As nurses we are exposed to new information on a daily basis. We encounter information in so many formats – listening to the news on our way to work, learning about a new patient condition that we were not aware of, listening to lectures, investigating medical therapies for our patients, and talking with colleagues. As a profession, nurses have the opportunity to learn every day. Many days we are exposed to an exorbitant amount of new information and don’t even realize we are learning. This month, in preparation for this blog, I attempted to be more mindful and aware of new information that I was learning, and I included a few of them below.

1. Hypoxia Inducible Factor

I learned that the Nobel Prize in Medicine and Physiology this year was awarded to three researchers, Gregg L. Semenza, Sir Peter J. Ratcliffe, and William G. Kaelin Jr., for their discoveries of how cells sense and adapt to oxygen availability. I learned about this on my drive to work, on the radio, and it piqued my interest. I work in an intensive care unit and almost all of our patients are on oxygen. For nurses, oxygen is a foundation of our efforts and interventions, the A and B of our ABCs. So, what did these researcher’s find? Essentially, they described shifts in gene expression that take place in response to oxygen levels at the cellular and molecular level which in turn affect cell metabolism, tissue remodeling, and physiologic responses such as heart rate and ventilation (Johnson, 2019). They identified a transcription factor, hypoxia inducible factor (HIF), that regulates these oxygen dependent responses. One of the researchers also found a direct link between a tumor suppressor gene and HIF which has implications as a target in treatment of oncologic conditions.

Listening to this, I was reminded how truly fascinating the human body is in its ability to adapt and respond to physiologic stressors and changes. In our day to day patient care work, we see clinically overt responses when we place a patient on oxygen, for example, an improvement in respiratory effort or improvements in oxygen saturation percentages, but there are so many other things taking place at the molecular level which I have not thought about in a long time. I am appreciative of the scientists doing the “behind the scenes” work and am also reminded how important it is as nurses to have an understanding of the science behind disease. The significance of their discovery is profound; understanding and isolating HIF is a promising potential target for oxygen sensitive disease and many cancers. Increased levels of HIF are seen in many cancers as well as in some cardiovascular diseases, including stroke, heart attack, and pulmonary hypertension (Johnson, 2019) as cells adapt to hypoxemia. If scientists can engineer how to inhibit or promote this important pathway, they could potentially change and improve physiologic responses to hypoxia and alternately block activation of pro-cancer pathways. This discovery is significant for the oncology community but also to the extensive population of patients with acute and chronic conditions that lead to hypoxemia.

2. Leukocytosis

I learned more about the vast differential for leukocytosis. We had a patient with unexplained leukocytosis, and it was clear infection or malignancy were not the cause. As a group, we had to dive deeper into the differential diagnoses for leukocytosis and as a result, I revisited and re-educated myself on the life of the white blood cell. Leukocytes play an important role in the immune system and provide a defense mechanism against foreign pathogens, infection, and harmful substances.

On a complete blood count (CBC), the white blood cell (WBC) count refers to the leukocytes that have been released into circulation. The remainder are stored in bone marrow and a small percentage are stored in the spleen and blood vessel walls. On the CBC, WBCs in circulation are differentiated based on type and are comprised of neutrophils, lymphocytes, monocytes, eosinophils and basophils. When a CBC reveals leukocytosis, the next step is to look at the WBC differential. The first things to always rule out are infection and malignancy. Acute infection is the most common cause of leukocytosis. When you can eliminate these from the differential diagnoses, it is helpful to use the WBC differential to look for clues to alternate etiologies. Below is an overview of potential causes of leukocytosis, other than acute bacterial infection or malignancy, based on an abnormal elevation of the particular WBC type.

Neutrophils

• Normal range: 40-80 % of total WBC count on differential
  • Subcategories of neutrophils
    • Bands (early immature neutrophils): 2-6%
    • Segmented (mature neutrophils): 60-70%
• Elevated neutrophil count: neutrophilia
  • Possible causes: chronic infection (tuberculosis, fungal infection, chronic abscess), chronic inflammation (rheumatoid arthritis, crohns and ulcerative colitis, chronic hepatitis ,vasculitis), acute gout, inflammation due to acute tissue injury (acute myocardial infarction), medications (lithium, epinephrine, steroids, colony-stimulating factors), metabolic disorders (thyroiditis), trauma, physical or mental stress, pregnancy, smoking/tobacco use, hypersensitivity reactions, hemorrhage, hemolytic anemia, post-splenectomy, immune thrombocytopenia, recovery from bone marrow suppression, poisons (mercury, black widow spider), or burns

Monocytes

• Normal range: 2-10 % of total WBC count on differential
• Elevated monocyte count: monocytosis
  • Possible causes:  autoimmune disease (lupus, rheumatoid arthritis, giant cell arteritis, vasculitis), splenectomy, viral infection (measles, mumps, mononucleosis), protozoan infections (malaria, trypanosomiasis), sarcoid, ulcerative colitis, recovery from bone marrow suppression, lipid storage diseases, connective tissues disorders

Basophils

• Normal range: 0-2 % of total WBC count on differential
• Elevated basophils: basophilia
  • Possible causes:  most commonly associated with malignancies; isolated basophilia rare, causes include inflammatory processes, allergies/hypersensitivity reactions, polycythemia vera, hemolytic anemia, splenectomy, hypothyroidism (myxedema), and rarely infection (influenza, chicken pox, TB, small pox)

Lymphocytes

• Normal range: 20-40% of total WBC count on differential
• Elevated Lymphocytes: lymphocytosis
  • Possible causes: viral infections (mononucleosis/Epstein Barr virus [will typically see “atypical lymphocytes”], mumps, measles, coxsackie virus, pertussis, chronic TB, CMV, hepatitis), hypersensitivity reaction (serum sickness, drug hypersensitivity), autoimmune disorders, transient stress, medications (efalizumab) 

Eosinophils

• Normal range: 0-6% of total WBC count on differential
• Elevated eosinophils (eosinophilia)
  • Possible causes: allergic diseases (allergic drug reactions, hay fever, asthma), chronic dermatologic conditions (eczema, urticaria), eosinophilic esophagitis or enteritis, vasculitis, parasitic infections (i.e. tapeworm), aspergillus, endocrine disorders (Addison’s disease, hypopituitarism), familial eosinophilia, poison (black widow spider, phosphorus), immunodeficiency disorders, collagen vascular or connective tissues disorders, pernicious anemia

Taking a step back to review the vast causes of leukocytosis has already been a valuable tool for me in clinical practice. It can be overwhelming when reviewing labs on patients, but understanding the components of the WBC differential provides important clues in what sometimes feels like detective work. What you may have noticed is that many of the possible causes appear in several of the WBC type lists, so it’s not a guarantee that you will figure it out. But hopefully, along with clinical clues, this information can be helpful in understanding a mysterious case of leukocytosis. In the patient that prompted my investigation, we never figured out the cause of his leukocytosis but as he recovered from his acute illness, it began to improve and eventually resolved. We felt comfortable not intervening because we had ruled out infection, he was hemodynamically stable, and he showed continual clinical improvement.

3. Sexually Transmitted Diseases

I learned that sexually transmitted disease (STD) rates are increasing in the United States (US). According to the annual Sexually Transmitted Disease Surveillance Report (CDC, 2019), between 2017 and 2018, there was a 13% increase in the number of cases of syphilis and a 40% increase in cases of newborn syphilis, a 5% increase in cases of gonorrhea, and a 3% increase in the rates of chlamydia (1.7 million cases, the highest number of cases ever reported to the CDC). In total, this is the highest number of syphilis, gonorrhea, and chlamydia ever in the US. Most concerning to me is the trend in newborn syphilis, which, with prenatal care, can be detected and treated in the mother and thus prevented in newborns. When I first heard this headline, I was interested in what was behind this trend. According to the CDC (2019), the increase is thought to be attributed to cuts to STD programs at the state and local level, decreased condom use among vulnerable groups (young people, gay and bisexual men), and socioeconomic factors limiting access to affordable STD prevention and care. Furthermore, syphilis cases have been increasing steadily after reaching an all all-time low in 2000.  It seems that in the late 80’s and 90’s with increased awareness of HIV, there were significant public health efforts geared at sexually transmitted infection (STI) awareness, prevention, treatment, and screening.

These findings are highly alarming and an impending public health crisis. The CDC remarks that more than half of local level programs have had budget cuts in the past several years resulting in clinic closures, decreased screening and decreased follow-up (CDC, 2019). Limitations to access to healthcare whether it be prenatal care, STD clinics, or primary care, can lead to decreased screenings, treatment, and education all crucial in the cycle of STD prevention and awareness. In response to this, the CDC is developing an STI Federal Action Plan (STI Plan) to address and reverse the STD epidemic in the US (CDC, 2019). Hopefully this will improve awareness and access to care and develop a plan to decrease the rates of STDs in the US, especially for the largely preventable cases of newborn syphilis, newborns being some of the most vulnerable patient’s in the healthcare system.

References:
 
Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2018. Atlanta: U.S. Department of Health and Human Services; 2019. doi: 10.15620/cdc.79370.
 
Centers for Disease Control and Prevention. (2019). New CDC Report: STDs Continue to Rise in the U.S. Retrieved from
https://www.cdc.gov/nchhstp/newsroom/2019/2018-STD-surveillance-report-press-release.html
 
Cerny, J. & Rosmarin, A.G. (2012). Why does my patient have leukocytosis? Hematology/Oncology Clinics of North America, 26(2), 303-319. Doi: 10.1016/j.hoc.2012.01.001
 
Ferri, F. F. (2015). Section II Laboratory Values and Interpretation of Results in Ferri's best test: a practical guide to clinical laboratory medicine and diagnostic imaging. Philadelphia, PA: Elsevier Saunders
 
Johnson, R.S. (2019). The Nobel Prize in Physiology and Medicine 2019. Advanced information. Retrieved from https://www.nobelprize.org/prizes/medicine/2019/advanced-information/
 
Riley, L.K. & Rupert, J. (2015). Evaluation of Patients with Leukocytosis. American Family Physician, 92(11), 1004-1011. 
 
Williamson, M. A, & Snyder, L. Michael. (Eds). (2015). Wallach's interpretation of diagnostic tests: pathways to arriving at a clinical diagnosis. Tenth edition. Philadelphia, PA: Wolters Kluwer