Conducting Airways
Plumbing. Transmit O2/co2, do not participate in gas exchange
Gas Exchange Airways
-Respiratory bronchioles
-Alveolar ducts
-Alveoli
*Primary gas-exchange unit of the lung (O2 enters the blood and CO2 is removed)
-Types of cells
Type I alveolar cells�provide structure
Type II alveolar cells�secrete surfactant
Alveolar macrophage
Type I
Pulmonary Circulation
Facilitates gas exchange
Delivers nutrients to lung tissues
Acts as a reservoir for the left ventricle
Serves as a filtering system to remove clots, air, and other debris from circulation
Function of the Pulmonary System
Ventilate the alveoli
Diffuse gases into and out of the blood
Perfuse the lungs so that the organs and tissues of the body received blood rich in oxygen and low in carbon dioxide
-Alveolar Macrophage: Defense mechanisms of the lung. Remove and kill bacter
Ventilation
Process of moving air between the atmosphere and alveoli
Lung volumes
1) Tidal volume �amount of air inspired or expired during each respiratory cycle
2) Vital capacity �maximal amount of air expired by forceful effort after maximal expiration
3) Residual
Mechanism of Breathing
-Mechanical aspects of inspiration and expiration
-Major and accessory muscles of inspiration and expiration
-Elastic properties of the lungs and chest wall
-Resistance to air flow through the conducting airways
Respiratory Muscles
-Diaphragm
-Accessory muscles of inhalation
External intercostals
Scalene
Sternocleidomastoid
-Accessory muscles of exhalation
Internal intercostals
Abdominal muscles
Compliance
How easily lungs can be inflated depends on:
Elastin and collagen fibers- alveoli expansion
Water content- increased water can cause stiffness
Surface tension- surfactant will keep it open, otherwise it'll collapse
Gas Exchange
Oxygen moves from alveolar air into blood
Carbon dioxide moves from blood into alveolar air
Blood Gases- Oxygen
Dissolved oxygen = PaO2 or PO2
Normal value >80 mm Hg. How the lungs carries oxygen.
Oxygen bound to hemoglobin = oxyhemoglobin
Normal value 95% to 100% saturation. How blood carries oxygen.
Blood Gases- Carbon Dioxide
Dissolved carbon dioxide = PaCO2 or PCO2 Normal value 35-45 mm Hg
Carbon dioxide bound to hemoglobin = carbaminohemoglobin
Carbonic acid bicarbonate ion and H+
Exhale-remove CO2 from blood,decrease the amount of carbonic acid, raising your blood pH
Oxygen Capacity
Amount of oxygen the blood can hold
What is the oxygen capacity of normal blood?
What is the oxygen capacity of anemic blood?
-Hemoglobin binds to oxygen, depending on the PH of the blood. So if the patient has an acidic pH, then the patient is typically
Chemoreceptors can adjust to respiratory rate
Central chemoreceptors
Measure PCO2 and pH in cerebrospinal fluid
Increase respiration when PCO2 increases or pH decreases
-If this mechanism doesn't work, then the peripheral chemoreceptors in the carotid arteries and in aortic arch measure oxygen when P
Regulation of Respiration
Automatic and voluntary components
Automatic- Sensors or receptors
Chemoreceptors- monitor blood levels of oxygen and carbon dioxide and pH
Lung receptors-monitor breathing patterns
Respiratory Tract Infections
Most common cause of short-term disability in the United States
-Common Cold
-Sinusitis
-Pneumonia
-Tuberculosis (TB)
-Acute Bronchitis
Signs and Symptoms of Pulmonary Disease
Dyspnea**
Abnormal breathing patterns
Kussmal respirations--Hyperventilating, shallow rapid breathing. Usually in the response to acidosis because CO2 is accumulating in body. Panicked feeling.
& Cheyne-Stokes resp--Irregular stopping and starting of brea
Common Respiratory Diseases
Common cold--within 7 days you should feel better; upper air way tract.
Rhinosinusitis
Influenza
The Common Cold
1) Rhinoviruses:
Occur in early fall and late spring in persons between ages 5 and 40
2) Parainfluenza viruses (Most common):
Occur in children younger than 3
3) Respiratory syncytial virus (Most Common)
Occurs in winter and spring in children younger tha
Rhinosinusitis
Infection or allergy obstructs sinus drainage
1) Acute: facial pain, headache, purulent nasal discharge, decreased sense of smell, fever
2) Chronic: nasal obstruction, fullness in the ears, postnasal drip, hoarseness, chronic cough, loss of taste and smel
Rhinosinusitis Clinical Features
-Classified as acute, subacute, or chronic
-Acute rhinosinusitis may be of viral, bacterial, or mixed viral-bacterial origin
-May last from 5 to 7 days in the case of acute viral rhinosinusitis
-Up to 4 weeks in the case of acute bacterial rhinosinusitis
Influenza
In the United States, approximately 36,000 persons die each year of influenza-related illness
Transmission is by aerosol (three or more particles) or direct contact
Upper respiratory infection (rhinotracheitis)
Like a common cold with profound malaise
Vir
Influenza Viruses
3 Types that cause disease in the USA-A,B,C
A-Humans, Pigs, Horses, Birds. Major cause of epidemics and pandemics
Pathogenesis
Uncomplicated upper resp. infection
Viral Pneumonia
Respiratory viral infection
Followed by a bacterial infection
Initially esta
Influenza Patho
The virus targets and kills mucus-secreting, ciliated and other epithelial cells (gaping holes in the underlying layer of basal cells)
Spread to the lower resp. tract , compromises natural defenses
Influenza promotes bacterial adhesion to epithelial cells
Clinical Manifestations of Influenza
Early stages-indistinguishable from other viral infections
Abrupt onset:
Fever
Chills
Malaise
Muscle aching
Headache
Profuse watery nasal discharge
Non-productive cough
Sore throat
Distinguishing feature
Rapid onset of profound malaise****
Influenza Treatment
Goal: Limit the infection to upper respiratory tract
Treatment is symptomatic:
Rest
Keeping warm
Consuming large amounts of fluids
Antipyretics and cough/cold syrups can be used
Fluids guarantees keeping the respiratory track from dehydrating
AVOID THE US
Pneumonia
Acute infection of the lower respiratory tract caused by bacteria, viruses, fungi, protozoa, or parasites (fungus is hard to treat from moistness of lungs)
Six leading cause of death in the United States
Highest mortality in the elderly
Risk Factors: adva
Causes of Pneumonia
Community acquired:
Streptococcus pneumoniae* (most common)
Myoplasma pneumoniae*
Haemophilus influenza*
Oral anaerobic bacteria
Influenza virus
Legionella pneumophilia
Chlamydia pneumoniae
Moraxella catarrhalis
Nosocomial acquired: (from hospital- occurs
Pneumonia Pathophysiology
Pathogen reached alveoli and replicates: Lungs are filled with fluid/debris and inflammatory mediators. Lungs now will have trouble with gas exchange because of fluid/debris filled alveoli. Alveoli are very sensitive to fluid shifts and debris. It is not
Pneumonica Clinical Manifestations
Abdominal pain (more common in children)
Changes in Mental Status***
Changes in sensorium
Cyanosis - from lack of 02
Diaphoresis - sweating
Diarrhea (mycoplasma, legionella)
Dyspnea -difficulty breathing?
Fever/chills
Headache
Malaise
Nausea/vomiting
Pleu
Diagnosis of Pneumonia
-Complete blood cell count (CBC) - WBC elevation indicative of infection
-Gram's stain and culture of sputum - detect causative agent
-Blood cultures before antibiotics - detect bacteremia
-Arterial blood gas (ABG) values - evaluate oxygenation
-CXR - inf
Treatment of Pneumonia
Administer prescribed medications (antibiotics, bronchodilators, antipyretics)
Position the patient to facilitate breathing
Provide humidified treatments and/or oxygen
Have suction available to assist with removal of secretions as necessary
Continuously m
Tuberculosis
-World's foremost cause of death from a single infectious agent
-Causes 26% of avoidable deaths in developing countries
-Drug-resistant forms
-Mycobacterium tuberculosis hominis
*Aerobic
*Protective waxy capsule
*Can stay alive in "suspended animation" fo
Initial TB infection
Macrophages begin a cell-mediated immune response
Takes 3-6 weeks to develop positive TB test
Results in a granulomatous lesion
or Ghon focus containing
Macrophages
T cells
Inactive TB bacteria
That lesion can be "cheesy".
-Transmitted from person to pers
TB
-Transmitted from person to person in airborne droplets
-Once the bacilli are inspired in the lungs (usually upper lobes), they multiply and cause nonspecific pneumonitis
-Some bacilli travel to the lymph nodes where they encounter lymphocytes and initiat
Primary TB
Just because you have TB, doesn't mean you're contagious. It has to be ACTIVE. Once it gets walled off and contained, you are no longer contagious, tho the ghon focus never goes away.
-If immune response is inadequate, then it is progressive primary TB
Clinical Manifestations of TB
May be asymptomatic
Fatigue
Anorexia
Weight loss
Low grade fever (afternoon temp goes up )***
Night sweats***
Lethargy**
Cough with purulent sputum develops slowly
Tuberculosis Diagnosis
Positive tuberculin skin test
Sputum culture
Chest radiography
TB skin test
*False POSITIVE reaction may occur in people who received BCG vaccine (latin america)
*False NEGATIVE reactions may occur in people with HIV infection, viral infections, Hodgkins, and those receiving corticosteroids or immunosuppressive drugs
*If BCG was
TB treatment
Antibiotic therapy to control active or dormant tuberculosis and prevent transmission
Treatment must be continued for a minimum of 6 months
*Isoniazid (INH)
*Rifampin (RIF)
*Pyrazinamide (PZA)
*Ethambutol (EMB)
Uncomplicated TB---
2 mos of INH, Rifampin,
Lung Cancer
- most common: adenocarcinoma
Manifestations of Lung Cancer
1) Changes in organ function (organ damage, inflammation, and failure)
2) Local effects of tumors (e.g., compression of nerves or veins, gastrointestinal obstruction)
3) Ectopic hormones secreted by tumor cells (paraneoplastic disorders)
4) Nonspecific si
Hypercapnea
Increased CO2 in arterial blood
Causes:
Hypoventilation of alveoli due to
Depression of respiratory center by drugs
Disease of the medulla
Abnormalities of spinal conduction pathways
Diseases of the neuromuscular junction or respiratory muscles
Thoracic c
Manifestations of Hypercapnea
Somnolence***
Electrolyte Disorders
Dysrhythmias
Coma
Death
Hypoxemia
Reduced oxygen concentration in arterial blood
Causes:
Decreased O2 content of inspired gas
Hypoventilation
Diffusion abnormalities- if alveoli are damaged
Abnormal ventilation-perfusion ratios
Pulmonary right to left shunt--Deoxygenated blood mixing with
Manifestations of Hypoxemia
Tissue Ischemia, Organ Dysfunction, Coma and Death
Cyanosis
Bluish discoloration of the skin and mucous membranes
Causes
Decreased arterial oxygenation
Pulmonary or cardiac right to left shunts
Cold environments
Anxiety
Lack of cyanosis does not necessarily indicate that oxygenation is normal
1) Central cyanosis=
Ventilation- Perfusion Mismatching
-Blood goes to parts of the lung that do not have oxygen to give it
-Blood does not go to parts of the lung that have oxygen
-If patient has pulmonary edema with swollen lungs that is full of fluid, alveoli will become edemedis. So it's not a problem with
Pleural Disorders Disease Ventilation
-Parietal pleura lines the thoracic wall and superior aspect of the diaphragm
-Visceral pleura covers the lung
-Pleural cavity or space between the two layers contains a thin layer of serous fluid
Pleural Effusion
-Presence of fluid in the pleural space
Causes:
-Migration of fluids and other blood components through the walls of intact capillaries bordering the pleura
-Severity dependent on volume of effusion
-Acts as a "space-occupying lesion" and results in atele
Pleural Effusion Types
1) Transudative (watery)
Watery fluid that diffuses from capillary bed due to changes in BP or capillary oncotic pressure
CHF, Protein malnutrition (no albumin)
2) Exudative
Thicker containing WBCs & plasma proteins - all products of inflammation are form
Flail Chest
Is defined as a fracture of two or more sites on two or more adjacent ribs or when rib fractures produce a free floating sternum.
When you take a breath, part of the hanging bone will stick up. Chest wall moves the opposite way�hallmark***
The chest wall
Pneumothorax
Presence of air or gas in pleural space caused by rupture in visceral pleura
Types:
1) Open (communicating)
2) Tension
3) Spontaneous
4) Bleb formation
5) Secondary
Pneumothorax
Air enters the pleural cavity
Air takes up space, restricting lung expansion
Partial or complete collapse of the affected lung
1) Spontaneous: an air-filled blister on the lung ruptures
2) Traumatic: air enters through chest injuries
* Tension: air enters
Pneumothorax Treatment
Re-expand lung
Needle decompression
Chest tube
Take a 18 gage needle to decompress, or put in a chest tube which is the better option. Lungs will immediately expand.
Pneumothorax Clinical Manifestations
(depends on size of pneumothorax)
Sudden pleural pain**
Tachypnea*
Possibly mild dyspnea*
Mediastinum moves towards unaffected lung*
Tension pneumo: depends on size of the pneumo, decreased lung sounds on the affected side, tension= blood pressure will go
Atelactasis
Collapse of lung tissue (alveoli)
Causes:
Conditions that reduce excursion of chest (deep breathing)
-Post-operative complication is the most common. Many times, your lungs need to be re-inflated. You need to do some deep-breathing for a few days. Lungs w
Types of Atelactasis
Compression--
External pressure against alveoli
Fluid, tumors, air, diaphragm displacement, absorption
Absorption--
Removal of air from obstructed hypoventilated alveoli
Inhalation of concentrated oxygen/anesthetic agents
COPD
Chronic Obstructive Pulmonary Disease
The fourth leading cause of death in the United States, affecting 16 million Americans
Deaths annually: 112,584
The prevalence of COPD and mortality rates based on the disease are relatively higher among
Males
Whites
COPD
Characterized by airway obstruction that is worse with expiration*
**Asthma
**Chronic Bronchitis
**Emphysema
-Underlying symptoms is dyspnea wheezing
-Individuals have an increase work of breathing, ventilation/perfusion mismatching, and a decrease forced
Mechanisms of COPD
Inflammation and fibrosis of bronchial wall
1) Hypertrophied mucous glands -- excess mucus
Obstructed airflow
2) Loss of alveolar tissue
Decreased surface area for gas exchange
3) Loss of elastic lung fibers
Airway collapse, obstructed exhalation, air
tra
Risk Factors for COPD
*Recurrent or chronic respiratory infections
*Allergies
*Genetics-. Alpha 1 deficiency of enzymes that protect the lung of injury (Genetic Component). They are good candidates for lung transplants.
*Occupational exposures
*Air pollution
*Smoking - impairs
Inspiration and Expiration in COPD
Inspiration: The lungs expand and airways are stretched open
Expiration: The airways decrease in size but remain patent due to the lack of significant mucus accumulation and the elasticity of bronchial walls that are seen in healthy lungs
Obstructive Lung Disease
The inspiratory stretch of the bronchi allows air to enter the alveoli, but bronchial obstruction occurs during expiration due to mucus accumulation and/or loss of the normal elasticity of the airways with resultant expiratory bronchial collapse. Air beco
Asthma
Chronic inflammatory** obstructive lung disease that affects 5% of adults and 7% to 10% of children in the United States
2 million emergency room visits/year
48% of respondents say that asthma limits their ability to take part in sports and recreation; 36
Etiology and Risk factors of Asthma
Heredity
Exposures to allergens
Emotional factors
Environmental factors
Exercise
Inherited T-cell disorders: They are responsible for starting and stopping the immune response when they are working properly.
Triggers for Asthma
Characterized by excessive sensitivity of the lungs to various stimuli. Each person reacts differently to the factors that may trigger asthma.
Viral infections
Respiratory infections, colds
Cigarette smoke
Allergic reactions to pollen, mold, animal dander
Asthma
Immune mediators are activated (look at the chart on power point). Bronchoconstriction, mucus formation, and narrow airways are what happen. Capillary permeability happens which causes edema; the bronchi becomes inflamed.
-There can be MILD to MODERATE to
Evaluation and Treatment of Asthma
Diagnosis:
-Pulmonary function tests
-Blood
*IgE levels-Signifies SENSITIZED MAST CELLS; the markers of allergic response. This test is a way to distinguish from other pulmonary diseases.
*CBC - increased eosinophils (WBC)
ABG's - hypercapnia, hypoxemia-
Acute Bronchitis
Acute infection or inflammation of the airways or bronchi that commonly follows a viral illness and is usually self-limiting
Chest X-Rays shows no infiltrates
Symptoms are similar to pneumonia-- though you don't really have systemic effects
Treated with a
Chronic Bronchitis
Inflammation of the bronchi caused by irritants or infection
Hypersecretion of mucus and chronic PRODUCTIVE cough for at least 3 months of the year (usually the winter months) for at least 2 consecutive years
Increased incidence in smokers, workers expose
Patho of Bronchitis
Irritants are inhaled for a prolonged period increase mucus production and increase the size and number of mucus glands and goblet cells in the epithelium
Mucus produced is thicker than normal - easier for bacteria to adhere
Ciliary function is impaired -
Clinical Manifestations of Bronchitis
Productive cough
Dyspnea
Decreased exercise tolerance
Wheezing, shortness of breath
Use of accessory muscles of breathing
Frequent pulmonary infections
Hypoxemia�(cyanosis)�late sign
Pulmonary hypertension
Diagnosis of Bronchitis
With Chronic Bronchitis and Emphysema, if you have it for long enough, the lung tissue will become permanently damaged. There will be significant changes on x-rays: there will be HYPERINFLATION. The lung will become huge on x-ray and it keeps growing beca
Bronchitis Treatment
Stop smoking, avoid air pollutants, get all the mucus broken up/thinned out with bronchodilators, expectorants, chest physical therapy, antibiotics, steroids�to help with inflammation, low flow oxygen since people who have chronic bronchitis are usually s
Emphysema
Abnormal permanent enlargement of gas exchange airways accompanied by destruction of alveolar walls
Obstruction results from changes in lung tissues, rather than mucus production and inflammation
Distinguishing characteristic is airflow limitation caused
Emphysema causes
Primary) 1%
Linked to inherited deficiency of the enzyme alpha1-antitrypsin (inhibits the action of proteolytic enzymes)
Therefore are unable to stop proteolysis in lung tissue
Autosomal recessive trait
Secondary)
Inability of body to inhibit proteolytic
Patho of Emphysema
-Recurrent inflammation leads to release of proteolytic enzymes from lung cells
-Causes irreversible enlargement of the air spaces distal to the terminal bronchioles
-Enlargement of air spaces destroys the alveolar walls
-Results in a breakdown of elastic
Clinical Manifestations of Emphysema
Dyspnea on exertion***
Barrel-shaped chest from lung overdistention
Prolonged expiration because accessory muscles are used for inspiration and abdominal muscles are used to force air out of the lungs**
Decreased breath sounds-On auscultation, you will NO
Emphysema vs. Bronchitis
Pink puffers (usually emphysema)
Increase respiration to maintain oxygen levels
Dyspnea; increased ventilatory effort
Use accessory muscles; pursed-lip breathing
Barrel chest= 2/1 diameter
Blue bloaters (usually bronchitis)
Cannot increase respiration eno
Diagnosis of Emphysema
Pulmonary Function Test
? residual volume and total lung capacity
Chest X-Rays
flattened diaphram
ABG
early: ? pO2 and normal pCO2; late: ? pO2, ? pCO2 and increased HCO3
Pulse Oxymetry
Decrease saturation
Treatment of Emphysema
Never too late to stop smoking, avoid air pollutants, anticholinergics will decrease any mucus, bronchodilators help to keep the alveoli open, low flow oxygen* for smokers, adequate hydration, steroid, patient teaching, teaching of pursed-lip breathing to
Pulmonary Vascular Disease
-Pulmonary Embolism
-Pulmonary Hypertension
-Cor Pulmonale
Pulmonary Embolism
Occlusion of a portion of the pulmonary vascular bed by an embolus
Caused primarily by deep vein thrombosis
100,000 Deaths/year
Clot/piece of fat that lodges in the lungs. Piece of fat can lodge in the lung from another part of the body; it is difficult t
Pulmonary Embolism
-Patient will be normal... and then all of a sudden they can't breathe and feel like they're going to die- the impending sense of doom is a sign of something that is really wrong. As nurses we have to pay attention to it; seeing low oxygen is a sure sign.
Pulmonary Hypertension
High blood pressure in the pulmonary arteries
Normal 15 to 18 mm Hg
Clinical manifestations:
RV hypertrophy
Fatigue
Chest discomfort
Tachypnea
Dyspnea with exercise
Pulmonary Hypertension
-
If a patient has had prolonged low oxygen, in order to compensate, a patient with chronic bronchitis can actually develop pulmonary hypertension. The body is trying to say "lemme give more pressure to the lungs to increase more oxygen", but as a result
Pulmonary Hypertension
Treatment
Symptomatic care
Treatment of primary disorder
Increase volume or pressure of blood entering the pulmonary arteries
Narrows or obstructs the pulmonary arteries
Cor Pulmonale
Right-sided heart failure secondary to respiratory disease
Decreased lung ventilation
Pulmonary vasoconstriction
Increased workload on right heart
Decreased oxygenation
Kidney releases erythropoietin more RBCs made
Polycythemia makes blood more viscous
I
Cor Pulmonale
-We are trying to compensate the secondary pulmonary disease by increasing ventricle, increasing RBC, vasoconstricting, decreasing O2, decreasing lung ventilationg, but they all have BAD effects.
-Pulmonary Vascular Resistance - if you vasoconstrict vesse
Clinical Manifestations of Cor Pulmonale
Heart may appear normal at rest, but with exercise, cardiac output falls
EKG may show right ventricular hypertrophy
Chest pain is common
Pulmonic valve murmur may be present
Tricuspid valve murmur may accompany the development of right ventricle failure
Evaluation and Treatment of Cor Pulmonale
Diagnosis
Physical examination
Radiologic examination
EKG
ECHO- shows function of the heart
Treatment:
Goal is to decrease to workload of the right ventricle by lowering pulmonary artery pressure
Reverse the underlying cause
There are prostaglandins to va
Acute Respiratory Distress Syndrome
Acute lung inflammation and diffuse alveolocapillary injury with noncardiogenic pulmonary edema.
Survivors�have almost normal lung function 1 year after the acute episode
Causes:
Sepsis and multiple trauma**
Pneumonia
Burns
Aspiration
Pancreatitis
Drug ov
ARDS
Acute Respiratory Distress Syndrome (ARDS)
Almost a quarter of a million people in the United States develop ARDS each year
most common causes of ARDS are sepsis and multiple trauma
ARDS
*Exudate enters alveoli
Blocks gas exchange
Makes inhalation more difficult
*Neutrophils enter alveoli
Release inflammatory mediators
Release proteolytic enzymes
ARDS
In summary, an insult to the body that results in the systemic release of high levels of inflammatory cytokines
can result in breakdown of the alveolar-capillary barrier with flooding of the alveoli with proteinaceous fluid and cells
This is complicated b
Respiratory Distress Syndrome (babies)
-Lack of surfactant; infants are not strong enough to inflate their alveoli
-Protein-rich fluid leaks into the alveoli and further blocks oxygen uptake
-Treatment with mechanical ventilation may cause bronchopulmonary dysplasia and chronic respiratory ins
Evaluation and Treatment of RDS
Evaluation:
Physical examination
ABG
Fine crackles
Infiltrates (CXR)
CT of the chest
Bronchoscopy
Treatment:
Based on early detection
Prevention of complications
Mechanical ventilation
Acute Respiratory Failure
Inadequate gas exchange
Hypoxemia pO2 < 50 mmHg
Hypercapnia pCO2 > 50 mmHg with pH < 7.25
Causes
Direct injury to lungs, airways or chest wall
Indirect injury due to other system failure
Causes of Respiratory Failure
Hypoventilation = hypercapnia, hypoxia
-Depression of the respiratory center
-Diseases of respiratory nerves or muscles
-Thoracic cage disorders
Ventilation/perfusion mismatching
-Impaired diffusion = hypoxemia but not hypercapnia
-Interstitial lung disea
Clinical Manifestations of Respiratory Failure
Rapid shallow breathing
Respiratory alkalosis
Marked dyspnea
Hypoxemia unresponsive to oxygen therapy
Diffuse alveolar infiltrates on CXR
If not treated, respiratory acidosis and further hypoxemia results in hypotension, decreased cardiac output, and deat
Evaluation and Treatment of Respiratory Failure
Evaluation
Diagnosis is based on physical examination, analysis of blood gases, and radiologic examination
Treatment
Mechanical ventilation
Oxygen
Prevent infection
Support cardiac function
ECMO (extracorporeal membrane oxygenation)