Introduction• The respiratory system is an organ system

which is used for gas exchange. The respiratory system generally includes tubes, such as bronchi, used to carry air to the lungs, where gas exchange takes place. In the lung the trachea (windpipe) divides into two main bronchi, the left and the right. The right main bronchus is winder, shorter, and more vertical than the left main bronchus.

Anatomy and Physiology

The air-conducting passage that bring air into the lung are the nose, pharynx, trachea bronchi, and bronchioles. The respiratory tract form the nose to the bronchioles is lined with ciliated mucous membranes.

These three processes (filtered, warmed and humidified) are primarily function of the respiratory mucosa. Which consists of pseudo stratified, ciliated, columnar epithelium and goblet cells.

The epithelial surface is covered by a mucous blanket, which is secreted by both the goblet cells and the serous glands.

Bronchioles are not supported by cartilaginous rings but are surrounded by smooth muscle, which allows alteration in size. All the airway down to the level of the terminal bronchioles are called conducting airway because to the gas exchanging areas of the lung.

The physiologic process of respiration by which O2 is transferred from the air to the tissues and CO2 is excreted in the expired air maybe divided into three main stages, the first stage is ventilation , which the flow of a mixture of gases into and out of the lungs. The second stage, diffusion, must be considered from several aspects:

)1 (The diffusion of gases between the alveolus and pulmonary capillary and exchange of gases between the systemic blood and tissue cells (perfusion)

) 2 (The distribution of the blood in the pulmonary circulation and its match with the distribution of the air in the alveoli.

) 3 (The chemical and physical reactions of O2and CO2with the blood.

Cell respiration, or internal respiration, is the final stage of respiration, during which substrates are oxidized to obtain energy and CO2is produced as a waste product of cell metabolism and excreted by the lungs.

Clinical presentation: “COPD” refers to chronic obstructive pulmonary

disease. )Chronic( means long term.

)Obstructive( means there is a blockage to airway. )Pulmonary( means to the lung.

Obstructive pulmonary encompasses several separate and distinct sets of pathologic changes, including asthma, chronic bronchitis and emphysema.

chronic obstructive pulmonary disease (COPD) describes the presentation of chronic cough, expectoration, and a significant and progressive reduction in expiratory airflow. This airflow obstruction may respond to varying therapeutic options, but it is largely irreversible.

CHRONIC OBSTRUCTIVE PULMONARY DISEASE

11--Asthma:Asthma: is characterized by narrowing of the airway as a result of bronchial hyper activity, excessive bronchial secretions, and airway inflammatory changes. The resulting airflow obstructing is usually reversible.

22--chronic bronchitischronic bronchitis:: is condition of bronchial

inflammation & hyper secretion of mucus manifested by cough, heavy septum production &hypoventilation.

33-- Emphysema: Emphysema: irreversible loss of alveolar wall and abnormal enlargement of alveoli and alveolar ducts ,therefore the airway tend to close in expiration whenever outside pressure exceeds that within. Patient suffer dyspnea & wheezing with any increase respiratory efforts.

* The three disease mentioned before are classified as:

**obstructive disorders: means air flow is limited during expiration due to bronchospasm, excessive amount cause obstruction of air flow & edema.

**Restrictive disease : means air flow is limited during inspiration duo to chest deformity(kyphoscoliosis) & low of elasticity of alveoli e.g,pneumonia.

Chronic bronchitis and emphysema are often grouped together &indistinguishable on clinical examination, and patient have overlapping features due to pathogenic common

denominator, cigarette smoking .With the onset of attacks infections of the nasal sinuses or tracheobronchial tree. The attacks become more frequent over time, and the condition merges into chronic bronchitis and sometimes emphysema.

Etiology: Passive smoking has been identified as a possible factor in COPD development, and other environmental factors as pollution and occupational exposures have been implicated.

Pathophysiology: With obstructive pulmonary disease, air exchange

is impaired in several ways. Airway integrity is compromised through smooth muscle contraction, inflammation, edema, and peribronchiolar fibrosis. Changes in pulmonary vasculature result from hypoxia. Pulmonary hypertension , pulmonary vascular resistance, may develop. Cor pulmonale, or hypertrophy of the right ventricular due to primary lung disease, may then develop & progress to heart failure.

Physical obstruction of the airways due to chronic or recurrent excessive mucus secretion, accompanied with inflammation, also interferes with normal mechanisms to maintain airway integrity in chronic bronchitis. This excessive mucus production is the result of irritation of the airway by smoke or other irritants. With chronic irritation, the mucous glands increase in number and size and their ducts dilate within the bronchial mucosa destruction of alveoli and further functional air exchange area reduction occurs.

Clinical presentation:

Screening programs to identify patients at risk for COPD, or in the earliest stages of the disease, are not prevalent compared with programs for detection of heart disease or cancer. Significant overlap between the clinical presentation of chronic bronchitis and emphysema exists. The presentation of chronic bronchitis begins with morning cough productive of sputum

1 -cough 2 -increased sputum production.

3-weight loss (sometimes profound) may be reported by the patient with primary emphysema.

•4-dyspnea5-Wheezes: may be heard

6-Increase in the anteroposterior diameter of the chest

7-The chest X-ray 8-hypoxemia

9-Resparatory acidosis (hypoventilation)10-Respiratory infections of bacterial, viral, and

mycoplasmal

DiagnosisDiagnosis::No specific laboratory information is useful in differentiating the various form a COPD, the diagnosis test (alpha1 antitrypsin deficiency )is made by a serum protein electrophoretic study.

Pulmonary function test (spirometry) provide the best information on degree of airway obstruction.

.

• Complications :

Patient in whom chronic bronchitis predominates may undergo repeated episodes of acute respiratory failure. These patients may develop cor pulmonale & right sided congestive heart failure. The term blue bloater has been associated with this type of COPD patients. Hypoxemia & respiratory acidosis are common finding. Acute respiratory failure is rare until the end stage of emphysema. These patients are termed “Pink puffers” because alveolar ventilation is maintained until the terminal stages of the disease . Respiratory infection of the bacterial, viral & mycoplasmal etiology can trigger an acute COPD exacerbation especially in the patient with chronic bronchitis.

Bronchial asthmaDefinition:

A chronic inflammatory disorder of the airways in which many cells and cellular elements play a role in particular mast cells, eosinophil, T-lymphocytes, macrophages, neutrophils, and epithelial cells

Asthma is a disease in which inflammation of the airways causes airflow into and out of the lung to be restricted. The muscle of the bronchial tree become tight and the lining of the air passage swells, reducing airflow and producing the characteristic wheezing sound. >>> this is known as ( Asthma attack ), or as a part of a complex disease cycle which may include reaction to stress or exercise >> ( chronic asthma). In children, boys show a greater risk for asthma than girls.

Etiology:)1-(allergen e.g., mold, mites pollen ,

animal dander.)2 -(exercise (the increase in temperature

cause bronchoconstriction).)3 (Environmental irritant e.g., cigarette

smoking , pollutant , cold dry )4 (Medications e.g., Aspirin ,NSAID ,B-

blockers .)5 (Viral respiratory tract infection.

Classes of asthma:Classes of asthma according to the cause:

1 -extrinsic ( allergic ) asthma.Found in a minority of adult patient, is clearly caused by a known allergen. This form generally beings in childhood in a member of family with a history of a topic disease.

Allergic asthma result from the sensitization of such a person to an allergen, usually a protein, animal dander, mold spores, feathers, dust, lint or food like milk or chocolate.

•exposure to the allergen, even in minute quantities, produces an asthmatic attack.

Allergen induced asthma is divided into:A- immediate asthma: where air flow limitation begins minutes after contact with allergens.

B- dual asthmatic resonce: immediate followed by late reaction.

C- late phase reaction : a more prolonged and sustained attack of air flow limitation.

D- recurrent asthmatic reaction: development of late phase reaction with an increase in airway hyperactivity

2 -intrinsic ( cryptogenic or idiopathic ) asthma.Is characterized by the absence of clearly defined precipitating factors. Non specific factors such as the common cold, exercise or emotion may trigger the asthmatic attack. The intrinsic type of asthma is more apt to develop after age 40.

3 -mixed asthma:Which is composed of components of both extrinsic & intrinsic asthma.

In children boys show a greater risk for asthma than girls.

In children younger than 14 years, the prevalence is twice as high in boys compared to girls.

Disease onset can occur in person of any age, but often present in children younger than 6 years.

Classes of asthma according to the course: Chronic asthma & acute asthma.

• 1) chronic asthma:• Individuals have

intermittent attack of dyspnea

• Wheezing & cough .

• 2) Acute sever asthma( status asthmaticus(

• Is compatible with bronchial obstruction.

• Not easily revered• Can be fatal & require

energetic treatment.• Hospitalization may

be necessary.

• Clinical manifestation:• Symptoms• Dyspnea: abnormal

shortness of breath.• Wheezing : is a high

pitched sound resulting from turbulent gas flow in the upper airway. It may be inspiratory, expiratory or present on both inspiration and expiration

• Cough with or without sputum production.

**Signs:-Reduced airflow

-Increase airway resistance-Reduce conductance

-Hyperinflation of the lung-Bronchial hyper-responsiveness

* In acutely obstructed patients:-Tachypnea: rapid breathing

-Tachycardia: rapid heart rate-Retraction (pilling of the skin between the ribs

when breathing)-Hypoxemia

-Cyanosis ( bluish color of lips and face)

• Pathophysiology:• The Pathophysiology of bronchial asthma is a

complex process. Its pathogenesis involves a number of cells, mediators, nerve & vascular leakage. Involving three main components

(i) airway inflammation (ii)bronchial hyper-responsiveness (iii)intermittent airflow obstruction .• There is a certain mechanism that causes

airway inflammation and by the way this happens one can judge whether asthma is acute ,chronic or sub-acute. Other signs that help in diagnosis here are the edema of the airway ,the mucus hyper-secretion and the bronchial hyper –reactivity ,all these are causes for airflow obstruction.

• Upon further inspection, it can be found that varying degrees of infiltration of eosinophil , hyper-secretion of mucus and desquamation of the epithelium will be present.

• Bronchial Hyper responsiveness:• Hyper responsiveness :is an exaggerated

bronchoconstrictive response to stimuli such as cold air, exercise, allergens, viral, infection, and certain chemicals. It is caused by interaction between an asthmatic's baseline bronchial responsiveness and airway changes caused by inflammation. The greater number of inflammatory cells (Eosinophill) in the air way, the greater its hyper responsiveness, the mechanism by which inflammatory cells and their mediators promote airway hyper responsiveness are not clear.

•Airway inflammation :characterized by (1)acute bronchoconstriction :causes include allergens, exercises aspirin ,

coldair,iritants .)2(Airway edema: caused by increase

microvascular permeability and leakage resulting in stiffer and narrow air way. (3)chronicmucus plug formation: which always present in sever asthma : .(4)airwayremodeling:result from epithelial fibrosis or collagen deposition.

• Airway inflammation:• It is a complex interaction of various cells and

mediators that result in bronchial hyper responsiveness and airway obstruction as well as ongoing inflammation.

• Role of inflammatory cells:• (a) Alveolar macrophage :( in the late state of

bronchial hyper responsiveness and airway obstruction )

• Non granular, present in the lumen of small and large airway flow. They produce mediators involved in the initiation of inflammatory process (leukotreines, eosinophil chiropractic factors), act as antigen - presenting cells by preparing antigen for presentation to T-lymphocyte, and have some anti –inflammatory effect.

• (b) T-lymphocyte: play an important role in the pathogenesis of asthma by coordinating the inflammatory response .T-lymphocytes produce cytokines, which promote inflammation.

• (c) Mast cells: known as acute response cell, they increased in both the epithelium and surface secretion of asthmatics .they release in early stage immediate –acting mediators such as histamine, leukotrienes, prostaglandins, platelet-activating factor (PAF) that cause immediate bronchoconstriction, and in the late stage they release longer-acting mediators such as eosinophil and neutrophil chemo tactic factors and cytokines. It appears that other cell such as important that mast cell in maintaining the chronic airway inflammatory processes. Further evidence of the importance of the mast cell is the finding in large number.

• Eosinophiles: present in the peripheral blood, bronchiol mucosa, and bronchoalveolar fluid of patients with asthma .Their granule contain major basic protein (MBP) and eosinophil cationic protein (ECP) which are responsible of airway epithelium damage . They release mediator (cytokines) to regulate their own function. The important of adhesion cell in drawing eosinophil to the site of inflammation.

• Neutrophiles: are source of proteases and oxygen radicals, which can cause tissue damage , and lipid mediator , because neutrophil can be produced in large amount by bone marrow and have very short half- life .They have a greater role in acute asthma than in chronic asthma symptoms

• Mediators: The cells involved in inflammatory processes present asthma produce and release mediators responsible of the pathophysiologic changes include epithelial damage ,smooth muscle contraction, mucosal edema, inflammation and mucus secretion .These mediators are rapidly produced by cells after activation or stimulation and can removed by inhibition or antagonism result in amelioration of the asthmatic response .

• Types of inflammatory mediators: • (1)Immediate acting mediators :( early attack),

characterized by bronchoconstriction. Such as, histamine, leukotrienes.

• (2) Long acting mediators :( late attack)• Characterized by inflammation, excess mucus

secretion and edema, e.g.:cytokines,neutrophile...

Mediators should have the followingcharacters:

)1(it must be capable of producing the pathologic changes observed in asthma or physiologic changes that that define

asthma .)2(it must be produced in the

lung during an asthmatic episode and measurable in

body fluid. )3(removable by specific

inhibition or antagonism result in amelioration or attenuation of the asthmatic response

• Adhesion molecules: They are glycoprotein expressed by cell membrane of endothelial cells, platelets, WBCs, and epithelial cells.

• Function:• -Adhesion of inflammatory cells to surface of

vasculature (an important early step in inflammatory response)

• -promoting cell activation.• -Cell-cell communication.• -Allow WBC migration( the recruitment of WBC

from vascular lumen to tissue site ) & infiltration.

• Classification of adhesion molecules:• Based on their chemical structure. • Integrins, immunoglobulin family,

selectine, endothelial adhesion molecules

• Transcription factor: It is the production of inflammatory proteins .e.g, cytokines, adhesion molecules and enzyme can be augmented by an increase the transcription of selected target genes.

• Nuclear factor-KB (NF-KB): It is the transcription factor that can be activated by cytokines and oxidants to increase the production of inflammatory cytokines, chemokines and adhesion molecules.

• Corticosteroids: They are potent inhibitors of the activity of NF-KB in airway inflammation.

• Nitric oxide: It is produced by endothelial and neuronal nitric oxide synthase which regulate vascular tone, platelet activation and neurotransmission. The amount of nitric oxide induced during inflammation is much greater than that produced normally and appears to have protective effects such as relaxation of bronchia.

Neuronal mechanism: Neural regulation of the

airway is complex and involves: parasympathetic, sympathetic, sensory system.

• It affects airway functioning by regulating epithelial, vascular and glandular and smooth muscle activity mechanism. This affected through release of neurotransmitters and neuropeptides.

• These affected are classified as:• (1) Cholinergic (bronchconstriction) increase

secretion. • (2) Adrenergic (bronchodilator) decrease

secretion. • (3) Inhibitory non-adrenergic non- cholinergic

(bronchodilator).

• (4) Excitatory non-adrenergic non- cholinergic (bronchoconstictor).

• (5) Sensory.

These results from the specific combination of neurotransmitters and neuropeptides within the sensory sympathetic and parasympathetic system.

• (1) Parasympathetic contains ACH vasoactive intestinal peptide which causes bronchoconstriction and glandular exudation.

•

• (2)Sensory nervous system: Present in human airway contains neuropeptides such as substance P and neurokinineA (collectively called tachykinine).Tachykinine are bronchoconstrictor to asthmatic patients and cause increased vascular permeability, mucus secretion and leukocyte Infiltration.

• NeuronalEndopeptidase (NED): The enzyme that degrades neuropeptide and NEP activity is reduced by external factors. e.g, cigarette smoke, viral infection, pollution and the presence of these factors will inhibit the activity of the enzyme and that will lead to asthma.

**Investigations:

A- detailed history:( family history or child medical history )

B- physical examination:Listening to the lung with stethoscope, examination of nasal passage.

C- laboratory & diagnostic tests: blood test (presence of eosinophiles indicate

asthma* * chest x-ray (may be done to exclude the

possibility of breathing problems being caused by something other than asthma or obtained when a patient of asthma needs to be hospitalized).

pulmonary function tests ( spirometry): it is breathing test which measure the amount & rate of air passage through airways.

-Vital capacity (VC) The maximum expiration after maximum

inspiration )also called full expiration(

residual volume :amount of air left in the lungs after a maximal exhalation

-functional residual capacity: volume of air remaining after normal expiration.

-total lung capacity (TLC)The volume of gas contained in the lung at the end of maximal inspiration. The total volume of the lung.Peak expiratory flow test: maximum rate of air flow produced by forced expiration

• Complications:(1)Asthma and pregnancy (2)pneumothorax.(3)Repiratory fatigue .(4)Adrenal insufficiency .(5)Status asthmaticus :sever acute disease that doesn’t respond todrug therapy and may cause death from acuterespiratory insufficiency.(6) Physiological problems such as depression.

Rhinitis• Definition: Is an inflammatory

condition affecting the mucous membrane of the nose and upper respiratory system, and it is the most common of all allergic disease.

• nasal symptoms characterized by:

1) rhinorrhea 2) Itching {pruritus} of the nasal

mucosa & throat. 3) Sneezing 4) Congestion 5) Postnasal drainage 6) Ears is often distressing

- These nasal symptoms can be accompanied

by ocular pruritus & conjunctival redness and lacrimation, and can be exacerbated by the development/presence of sinusitis. The involved mucous membranes show dilation of blood vessels (particularly venules) & extensive edema with prominent eosinophils in both tissue & secretions. All these features including pruritus, can be duplicated by applying histamine alone to the normal mucosa.

• Etiology of allergic rhinitis:Etiology of allergic rhinitis:

• Both genetic factors and environmental influences are associated with the development of allergic rhinitis.

• in patients with intermittent allergic rhinitis, pollens and airborne mold spores are the most common allergens.

• Although the pollen season varies with geographic location, grasses, trees and weeds can be problematic for many people during active pollination.

• In patients with persistent allergic rhinitis, the major allergens are house dust mites, indoor molds, animal danders, and cockroach antigen.

• Another common occupational exposure, in which symptoms can be precipitated by agent such as flour, wood and detergents.

• Pathophysiology:Pathophysiology: The primary pathophysiologic features in allergic

rhinitis are inflammation of mucous membrane of the nose.

• Allergic rhinitis is characterized by immunoglobulin [IgE]-mediated response that involves three primary steps:

• sensitization, early phase event, late phase event.

• Sensitization:Sensitization:

In a topic patient the result of initial exposure to allergens is production of IgE. Following initial exposure antigen-presenting cells of the immune system react to allergens disposition in the nasal mucosa. This result in helper T-lymphocyte differentiation into Th2 cells which are associated with production of cytokines and other mediators of inflammation. As a result memory cells programmed for IgE production are produced.

• Early response:Early response: When a susceptible patient is exposed to

allergens previous sensitization has occurred, an early-phase allergic response generally occurs. This reaction is attributed largely to the interaction between the allergen, IgE and the sensitized mast cell resulting in mast cell degranulation.

• Late response:Late response: In this phase the nature of inflammation is even

more complex and nasal congestion is prominent feature. Numerous cells and mediators play important roles, including

T-lymphocytes, cytokines, eosinophiles, neutrophiles, macrophages, mast cells and leukotrienes.

• Classification:Classification:• 1) Acute rhinitis:1) Acute rhinitis:• the causes of acute rhinitis are:• a- viral or bacterial upper respiratory infection or the

common cold [the most common cause]• b- Hormonal causes of acute vasomotor rhinitis [ usually

associated with a clear watery discharge without other symptoms include hyporthyroidism and pregnancy.

• - Finally the development of rhinitis-like symptoms has been attributed to some medications.

• c- Drugs like: angiotensin-converting enzyme inhibitor, B-blockers, resrpine, non steroidal anti-inflammatory drugs[NSAID], oral contraceptive and topical decongestant all have been associated with these effects.

• 2) Chronic rhinitis:2) Chronic rhinitis: chronic rhinitis can be classified into:

• A- allergic: an inherited tendency to develop a clinical hypersensitivity condition. It has been classified as:

• 1) - seasonal [intermittent]: this is often called (hay fever). There symptoms are:

• Nasal irritant-sneezing.• Itching of the eyes and soft

palate and occasionally even itching of the ears because of the innervations of the pharyngeal mucosa and ear.

• 2)- perennial [persistent]: its symptoms are: have the affect the eyes or throat, sneezing, watery rhino rhea, lose of sense of smell and taste.

• Can be divided into four main types:• * Perennial non-allergic rhinitis with eosinophilia

(NARES)(NARES) • * Perennial allergic rhinitis.• * Vasomotor rhinitis.• * Nasal polyps.• - The demonstration of specific IgE antibodies by

skin testing or in vitro testing can be important for confirmation of sensitivity to specific allergens.

• Diagnosis & Assessment of Rhinitis:• Because it is difficult to measure nasal function

in a completely satisfactory manner, the specific cause of rhinitis is based on a carefully obtained patient history, physical examination, and a limited number of relevant laboratory examinations. A thorough medication history can also add insight into nasal function.

• Other diagnostic tests: sinus X-ray, computed tomography, rhinomanometry, and spirometry maybe useful

• Complications:Complications:

1- Sleep disorder.2- Loss of appetite.3- General weakness.4- Fatigue5- Mood disorder.6- Decrease contraction.7- Difficulty learning.

ReferencesReferences::

• 1)-Text book of Pathophysiology.

• 2) - Applied therapeutics.

• 3) – clinical concepts of disease:

Thank YouThank You……Done by :Done by :

Afnan Al-AddadNouf Al-Fadel

Refa’ah Al-AjmiAsma’a Al-RuwailiSupervised by :Supervised by :

Dr.Azza AzzoDr.Azza AzzoTeach.Raniah Teach.Raniah