Anemia, characterized by a deficiency of red blood cells or hemoglobin, can present with a myriad of symptoms, including fatigue, weakness, and shortness of breath. While the condition itself can influence weight, the relationship is often intertwined with underlying causes and individual circumstances. This article explores the multifaceted connection between anemia and weight loss, drawing upon a case study and existing research to provide a comprehensive understanding.
Introduction
Anemia is a condition in which the blood lacks enough healthy red blood cells. Red blood cells carry oxygen to the body's tissues. Having anemia can make you feel tired and weak. There are many forms of anemia, each with its own cause. Anemia can be temporary or long term, and it can range from mild to severe. In many cases, anemia has more than one cause. See your doctor if you suspect you have anemia. It can be a sign of serious illness. Treatments for anemia range from taking supplements to undergoing medical procedures.
Anemia: A Primer
Anemia is a condition characterized by a deficiency of red blood cells or hemoglobin in the blood, impairing the delivery of oxygen to the body's tissues. This can manifest in various symptoms, including fatigue, weakness, shortness of breath, and pale skin.
Types of Anemia
There are several types of anemia, each with its own cause:
- Iron-deficiency anemia: This is the most common type of anemia, caused by a lack of iron in the body. Iron is essential for producing hemoglobin, the protein in red blood cells that carries oxygen.
- Vitamin-deficiency anemia: This type of anemia occurs when the body doesn't get enough vitamin B12 or folate, which are needed to produce healthy red blood cells.
- Anemia of chronic disease: Certain chronic diseases, such as cancer, kidney disease, and inflammatory conditions, can interfere with the production of red blood cells, leading to anemia.
- Aplastic anemia: This rare and life-threatening condition occurs when the bone marrow stops producing enough red blood cells.
- Hemolytic anemia: This type of anemia occurs when red blood cells are destroyed faster than they can be replaced.
Weight Loss and Anemia: A Complex Relationship
The interplay between anemia and weight loss is complex and can be influenced by several factors:
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Anemia-Induced Appetite Changes
Some types of anemia can cause a decrease in appetite or a change in taste, which can lead to a decrease in food intake and subsequent weight loss.
Underlying Causes of Anemia
Weight loss can also be a symptom of the underlying condition causing the anemia. For example, nutrient deficiency-related anemia can lead to weight loss. Conversely, weight loss can result in this type of anemia. A chronic illness or disease such as cancer may also be associated with anemia and unexpected weight loss.
Impact on Activity Levels
Anemia-related fatigue can make individuals less likely to be active, which may contribute to weight gain in some cases.
Case Study: Tuberculosis-Induced Anemia and Weight Loss
A 17-year-old female presented with a 1-month history of more noticeable weight loss and increased tiredness. Over the last 6 years since immigrating to the United States with her family from Burma and going through puberty, her body habitus has changed to a very thin appearance. This period of time began with menarche, which subsequently demonstrated intermittent oligomenorrhea occasionally alternating with amenorrhea. Apparently, workup by a gynecologist was negative and a yearlong period of oral contraceptive use did little to change the scant flow pattern. She discontinued these 6 months ago. The patient’s diet history revealed 3 meals a day of normal type foods but always smaller portions than other members of her family. Mother agreed that she does not eat much fried or fast foods, usually what is prepared for the family at home. The patient eventually suggested after repetitive questions that there was an increase in early satiety over the last month and she clearly was overall more tired. Five months ago, she had an outpatient visit for viral syndrome with vomiting and diarrhea, which resolved in 48 hours. At that time, her weight was 42 kg and no fever noted.
Review of systems was notable for fatigue, intermittent chills, hair loss with nonvigorous brushing, intermittent “shakiness” when getting up, and shortness of breath on exertion. She denied any fever, upper respiratory tract infection symptoms, coughing, nausea, vomiting, dysuria, abdominal pain other than associated with her menstrual cycle, rashes, easy bruising or bleeding. Her past medical history was notable for the oligomenorrhea and scoliosis, but prior testing for anemia reported negative 6 months ago, and all chronic diseases, including in other members of the family, was denied, including anemia, thalassemia, and tuberculosis. The patient reports feeling “sad sometimes” but denied any suicidal or homicidal ideation.
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In the emergency department, her physical exam (PE) was notable for a tired appearing but otherwise well teenage girl with a temperature of 101.6°F, heart rate 125, respiratory rate 16, pulse oxygenation saturation of 97% on room air, weight 40 kg, height 144.78 cm, body mass index 20.1, some hair loss with brushing, II/VI systolic murmur over LUSB, and mild nonpitting bilateral edema. The remainder of the PE was unremarkable. Laboratory values were remarkable for white blood cell count 4700/µL with neutrophilic predominance, hemoglobin 7.3 g/dL, hematocrit 24.8%, mean corpuscular volume 74.9 fL, red cell distribution width 18.4%. Chemistry panel was within normal limits except for low albumin 2.9 g/dL, and a slightly elevated aspartate transaminase 54 U/L. Thyroid studies demonstrated slightly elevated thyroid-stimulating hormone of 6.68 mIU/L (05-6.0) with normal free T4 of 1.08 ng/dL (0.7-1.9). C-reactive protein and erythrocyte sedimentation rate were elevated to 65.4 mg/L (normal 0-5) and 132 mm/h (normal 0-20), respectively. Urinalysis was unremarkable and urine pregnancy test was negative. Additional iron studies demonstrated levels of iron 29 µg/dL, ferritin 3 ng/mL, and a total iron binding capacity of 144 µg/dL.
The typical consideration for severe anemia in an American adolescent female usually includes dietary iron deficiency, menorrhagia, and/or risk of hemoglobinopathy/thalassemic state. The differential diagnosis for this patient was broader and included gastrointestinal, infectious, rheumatologic, oncologic, psychiatric, and volitional etiologies. Her hematologic labs coupled with her inflammatory markers were most consistent with a mixed picture of iron deficiency anemia coupled with anemia of chronic disease. Her description of increasing early satiety raised concerns for an inflammatory bowel disease or possible slow growing abdominal mass. Abdominal ultrasounds demonstrated complex solid and cystic masses in the region of the porta hepatis concerning for peritoneal lymphadenopathy. Follow-up abdominal computed tomography (CT) did not appear to be consistent with inflammatory bowel disease but several likely enlarged peritoneal and abdominal lymph nodes were present. Subsequent chest X-ray and thoracic CT were notable for a right apical consolidation and parabronchial masses, some with calcifications. Therefore, pulmonary tuberculosis (TB) with abdominal involvement was considered.
Gastric aspirates were negative for acid-fast bacilli. Induced sputum samples were attempted, but the patient was unable to produce sputum. Subsequent PPD (purified protein derivative) and T-Spot results were positive. Thus, she was taken for a bronchoscopy for sputum collection and a lymph node needle biopsy, both of which showed acid-fast stains positive for likely mycobacteria. These were only observed in combined samples enriched by centrifugation. The patient was started on RIPE therapy (rifampin, isoniazid, pyranizamide, ethambutol). An extensive infectious disease workup including HIV, viral hepatitis, RPR, Helicobacter pylori were all negative. Autoimmune workup including ANA, anti-dsDNA, RF, and thyroid peroxidase antibodies were negative. Of note, secondary review of the history directly with mother through an interpreter revealed that mother and maternal aunt were treated for TB upon arrival to the United states 6 years prior, but the mother thought patient was not positive to screening because she never received similar anti-TB treatment.
Throughout the hospital course, the patient had intermittent fevers to 104°F and hypothermia to 93°F, which self-resolved. On discharge, the appropriate communications with local health department officials were made for direct observed therapy and appropriate follow-up was arranged.
Diagnostic Challenges and Importance of Comprehensive History
This case highlights the challenges in diagnosing anemia, especially when accompanied by weight loss and other constitutional symptoms. The initial presentation was concerning for an underlying hematologic process or possible abdominal mass, but the normal platelet and white blood cell counts made leukemia or lymphoma unlikely. While the patient did endorse a decreased appetite, there was no evidence of overt nutritional deficiency nor eating disorder. Preliminary psychological evaluation was also reassuring. It is important to consider hyperthyroidism given the clinical presentation; however, the patient had only slightly elevated thyroid-stimulating hormone and normal free T4.
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The Crucial Role of Social History
The history of immigration from an endemic region, coupled with exposure from her mother and aunt who had been previously treated for TB, pointed to the underlying infectious process. This underscores the importance of obtaining a thorough social history, especially in patients from diverse backgrounds. Only specifically directed questions to the mother subsequently revealed what should now be considered an obvious set of clues, that of a teenager with a long history of weight loss immigrating from a TB endemic region of the world with prior exposure to TB and now presenting with severe anemia.
Tuberculosis and Anemia
Anemia without iron deficiency has been associated with a 4-fold increased risk of TB recurrence. Iron deficiency and anemia, with or without co-presentation in a patient with TB, are associated with a 2- to 3-fold increase in the risk of death. Thus, TB screening tests including a chest radiograph and either PPD or interferon-γ release assays (IGRA) should be performed during the early evaluation of possible infectious causes.
TB in the United States
With a rising immigrant population in the United States, TB-the second most common infectious cause of mortality worldwide-should be included in the differential for a patient with generalized symptoms, weight loss, and anemia. Contracted through airborne droplets, pulmonary TB classically presents with fever, long history of cough, hemoptysis, and several constitutional symptoms including weight loss, diaphoresis, and malaise. Typical risk factors include recent contact with infected individual, immunocompromised state, homelessness, and incarceration.
Diagnostic Testing for TB
Laboratory analysis can include PPD, usually now referred as tuberculin skin test (TST), as well as IGRA, such as the QuantiFERON-TB Gold or T-SPOT TB Test. It is also important to consider prior history of BCG vaccination in immigrant populations, as this may lead to positive PPD testing with no evidence of concurrent infection. IGRAs are unaffected by prior BCG vaccination. The current recommendation by many infectious disease experts is that all persons with a positive PPD, irrespective of prior BCG vaccine, be further tested with IGRAs to ensure that there is not latent, if not active, TB. Both IGRA tests available in the United States, QuantiFERON-TB Gold In-Tube Test (QFT-GIT) and the T-SPOT TB Test (T-Spot), are approximately similar in turnaround time, cost, and accuracy.
Extrapulmonary Tuberculosis
Extrapulmonary tuberculosis (EPTB) constitutes 15% to 20% of all cases of TB in immunocompetent patients in some areas, but accounts for more than 50% of the cases in HIV-positive individuals. The exact frequency in immunocompetent patients varies among studies from different sites, but it has been suggested that, overall, approximately 10% of HIV-negative patients present with EPTB. In contrast, in HIV-positive patients, 33% present with EPTB alone and 33% present with both pulmonary and extrapulmonary disease, although many will have negative initial chest X-ray.
Importance of Considering TB in Differential Diagnosis
While multiple processes could create the clinical presentation herein (eg, autoimmune, hematological, infectious), our case is unique in that the final diagnosis of TB lacked some typical features (eg, cough, hemoptysis). Given the social history, it is important to remember that foreign-born patients have a case rate approximately 13 times higher than US-born patients. Even with initial presentation suggesting other underlying causes of the clinical presentation, TB must remain on the differential. The final diagnosis was established taking into account the clinical history as well as social history.
Iron Deficiency Anemia and Obesity: A Paradoxical Relationship
Obesity is a risk factor for several comorbidities and complications, including iron deficiency anemia. Iron deficiency anemia is a serious global public health problem, with a worldwide prevalence. The high prevalence of obesity in combination with iron deficiency incidence observed in different age and sex categories suggests an association between obesity and iron status. Obesity may disrupt iron homeostasis, resulting in iron deficiency anemia. The association between obesity and iron deficiency may be due to increased hepcidin levels mediated by chronic inflammation. Hepcidin is a small peptide hormone that functions as a negative regulator of intestinal iron absorption. Significant body weight loss in overweight and obese individuals decreases chronic inflammation and serum hepcidin levels, resulting in improved iron status due to increased iron absorption.
The Role of Hepcidin
Hepcidin is a small peptide hormone that is considered a key regulator for body iron homeostasis. Hepcidin is synthesized mainly in the liver and produced at low levels in other organs like adipose tissue. Hepcidin regulates plasma iron level by binding to ferroportin leading to internalization and degradation of ferroportin through blockage of cellular iron transport. Consequently, dietary iron absorption from the small intestine is downregulated, and thus, serum iron concentration is dropped. In addition, hepcidin slows down the release of recycled iron by macrophages to peripheral and iron mobilization from iron stores in the liver or spleen.
Chronic Inflammation
Obesity is associated with low-grade chronic inflammation. Several pro-inflammatory cytokines are secreted by adipose tissues, including interleukin-6 and tumor necrosis factor alpha. Indeed, about one-third of interleukin-6 in the circulation is released from adipose tissue. The principal mechanism that links obesity and iron deficiency is low-grade systemic inflammation, observed in people with obesity. In people with overweight and obesity, serum hepcidin and serum interleukin-6 are significantly higher than those with normal weight. Hepcidin which is synthesized in the liver is stimulated by pro-inflammatory cytokines such as interleukin-6.
Effect of Weight Loss on Iron Status
Weight loss that is induced by an energy-restricted diet and/or exercise may improve obesity-related hypoferremia and help to restore iron homeostasis in individuals with overweight and obesity. In addition, a reduction in adipose tissue is associated with alterations in the levels of pro-inflammatory cytokines, which may lead to diminished hepcidin release and improved iron status in people with overweight and obesity.
A few studies investigated the effect of weight loss on iron status, low-grade chronic inflammation, and/or hepcidin release in individuals with overweight and obesity. Amato et al (2010) examined the effect of BMI reduction on serum hepcidin levels and iron status in obese children. They observed a significant decrease in hepcidin and leptin levels and a significant increase in iron absorption. Similarly, Gong et al (2014) reported an improvement of iron status with unchanged serum ferritin concentrations and an increase in transferrin saturation after the intervention, along with an improvement of inflammatory markers.
Addressing Anemia and Weight Changes
To treat anemia, a healthcare professional will first need to determine the underlying cause. The cause may be nutritional, such as in iron deficiency anemia or pernicious anemia, where the body cannot absorb enough vitamin B12. Or it may be the result of an autoimmune disease or inherited condition such as sickle cell disease. Once your doctor identifies the cause, they can develop a treatment plan. This may involve treatments such as iron or B12 supplements or injections. In severe cases, they may recommend medications to boost red blood cell production.
Nutritional Strategies
Eating fortified, iron-rich foods is always a good idea. Here are some foods to consider:
- Animal proteins: Beef, poultry, eggs, liver and fish
- Breads and cereals: Whole wheat bread, enriched white bread, rye bread, bran cereals and cereals with wheat
- Fruits: Figs, dates and raisins
- Legumes: Peas, beans, tofu and tempeh
- Vegetables: Spinach, broccoli, string beans, dark leafy greens, potatoes, cabbage and tomatoes
If you follow a vegan or vegetarian diet, look for iron-fortified breads and cereals. There are several non-meat options for boosting your iron intake, like beans, tofu, dried fruits and dark leafy greens. You can also try iron supplements. Always talk to your healthcare provider before adding any supplement to your regimen. You can enhance your body's absorption of iron by drinking citrus juice or eating other foods rich in vitamin C at the same time that you eat high-iron foods.
If you’ve gained or lost weight as a result of anemia, there are several things to focus on alongside appropriate anemia treatment. Speak with a healthcare provider you trust about what types of exercise are safe and appropriate for you. If you’re experiencing unintended weight loss with anemia, it’s important to consume enough calories to meet your body’s energy needs. Speak with a health and nutrition professional to develop a meal plan that provides enough calories and nutrients to support your health.
When to Seek Medical Attention
You should see your healthcare provider regularly so they can monitor your iron levels and your overall health. You might see your healthcare provider every three months for a year or longer if you’re being treated for iron-deficiency anemia. Weight can fluctuate slightly, but persistently losing or gaining weight when you haven’t changed your diet or activity levels can be a cause for concern.
If you or a loved one are experiencing unexplained weight changes or other symptoms, it’s important to speak with a physician for a proper diagnosis and treatment plan. This is also true if you have any other potential anemia symptoms, such as fatigue or dizziness.