Nursing Pharmacology Chapter 25:  Pulmonary Pharmacology: Asthma

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)