Certain health problems tend to occur in clusters or ‘families, often with related symptoms that have a common cause. One such cluster, dysautonomia, refers to a collection of dysfunctions relating to the autonomic nervous system. Mast Cell Activation Syndrome (MCAS) is one of these conditions.

1. Mast Cell Activation Syndrome: The
Immune System Gone Wrong – Part 1
Certain health problems tend to occur in clusters or ‘families, often with related symptoms that have a
common cause. One such cluster, dysautonomia, refers to a collection of dysfunctions relating to the
autonomic nervous system. Mast Cell Activation Syndrome (MCAS) is one of these conditions.
Other Conditions Associated with Dysautonomia Include:
 Chronic Fatigue Syndrome (CFS)
 Chronic Lyme Disease
 Postural Orthostatic Tachycardia (POTS)
 Fibromyalgia
 Gastrointestinal issues (Irritable Bowel Syndrome, gut dysbiosis, food intolerances, and others)
 Neurological problems (restless leg syndrome, narcolepsy, and others)
 Immune disorders (multiple sclerosis, severe or recurring infections, and others)
 Psychological issues (ADD, panic/anxiety attacks, chronic insomnia, compulsive behavior, stress,
and others)
 Hormonal issues (fertility problems, adrenal gland problems and adrenal fatigue, high/low
cortisol, thyroid disorders, weight gain, acne, and others)
 Renal problems (diabetes insipidus, interstitial cystitis, and others)
The list goes on. Many of these conditions seem to have nearly the same, though wide, set of
symptoms. Many of these dysautonomia conditions include symptoms such as:
 Stomach problems such as diarrhea, constipation, stomach pain, etc. headaches, migraines,
dizziness
 Food sensitivities and allergies
 Rashes/hives
 Tiredness
 Aches and pain of unknown origin
 Weight gain or weight loss
 Hormonal imbalances
 Brain fog
 Anaphylaxis
Most of these health issues are well known, but MCAS, also called Mast Cell Activation Disorder (MCAD),
is unique in that it has only recently been recognized by the medical establishment. Those with MCAS
have overactive mast cells that release too many chemicals into the body at inappropriate times,
resulting in a variety of symptoms that, up until recently, have been difficult for physicians to identify.

2. Interestingly, many people with POTS also have MCAS. POTS, or Postural Orthostatic Tachycardia
Syndrome, is a condition that results in an unusually fast heart rate (tachycardia) when transitioning
from lying down to standing up.
Research has not, as yet, given a clear indication of just how much these two conditions overlap, but
they may be connected with adrenal fatigue treatment, as symptoms presented in all three conditions
can be very similar and seem to have similar root causes.
Facts About POTS
POTS is most prevalent in women (about 80%) of menstrual age. The condition usually arises after a
bacterial or viral infection or after a growth spurt. Some women develop it during pregnancy.
What happens when you have POTS physiologically is that, when standing quickly, blood rushes from
the upper extremities to the heart due to gravity. There is less oxygen for the brain and the possibility of
fainting, so the hormone norepinephrine is released by the brain as an alert. The norepinephrine makes
its way to the heart and peripheral blood vessels, where it increases the heart rate by narrowing the
blood vessels, increasing blood flow to the brain so that you don’t faint.
Epinephrine (also called adrenaline) is released during stressful situations to ensure blood flow to the
brain, as this is deemed necessary for survival. In some situations, however, activation of the body’s
sympathetic response (for fight or flight) fails, resulting in lower blood pressure and increased heart
rate.
The adrenal glands secrete the hormones epinephrine, norepinephrine, and cortisol in response to
stress. These hormones ensure your body readies itself for survival. When the stressful situation
continues for a prolonged period, the adrenals need to produce more hormones to ensure survival.
After a while, they become taxed, leading to the burnout so common in the later stages of adrenal
fatigue.
Because of its connection to norepinephrine, the adrenals, and how the body responds to the stress of
standing, POTS is strongly associated with Mast cell activation and adrenal disorders in both its action
and symptoms. It also has a widespread effect on your autonomous nervous system.
Mast Cell Activation Syndrome (MCAS)
MCAS was only recognized as a condition in 1991 and given a name in 2007.
In order to understand MCAS, one first needs to understand what mast cells are and how they function.
Mast Cells
Mast cells, also called mastocytes or labrocytes, are a certain type of white blood cell. Originating in the
bone marrow, these cells travel to the different tissues of the body.

3. Each mast cell has what is known as secretory granules, which contain mediators. These are biologically
active molecules, that, once a mast cell is triggered, are secreted and cause an allergic or inflammatory
response. These biologically released mediators include histamines and leukotrienes, amongst others.
Mast cell triggers depend on the person, but there are a number of possibilities, including:
 Smell (perfumes or chemicals)
 Infections (bacterial or viral)
 Sunlight
 Fatigue
 Sudden temperature changes
 Diet (food or beverages)
 Certain drugs (antibiotics, opioids, and others)
 Certain venoms (from wasps, snakes, jellyfish, mosquitoes, bees, or spiders, for example)
 Exercise
 Stress (psychological, physiological, or due to environmental factors)
 Mechanical (due to friction or vibration, for example)
Under normal circumstances, these mast cells have a protective role, helping wounds heal and
defending your body against pathogens.
They are found throughout the body, including in the stomach and intestine lining, in the connective
tissues, and in the skin. The chemical trigger most often released when these mast cells face a problem
is a histamine, which forms an important part of the body’s immune defense system.
Mast cells also help wounds heal, as they gather around a wound to form a scab. According to research,
they may also have a role to play in blood vessel growth, and there are indications they are essential to
our continued survival.
Sometimes, however, things go wrong with mast cells or how they are produced, which can cause Mast
Cell Activation Syndrome, among other conditions.
MCAS should not be confused with mastocytosis, however. MCAS is associated with a severe allergic
reaction due to mast cells releasing too many chemicals into the body. Mastocytosis, on the other hand,
is the result of a genetic mutation that causes the body to produce too many mast cells.
Mast Cell Activation: When Things Go Wrong
MCAS is a condition that occurs when the mast cells get activated too easily by a trigger, thereby
releasing their chemical mediators – histamine and leukotriene. The body may be in a state of
hyperactivation. This results in a number of symptoms that, at first glance, may seem totally unrelated.
Amongst these are bloating, skin rashes, abdominal pain, nausea, aches and pains, and headaches, to
name a few.

4. Histamine Reaction
Histamine is a chemical made by the immune system that helps the body get rid of anything causing it
stress. It does this by helping the body get rid of allergy triggers (allergens) by causing you to sneeze or
itch. Think of the classic symptoms associated with hayfever. This is how histamine forms a part of your
body’s defense system, the immune system.
The process by which your body reacts is simple. Once an allergen is identified, your immune system is
triggered. Mast cells are sent to the parts of the body affected, i.e. blood, nose, gut, skin, mouth, and
lungs, and there they release the histamines carried around inside the granules inside them. These
granules are tiny storage areas surrounded by membranes. Once the histamines are released from the
granules in the mast cells, they trigger an increase in blood flow to the affected area, causing
inflammation. This, in turn, triggers other chemicals within the body to carry out repairs in the affected
areas.
Histamine receptors in the nervous system are activated when this allergic reaction process starts. They
bind to receptors in the blood vessels, thereby making the blood vessels more permeable. This results in
hives, redness, swelling, and inflammation. It also causes contractions in the bronchial muscles, resulting
in conditions such as asthma or anaphylaxis, which is life-threatening.
Histamine receptors found in the gut are located in your parietal cells, which secrete gastric juices. A
histamine increase results in an increase in the secretion of gastric acids. This often results in peptic
ulcers and gastroesophageal reflux disease (GERD).
Histamine may also inhibit the production of certain neurotransmitters in the brain, including dopamine
and serotonin. Research indicates that when the production of these hormones is compromised, anxiety
increases. Histamine has also shown to be implicated in a number of other mental disorders, including
Alzheimer’s, schizophrenia, and attention deficit hyperactivity disorder (ADHD).

5. There are, as previously mentioned, many triggers that could cause this release of histamine, including
the environment, food, and physical factors.
Leukotriene Reaction
Leukotrienes are another compound released by mast cells. There are two families of leukotrienes, and
each has a unique presentation in regards to symptoms and areas of action in the body.
The first family is involved in cases of neutrophil-dependent inflammation. The main function of
neutrophils is to kill as many germs as possible. They are the most abundant immune cells found in the
blood, making up 60%, and are the body’s first line of defense, killing off foreign invaders by “engulfing”
them, thereby making them harmless.
Neutrophils mainly act in inflammation-related illnesses such as psoriasis, inflammatory bowel disease,
and cystic fibrosis.
The second leukotriene family is cysteinyl-leukotrienes. They primarily act on the airway tissue and
bronchial smooth muscles. They are acutely active in cases of infection and asthma, for example, where
they reduce airflow to the alveoli.
Prostaglandin Reaction
Prostaglandin, also released by mast cells, is primarily found in the central nervous system and
peripheral tissues. It has an inflammatory action.
Prostaglandin helps with the regulation of sleep and perception of pain. It is also a strong
bronchoconstrictor and is considered ten times more potent than histamine. Those who suffer from
asthma can have prostaglandin levels more than 150 times that of those who have never suffered an
attack. Elevated levels of prostaglandin have also been found in those who suffer from chronic coughing.

6. In those with asthma, prostaglandin may cause airway inflammation and hyperreactivity and inhibit
eosinophil cell death. Eosinophil cells play an important role when it comes to allergies. If their removal
is inhibited, the result is an inflammatory illness such as asthma.
Mast cells, in many instances, are often paired with neurons and autonomic nerve fibers. Besides
histamine, leukotrienes, and prostaglandin, they secrete up to 200 different chemicals, each with its
own action and response to different environmental stimuli.
In the case of those with Mast Cell Activation Syndrome, the mast cells secrete these chemicals
inappropriately.
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