Medical Pharmacology Chapter 25:  Pulmonary Pharmacology

Asthma:  Systems Pathophysiology

• Pathophysiologic Manifestations  

  • Airway diameter reduction, caused by smooth muscle contraction, vascular congestion, bronchial wall edema and thick, tenacious secretion.

  • Consequences of Airway Diameter Reduction in Acute Asthma

    • Increased airway resistance

    • Decreased forced expiratory rates

    • Increased work of breathing

    • Changes in respiratory muscle function

    • Changes in elastic recoil

    • Abnormal ventilation/pulmonary blood flow distribution

    • Ventilation/perfusion mismatching

    • Lung and thorax hyperinflation

      • image from: © Edward C. Klatt MD, Department of Pathology, University of Utah, Salt Lake City, Utah, USA, and by designated contributors: used with permission.

       

• ⁹Compromised pulmonary function in Asthma

  •  ECG changes indicative of right ventricular hypertrophy and pulmonary hypertension

  •  Vital capacity < 50% of normal

  •  1-second forced expiratory volume (FEV₁): reduced to 30% of expected

  •  Maximum/a minimum midexpiratory flow rates: reduced to 20% or less of expected

  •  Significant Air Trapping

    • In acute illness: residual volume (RV): may approach 400% of normal; functional residual capacity doubles

    • Patients report that the attack has ended clinically when RV has fallen to 200% of expected and FEV₁ reaches 50% of expected level

  • Hypoxia:

    • Very common finding during acute phase

    • Respiratory failure -- relatively uncommon: 10% to 15% of presenting patients

    • Hypercapnea: common

    • Respiratory alkalosis: common

  • Acute Asthma:

    • Normal arterial carbon dioxide tension but severe airway obstruction present is suggestive of possibly impending respiratory failure

    • Metabolic acidosis in acute asthma with severe obstruction

    •  Clinical presentations may not correlate with blood gas data; however, estimating patient's ventilatory state solely on clinical presentation may be dangerous

      • Patients with possible alveolar hypoventilation should have arterial blood gas tension measurements

      •  Cyanosis: -- very late sign; suggestive that extreme hypoxia may go undetected.

• Some Clinical Features in Asthma

  • There are three principal symptoms that characterize asthma.

    • These are dyspnea, cough, and wheezing with wheezing being particularly prominent. 

  • Asthma is an episodic disorder with the above symptoms commonly exhibited. 

  • Initially patients experienced chest constriction perhaps with a nonproductive cough. 

    • Audibly harsh, wheezing respiration is then noted; expiration is prolonged and difficult. 

    • Tachypnea, mild systolic hypertension and tachycardia are frequent presentations. 

    • Lung overinflation is typical in the anterioposterior thoracic dimension (diameter) increases. 

    • Severe or prolonged asthma attacks are associated with a loss of adventitial breath sounds along with notably high pitched wheezing. 

    • Respiratory accessory muscles become more prominent as well as paradoxical pulse-signs indicative of severe obstruction with impaired, significantly impaired pulmonary function.

    • Paradoxical pulse requires significantly large negative intrathoracic pressures; therefore, with shallow breathing, condition which does not favor development of large negative intrathoracic pressures, significant obstruction can be present even in the absence of paradoxical pulse. 

      • [Paradoxical pulse definition: Inspiratory decrease in arterial pressure >10 mm Hg with Inspiratory venous pressure unchanged (Kussmaul's Sign); Paradoxical pulse signs: Palpable decrease in pulse with inspiration Inspiratory systolic blood pressure decreased over 10 mm Hg less than expiratory pressure]. Significant disease may remain if the endpoints are only an a reduction in wheezing and the resolution of subjective complaints.

    • The conclusion of an asthmatic episode may be associated with coughs producing a thick, stringy me at this in the form of distal airway casts (Curschmann's spirals) which when microscopically evaluated shows the presence of eosinophils and Charcot-Leyden crystals. 

      •  

        ¹⁰Charcot-Leyden crystals

        "CHARCOT LEYDEN CRYSTALS, MICRO - Eosinophilic needle-shaped crystalline structures. Represents breakdown products of eosinophils. Seen in asthma and eosinophilic pneumonia."

      •  

        Curschmann's spirals

    • Severe mucus plugging with possibly imminent suffocation may occur and in this case the cough would be ineffective and the patient will be gasping.

      • Such circumstances may necessitate mechanical ventilation. Atelectasis (collapsed lung) may also occur in asthma.

• Bronchial wall characteristics during an acute asthma attack

  • Above Figure from: Chapter 13 in: Textbook in Medical Physiology And Pathophysiology  Essentials and clinical problems Copenhagen Medical Publishers  1999 - 2000, Poul-Erik Paulev, M.D., D.Sci   used with author's permission

• Animation of asthmatic breathing cycle noting residual lung volume (copyright (C) 1996, Stephen M. Borowitz)

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• ¹ McFadden, E.R., Jr. "Asthma: Diseases of the Respiratory System" in Harrison's Principles of Internal Medicine, 15th Edition (Braunwald, E., Fauci, A.S., Kasper, D.L., Hauser, S.L, Longo, D.L. and Jameson, J.  Larry, eds) pp. 1456-1463,  McGraw-Hill Medical Pubishing, Division, New York, 2001

• ² Kelley, H. William, "Asthma" in  Pharmacotherapy:  A Pathophysiologic Approach, (Dipiro, J.T., Talkbert, R.L.  Yee, G.C., Matze, G.R., Wells, B.G. and Posey, L. Michael, eds.)  pp 430-459. McGraw-Hill Medical Pubishing, Division, New York, 1999.

• ³Spencer SM., Sgro JY., Dryden KA., Baker TS., Nibert ML. (1997) Rhinovirus 14 (3D image reconstruction from electron microscopy data) Journal of Structural Biology. 120(1):11-21

• ⁴Attribution:  Michigan State University Website:

• ⁵State University of New York, Upstate Medical University, Cytotechnology, On-Line Courseware,

• ⁶Steve Dewhurst, Ph.D., Structure of the CC-chemokine, RANTES, (c) University of Rochester and Stephen Dewhurst, 1999

• ⁷Ealick SE, Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor, Cornell University

  • Walter MR, Cook WJ, Ealick SE, Nagabhushan, TL, Trotta, PP and Bugg, CE. Three-Dimensional Structure of Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor, J. Mol. Biol. 224:1075-1085 (1992).

  • Reichert P, Ealick SE, Cook WJ, Trotta P, Nagabhushan TL, Bugg CE. Crystallization and Preliminary X-ray Investigation of Human Granulocyte-Macrophage Colony Stimulating Factor, J. Biol. Chem. 265(1):452-453 (1990)

• ⁸Williams, TJ and Conroy, TM  Eotaxin and the attraction of eosinophils to the asthmatic lung, Respir Res 2001, 2: 150-156

• ⁹McFadden, Jr., E. R., Diseases of the Respiratory System: Asthma, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, p 1422.

• ¹⁰Daroca, P, Lung and Respiratory System Review, Tulane University Pathology, (Figure & caption attribution)