Under normal conditions, only approximately 1 mL of the 125 mL of glomerular filtrate that is formed each minute is excreted in the urine. The other 124 mL is reabsorbed in the tubules. This means that the average output of urine is approximately 60 mL/hour… approximately 1.5L urine per day.

1. Bronchial asthma

2. Bronchial asthma definition
Bronchial asthma is a chronic disorder of the
airways that causes episodes of
airway obstruction
 bronchial hyper-responsivenes
Airway inflammation that are usually reversible
Expert Panel on the Management of Asthma
defined bronchial asthma as “a chronic
inflammatory disorder of the airways in which many
cells and cellular elements play a role
mast cells
 eosinophils
T lymphocytes
epithelial cells.”
Neutrophils

3. EPIDEMIOLOGY AND ETIOLOGY
• Asthma is the most common chronic disease of childhood, and it causes significant
morbidity and mortality in both adults and children.
1. Extrinsic (Atopic) Asthma.
- Extrinsic or atopic asthma is typically initiated by a type-I hypersensitivity
reaction induced by exposure to an extrinsic antigen or allergen
- It usually has its onset in childhood or adolescence and is seen in persons with a
family history of atopic allergy
- (lgE)-associated hyper-sensitivity.
2. Intrinsic (Nonatopic) Asthma.
- Intrinsic or non atopic asthma triggers include respiratory tract infections, exercise,
hyperventilation, cold air, exercise, drugs and chemicals, hormonal changes and
emotional upsets, airborne pollutants, and gastro-esophageal reflux

4. Common risk factors
 Atopy (family history)
 Allergens
 Chemicals
 Infections
 Small weight at Birth
 Diet
 Exposure to Smoke
 environmental pollutants.
 Weather conditions
 Domestic animal

5. Pathophysiology
 After exposure to an asthma-precipitating factor
(e.g., aeroalalergens):
 inflammatory mediators are released from bronchial
mast cells, macrophages, T lymphocytes, and
epithelial cells.
 T H2 lymphocytes and mast cells release cytokines IL 4 and
IL-5 direct the migration and activation of other
inflammatory cells, most notably eosinophils, to the
airways.
 Eosinophils release biochemicals.
Major basic protein and eosinophil cationic protein that
cause
 airway injury, including epithelial damage,
 mucus hypersecretion, and increased reactivity of smooth
muscle.

6. • Bronchial NO has been found to be
elevated during periods of exacerbations.
• It is measurably decreased with
administration of inhaled steroids but not
B2-agonists.
• Failure to adequately minimize severe and
long-term airway inflammation in asthma may
result in airway remodeling in some patients.

7. Mechanisms of early- and late phase
IgE-mediated bronchospasm.

9. Hyper-reactivity is an exaggerated response of
bronchial smooth muscles to triggered stimuli of
the airways
to physical,
chemical,
Immunologic
pharmacologic stimuli
Endogenous stimuli that can worsen asthma
include:
poorly controlled rhinitis, sinusitis, and
gastroesophageal reflux disease
During times of remission, a more intense
stimulus is required to produce bronchospasm
than during times of increased symptoms.

18. Diagnosis
 Symptoms of asthma
 SPIROMETRY
 VC(Vital capacity)- volume of air blown off after
maximal inspiration
 RV(residual volume)-is the volume of air left in the
lung after maximal expiration
 FRC(Functional residual capacity)- The volume of air
left after a normal expiration
 TLC(Total lung Capacity)- is the VC plus the RV P
 FEV (Forced expiratory Volume)- having the patient
exhale into the spirometer as forcefully and
completely as possible after maximal inspiration.
 FEV1- usually is expressed as a percentage of the total
volume of air exhaled to FVC ratio.
 Peak expiratory flow (PEF) is the maximal flow that
can be produced during the forced expiration (550
to 700L/min)

19. Treatment of asthma
Treatment of asthma involves:
 Voidance of triggers known to precipitate or worsen asthma
the use of long-term control
Use quick relief medications
Aerosol Therapy for Asthma
• Long term control medications: ICS, ILABA.
• Quick relief medications: SABA, anticholenirergic
• Treatment of asthma exacerbation -systemic steroids

20. Acute Severe Asthma
 Goal of therapy
Correction of significant hypoxemia
Rapid reversal of airflow obstruction
Reduction of the likelihood of relapse of the exacerbation
or future recurrence of severe airflow obstruction
 Early response to treatment as measured by the
improvement in FEV1 at 30 minutes following inhaled
β2 -agonists is the best predictor of outcome
 Providing adequate O2 supplementation to maintain
O2 saturations above 90% (0.90) (or >95% [0.95] in
pregnant women and those who have coexistent heart
disease) is essential.

21. Acute Severe Asthma

22. Classification of Asthma Severity

25. Pharmacologic Therapy: Beta2-Adrenergic
Agonists
• β2-Agonists relax airway smooth muscle by directly
stimulating β2-adrenergic receptors.
• They also increase mucociliary clearance and stabilize mast
cell membranes.
• Inhalation, oral, and injectable dosage forms are available,
and the inhalation dosage forms are most commonly used.
• Oral β2-agonists should not be used in acute asthma because
of a delayed onset of action compared to the inhaled route.
• Inhaled β2-agonists are classified as either short- or long-
acting based on their duration of action.

26. Short-Acting Inhaled Beta2-Agonists
• Inhaled short-acting b2-agonists are the most effective
agents for reversing acute airway obstruction caused by
bronchoconstriction and are the drugs of choice for
treating acute severe asthma and symptoms of chronic
asthma
• Short-acting inhaled β2-agonists have an onset of
action of less than 5 minutes and a duration of action
of 4 to 6 hours
• Albuterol, pirbuterol and terbutaline, Levalbuterol
- tachycardia, tremor, and hypokalemia

27. Long-Acting Inhaled Beta2-Agonists
• Salmeterol and formoterol ( onset of action, 30 minutes)are long-acting inhaled β2-
agonists that provide up to 12 hours of bronchodilation after a single dose
• Inhaled long-acting β2-agonists are indicated for add on therapy for asthma not
controlled on low to medium doses of inhaled corticosteroids
• Adding a long-acting inhaled β2-agonist is at least as effective as doubling the dose
of an inhaled corticosteroid with respect to improving lung function and symptom
scores and decreasing nocturnal symptoms, reliever medication use, and asthma
exacerbations.
• Addition of a long-acting inhaled β2-agonist to inhaled corticosteroid therapy also
reduces the amount of inhaled corticosteroids necessary for asthma control
• Neither agent should be used as monotherapy for chronic asthma. Patients treated
with salmeterol alone are at greater risk of worsening asthma than those treated
with inhaled corticosteroids

28. Corticosteroids
• Corticosteroids are the most potent anti-inflammatory agents available for
the treatment of asthma.
• The efficacy of corticosteroids is due to their ability to affect multiple
inflammatory pathways, resulting in the suppression of inflammatory cell
activation and function, prevention of microvascular leakage, decreased
mucus production, and upregulation of β2-adrenergic receptors.
• Clinically, corticosteroids decrease airway inflammation, decrease AHR,
decrease mucus production and secretion, and improve the response to β2-
agonists.
• Corticosteroids for the treatment of asthma are available in inhaled, oral,
and injectable dosage forms

29. Corticosteroids
Multiple daily dosing of systemic corticosteroids
for the initial therapy of acute asthma
exacerbations appears warranted because
receptor binding affinities of lung corticosteroid
receptors are decreased in the face of airway
inflammation.
However, patients with less severe exacerbations
may be treated adequately with once-daily
administration.

30. Anticholinergics
Inhaled ipratropium bromide produces a
further improvement in lung function of 10% to
15% over inhaled β2 -agonists alone.
In children and adults, multiple-dose
ipratropium bromide added to initial therapy
reduces hospitalization rate in the subset of
patients with a baseline FEV1 of less than 30%
of predicted
Unlike β2 -agonists, they are not functional
antagonists; they only reverse cholinergic-
mediated bronchoconstriction.

31. Mechanism of steroid
The corticosteroids are the most effective anti-
inflammatory available to treat asthma.
increasing the number of β2 -adrenergic receptors and
improving the receptor responsiveness to β2 -adrenergic
stimulation
 reducing mucus production and hypersecretion,
 reducing BHR,
reducing airway edema and exudation.

32. Systemic Corticosteroids
Adverse effect of systemic steroid
Serious adverse effects include
hypothalamic-pituitary-adrenal suppression
 growth retardation, osteoporosis,
psychiatric disturbances
sodium and water retention
Hyperkalemia
hyperglycemia, immunosuppression,
impaired wound healing
Glaucoma
posterior subcapsular cataracts
skin thinning and easy bruising
Central redistribution of fat, and moon facies

33. Inhaled Corticosteroids
• In persistent asthma, inhaled corticosteroids provide the most
comprehensive control of the inflammatory process and are the cornerstone
of therapy
• Inhaled corticosteroids are more effective than cromolyn, leukotriene
modifiers, nedocromil, and theophylline in reducing markers of
inflammation and AHR, improving lung function, and preventing emergency
department visits and hospitalizations due to asthma exacerbations
• Although some effect is seen from inhaled corticosteroids within 12 hours,
2 weeks of therapy is necessary to see significant clinical effects, and longer
treatment periods may be necessary to see the full effect of these agents
on airway inflammation and remodeling.

34. Inhaled Corticosteroids
• Inhaled corticosteroids are not equivalent on a
milligram basis; however, equivalent doses have
been approximated
• Low to moderate doses have been shown to be safe
and effective in all age groups
• Adverse effects: osteoporosis, candidiasis and
dysphonia

35. Magnesium sulfate
• Magnesium sulfate is a moderately potent
bronchodilator, producing relaxation of smooth
muscle and central nervous system depression.
• The use of IV magnesium sulfate in patients
presenting to the ED is controversial
• The adverse effects of magnesium sulfate include
hypotension, facial flushing, sweating, nausea,
loss of deep tendon reflexes, and respiratory
depression

36. Treatment of Chronic Asthma
• Prevent chronic and troublesome symptoms (e.g.,
coughing or breathlessness in the daytime, in the night,
or after exertion)
• Require infrequent use (≤2 days a week) of short-acting
inhaled β2 -agonist for quick relief of symptoms 2 (not
including prevention of EIB).
• Maintain (near) normal pulmonary function.
• Maintain normal activity levels (including exercise and
other physical activity and attendance at work or school).
• Prevent recurrent exacerbations of asthma and minimize
the need for ED visits or hospitalizations.
• Minimal or no adverse effects of therapy.