Aplastic anemia pathophysiology: Difference between revisions

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* Bone marrow is a spongy tissue, found within the spongy or [[Cancellous bone|cancellous portions of bones]]
* Bone marrow is a spongy tissue, found within the spongy or [[Cancellous bone|cancellous portions of bones]]
* It is higly vascularized and richly innervated
* It is higly vascularized and richly innervated
* [[Bone marrow]] is the primary site of [[hematopoiesis]]  
* [[Bone marrow]] is the primary site of [[hematopoiesis]].
* It is composed of [[Hematopoietic cell|hematopoietic cells]], marrow [[adipose tissue]], and  [[Stromal cells|stromal cells.]]
* It is composed of [[Hematopoietic cell|hematopoietic cells]], marrow [[adipose tissue]], and  [[Stromal cells|stromal cells]].
* [[Hematopoietic stem cells]] (HSC) in the [[bone marrow]] are the source of all mature cells in the peripheral blood and tissues and are [[Multipotent|multipotent.]]
* [[Hematopoietic stem cells]] (HSC) in the [[bone marrow]] are the source of all mature cells in the peripheral blood and tissues and are [[Multipotent|multipotent]].
* HSC are recognized and isolated according to their [[immunophenotype]].  
* HSC are recognized and isolated according to their [[immunophenotype]].  
* HSCs make a small population within the CD34+/CD38 fraction of [[bone marrow cells]].
* HSCs make a small population within the CD34+/CD38 fraction of [[bone marrow cells]].

Revision as of 23:28, 22 October 2018

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Priyamvada Singh, M.D. [2] Nazia Fuad M.D.

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Overview

Bone marrow is a spongy tissue, found within the spongy or cancellous portions of bones. It is higly vascularized and richly innervated Bone marrow is the primary site of hematopoiesis and is composed of hematopoietic cells, marrow adipose tissue, and stromal cells. The most defenitive feature in pathophysiology of aplastic anemia is loss of hematopoietic stem cells. It may be in the form of hematopoietic failure or immune mediated destruction of bone marrow. Drugs, chemicals, viruses, and different kind of mutations change the immunologic appearance of HSCs resulting in autoimmune destruction of marrow cells. AA may develop gradually into other hematologic disorder which include paroxysmal nocturnal hemoglobinuria [PNH], myelodysplastic syndromes [MDS] and acute myeloid leukemia [AML]). Clonal evolution in AA can occur due to mutations or cytogenetic abnormalities. The genes that are commonly found to be mutated are DMNT3A, ASXL1, BCOR, BCORL1, PIGA.

Pathophysiology

Physiology

The normal physiology of bone marrow can be understood as follows:[1]

.

Pathogenesis

Image yellow fat ladden marrow https://www.wikidoc.org/index.php/File:Aplasticanemia.jpg source:By Wmheric [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0)] [Public domain], from Wikimedia Commons]

The most defenitive feature in pathophysiology of aplastic anemia is loss of hematopoietic stem cells.[2][3]

Pathophysiologic mechanisms that result in loss of HSCs and cause aplastic anemia include:

Hematopoietic Failure

Immune-mediated T-cell destruction of marrow

Clonal Evolution

  • AA may develop gradually into other hematologic disorder which include[3]
  • The genes that are commonly found to be mutated are
    • DMNT3A
    • ASXL1
    • BCOR
    • BCORL1
    • PIGA

Genetics

Genes involved in the pathogenesis of aplastic anemia include:[3]

  • HLA-DR15
  • CD4+ CD25+ FOXP3+ regulatory T cells
  • STAT3
  • TERT
  • TERC

Associated Conditions

Aplastic anemia is associated with following conditions:[4]

Gross Pathology

Aplastic anemia does not exhibit any gross pathology

Microscopic Pathology

In aplastic anemia bone marrow microscopy reveals hypo and even acellularity, adipose tissue and pale stroma.[3]

References

  1. Hays K (February 1990). "Physiology of normal bone marrow". Semin Oncol Nurs. 6 (1): 3–8. PMID 2406826.
  2. Bacigalupo A (2007). "Aplastic anemia: pathogenesis and treatment". Hematology Am Soc Hematol Educ Program: 23–8. doi:10.1182/asheducation-2007.1.23. PMID 18024605.
  3. 3.0 3.1 3.2 3.3 Brodsky, R. A. (2000). "Aplastic Anemia: Pathophysiology and Treatment". Journal of the National Cancer Institute. 92 (9): 754–754. doi:10.1093/jnci/92.9.754. ISSN 1460-2105.
  4. 4.0 4.1 Young, Neal S. (2002). "Acquired Aplastic Anemia". Annals of Internal Medicine. 136 (7): 534. doi:10.7326/0003-4819-136-7-200204020-00011. ISSN 0003-4819.