The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 63

77. Can you have anaphylaxis with high blood pressure?

  • Yes.
  • The misconception that a person with high blood pressure cannot be experiencing anaphylaxis is enduring and dangerous.
  • Author’s note: Thanks to the intrepid reader who caught a big typo right here. When I published the post, it said, “The misconception that a person with high blood pressure can be experiencing anaphylaxis is enduring and dangerous.” This is a whopper mistake. It should say,  “The misconception that a person with high blood pressure canNOT be experiencing anaphylaxis is enduring and dangerous.” You CAN have high blood pressure and anaphylaxis at the same time. Thanks again!
  • Lots of providers (and patients) think that high blood pressure rules out anaphylaxis. This is not true.
  • This misunderstanding comes from confusing two closely related but distinct concepts: anaphylaxis and anaphylactic shock.
  • Anaphylaxis is a severe allergic reaction affecting multiple organ systems.
  • Anaphylactic shock is when anaphylaxis causes such poor blood circulation that the heart cannot pump out enough blood to the body.
  • Anaphylactic shock is a form of circulatory shock, which means exactly what I just described: oxygenated blood is not being pumped out of the heart and through the blood vessels to the tissues that need it.
  • Anaphylactic shock is defined as blood pressure 30% below the patient’s baseline or a systolic blood pressure below 90 mm Hg. The systolic blood pressure is the top number when you get your blood pressure checked. If that top number is below 90 mm Hg, and that is the result of anaphylaxis, you are in anaphylactic shock.
  • Anaphylactic shock is the most serious potential complication of anaphylaxis. Anaphylactic shock happens when the chemicals released by mast cells cause a lot of the fluid in the bloodstream to “fall out” of the bloodstream and get stuck in the tissues.
  • When this happens, that fluid loss causes the blood pressure to drop. In response, the heart beats faster to try and use the blood it still has left to get oxygen to the body. However, at a certain point, even beating really fast is not enough to get enough blood to the tissues. At this point, shock sets in.
  • Anaphylactic shock occurs specifically as a result of low blood pressure. Because of this, providers strongly associate low blood pressure with anaphylaxis. They may not realize that while a person with high blood pressure cannot be having anaphylactic shock, they can be having anaphylaxis.
  • Part of the confusion is that anaphylaxis has been defined lots of different ways by many different groups. I have written a very detailed post about this (see the link below). Even today, exactly what constitutes anaphylaxis not agreed upon by everybody.
  • The most widely used criteria in the US are the criteria published in 2006 by the World Allergy Organization journal. These criteria explicitly state that a person does not need to have low blood pressure to be having anaphylaxis. A person can meet these criteria based upon a variety of combinations of symptom and vital signs that do not include low blood pressure.

2006 WAO Anaphylaxis Criteria

For additional information, please visit the following posts:

The definition of anaphylaxis
Anaphylaxis and mast cell reactions

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 49

 

 

Cardiovascular manifestations of mast cell disease: Part 3 of 5

Recurrent or perpetual elevation in blood pressure has been observed in multiple studies and may affect up to 31% of patients with mast cell activation disease (systemic mastocytosis, mast cell activation syndrome/disorder, monoclonal mast cell activation syndrome). Despite this high prevalence, many providers continue to believe that this symptom cannot be inherently from mast cell activation.

A number of mast cell mediators are vasoconstrictors, narrowing the blood vessels and elevating blood pressure. Histamine can both increase and lower blood pressure depending on which receptor it acts upon (H1: hypotension; H2: hypertension).

Several mediators participate in the angiotensin-renin pathway. Angiotensin II, the level of which is largely determined by mast cell mediators like renin, strongly elevates blood pressure. Chymase, involved in the angiotensin-renin pathway, can also either increase or lower blood pressure depending on concentration relative to other mediators present. Carboxypeptidase A can also affect angiotensin II level as well. Renin regulates the level of a molecule that becomes angiotensin II and can increase blood pressure this way.

Phospholipases, which help produce the molecule needed to make prostaglandins, leukotrienes and thromboxanes can contribute to either high or low blood pressure depending upon which molecule is made. Prostaglandin D2 (PGD2) is a vasodilator, lowering blood pressure; but its metabolite, 9a,11b-PGF2, increases blood pressure. (Author’s note: I personally believe this to be the reason for the rapid blood pressure fluctuations in mast cell patients, but do not have evidence to directly support this.) Thromboxane A2, a molecule related to prostaglandins and leukotrienes, increases blood pressure, as do leukotrienes.

Management of high blood pressure is complicated in mast cell patients by the interaction of common antihypertensives with mast cell activation. Beta blockers are contraindicated in mast cell patients because they interfere with epinephrine, both naturally produced and medicinally.  Use of beta blockers is a risk factor for fatal anaphylaxis.  Any patient on beta blockers that carries an epipen should also carry a glucagon pen, which can be administered prior to the epipen to increase efficacy.

ACE inhibitors interfere with angiotensin converting enzyme, which increases blood pressure through the angiotensin II pathway.  ACE inhibitors affect bradykinin levels, a mast cell mediator that is also mast cell activating.  For this reason, ACE inhibitors can increase mast cell reactivity and symptoms like angioedema.

Author’s note:  I extended this series to four posts to discuss heart failure in mast cell patients.  Following this series, I will be posting a series dedicated exclusively to Kounis Syndrome, including diagnosis and treatment.  Sit tight!

References:

Kolck UW, et al. Cardiovascular symptoms in patients with systemic mast cell activation disease. Translation Research 2016; x:1-10.

Gonzalez-de-Olano D, et al. Mast cell-related disorders presenting with Kounis Syndrome. International Journal of Cardiology 2012: 161(1): 56-58.

Kennedy S, et al. Mast cells and vascular diseases. Pharmacology & Therapeutics 2013; 138: 53-65.

 

Mast cells and metabolic syndrome: Hypertension, obesity and atherosclerosis

Metabolic syndrome is defined as impaired glucose tolerance (IGT) or type 2 diabetes and/or insulin resistance with two or more of the following findings:

1.       Abdominal obesity, defined as a BMI 30; and/or waist to hip ratio >0.90 in men and >0.85 in women
2.       Baseline blood pressure >160/90 mm Hg
3.       Increased plasma triglycerides >1.7 mmol/L; and/or low levels of HDL cholesterol (<0.9 mmol/L in men; <1.0 mmol/L in women
4.       Microalbuminuria (overnight urinary albumin excretion rate > equal to 20 ug/min.)
Inflammation is a known effector of obesity.  Microscopic examination of obese adipose tissue reveals chronic inflammation and excessive amounts of white blood cells, leukocytes.  Macrophages, white cells that are very important in the inflammatory response, are found in adipose tissue in numbers that are directly proportional to the degree of obesity.  T cells, other white cells, also accumulate in adipose tissue. 
Until recently, most of the research on inflammatory cells in adipose tissue focused on macrophages and T cells.  However, we now know that mast cells congregate in larger than normal numbers in white adipose tissue in obese patients.  These patients also demonstrate a higher serum tryptase concentration than in lean individuals.  Mast cells are usually found near microvessels, very small blood vessels, in white adipose tissue.  The number of microvessels correlate with mast cell count in the tissue, implying that a relation between the microvessels and mast cells.
Mast cells release many chemicals, including TNF (tumor necrosis factor.)  TNF is known to mediate insulin resistance, and is overexpressed in white adipose tissue in obese patients.  Treatment with TNF blockers in patients with inflammatory diseases has demonstrated a significant reduction of blood insulin levels as well as the insulin/glucose index.  Several other mast cell mediators contribute to insulin resistance in fat cells, including IL-6, iNOS, MCP-1 and IL-1. 
Research has shown that mast cell stabilizers, cromolyn and ketotifen, can prevent diet induced obesity and diabetes.  In mice, these medications have been able to reverse obesity and diabetes, as well as reducing body weight and glucose intolerance.  These findings have been very exciting for mast cell patients with diabetes.
It is important to know that while metabolic syndrome is usually associated with obesity, patients of normal weight may also be insulin resistant and have metabolic syndrome.
Hypertension (high blood pressure( in mast cell disease is a topic of a lot of recent debate.  In spontaneously hypertensive rats (SHR), the density of cardiac mast cells is significantly higher than normal immediately after birth.  Throughout life, cardiac mast cell density is much higher in these rats than in controls of the same age.  Mast cell chemicals TNF, NF-kB and IL-6 were overexpressed in these rats even before they became hypertensive.  In later stages of hypertension, hearts of these rats showed increased areas of fibrosis in the heart.  These areas of fibrosis were full of activated mast cells.  Expression of two mast cell chemicals, TGF-B1 and bFGF (basic fibroblast growth factor) is much higher than normal in aging and failing hearts in spontaneously hypertensive rats. 
Importantly, mast cell stabilizer nedocromil was able to prevent fibrosis in SHR rats.  Tryptase levels were elevated in SHRs that were not receiving treatment, but returned to normal after treatment with nedocromil.  In untreated SHRs, levels of interferon gamma and IL-4 were elevated, while IL-6 and IL-10 were lower than normal.  All of these levels normalized after treatment with nedocromil.  This medication also prevented macrophage infiltration in the heart ventricle.  This finding indicates that mast cell signaling to macrophages is an important process in fibrosis.
Atherosclerosis is the accumulation of low density lipoprotein (LDL) cholesterol in the arterial wall.  Macrophages eat particles of LDL, and when they do, they turn into weird looking cells called foam cells.  Mast cells often live very close by foam cells, and many researchers think that mast cells help macrophages transform into foam cells. 
When mast cells release chemicals, chymase and carboxypeptidase A are bound to heparin.  After release, these components form insoluble granules called remnants.  When mast cells are activated, LDL uptake by macrophages rises by 7-24X.  Treatment with cromolyn has been shown to block mast cell dependent LDL uptake by macrophages. 
HDL passes from the bloodstream into the arterial wall.  When mast cells degranulate, those remnants degrade HDL components in the blood, peritoneal fluid and maybe also in atherosclerotic lesions.  Mast cell deficient mice have lower serum total cholesterol, triglycerides, phospholipids and a less atherogenic lipoprotein profile in general.
Mast cells are heavily involved in obesity, hypertension and atherosclerosis.  For this reason, many mast cell patients have these problems. 

Reference:

Zhang J, Shi GP. Mast cells and metabolic syndrome. Biochim. Biophys. Acta 2012 Jan, 822(1):14-20.