– Emphysema

– Bronchiectasis

Bronchiectasis

• A permanent dilatation of the bronchi

• Occurs as a result of persistent inflammation inside the airways

• Larger bronchi show saccular dilatation, smaller bronchi show cylindrical dilatation

• Dilated bronchi are filled with mucopurulent material which cannot be cleared by coughing

• Infection spreads to adjacent alveoli causing recurrent pneumonias

Bronchiectasis

Figure 8-12

Chronic Bronchitis

• Excessive production of tracheobronchial mucus causing cough and expectoration for at least three months during 2 consecutive years

• Smoking is the cause in more than 90% of cases

• Non-specific pathology

• The walls of the bronchi are thickened and the lumen contains thick mucus

• The mucosa becomes infiltrated with lymphocytes, macs and plasma cells

• The submucosa shows marked mucous gland hyperplasia, chronic inflammation and fibrosis

Emphysema• Enlargement of the airspaces distal to the terminal

bronchioles with destruction of alveolar walls

• Is linked to chronic cigarette smoking but can be found in non-smokers with Alpha-1-antitrypsin deficiency

• Irritants in smoke cause an influx of inflammatory cells into the alveoli.

– proteolytic enzymes are released from leukocytes and destroy the alveolar walls

– Oxygen radicals produced by cigarettes kill alveolar cells and leukocytes which releases even more enzymes

• Elastase breaks down elastin fibers and its activity is increased

• Oxygen radicals also inactivate antiproteolytic enzymes (Alpha 1 theory)

Emphysema• Centrilobular

– Widening of the airspaces in the center of a lobule

– MC form and is found in smokers

– Remaining bronchioles are infiltrated with antracotic macs and chronic inflammatory cells

• Panacinar

– Involves all the airspaces distal to the terminal bronchioles

– Occurs with alpha 1 def.

COPD—Emphysema (Pink Puffer)

Figure 8-14A

COPD—Chronic Bronchitis (Blue Bloater)

Figure 8-14B

Comparison of Chronic Bronchitis and Emphysema

Table 8-2

Asthma• Extrinsic

• Intrinsic—attacks precipitated by:

– Physical factors

– Exercise

– Psychological stress

– Chemical irritants and air pollution

– Bronchial infection

– Aspirin

Pathogenesis of Asthma

Figure 8-15

Histopathology of Asthma

Figure 8-16

Sympathomimetics

Albuterol (Ventolin)

MOA: beta-2 agonist which causes bronchodilation

Rapid onset of action

Indications: DOC for the treatment of acute asthma symptoms and prevent exercise induced asthma.

Side Effects: vasodilation, tachycardia, CNS stimulation.

Levalbuterol (Xopenex)

Less side effects than albuterol

BronchodilatorsBronchodilators

SalmeterolSalmeterol MOA: long acting beta-2 agonistMOA: long acting beta-2 agonist

Indications: chronic treatment of asthma or Indications: chronic treatment of asthma or bronchospasm in adults.bronchospasm in adults.

Is not used for acute exacerbationsIs not used for acute exacerbations

Epinephrine (Primatene Mist)Epinephrine (Primatene Mist) MOA: beta-2 bronchdilation, alpha-1 vasoconstriction MOA: beta-2 bronchdilation, alpha-1 vasoconstriction

and decreased secretionsand decreased secretions

Indications: emergent use for sever Indications: emergent use for sever bronchoconstriction/vasodilation seen in anaphylaxisbronchoconstriction/vasodilation seen in anaphylaxis

Side Effects: tachycardia, CNS stimulationSide Effects: tachycardia, CNS stimulation

BronchodilatorsBronchodilators

Ipratropium (Atrovent)Ipratropium (Atrovent)

MOA: muscarinic antagonist which MOA: muscarinic antagonist which reverses AcH induced bronchconstrictionreverses AcH induced bronchconstriction

Indications: bronchospasm associated Indications: bronchospasm associated with COPD in adultswith COPD in adults

Side effects: very few systemic Side effects: very few systemic anticholinergic s/sx because it poorly anticholinergic s/sx because it poorly crosses into the systemic circulationcrosses into the systemic circulation

BronchodilatorsBronchodilators

Drugs: Beclomethasone (Beclovent), Triamcinolone (Azmacort), Drugs: Beclomethasone (Beclovent), Triamcinolone (Azmacort), Dexamethasone (Decadron)Dexamethasone (Decadron)

SystemicSystemic MOA: decrease inflammation and edema in respiratory tract.MOA: decrease inflammation and edema in respiratory tract.

Indications: asthma which can not be controlled by sympathomimetics Indications: asthma which can not be controlled by sympathomimetics alonealone

Side Effects: sodium/water retention, osteoporosis, PUD, avascular Side Effects: sodium/water retention, osteoporosis, PUD, avascular necrosis of the femoral headnecrosis of the femoral head

Should be discontinued ASAPShould be discontinued ASAP

InhaledInhaled MOA: same as systemicMOA: same as systemic

Indications: same as systemicIndications: same as systemic

Side Effects: don’t induce systemic toxicity. Their action is mostly in Side Effects: don’t induce systemic toxicity. Their action is mostly in the lungs. They have an increased risk of oral thrush (Candida the lungs. They have an increased risk of oral thrush (Candida albicans infection)albicans infection)

CorticosteroidsCorticosteroids

Lung Carcinoma

• Most common malignant tumor of internal organs in the United States

• Most often related to cigarette smoking

• Rare before the age of 40 years, but its incidence rises with age

• Poor prognosis

Histogenesis of Lung Carcinoma

Figure 8-25

Histopathology of Lung Tumors

• Squamous cell carcinoma

• Adenocarcinoma

• Large-cell undifferentiated carcinoma

• Small-cell carcinoma

• Mesothelioma --> Asbestos

Clinical Features of Lung Cancer

• Bronchial irritation

• Local extension into the mediastinum or pleural cavity—pleural effusion

• Distant metastases

• Systemic effects of neoplasia

• Paraneoplastic syndromes

Metastases of Lung Carcinoma

Figure 8-27