Pathophysiology of anemia
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Pathophysiology of Anemia
Introduction to Anemia Pathophysiology
Anemia is a condition characterized by a decrease in the oxygen-carrying capacity of the blood, which can result from various underlying mechanisms. Understanding the pathophysiology of anemia is crucial for effective diagnosis and treatment. The primary causes of anemia include blood loss, decreased red blood cell (RBC) production, poor RBC maturation, and increased RBC destruction1.
Mechanisms of Anemia Development
Blood Loss and RBC Destruction
Blood loss, whether acute or chronic, is a common cause of anemia. Acute blood loss can occur due to trauma or surgery, while chronic blood loss might be due to gastrointestinal bleeding or heavy menstrual periods. Increased RBC destruction, or hemolysis, can be caused by autoimmune diseases, infections, or inherited conditions like sickle cell anemia1.
Decreased RBC Production
Decreased RBC production can result from bone marrow failure syndromes, such as aplastic anemia, where the bone marrow fails to produce sufficient blood cells. This can be due to inherited genetic mutations or acquired conditions like autoimmune attacks on hematopoietic stem and progenitor cells (HSPCs)2. In chronic kidney disease (CKD), reduced production of erythropoietin (EPO) by the kidneys leads to decreased RBC production5.
Nutritional Deficiencies
Nutritional deficiencies, particularly of iron, vitamin B12, and folate, are significant contributors to anemia. Iron deficiency anemia is prevalent in low- and middle-income countries due to poor dietary intake and increased iron loss from infections and inflammation3. Vitamin B12 and folate deficiencies impair DNA synthesis, leading to ineffective erythropoiesis and megaloblastic anemia9.
Anemia in Specific Conditions
Chronic Kidney Disease (CKD)
In CKD, anemia is primarily due to decreased EPO production, iron deficiency, and inflammation. Elevated hepcidin levels, a hormone that regulates iron metabolism, further complicate iron utilization. Treatments include iron supplements and erythropoiesis-stimulating agents (ESAs), although new therapies like hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are emerging5.
HIV Infection
Anemia in HIV-infected individuals is multifactorial, involving direct effects of the virus, opportunistic infections, and side effects of antiretroviral therapy. HIV proteins and cytokines can inhibit bone marrow function, while deficiencies in iron, vitamin B12, and folate are common but often not the primary cause of anemia in these patients6. In children, HIV infection can alter the risk and presentation of anemia-related factors like malaria and undernutrition4.
Cancer
Cancer-related anemia is caused by reduced erythroid progenitor cells, increased inflammatory cytokines, and impaired iron utilization. Chemotherapy can also induce anemia by damaging the bone marrow and kidneys. EPO production is often inadequate in response to anemia, necessitating the use of ESAs and iron supplements8.
Autoimmune Hemolytic Anemia
In autoimmune hemolytic anemia, the immune system mistakenly targets RBCs for destruction. This involves antibodies like IgG and IgM, which mark RBCs for clearance by the reticuloendothelial system. Complement proteins also play a role in mediating RBC destruction10.
Conclusion
Anemia is a complex condition with diverse etiologies, including blood loss, decreased RBC production, nutritional deficiencies, and increased RBC destruction. Understanding the specific pathophysiological mechanisms in different contexts, such as CKD, HIV, cancer, and autoimmune diseases, is essential for effective management and treatment. Advances in therapies, particularly for conditions like CKD-related anemia, offer promising new avenues for improving patient outcomes.
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Most relevant research papers on this topic
Pathophysiology of anemia.
Anemia is a decrease in blood's oxygen-carrying capacity, affecting surgical patients, and understanding its pathophysiology can help develop new treatments and avoid transfusions.
Aplastic anemia: Pathophysiology.
Acquired aplastic anemia is driven by an immune-mediated disruption of bone marrow stem cells, driven by cytotoxic T cell-mediated autoimmune attacks against hematopoietic stem and progenitor cells.
Anemia epidemiology, pathophysiology, and etiology in low‐ and middle‐income countries
Anemia's complex etiology, influenced by factors such as nutritional deficiencies, infection/inflammation, and genetic hemoglobin disorders, requires further research for effective interventions and monitoring.
Rigorous Journal
Highly CitedPathophysiology of Anemia in HIV-Infected Children Exposed to Malaria.
Anemia in HIV-infected malaria-exposed children is not related to HIV-specific effects, with iron deficiency prevalence being similar in both HIV-infected and uninfected children, suggesting no need for different iron supplementation recommendations.
Observational StudyRigorous JournalAnemia in Chronic Kidney Disease: From Pathophysiology and Current Treatments, to Future Agents
Current treatments for chronic kidney disease-related anemia include iron supplements and erythropoiesis stimulating agents, but new drugs like HIF-PHIs show promise for improving anemia management.
Highly CitedPathogenesis and pathophysiology of anemia in HIV infection
HIV-associated anemia is a multifactorial condition, with opportunistic complications, iatrogenic anemia, vitamin B12, folate, and iron deficiencies, and a blunted erythropoietin feedback mechanism contributing to its pathogenesis.
Highly CitedPathophysiology of anemia and erythrocytosis.
Understanding erythropoiesis and its role in anemia and erythrocytosis can improve diagnosis and treatment, but caution is needed due to potential negative effects in non-erythroid tissues.
Highly CitedAnemia in cancer patients.
Chronic anemia in cancer patients is caused by reduced bone marrow progenitor cells, increased inflammation, and reduced erythropoietin production, as well as nephrotoxic chemotherapy.
Highly CitedAnemia in Clinical Practice-Definition and Classification: Does Hemoglobin Change With Aging?
Anemia is a global public health issue affecting all ages, with new lower limits of normal hemoglobin values proposed for ethnicity, gender, and age, and is often multifactorial and not an independent phenomenon.
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