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Updated: 08/23/14

LAB 1: THE HEMATOPOIETIC SYSTEM CLINICAL CASES

The focus of this weeks lab will be pathology of the hematopoietic system. Diseases of the blood can be
organized into disorders that mainly affect red blood cells (erythrocytes), white blood cells (leukocytes),
or the hemostatic system (including platelets and clotting factors).
Disorders of red bloods cells usually result in a deficiency of red blood cells called anemia. In contrast,
disorders of white blood cells usually result in excess white blood cells called leukocytosis. Disorders
affecting the hemostatic system can result in hemorrhagic diatheses (bleeding disorders).
Red cell disorders most often result in anemia. Anemia can be caused by 1) loss of blood, 2) increased
red cell destruction, or 3) decreased red cell production. Red blood cells are approximately 45% of blood
volume; this is expressed clinically as a hematocrit of 45. The red blood cell is a soft, elastic, biconcave
disc with a diameter of approximately 7.5 m in a blood film and about 8.5 m in vivo. Specific features
of the red blood cell can be examined and correlated with pathological changes including cell size
(normocytic, microcytic, macrocytic), extent of hemoglobinization observed by cell color (normochromic,
hypochromic), and shape of cells. The presence of darkly staining ribosomal RNA in a red blood cell
may indicate an immature red blood cell called a reticulocyte, which should comprise approximately 1%
of red blood cells. Reticulocytes can increase (reticulocytosis) with increased regeneration of red blood
cells following anemia.
Diseases of white blood cells may involve deficiencies (leukopenias) or, more often, proliferation of
white blood cells (leukocytosis). Proliferation may be reactive in response to microbial disease or
neoplastic. White blood cells include monocytes, lymphocytes, neutrophils, eosinophils, and basophils.
Neutrophils are the most prevalent (55-60%) of all white blood cells and are 10-12 m in diameter and
have a segmented nucleus (referred to as segs clinically); immature neutrophils have a band shaped
nucleus (referred to as bands) and can be increased with infection or inflammation. Lymphocytes make
up 30% of leukocytes and although they look alike in blood smears, lymphocytes are composed of
different types, including B and T cells. Monocytes are larger cells (12-19 m in diameter) and are the
precursors of macrophages. Proliferation of leukocytes can occur in response to infection or as part of a
neoplastic process.
Platelets are small pieces of a large cell found in bone marrow called a megakaryocyte. Platelets are
important for blood clotting and disorders that reduce platelets numbers can result in hemorrhage and
increasing platelet number can increase the risk of thrombosis.
The cases we will cover are:
A. Hereditary Spherocytosis
B. Iron Deficiency Anemia
C. Megaloblastic Anemia (Pernicious Anemia)
D. Infectious Mononucleosis
E. Immune Thrombocytopenia Purpura

A. HEREDITARY SPHEROCYTOSIS
CC/HPI: A 9-month-old infant is brought to the pediatrician because of jaundice, lethargy, and easy
fatigability. The parents of the child are immigrants of northern European origin. The childs mother
suffers from a blood disorder.
What proteins are most frequently mutated in hereditary spherocytosis? Does the patients
mother likely have this disease too?

PE: Physical exam reveals fever, pallor, and jaundice. The child also has splenomegaly.
What does the spleen do? Why is a splenectomy helpful to these patients?

Labs: Microcytic anemia; hematocrit (15); small, dark, rounded RBCs lacking central pallor
(spherocytes). Elevated indirect serum bilirubin; increased reticulocytes; increased mean corpuscular
hemoglobin count; decreased mean corpuscular volume; abnormal RBC osmotic lysis test.
Is this patients hematocrit normal? What is normal?

What is the function of the proteins that are mutated in this disease?

Pathology: A peripheral blood smear shows the following:

(From Robbins and Cotran, Pathological Basis of Disease, 8th Ed.)

Do these RBCs look normal? Why or why not?

B. IRON DEFICIENCY ANEMIA

CC/HPI: A 20-year-old vegetarian female presents to her physician complaining of weakness,
listlessness, and fatigue. She also complains of cravings to eat non-food items (pica) particularly dirt and
clay. She has a history of peptic ulcer disease and heavy menstrual periods.
PE: Physical exam reveals pallor of skin and mucous membranes. Thin, flat, spooned fingernails.
Labs: Hematocrit is low; low serum ferritin and iron. Low transferrin saturation, but increased binding
capacity; increased serum erythropoietin. Microcytic and hypochromic RBCs present. Stool guaiac test
reveals fecal occult blood.
Why does a decrease in iron availability result in anemia?
What are the contributing factors to this patients anemia and what is their relevance?
Pathology: A peripheral blood smear shows the following:

Do these RBCs look normal? Why or why not?

C. MEGALOBLASTIC ANEMIA (PERNICIOUS ANEMIA)

CC/HPI: A 55-year-old woman presents to her physician complaining of weakness, dizziness, fatigue,
dyspnea, and nausea over the past three months. She also reports tingling and burning sensations in her
feet and hands and has felt unsteady during walking. Patient has a history of Addisons disease.
PE: Physical exam reveals decreased sensation and reflexes in extremities. Pallor and mild jaundice are
present, as well as hepatosplenomegaly, mild icterus (jaundice). Patient has beefy red tongue (glossitis).
Glove and stocking distribution of parathesias; loss of balance, vibratory and positional sense in both
lower extremities.
Labs: Macrocytic, hypochromic anemia, leukopenia. Hematocrit is low; serum B12 is low, folate is
normal, serum antibodies to intrinsic factor are present. Hypersegmented neutrophils and macroovalocytes present.

This patient has an autoimmune disorder that affects B12 absorption (by immune
destruction of intrinsic factor). What is the significance of B12 deficiency for myeloid
maturation and division?

Deficiency in what other vitamin produces megaloblastic anemia due to its role in DNA
synthesis?

Pathology: A peripheral blood smear shows the following:

Do these RBCs look normal? Why or why not?

Do these WBCs look normal? Which WBC type is seen here and what looks unusual?

What happens to myeloid precursor cells in the bone marrow? How does this result in the
cells seen in the peripheral blood smear?

D. INFECTIOUS MONONUCLEOSIS
CC/HPI: A 20-year-old male college student presents to the ER complaining of sore throat, fatigue,
swollen lymph nodes on the back of his neck, cough, and malaise for the past ten days. He was initially
prescribed ampicillin by student health five days ago and has had no improvement in his symptoms.
PE: Fever; submaxillary and cervical lymphadenopathy; exudative tonsillitis; enlargement of spleen and
liver.

Labs: Hematocrit is low; anemia, thrombocytopenia; leukocytosis with absolute lymphocytosis. Elevated
ALT, AST, and bilirubin. Positive heterophil antibody test (monospot test); IgM antibodies to viral capsid
antigen positive.
What virus is responsible for infectious mononucleosis?
What two cell types are infected with this virus during the course of the disease?

The function of one of these cells is ultimately to produce antibodies. Explain how this is
related to the presence of heterophil (anti-sheep RBC) antibodies in this patient.

Pathology: A peripheral blood smear shows the following:

Do these WBCs look normal? Which WBC type is seen here and what looks unusual?

What is the function of this WBC type?

E. IMMUNE THROMBOCYTOPENIA PURPURA

CC/HPI: A 3-year-old female is brought to the emergency room with a skin rash and severe epistaxis.
The patient had an upper respiratory tract infection with a severe cough and runny nose 10 days ago that
has resolved. She has no history of prolonged bleeding or clotting disorder.
PE: She has mucousal petechiae; epistaxis; hemorrhagic bullae in buccal mucosa; extensive purpuric skin
rash. Purpura (3-10 mm purple hemorrhages), petechiae (pin-sized hemorrhages) and ecchymoses
(bruises) present on skin.

Labs: Mild anemia; low platelet count (10,000); RBCs and WBCs are normal. Prolonged bleeding time;
normal PTT; normal PT; antiplatelet antibodies detected in serum.
What cell type is reduced in number in this patient? What is the normal number of this cell
type in peripheral blood?
What are PT and PTT? Why are they normal in this patient?

Pathology: A peripheral blood smear shows the following:

What is the function of the formed element missing in the patients blood smear?

What bone marrow cell type are these cells derived from?

How does a deficiency in these cells correlate with this patients symptoms?