Question

A 35-year-old woman with type I diabetes was admitted to the hospital with severe anemia, vomiting, and fever. She had not felt well for the past several months. She had lost more than 25 lb without dieting.Physical examination revealed a pale and slightly obese female with a distended abdomen. She was the mother of two young children, ages 3 and 5. Her menstrual periods were regular.

A CBC, blood glucose, urinalysis, and pregnancy test were ordered.

■ Laboratory Data

Hemoglobin 11.40 g/dL

RBC 4.06 ́ 1012/L

Hematocrit 35.5%

MCV 87 fL

MCH 28.1

MCHC 32 g/dL

RDW 16%

WBC 22.1 ́ 109/L

Her peripheral blood smear showed abnormal erythro-cyte morphology, anisocytosis, poikilocytosis, and some teardrop (dacryocytes) cells. Her serum blood glucose was elevated. Her urinalysis was normal, except for an elevated blood glucose. The result of her pregnancy test was negative.

A follow-up ultrasound of the abdomen revealed a 20-cm extrauterine mass. Subsequent surgical excision of the mass revealed a malignant epithelial tumor of the left ovary with metastases to the pelvic lymph nodes, opposite ovary, and right lung.

■ Questions

1. Does this patient have Anemia of Inflammation?

2. Which hematopoietic cells are involved in an inflammatory response?

3. What are the characteristic iron and iron storage results in anemia of chronic inflammation?

Answer 1

1. Since the 35-year-old woman with type I diabetes has an alarming WBC count of 22.1 ́ 109/L, which is way more than the normal WBC count, it indicates that her body is fighting some sort of infection. Anemia of chronic inflammation or anemia of chronic disease refers to low red blood cell count that can be associated with many chronic disease states like infection, malignancy, diabetes or autoimmune disorders and it affects people who have conditions that cause inflammation. In this case, the women has diabetes, infection as well as a malignant epithelial tumor that must be causing an inflammation in the body and hence it can be said that this patient has Anemia of Inflammation.

2. Though there are a number of cells involved in an inflammatory response, but Neutrophils that make up of about 60-70% of white blood cells are said to be the key followed by lymphocytes and monocytes.

3. In Anemia of chronic inflammation, the underlying cause of anemia is the continuous inflammation generated by chronic disease which impairs iron metabolism and RBC production. RBC are produced in the bone marrow and are loaded with millions of copies of protein called hemoglobin. Each hemoglobin molecule is made up of four small heme molecule which have iron right in the middle. Iron is an important part of protein like myglobin which delivers and stores oxygen. Iron is mainly absorbed in small intestine specifically the duodenum. Inside duodenum, iron molecules binds to a protein called ferritin which temporarily stores the iron. When the body needs iron, some are released from ferritin and bind to iron transport protein called transferrin. Mechanism of anemia of chronic inflammation are complex and a tow fold process; decreased RBC lifespan and decreased RBC production. Dysregulation of iron homeostasis is known to be a typical reason behind decreased RBC production. Tumor necrosis factor alpha promotes RBC degradation in macrophages via phagocytosis and interferon gamma increase the expression of a protein channel called divalent metal transporter one. This channel serves as a pathway for iron to enter the macrophage at increased rates. Hence, less iron is available for the production of hemoglobin. Another cytokin called IL-10 mediates the expression of increased ferritin receptors on the surface of macrophages which then sequester even more iron. Finally IL-6 also works in the liver by increasing production of a molecule called hepcidin which blocks further uptake of iron from the small intestine. Hence it can be said in a condition of Anemia of chronic inflammation, iron is either locked up in macrophages or unable to be absorbed.