Hypoxemia & Cellular Hypoxia
by
Mark J Donohue
Oxygen is the single most important element in the human body. Without
oxygen death occurs within a matter of minutes. Though not as drastic,
when sub-optimal levels of oxygen occur within the body, human tissues
also function at a suboptimal level. This is because when we breathe air,
the lung tissues extract oxygen and pass it into the blood where it is
picked up by hemoglobin (the pigment that gives our red cells their color).
Hemoglobin combines with oxygen to transport it in the blood stream. It
carries the oxygen to all the body’s tissues where it is able to give it up
and donate it to cells. Once in the cell oxygen is used for the production of ATP
within the mitochondria.
“It is the efficient use of oxygen in the brain/body connection that is the secret of
maintaining health”. (Lonsdale 2010)
“The brain computer has a heavy oxygen requirement and a curious thing happens when
energy production is mildly to moderately limited. It becomes hyper-reactive in its adaptive
response to environmental stimuli, conveyed to it by sensory input.” (Lonsdale 2011)
Low or sub-optimal levels of oxygen within arterial blood is referred to as hypoxemia. The more broader
term hypoxia - is a condition in which the body’s tissues (cellular level) are deprived of adequate oxygen
and whereby human tissues are literally starved of oxygen. Hypoxemia causes hypoxia and the organs
most affected by hypoxia are the brain, the heart and the liver.
“All chronic pain, suffering and diseases are caused from a lack of oxygen at the cell level”
(Guyton 2011)
There are four types of hypoxia which are listed and described below.
1. Hypoxic or Hypoxemic Hypoxia
Hypoxic or hypoxemic hypoxia – is a condition that occurs when the oxygen pressure in the blood going
to the tissues is too low to saturate the hemoglobin. Or put more simply, hypoxic hypoxia is
characterized by a lack of oxygen entering the blood. This is generally caused by decreased oxygen in the
air/atmosphere or the inability to diffuse the oxygen across the lungs. The most common causes of
hypoxic hypoxia are:
Altitude Sickness
The Earth’s atmosphere is composed primarily of nitrogen (78%) and oxygen (21%) with small amounts
(1%) of other gases. The proportion of these gases does not change with altitude, however, the total
amount of air or air pressure does change with altitude. As one ascends in altitude and moves further
and further into the atmosphere, the total amount of air or air pressure decreases. This is what is meant
by a decrease in barometric pressure.
 Science Boom Episode #5 – Barometric Pressure and Temperature, You Tube (4:11) Link
When we breathe in air at sea level, the atmospheric pressure is about 14.7 pounds per square inch.
This pressure causes the atmospheric oxygen to easily pass through the pulmonary (lungs) membranes
and into the vascular system (blood). However, at high altitudes, the lower air pressure makes it more
difficult for oxygen to pass through the pulmonary membranes. This results in lower levels of oxygen
within a person’s blood (hypoxemia) and tissues (hypoxia).
Hypoxia which results due to high altitude environments and low atmospheric pressure is known as
altitude sickness. Symptoms of altitude sickness are:
lack of appetite
dizziness
shortness of breath
confusion
elevated respiratory rate
euphoria
vomiting
distorted vision
trouble sleeping
lack of coordination
elevated BP
bluish tinge on lips
headache
fatigue
poor memory
rapid heart rate
In severe cases, pneumonia-like symptoms (pulmonary edema), due to hemorrhaging in the lungs, and
the accumulation of fluid around the brain (cerebral edema) develop. These conditions can lead to
death if there is not a return to normal air pressure levels.
 Hypoxia (altitude chamber), YouTube (4:02) Link
 Altitude Sickness, You Tube (1:56) Link
When a person travels to high mountain areas their body will initially develop a physiological response
of – increased breathing and heart rate to compensate for the lower air pressure. After several days
their body’s will acclimate to the lower air pressure by producing additional red blood cells, capillaries,
along with the lungs increasing in size.
On returning to sea level after successful acclimatization to high altitude, the body usually has more red
blood cells and greater lung expansion capability than needed. Since this provides athletes in endurance
sports with a competitive advantage, the U.S. maintains an Olympic training center in the mountains of
Colorado. Several other nations also train their athletes at high altitude for this reason. However, the
physiological changes that result in increased fitness are short term at low altitude. In a matter of
weeks, the body returns to a normal fitness level.
Hypoventilation
The main function of the respiratory system is simply to supply the body with oxygen while
simultaneously removing carbon dioxide. This is done by inhaling air through the nose or mouth. From
there the air passes through the larynx (voice box), and enters the chest cavity through the trachea. The
trachea splits into two tubes called bronchi, each of which leads into a lung. The airways become
progressively smaller and end as small sacs known as alveoli. The alveoli are surrounded by capillaries,
and it is here where the exchange of blood gases takes place. Oxygen diffuses across the membrane
thereby entering the vascular system, while carbon dioxide is released from the blood and enters into
the lungs to be exhaled.
 The Respiratory System, bozemanscience.com videos, (8:46) Link
The whole process sounds simple enough. Unfortunately, there is a long list of respiratory/pulmonary
diseases and disorders which can interfere with the exchange of these blood gases. These diseases and
disorders result in insufficient ventilation leading to low levels of oxygen (hypoxemia)and high levels of
carbon dioxide – hypercapnia in the blood. Some of the hypoventilation diseases and disorders which
create an imbalance in the blood gases which can result in hypoxia are:
 Improper breathing (hypopnea)
 Shallow breathing
 Slow breathing
 COPD (chronic obstructive pulmonary disease)
 Emphysema
 Chronic bronchitis
 Respiratory infections
 Pneumonia
 Tuberculosis
 Hypoventilation syndromes
 Primary alveolar hypoventilation or Congenital central alveolar hypoventilation
 Obesity hypoventilation syndrome
 Chest wall deformities
o Kyphoscoliosis
o Fibrothorax
 Neuromuscular disorders
o Myasthenia gravis
o Amyotrophic Lateral Sclerosis (Lou Gehrig’s Disease)
o Guillain-Barre Syndrome
o Muscular Dystropy
 Neurological Disorders
 Encephalitis
 Brainstem disease
 Brain trauma
 Poliomyelitis
 Multiple Sclerosis
 Other causes of hypoventilation
 Smoking, air pollution
 Alcohol abuse
 Drugs (sedatives, opiates, benzodiazepines, barbiturates, etc.)
 Asthma
 Cystic Fibrosis
 Pulmonary Fibrosis
 Obstructive Sleep Apnea
 Lung Cancer
2. Hypemic or Anemic Hypoxia
Hypemic or Anemic Hypoxia – is a condition in which there is a reduction in the oxygen carrying capacity
of the blood. Oxygen is present and abundant, however, it is unable to bind with hemoglobin.
Hemoglobin (Hb), the iron-containing respiratory protein in red blood cells, is responsible for
transporting oxygen from the lungs to the rest of the body.
A low hemoglobin level is called anemia and the most commonly-reported symptoms include: weakness
or fatigue, general malaise (feeling unwell), poor concentration, pallor (pale skin, mucosal linings and
nail beds), shortness of breath on exertion, palpitations and sweatiness.
This type of anemic hypoxia can occur
due to conditions such as:




Hypercapnia
Carbon Monoxide Poisoning
Smoking
Anemia
o Iron deficiency
o Pernicious anemia
o Sickle cell anemia





Hemorrhage
Methemoglobinemia
Hypercoagulation
Hyperventilation
Use of Nitrate & Sulfa Drugs
3. Stagnant or Ischemic Hypoxia
Stagnant or Ischemic Hypoxia – is a condition where the blood has normal oxygen saturation, but the
flow of the blood to tissues is reduced or unevenly distributed. This is generally caused by a reduction in
total cardiac output and blood flow due to heart failure. It can also occur due to the pooling of blood in
the lower extremities, which occurs in jet fighter pilots while “pulling Gs”. Or it can occur in people who
sit for extended periods of time.
4. Histotoxic Hypoxia
Histotoxic Hypoxia – is the cell’s inability to adequately use oxygen. Plenty of oxygen is available to the
cell, but tissues cannot accept it. Or oxygen cannot offload from the hemoglobin. During histotoxic
hypoxia, the venous hemoglobin oxygen saturation is higher than normal because the oxygen is not
being unloaded to the tissues because the tissues are unable to metabolize the delivered oxygen.
Histotoxic hypoxia is generally caused by tissue cells becoming poisoned (i.e. cyanide). This condition is
also exacerbated by the use of narcotics, tobacco, and alcohol.
Hypoxia and Neuro-Endo-Immune Disorders
 Hyperventilation, by Dr. Sarah Myhill (2012) Link
“The blood is very efficient at gathering oxygen and all arterial blood is 100% saturated
with oxygen. But here comes the crunch! Oxygen is only readily released from red blood
cells to supply oxygen to the tissues in the presence of high levels of carbon dioxide.
Many patients (CFS) have a sensation that they are not getting enough oxygen to their
tissues. Their response to this is to breathe more deeply. However blood cannot become
more than 100% saturated with oxygen. All that happens is that more carbon dioxide is
washed out of the blood. This makes oxygen cling more fiercely to hemoglobin in red blood
cells and therefore oxygen delivery to the tissues is made worse! Paradoxically, to improve
oxygen supply to the tissues you have to breathe less! Breathing less increases carbon
dioxide levels and improves oxygen delivery.
Lowering carbon dioxide levels in the blood has other dire effects. It upsets the acidity of
the blood and causes what is known in medical jargon as a respiratory alkalosis. This causes
all sorts of awful symptoms such as panic attacks, pain, fatigue, feeling spaced out and dizzy,
brain fag, brain fog and so on.”
 Cellular Hypoxia and Neuro-Immune Fatigue, by David Bell, MD, WingSpan Press (2007) Link
“It describes a theory that fibromyalgia and ME/CFS are parts of a spectrum of illnesses,
called here Neuro-Immune Fatigue, and that the common end pathway of these illnesses is a
dysregulation of cellular metabolism leading to the inability of the cell’s mitochondria to
utilize oxygen. “
 Ross R.S., et al, Erythrocyte Oxidative Damage in Chronic Fatigue Syndrome, Archives of Medial
Research, Jan 2007; 38(1):94-98 Link
NOTE: This study contradicts the studies below about the levels of 2,3-DPG, but still indicate there are
abnormalities in the oxygen delivery system in those with CFS
“Level of 2,3-DPG was significantly increased in the erythrocytes of the CFS group.
Erythrocyte membrane function is regulated (at least in part) by 2,3-DPG, and it has been
shown that the level of erythrocyte 2,3-DPG is important in determining deformability of
erythrocyte membranes. Increased 2,3-DPG increases erythrocyte fragility and decreases
deformability. Erythrocyte 2,3-DPG also functions as a regulator of hemoglobin oxygen
affinity. Increased levels of 2,3-DPG have the effect of decreasing oxygen affinity and
therefore would allow more oxygen to be delivered to the tissues in these cases. Thus,
erythrocytes in CFS would be more rigid than normal and would be slow to recover from
mechanical deformation. This would have the physiological effect of reducing oxygen
delivery to the tissues, which may be compensated for by the increased 2,3-DPG levels.
Morphological studies of the CFS and control subjects demonstrated increased stomatocyte
formation in CFS. This may be explained by the increased 2,3-DPG levels mentioned
above…”
 Effective Treatment of Chronic Fatigue Syndrome and Fibromyalgia, by Kent Holtorf, MD,
ProHealth (2003) Link
“Recent studies have shown that the coagulation dysfunction is usually initiated by a viral
infection and has genetic predisposition. This abnormal coagulation results in increased
blood viscosity (‘slugging’) and a deposition of soluble fibrin monomers along the capillary
wall. This results in tissue and cellular hypoxia, resulting in fatigue, and decreased cognition
(brain fog).”
 Paul Cheney, MD’s Oxygen Treatment for Chronic Fatigue Syndrome, by Carol Sieverling, ProHealth
(2002) Link
"… ladies and gentlemen, I'm here to tell you that CFS patients are alkalotic.
Blood alkalosis inhibits the transport of oxygen to tissues and organs, constricts the blood
vessels, and lowers overall circulating blood volume.
The purative cause of the alkalosis is the glutathione deficiency that is pervasive in CFIDS.
Low glutathione causes an elevation in citrate, which in turn lowers a substance (2.3 DPG)
that controls the release of oxygen from the hemoglobin. Our blood could be full of oxygen,
but without enough of this substance it cannot break free of the hemoglobin and get into the
cells. This causes oxygen deprivation in the tissues (hypoxia), which makes the body switch
over to anaerobic metabolism, and that produces tissue acidosis, which can be painful. The
acidosis here is unusual because instead of generating a lot of carbon dioxide, it generates a
lot of organic acids that stay inside the cell. The body compensates for tissue acidosis by
increasing renal bicarbonate reabsorption, and developing tissue alkalosis.
This blood alkalosis is unusual in that Cheney usually sees venus blood pH values over 7.4
and urine pH values under 6.0. (Optimum venus pH values are 7.30 to 7.35.) When both
blood alkalosis and urine acidosis are seen, it's a metabolic problem - not a psychogenic
reaction to a needle stick. A blood pH above 7.4 shows impairment, and above 7.5 there is
significant impairment - almost no oxygen transport at all.
The really terrible thing is the presence of a vicious cycle. The blood alkalosis further lowers
the levels of 2.3 DPG (inhibiting the release of oxygen), causing tissue hypoxia, which causes
tissue acidosis and pain, which then causes blood alkalosis, which lowers 2.3 DPG even
further. And around and around we go.”
 Intravenous Very-Dilute Hydrogen Peroxide, by Dr. Holtorf Link
“There is evidence that there is poor oxygen offloading to tissues in CFS and FM that can
result in relative tissue hypoxia and subsequent fatigue and pain, and there is evidence that
abnormally low 2,3-diphosphoglycerat (2,3-DPG) in CFS patients causes or contributes to
this tissue hypoxia. Oxidative therapies result in an increase in the red blood cell glycolysis
rate. This leads to the stimulation of 2,3-DPG which leads to an increase in the amount of
oxygen released to the tissues.”
 Ross P.M, Chemical Sensitivity and Fatigue Syndromes from Hypoxia/Hypercapnia, Medical
Hypothesis, 2000; 54(5):734-738 Link
“It is proposed here, in contrast to the published hypotheses, that the symptoms of fatigue,
headache, malaise, or ‘spaciness’ in MCS, and possibly in similar conditions, results from
dysregulated oxygen delivery to the CNS, possibly secondary to a breathing disturbance.
This concept is next developed by analogy to sleep apnea because of some striking
similarities”
“…the major symptoms of MCS – headache, fatigue, and spaciness- overlap those of sleep
apnea and could, therefore, result directly from hypoxia/hypercapnia due to airway
obstruction, neurogenic inflammation, CNS toxicity, autonomic imbalance or a combination
of any of these”
Bottom Line
There is some research indicating that people with neuro-endo-immune disorders such as CFS, MCS, FM
have difficulty utilizing oxygen. There appears to be no consensus about the mechanism responsible for
this issue. It also appears that very little research is being done to resolve this issue. Further research is
needed
References
Books
Note: all books were obtained either at UW Library, King County Library, Snohomish County Library or Bastyr
University Library. A couple of books were available on line (e-books, PDFs, googlebooks). Links are provided to
give a visual of book cover and other information.
-
Brunner and Suddarth’s Textbook of Medical-Surgical Nursing, by Suzanne Smelter, Lippincott Williams
& Wilkins, (2009) Link
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Cardiopulmonary Anatomy and Physiology, by Terry Des Jardins, Cengage Learning (2008) Link
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Critical Care Transport, American Academy of Orthopedic Surgeons, Jones & Bartlett Learning (2011) Link
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Textbook of Medical Physiology, by John Hall & Arthur Guyton, Elsevier Health Sciences (2010) Link
Publications
Publications are sited within the report
Videos and Audio Productions
Video and Audio Productions are sited within the report
WWW
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Altitude Research Center Link
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bozemanscience.com Link
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Encyclopedia Britannica Link
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Harrison’s Practice – Hypoventilation Link
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Human Biological Adaptability Link
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Normal Breathing Defeats Chronic Diseases Link
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Oxygen, The Spark of Life (blog) by Derrick Lonsdale MD (2012) LInk
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Wikipedia Link