Pathophysiology of obstructive sleep apnea

In obstructive sleep apnea, breathing is interrupted by a physical block to airflow, despite the effort to breathe. It is characterized by pauses in breathing during sleep. These episodes, called apneas (literally, "without breath"), each last long enough that one or more breaths are missed, and occur repeatedly throughout sleep.

Normal sleep/wakefulness in adults has distinct stages numbered 1 to 4, REM sleep, non-REM sleep (NREM) and consciousness. The deeper stages (3 to 4) of REM sleep are required for the physically restorative effects of sleep, and in pre-adolescents are the focus of release for human growth hormone. Stages 2 and REM, which combined are 70% of an average person's total sleep time, are more associated with mental recovery and maintenance. During REM sleep in particular, muscle tone of the throat and neck, as well as the vast majority of all skeletal muscles, is almost completely attenuated, allowing the tongue and soft palate/oropharynx to relax, and in the case of sleep apnea, to impede the flow of air to a degree ranging from light snoring to complete collapse. In the cases where airflow is reduced to a degree where blood oxygen levels fall, or the physical exertion to breathe is too great, neurological mechanisms trigger a sudden interruption of sleep, called a neurological arousal(electroencephalographic arousal). These arousals rarely result in complete awakening, but can have a significant negative effect on the restorative quality of sleep. In significant cases of obstructive sleep apnea, one consequence is sleep deprivation due to the repetitive disruption and recovery of sleep activity. This sleep interruption in stages 3 and 4 (also collectively called slow-wave sleep), can interfere with normal growth patterns, healing, and immune response, especially in children and young adults.

Prognosis

Sleep apnea has a strong association with several diseases, particularly those related to the heart and circulation.
Adverse Effects of Sleep Apnea on Heart and Circulation

Researchers are intensively investigating why a problem in the upper airways is associated with serious conditions of the heart and circulatory system. Here are some of their findings:

* Major known risk factors for hypertension and heart disease (obesity, smoking, and alcohol abuse) are associated with sleep apnea. These factors, however, do not explain all cases of higher heart-related risks in people with sleep apnea. For example, among overweight people, those who have sleep apneas have a greater risk of heart problems than those without them.
* When breathing stops during episodes of apnea, carbon dioxide levels in the blood increase and oxygen levels drop. This effect may trigger a cascade of physical and chemical events that can then increase risk for heart problems.
* Apnea also causes decreased levels of the gas nitric oxide (NO), a potent substance that causes blood vessels to be elastic and expand. NO plays a crucial role in blood pressure control and heart health.
* Apnea may also increase levels of a substance called angiotensin-converting enzyme (ACE), which is known to play a role in high blood pressure and congestive heart failure.
* Researchers have reported high levels of certain immune factors called tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) in people with sleep apnea, particularly those who are obese. High levels of TNF-alpha and IL-6 produce a damaging inflammatory response, which can harm cells in the body, including those in the arteries. Elevated TNF-alpha may be associated with fatigue, shortness of breath, and a diminished heart-pumping action.

At this time, however, evidence of a clear causal relationship with any of these health problems is still weak. Some studies have found no significant independent risk for heart disease from obstructive sleep apnea. The following are some discussions on the possible effects of apnea on specific health problems.

Investigations of OSA

Laboratory Studies

• A thyrotropin test (if patient has other signs or symptoms of hypothyroidism)
• An arterial blood gas determination for patients presenting with cor pulmonale, in order to rule out daytime hypoxemia or hypercapnia.

Other Tests

• Pulmonary function tests (Spirometry)
• An overnight sleep study, or polysomnography (PSG)
• Sleep stages are recorded via an electroencephalogram (EEG), electrooculogram (EOG), and chin electromyogram (EMG).
• Heart rhythm is monitored with a single-lead ECG.
• Leg movements are recorded via an anterior tibialis EMG.
• Breathing is monitored in terms of:
• Airflow at the nose and mouth (using both a thermal sensors and a nasal pressure transducer)
• Effort (using inductance plethysmography)
• Oxygen saturation.

The breathing pattern is analyzed for the presence of apneas and hypopneas. Definitions have been standardized by the American Academy of Sleep Medicine (AASM).

• Obstructive apnea is the cessation of airflow for at least 10 seconds with persistent respiratory effort.
• Central apnea is the cessation of airflow for at least 10 seconds with no respiratory effort.
• Mixed apnea is an apnea that begins as a central apnea and ends as an obstructive apnea.
• Hypopnea is a 30% or greater decrease in flow lasting at least 10 seconds and associated with a 4% or greater oxyhemoglobin desaturation.

• Respiratory event–related arousal is an event in which patients have a series of breaths with increasing respiratory effort or flattening of the nasal pressure waveform leading to an arousal from sleep that does not otherwise meet the criteria for an apnea or hypopnea.
• The AHI is derived from the total number of apneas and hypopneas divided by the total sleep time.
• Recommendations for cutoff levels on AHIs are as follows:
• Mild - Five to 15 episodes per hour
• Moderate - Fifteen to 30 episodes per hour
• Severe - More than 30 episodes per hour

PSG is often followed by a Multiple Sleep Latency Test (MSLT). The MSLT is considered an objective measurement of Excessive Daytime Sleepiness (EDS). It is used to see how quickly you fall asleep in quiet situations during the day.

• The MSLT consists of 4-5 naps of 20-minute duration every 2 hours during the day. The latency to sleep onset for each nap is averaged to determine the daytime sleep latency.
• Normal daytime sleep latency is greater than 10-15 minutes. OSAHS is generally associated with latencies of less than 10 minutes.

Aetiology of OSA

Snoring is a result of incomplete pharyngeal obstruction.

Turbulent airflow and subsequent progressive vibratory trauma to the soft tissues of the upper airway are important factors that contribute to the condition.

Anatomic obstruction leads to increased negative inspiratory pressure, which propagates further airway collapse, turbulence, and noise.

The imbalance between the forces that act to maintain airway patency (the force of the pharyngeal muscles) and the negative inspiratory forces generated by the diaphragm is thought to be the primary etiology of anatomic obstruction in OSA.

In OSA, the tongue contacts the soft palate and posterior pharyngeal wall in the presence of lateral collapse of the pharynx, generating occlusion.

Significant factors that contribute to this condition include

• obesity
  
• redundant tissue in the neck
• retrognathia
  
• craniofacial anomalies
  
• anatomic abnormalities of the nasal airway (eg, septal deviation, inferior turbinate hypertrophy, nasal-valve narrowing, adenoid hypertrophy)
  
• Alcohol and other sedatives may increase the severity of OSA.
  
• Data from a recent meta-analysis by Rada also suggested a causal relationship between OSA and head and neck cancer (which may first manifest as OSA).

In children :

OSA in children is usually due to large tonsils and adenoids. There is no relation, however, between tonsils and adenoid size and the degree of OSA. This is probably due to the combined effects of muscle tone, pharyngeal size and adenotonsillar hypertrophy.

High risk groups include children with craniofacial anomalies, cerebral palsy, muscular dystrophy and Down syndrome.
Children with OSA are not usually obese, but OSA does occur frequently in morbidly obese children and adolescents.

Source : The American Sleep Apnea Association (ASAA)

Treatment of Sleep Apnea

Whom to Treat
There is evidence obtained from robust randomized controlled trials (RCT) that treatment improves symptoms, sleepiness, driving, cognition, mood, quality of life, and blood pressure in patients who have an Epworth score of >11, troublesome sleepiness while driving or working, and >15 apneas + hypopneas per hour of sleep. For those with similar degrees of sleepiness and 5–15 events per hour of sleep, RCTs indicate improvements in symptoms, including subjective sleepiness, with less strong evidence indicating gains in cognition and quality of life. There is no evidence of blood pressure improvements in this group, nor is there is evidence that treating nonsleepy subjects improves their symptoms, function, or blood pressure. Thus, treatment cannot be advocated for this large group.

How to Treat
All patients diagnosed with OSAHS should have the condition and its significance explained to them and to their partner. This should be accompanied by provision of written and/or web-based information and a discussion of the implications of the local regulations for driving. Rectifiable predispositions should be discussed; this often includes weight loss and sometimes reduction of alcohol consumption to reduce caloric intake and because alcohol acutely decreases upper-airway dilating muscle tone, thus predisposing to obstructed breathing. Sedative drugs, which also affect airway tone, should be carefully withdrawn.

Continuous Positive Airway Pressure (CPAP)
CPAP therapy works by blowing the airway open during sleep, usually with pressures of 5–20 cmHg. CPAP has been shown in randomized placebo-controlled trials to improve breathing during sleep, sleep quality, sleepiness, blood pressure, vigilance, cognition, and driving ability, as well as mood and quality of life in patients with OSAHS. However, this is obtrusive therapy, and care must be taken to explain the need for the treatment to the patient and his/her partner, and to support all patients on CPAP intensively, providing access to telephone support and regular follow-up. Initiation should include finding the most comfortable mask from the ranges of several manufacturers and trying the system for at least 30 min during the daytime to prepare for the overnight trial. An overnight monitored trial of CPAP is used to identify the pressure required to keep the patient's airway patent. The development of pressure-varying CPAP machines may make the in-lab CPAP night trial unnecessary, but treatment must be initiated in a supportive environment. Thereafter, patients can be treated with fixed-pressure CPAP machines set at the determined pressure or by a self-adjusting, intelligent CPAP device. The main side effect of CPAP is airway drying, which can be countered using an integral heated humidifier. CPAP use, like that of all therapies, is imperfect, but around 94% of patients with severe OSAHS are still using their therapy after 5 years on objective monitoring.

Mandibular Repositioning Splint (MRS)
Also called oral devices, MRSs work by holding the lower jaw and the tongue forward, thereby widening the pharyngeal airway. MRSs have been shown in RCTs to improve OSAHS patients' breathing during sleep, daytime somnolence, and blood pressure. As there are many devices of differing design with unknown relative efficacy, these results cannot be generalized to all MRSs. Self-reports of the use of devices long-term suggest high dropout rates.

Surgery
Four forms of surgery have a role in OSAHS, although it must always be remembered that these patients have a raised perioperative risk. Bariatric surgery can be curative in the morbidly obese. Tonsillectomy can be highly effective in children but rarely in adults. Tracheostomy is curative but rarely used because of the associated morbidity; nevertheless, it should not be overlooked in extremely advanced cases. Jaw advancement surgery—particularly maxillo-mandibular osteotomy—is effective in those with retrognathia (posterior displacement of the mandible) and should be particularly considered in young and thin patients. There is no robust evidence that pharyngeal surgery, including uvulopalatopharyngoplasty (whether by scalpel, laser, or thermal techniques) helps OSAHS.

Drugs
Unfortunately, no drugs are clinically useful in the prevention or reduction of apneas and hypopneas. A marginal improvement in sleepiness in patients who remain sleepy despite CPAP can be produced by modafinil, but the clinical value is debatable and the financial cost significant.

Choice of Treatment
CPAP and MRS are the two most widely used and best evidence-based therapies. Direct comparisons in RCTs indicate better outcomes with CPAP in terms of apneas and hypopneas, nocturnal oxygenation, symptoms, quality of life, mood, and vigilance. Adherence to CPAP is generally better than to an MRS, and there is evidence that CPAP improves driving, whereas there are no such data on MRSs, Thus, CPAP is the current treatment of choice. However, MRSs are evidence-based second-line therapy in those who fail CPAP. In younger, thinner patients, maxillo-mandibular advancement should be considered.

Sign and Symptoms of Sleep Apnea

Sign and Symptoms of Sleep Apnea

Signs:

1. Abnormal heart rhythm and increase blood pressure (caused by decrease oxygen levels in blood.)

2. Prolonged sleep apnea leads to heart failure and malfunction of the lungs

Symptoms:

1. Snore: loudest when sleep on the back and lessen when sleep on the side. (Prominent in Obstructive Sleep Apnea)

2. Observed episodes of breathing cessation during sleep (choking and gasping)

3. Abrupt awakenings accompanied by shortness of breath

4. Breathing become slow and shallow

5. Excessive daytime sleepiness especially when inactive (hypersomnia).

6. Morning headache

7. Memory and learning problems and not able to concentrate

8. Feeling irritable, depressed, or having mood swings or personality changes

9. Sex drives reduced.

10. Urination at night

11. A dry throat when you wake up

12. Difficulty staying asleep (insomnia)

p/s: partners or family members will notice these before the patient.

In children

1. Hyperactivity, poor school performance, and aggressiveness

2. Unusual sleeping positions, bedwetting, and may breathe through their mouths instead of their noses during the day.

References:

http://www.mayoclinic.com/health/sleep-apnea/DS00148/METHOD=print

http://www.nhlbi.nih.gov/health/dci/Diseases/SleepApnea/SleepApnea_Signs.html

The Merick Manual of Medical Information

PCL and Anatomy Practical Delegations for Week 5

PCL :
Definition & Incidence and Prevalance : Timothy
Pathophsyiology : Chesvin
Aetiology : Nabila
Signs and Symptoms : Wen Jye
Investigations : Xin Yi
Examination : Rebekah
Treatment and Management : Da Wei
Prognosis : Nabeela

Anatomy Practical

Task 1 : Nicholas and Da wei
Task 2 : Phey Chien
Task 3 : Chesvin and Fahad
Task 4 : Nabeela and Timothy
Task 5 : Rebekah and Wen Jye
Task 6 : Yi Zhen and Xin Yi

Signs and symptoms of asthma

Asthma signs and symptoms range from minor to severe, and vary from person to person. You may have mild symptoms such as infrequent wheezing, with occasional asthma attacks. Between episodes you may feel normal and have no trouble breathing. Or, you may have signs and symptoms such as coughing and wheezing all the time or have symptoms primarily at night or only during exercise.

Asthma signs and symptoms include:

• Dypsnoea
• Chest tightness or pain
• Trouble sleeping caused by shortness of breath, coughing or wheezing
• An audible whistling or wheezing sound when exhaling
• Bouts of coughing or wheezing that are worsened by a respiratory virus such as a cold or the flu

Signs of worsening asthma:

• An increase in the severity and frequency of asthma signs and symptoms
• A fall in peak flow rates as measured by a peak flow meter, a simple device used to check how well your lungs are working
• An increased need to use bronchodilators — medications that open up airways by relaxing the surrounding muscles

Differential Diagnosis for Asthma

1.Cystic fibrosis

Differential symptoms/signs:

Chronic, sometimes productive cough with a possible family history of CF. Nasal polyposis at or before age 12 and symptoms related to other organ involvement, such as diarrhoea, malabsorption or failure to thrive.

Test:

Sweat chloride testing: level of sweat chloride >67.

Consider repeat testing.

2.Tracheomalacia

Differential signs/symptoms:

Symptoms are usually positionally dependent and occur within the first weeks or months of life.

Expiratory stridor and a barking brassy cough, wheezing respiratory distress with additional breath sound at the end of expiration (the bagpipe sign) are accompanied by the occasional extension of the neck with breathing, inspiratory stridor, episodes of holding of breath, anoxia, recurrent respiratory infections, retraction of intercostal and subcostal muscles, failure to thrive and respiratory and cardiac arrest.

Test:

The sensitivity of plain radiographs is 62%, using microlaryngoscopy and bronchoscopy as the reference standards.

In addition to CXR, barium oesophagography is useful for evaluating associated disease processes, such as tracheo-oesophageal fistula and reflux disease.

3.Vascular ring

Differential signs/symptoms:

Wheezing, shortness of breath, occasional stridor.

Test:

CT chest with contrast: double aortic arch, abnormal take-off of the innominate artery, anomaly of left pulmonary artery, right aortic arch, aberrant right subclavian, enlarged pulmonary veins.

4.Foreign body aspiration

Differential signs/symptoms:

Wheezing, shortness of breath, occasional stridor are common.

If the foreign body is in the peripheral airway, localised one-sided wheezing or collapse of the distal lung tissue is found.

Test:

CXR, CT chest or bronchoscopy shows the foreign body.

5.Vocal cord dysfunction

Differential Signs/symptoms:

Inspiratory and expiratory wheezing is often difficult to differentiate. Should be considered in steroid-resistant asthma patients.

Test:
Direct visualisation of the vocal cords with rhinolaryngoscopy during a spell. Inspiratory flow volume loop is helpful when abnormal (flattened).

6.Alpha-1 antitrypsin deficiency

Differential signs/symptoms:

Wheezing, resistant to management. May have family history of parents or grandparents dying of lung disease.

Test:
Testing for the alpha-1 antitrypsin phenotype.

7.COPD

Differential signs/symptoms:

Dyspnoea occurs with or without wheezing and coughing.

Examination may show barrel chest, hyper-resonance to percussion and distant breath sounds.

Test:
PFTs with residual volume (RV), total lung capacity (TLC) and a flow volume loop with bronchodilator showing an obstructive pattern with an increase in TLC and RV and a reduction in forced expiratory flow at one second (FEV1), FEV1/forced vital capacity (FVC) ratio with no response to bronchodilator.

CXR showing hyper-inflation of the lungs.

8.Bronchiectasis

Differential signs/symptoms:

Dyspnoea, cough and wheezing and, if severe, recurrent pulmonary infections.

Test:
High resolution CT chest: dilated airways, bronchial wall thickening.

Can occasionally be seen on CXR.

9.Pulmonary embolism

Differential signs/symptoms:

Patients have a wide variety of presentations but most common is shortness of breath and pleuritic pain.

Test:
Pulmonary angiogram is the preferred test, but carries risks. An acceptable alternate test is CT angiogram of the lung, which, if not available, can be replaced with the less sensitive V/Q scan.

10.Congestive heart failure

Differential signs/symptoms:

History of CAD or uncontrolled HTN; examination showing dependent oedema, elevated jugular venous pressure, and basal pulmonary crepitations.

Test:
CXR may show increased alveolar markings, fluid in fissures and pleural effusions.

Echocardiogram: reduced left ventricular ejection fraction.

11.Common variable immunodeficiency

Differential sign/symptoms:

History of recurrent, usually sinopulmonary, infections.

Test:
Serum IgG level below 5g/L (500 mg/dL).

Pathophysiology of Asthma

Pathophysiology

The pathophysiology of asthma is complex and involves the following components:

• Airway inflammation
• Intermittent airflow obstruction(Airway remodelling)
• Bronchial hyperresponsiveness

Asthma, allergic rhinitis, and atopic dermatitis are almost invariably accompanied by elevated levels of IgE.

Airway inflammation

Many asthmatics are atopic (an inherited a predisposition towards allergy) where your immune system develops an exaggerated response to certain foreign substances or allergens. Your body's immune system senses these allergens, perceives them as foreign, and begins to prepare to fight off them off as a foreign intruder. The process that takes place is often referred to as the allergic cascade, which generally occurs in 3 steps:

1. Sensitization
2. Early phase response
3. Late Phase response

1. Sensitization

Immunologically, your body senses the allergen as foreign and sets off a cascade of events stimulating several different types of immune cells (see diagram):

• T cells rapidly stimulate B cells
• B cells transform into plasma cells
• Plasma cells produce IgE antibodies specific to the allergen
• IgE antibodies bind to mast cells, lymphocytes, basophils

2. Early phase response

With re-exposure to the allergen your immune system senses the allergen as foreign leading to:

• The mast cell/ IgE complexes produced in the sensitization phase, binding to the allergen thinking that it is a foreign invader
• Mast cells then release inflammatory cells called mediators (e.g. histamine) that quickly travel throughout your body with the purpose of fighting off the foreign invaders such as bacteria and viruses.
• You begin to experience symptoms of your body’s overreaction to the allergen.

Cross-linking of IgE bound to mast cells triggers the release of preformed vasoactive mediators, synthesis of prostaglandins and leukotrienes, and the transcription of cytokines.

In the bronchial mucosa, these mediators of immediate-hypersensitivity reactions rapidly induce mucosal edema, mucous production, and smooth muscle constriction, and eventually elicit an inflammatory infiltrate.

You may begin wheezing, coughing or feeling short of breath as the immunologic response causes swelling and narrowing of the airways in your lung. You may only experience runny nose or watery, itchy eyes. The immunologic response begins nearly immediately with symptoms occurring very shortly after re-exposure lasting 3-4 hours.

3. Late Phase Response

Beginning at the same time as the early phase response, but not causing symptoms for several hours, is the late phase response. Mediators released by the re-exposure to an allergen also stimulate other kinds of immune cells called eosinophils. Eosinophils contain substances that when released normally fight off infections, but in asthma, the cells damage the lung causing more inflammation and worsening symptoms.

In the late phase, symptoms will not develop for at least 4 hours, but may last as long as 24 hours. Increased inflammation and obstruction of airflow may be more severe than what is seen during the early phase.

Airway remodelling

Airway remodeling in asthma is what happens in response to long-term, unresolved airway inflammation. When airway inflammation is not adequately treated, it can result in permanent structural changes in the airways.

In these cases, a certain degree of airway inflammation is always present. Over time, the body tries to fix this inflammation by triggering changes in the repair function of the lining of the airways.

• Increased airway wall thickness that involves both smooth muscle and collagen tissue
• Increased mucous glands and mucus production
• Increased vascularity, or blood supply, in the airways

Bronchial hyperresponsiveness(BHR)

Airway hyperresponsiveness is a characteristic feature of asthma and consists of an increased sensitivity of the airways to an inhaled constrictor agonist. Certain inhaled stimuli, such as environmental allergens, increase airway inflammation and enhance airway hyperresponsiveness. They are, however, similar to changes occurring in asthmatic patients that are associated with worsening asthma control.

The pathogenesis of exercise-induced bronchospasm is controversial. The disease may be mediated by water loss from the airway, heat loss from the airway, or a combination of both. The upper airway is designed to keep inspired air at 100% humidity and body temperature at 37°C (98.6°F). The nose is unable to condition the increased amount of air required for exercise, particularly in athletes who breathe through their mouths. The abnormal heat and water fluxes in the bronchial tree result in bronchoconstriction, occurring within minutes of completing exercise. Results from bronchoalveolar lavage studies have not demonstrated an increase in inflammatory mediators. These patients generally develop a refractory period, during which a second exercise challenge does not cause a significant degree of bronchoconstriction.

AV nicking (the Gunn sign): Impeded circulation results in a dilated or swollen vein peripheral to the crossing, causing hourglass constrictions on both sides of the crossing and aneurysmal-like swellings.