AssessmentsApnea, hypoventilation and pulmonary hypertension: Pathology review
USMLE® Step 1 style questions USMLE
A 6-year-old girl is brought to her primary pediatrician for evaluation of dyspnea. The patient feels tired throughout the day, despite sleeping for nine hours every night. She additionally describes intermittent trouble breathing with exertion. The patient’s mother and grandmother have suffered from similar symptoms throughout their lives and have a “problem with the vessels in our lungs.” An echocardiogram is performed, which is within normal limits. Cardiac catheterization is performed, and the patient’s mean pulmonary artery pressure is 32 mmHg (normal <25 mmHg). A mutation in which of the following genes is the most likely etiology of this patient's symptoms?
Content Reviewers:Antonella Melani, MD
Joseph, a 42 year old man comes to the clinic because he’s been waking up many times at night, which makes him very sleepy during the day.
His partner also complains that Joseph has always snored but recently it’s louder than ever.
On physical examination he has a BMI of 35 kilograms per square meter, and has a blood pressure of 140 over 90 millimeters of mercury.
You decide to conduct a sleep study, which reveals a very low partial pressure of oxygen.
Later, a 35 year old woman called Robin also comes to the clinic.
She tells you that, lately, she’s been experiencing shortness of breath and fatigue.
Robin is quite worried, and mentions that she has a congenital heart defect.
On physical examination, she has a mean pulmonary arterial pressure of 28 millimeters of mercury.
Based on the presentation, both cases seem to have some respiratory disease, associated with some cardiovascular issues.
So, let’s begin with sleep apnea!
This is when a person, during their sleep, experiences recurrent and intermittent episodes in which they stop breathing for more than 10 seconds.
Now, the recurrent epinephrine surges have several effects.
Firstly, this wakes up the person so that they can breathe again.
To do so, our kidneys produce a hormone called erythropoietin, or EPO, which stimulates the bone marrow to produce more red blood cells, and this process is known as erythropoiesis.
Over time, this can result in vascular remodeling, which can lead to the development of both pulmonary and systemic hypertension.
Diagnosis of sleep apnea involves a sleep study, also known as polysomnography, which counts the number of apnea episodes, and monitors several parameters like heart rhythm and oxygen saturation.
Another important diagnostic value is partial pressure of oxygen in the arteries, since it helps us understand if the tissues are receiving adequate oxygen supply.
This value can be easily and indirectly obtained with a pulse oximeter, or directly obtained via blood gas sampling.
For your exams, remember that people with sleep apnea have low oxygen saturation levels, and thus low partial arterial pressure of oxygen during sleep, but bear in mind that this partial pressure is typically normal when they’re awake.
Now, when the cause of sleep apnea originates in the central nervous system, it’s called central sleep apnea.
And when a person experiences both obstructive and central sleep apnea, it’s called complex or mixed sleep apnea.
Okay, let’s start with central sleep apnea or CSA for short.
Central sleep apnea is caused by an imbalance in the respiratory center of the brain, so during sleep it fails to activate the muscles that control breathing.
The main causes of central sleep apnea include central nervous system injury involving the respiratory center, as well as central nervous system toxicity, often due to use of opioid medications.
Another major risk factor for central sleep apnea is congestive heart failure.
What’s important for your exams is that congestive heart failure leads to increased chemosensitivity, which is how the body senses and responds to changes in the partial pressures of oxygen and carbon dioxide.
So when there’s an apnea episode, oxygen levels decrease while carbon dioxide levels rise.
Now, keep in mind that carbon dioxide is the main stimulus for the respiratory center, so when there are high levels of carbon dioxide, the respiratory center responds by increasing our respiratory rate.
So now the CO2 level is too low, and this ultimately causes depression of the respiratory center and thus another apnea episode.
As a result, there’s a vicious cycle that leads to central sleep apnea.
This is a periodic breathing characterized by oscillation between periods of apnea alternated with deep breaths or hyperpnea.
So, for your exams, remember that the three main things you need to know all start with a ‘C’ for central sleep apnea!
The first is central nervous system injury or toxicity, the second ‘c’ is congestive heart failure, and the third ‘c’ is for- Cheyne-Stokes respiration.
Treatment of central sleep apnea mainly involves positive airway pressure therapy, as well as taking care of the underlying cause.
And then we have obstructive sleep apnea, or OSA for short.
As the name suggests, it is caused by a narrowing or obstruction of the airways.
Now, normally, the airway muscles relax while sleeping
In healthy people though, the airway muscle tone is strong enough to counteract factors that would cause the airway to collapse, such as gravity while lying down, and the negative pressure in the airway during inspiration.
In obstructive sleep apnea, the airway muscle tone is not strong enough to counteract these factors, and so the airway collapses.
In adults, the most common cause is an excess of parapharyngeal tissue, which basically means that there’s excess fat in the neck region.
That’s why obstructive sleep apnea is most common in obese individuals, so those with a BMI over 30 kilograms per square meter.
On a test question, the most important clue suggesting obstructive sleep apnea is loud snoring in an obese individual, like they’re trying to gasp for air until they wake up.
This leads to disrupted sleep, which in turn causes excessive sleepiness during the day or while awake.
Sometimes though, obstructive sleep apnea may affect children; in this case, the most common cause is adenotonsillar hypertrophy, meaning an enlargement of the pharyngeal and palatine tonsils.
In addition, weight loss is highly recommended for overweight people.
Finally, one last option is surgery to remove the excess parapharyngeal tissue.
Obesity hypoventilation syndrome is also named Pickwickian syndrome after Charles Dickens’ novel “The Pickwick Papers”, in which there is an overweight character who’s constantly falling asleep at any time of the day.
As the name suggests, obesity hypoventilation syndrome only affects obese individuals.
That’s because the excess weight can restrict the movement of the diaphragm and chest wall, which impairs lung expansion.
As a result, affected individuals develop hypoventilation, meaning slow or shallow breathing.
In most cases, obesity hypoventilation syndrome also causes obstructive sleep apnea and hypoventilation during sleep, but bear in mind that these individuals also experience hypoventilation while awake.
And that’s a high yield fact!
Because of that, diagnosis of obesity hypoventilation syndrome includes an increased partial pressure of carbon dioxide while awake, and while sleeping, they’ll also have a decreased partial pressure of oxygen.
Treatment is mainly focused on weight loss, and some cases can also get positive airway pressure during sleep.
- "Robbins Basic Pathology" Elsevier (2017)
- "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
- "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
- "Diagnostic and Statistical Manual of Mental Disorders" A.P. Association and A.P.A.T.F.O.N.A. Statistics (1980)
- "Robbins Basic Pathology" Elsevier (2017)
- "Sleep Apnoea In The Older Adult" Drugs & Aging (2003)
- "Obesity hypoventilation syndrome" European Respiratory Review (2019)
- "Pathology of Pulmonary Hypertension" Clinics in Chest Medicine (2007)
- "Plexiform Lesions in Pulmonary Arterial Hypertension" The American Journal of Pathology (2011)
- "Heart rate and blood pressure responses during hypoxic cycles of a 3-week intermittent hypoxia breathing program in patients at risk for or with mild COPD" International Journal of Chronic Obstructive Pulmonary Disease (2015)
- "Cheyne-Stokes respiration in patients with congestive heart failure: causes and consequences" Clinics (2005)
- "Congestive Heart Failure and Central Sleep Apnea" Critical Care Clinics (2015)
- "Pulmonary hypertension due to lung diseases: Updated recommendations from the Cologne Consensus Conference 2018" International Journal of Cardiology (2018)
- "Update on Chronic Thromboembolic Pulmonary Hypertension" Circulation (2014)