Patients A and B


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Patient A

The following is a description of a patient that was presented in the Journal of the American Medical Association, 2015, volume 314, number 6.

A 67-year-old woman presented with fatigue for 4 weeks. She had a history of type 2 diabetes, hypertension, hyperlipidemia, and allergic rhinitis. Her medications included metformin, lisinopril, and verapamil........She had no fever or lymphadenopathy. The spleen was palpable 5 cm below the left costal margin. Laboratory evaluation revealed a white blood cell (WBC) count of 91 x 10+3/ul (normal 4.5-10 x 10+3/ul), with 54% neutrophils, 1% blasts, 2% basophils, 8% metamyelocytes, 23% myelocytes, and 1% promyelocytes (increased immature granulocytes). (Hemoglobin and platelet levels were normal.)

Optional:

Observe the micrograph of the blood in Figure 1 in the article. (URL = http://jama.jamanetwork.com/article.aspx?articleid=2425720) From your lab work, see if you can identify the cells that you did not see in your normal blood slides.


QUESTION: Does her history or medications suggest a possible cause of the fatigue?

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QUESTION: "Costal" means "ribs". Feel 5 cm below your left costal margin. Do you feel anything? What does the observation in this patient suggest?

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QUESTION: The increased WBC count could indicate an infection or an abnormal increase in synthesis in the bone marrow. (Two other possibilities are a drug effect or an autoimmune disorder.) Pick out a factor above that argues against an infection (but does not rule it out).

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QUESTION: What do the promyelocytes, myelocytes, and metamyelocytes, in general, indicate?

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QUESTION: What type of white blood cell does not develop from myeloid stem cells?

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QUESTION: Blasts are immature, precursor cells. Note that the number of blasts is much lower than the promyelocytes, myelocytes and metamyelocytes. What would be your guess -- is this a "chronic" or an "acute" type condition?

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QUESTION: OK, assuming we have a type of leukemia here, would you select ALL, CLL, AML, or CML?

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(Additional factors were used to confirm the diagnosis, which are given in the paper if you are interested.)


A bone marrow biopsy showed hypercellular marrow, with increased granulocytes with a mild shift to immaturity.....One month after beginning therapy with dasatinib, the patient's blood counts normalized and her splenomegaly resolved.



QUESTION: Dasatinib is a tyosine kinase inhibitor. What type of reaction does a tyrosine kinase facilitate?

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QUESTION: A growth factor receptor is involved here. Can you guess the general organization of a growth factor receptor?

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Patient B

The following is a description of a patient that was presented in the New England Journal of Medicine, 2010, volume 362, number 21, pp. 1993-1998.

A 16-year-old, previously healthy girl presents with a several-day history of fever, sore throat, and malaise. She appears very tired and has a temperature of 39 oC. A physical examination is remarkable for diffuse pharyngeal erythema with moderately enlarged tonsils and the presence of several enlarged, tender anterior and posterior cervical lymph nodes....



QUESTION: What is a tonsil?

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QUESTION: What word was used above in Patient A for enlarged lymph nodes?

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QUESTION: Look at the word "erythema". Can you can guess the meaning from the word root?

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If you are already speculating that this could be mononucleosis, you are correct. The pharyngitis, fever and adenopathy, especially in a teenager or young adult, is classic, but not definitive, of course. Splenomegaly might eventually be detected.

Usually mononucleosis is caused by infection with the Epstein-Barr virus (EBV). About 95% of adults are infected with this virus, which is a lifelong infection. EBV is primarily transmitted via the saliva and symptoms occur about a month or so after the infection. Lymphocytes are infected. A test for an antibody for EBV confirms a diagnosis of infectous mononucleosis due to EBV.

Optional:

A blood smear would show abnormal, large lymphocytes, which are shown in Figure 1 in the article. (URL = http://www.nejm.org/doi/full/10.1056/NEJMcp1001116) In both patient A and patient B, there is a patient with fatigue with a blood smear showing abnormal white blood cells with a bent nucleus. But they are actually different cells.

The name, "mononucleosis", refers to the abnormal blood cells, which resemble monocytes. Thus, the name of the disorder is misleading. At one time monocytes were classified as a "mononuclear" phagocyte, as opposed to neutrophils. But neutrophils actually have one nucleus, which is pinched into segments.