Abnormality Information and Courses from MediaLab, Inc.

The appearance, composition and associated physiology is specific for each type of inclusion. Identification and quantification of these inclusions is important because their presence may indicate an abnormality in the red cell system. Each of the inclusions listed above can be seen in more than one condition. There are erythrocyte inclusions specific to disorders which cannot be seen with either Wright-Giemsa stain or Perls' Prussian blue iron stain.

Reference ranges can help show when a test result is drastically out-of-line with expectations by providing a range of most likely values for any given analyte. Reference ranges should reflect the mean value in the population and a certain level of variation (usually 2 standard deviations). 95% of all normal patients will fall inside the reference range of an analyte. Values outside the reference ranges could indicate not only an abnormality in the patient, but also a problem with the test results. For example, should 20% of results suddenly begin to exceed a given reference range, there is most likely an testing error.

The patient whose blood smear is shown in the photograph was a 32-year-old female from Virginia who came to the high country of Colorado to ski. The day after arrival, she experienced shortness of breath, fatigue, and upper abdominal pain. She was seen in a medical center in the mountains where a working diagnosis of altitude sickness was made. A CBC revealed RBCs 5.1 x 1012/L, hemoglobin 12.8g/dL, MCV 60fL, hematocrit 40.9%, and normal total WBC, differential, and platelet count. The RDW was normal. Further questioning revealed a previous diagnosis of heterozygous beta-chain thalassemia. No other abnormal hemoglobins were found on hemoglobin electrophoresis, but HbA-2 was elevated to 5%, supporting the diagnosis of beta thalassemia. The patient's poikylocytosis and anisocytosis may be a clue to an underlying erythrocyte abnormality. Persons with iron deficiency anemia may experience various degrees of hypoxia upon arriving at high altitudes. Those with sickle cell disease and thalassemia minor (as in this case) may experience bone pain or other symptoms of "crisis" and/or alteration in the appearance of their erythrocytes upon sudden high altitude exposure. The classic teaching is that in differentiating iron deficiency anemia from thalassemia, increased RDW would favor iron deficiency; normal RDW favors thalassemia.

Anisocytosis is a general term used to describe increased variation in size of the red cell population present on a blood smear. The normal size of red cells varies from approximately 6 to 9 microns. Notice that normal, small and large cells can be seen in this field. Since several populations of cells are present, this abnormality will not be reflected in the MCV value (However, it will show up as an increase in the RDW, which is a measure of red cell size variation.) As the severity of the anemia increases, the amount of significant anisocytosis present also increases.

This course will give you an overview of the methods involved in performing a semen analysis. Semen analysis may be performed for one of several reasons. One of these is evaluation to assess male fertility. Infertility is a problem for approximately 1 in 7 couples who attempt a first pregnancy. In almost half of these cases (~50%) the cause of infertility can be traced, at least in part, to an abnormality in the male. Examination of sperm is the first step in evaluating male infertility. Semen analysis can also be used to: confirm the absence of sperm in post vasectomy patients; confirm the presence of sperm after vasectomy reversal; and to determine the presence of sperm for certain legal purposes, such as rape.

Chediak-Higashi syndrome is a rare autosomal recessive disorder. It results from a mutation of the gene LYST which encodes a protein with multiple phosphorylation sites. This defect causes a cellular abnormality involving the fusion of cytoplasmic granules. Early in neutrophil maturation normal azurophilic granules form, but they fuse together to form megagranules. Later during the myelocyte stage, normal specific granules form. The mature neutrophils contain both normal specific granules and abnormal azurophilic granules. These large abnormal granules can be seen in the cytoplasm of neutrophils, eosinophils, basophils, monocytes and lymphocytes. These abnormal granules are able to kill bacteria in neutrophils and monocytes; however, the process is much less effective than in normal cells in part, because these neutrophils have impaired locomotion. For these reasons, individuals with Chediak-Higashi have recurrent infections. An accelerated lymphoma-like phase occurs, with lymphadenopathy, hepatosplenomegaly, and pancytopenia. Death often occurs at an early age.

In 1952 Chediak (a Cuban physician) reported a childhood disorder in which abnormal cytoplasmic inclusions appeared in the neutrophils of four family members. In 1954 Higashi reported a similar abnormality in an 11-month old Japanese infant. These inclusions were identified as lysosomal in origin and found in this rare autosomal recessive disorder Death was usually related to recurrent infections or hemmorhage though now some of the affected patients live to reproduce. Ocular and cutaneous albinism, increased susceptibility to pyogenic infections, abnormal granules in neutrophils, and a bleeding tendency are prominent findings. The striking neutrophilic inclusions appear as coarse intra-cytoplasmic azurophilic granules (see photograph).These granules arise from dilated portions of the Golgi-endoplasmic reticulum lysosomal apparatus. Aleutian mink and other animals are known to have Chediak-Higashi syndrome. Azurine pelts from infected mink were once prized by coat makers.