Polycythemia Flashcards
Anemia of Chronic Disease
Impaired red cell production associated with chronic diseases that produce * systemic inflammation is perhaps the most common cause of anemia among * hospitalized patients in the United States
diseases that lead to anemia of chronic disease
Chronic microbial infections, such as osteomyelitis, bacterial endocarditis, and lung abscess
Chronic immune disorders, such as rheumatoid arthritis and regional enteritis
Neoplasms, such as carcinomas of the lung and breast, and Hodgkin lymphoma
difference between labs in iron deficiency and chronic disease anemia
TIBC– high in iron deficiency, low in chronic dz
Fe saturation super low in deficiency, just low in chronic dz
** ferritin low in defic, high in chronic dz (hepcidin locks the iron in the cell)
where is iron stored in anemia of chronic disease?
The anemia of chronic disease occurs in the setting of persistent systemic inflammation and is associated with low serum iron, reduced total iron-binding capacity, and abundant stored iron in tissue macrophages.
Important effect of inflammation contributing to the abnormalities chronic dz anemia
Most notably, certain inflammatory mediators, particularly interleukin-6 (IL-6), stimulate an increase in the hepatic production of hepcidin.
Hepcidin inhibits ferriportin function in macrophages and reduces the transfer of iron from the storage pool to developing erythroid precursors in the bone marrow. As a result, * the erythroid precursors are starved for iron in the midst of plenty.*
In anemia of chronic dz, RBC progenitors do not proliferate adequately because
erythropoietin levels are inappropriately low for the degree of anemia. (you have plenty of iron, just aren’t using it)
symptoms, RBCs of anemia of chronic disease
The anemia is usually mild, and the dominant symptoms are those of the underlying disease.
The red cells can be normocytic and normochromic, or hypochromic and microcytic, as in anemia of iron deficiency.
how we can rule out iron deficiency as the cause of anemia in the anemia of chronic dz
The presence of increased storage iron in marrow macrophages, a high serum ferritin level, and a reduced total iron-binding capacity readily rule out iron deficiency as the cause of anemia.
treatment of anemia of chronic dz
Only successful treatment of the underlying condition reliably corrects the anemia. However, some patients, particularly those with cancer, benefit from administration of erythropoietin.
parvovirus loves
precursor red cells
aplastic anemia
refers to a syndrome of chronic primary hematopoietic failure and attendant pancytopenia (anemia, neutropenia, and thrombocytopenia)
2 questions you need to ask when someone has aplastic anemia
what do you do for a living?
what drugs are you on?
etiology of aplastic anemia
Most cases of “known” etiology follow *exposure to chemicals and drugs. Certain drugs and agents (including many cancer chemotherapy drugs and the organic solvent benzene) cause marrow suppression that is dose related and reversible.
In other instances, aplastic anemia arises in an unpredictable, idiosyncratic fashion following exposure to drugs that normally cause little or no marrow suppression. The implicated drugs include * chloramphenicol and gold salts.
two major processes in the development of aplastic anemia
- an extrinsic, immune-mediated suppression of marrow progenitors
- an intrinsic abnormality of stem cells
stem cell abnormalities
Stem cells may first be antigenically altered by exposure to drugs, infectious agents, or other unidentified environmental insults. This provokes a cellular immune response, during which activated TH1 cells produce cytokines such as interferon-γ (IFN-γ) and TNF that *suppress and kill hematopoietic progenitors
aplasias can transform into
myeloid neoplasms, typically myelodysplasia or acute myeloid leukemia
Clinical Features of aplastic anemia
Aplastic anemia can occur at any age and in either sex. The onset is usually insidious. Initial manifestations vary somewhat, depending on which cell line is predominantly affected, but * pancytopenia ultimately appears
The diagnosis rests on examination of a * bone marrow biopsy. It is important to distinguish aplastic anemia from other causes of pancytopenia, such as “aleukemic” leukemia and myelodysplastic syndromes
The prognosis is variable. * Bone marrow transplantation is the treatment of choice in those with a suitable donor and provides a 5-year survival of more than 75%. Older patients or those without suitable donors often respond well to immunosuppressive therapy
aplastic anemia and the spleen
Splenomegaly is characteristically absent; if it is present, the diagnosis of aplastic anemia should be seriously questioned
also, you should not have reticulocytes in aplastic anemia
Pure Red Cell Aplasia
Pure red cell aplasia is a primary marrow disorder in which only erythroid progenitors are suppressed
It may occur in association with neoplasms, particularly thymoma and large granular lymphocytic leukemia, drug exposures, autoimmune disorders, and parvovirus infection
what do we need to do when we see pancytopenia?
bone marrow biopsy
Myelophthisic anemia
describes a form of marrow failure in which space-occupying lesions replace normal marrow elements
The commonest cause is metastatic cancer, most often carcinomas arising in the breast, lung, and prostate. However, any infiltrative process (e.g., granulomatous disease) involving the marrow can produce identical findings
Marrow failure –>
All of the responsible diseases cause marrow distortion and fibrosis, which act to displace normal marrow elements and disturb mechanisms that regulate the egress of red cells and granulocytes from the marrow.
The latter effect causes the abnormal release of nucleated erythroid precursors and immature granulocytic forms *(leukoerythroblastosis) into peripheral smears, and the appearance of *teardrop-shaped red cells, which are believed to be deformed during their tortuous escape from the fibrotic marrow
Other Forms of Marrow Failure
Chronic renal failure, whatever its cause, is almost invariably associated with an anemia that tends to be roughly proportional to the severity of the uremia
Hepatocellular liver disease, whether toxic, infectious, or cirrhotic, is associated with anemia attributed to decreased marrow function
Endocrine disorders, particularly *hypothyroidism, may also be associated with a mild normochromic, normocytic anemia
Polycythemia denotes
an abnormally high red cell count, usually with a corresponding increase in the hemoglobin level.
It may be relative when there is hemoconcentration due to decreased plasma volume, or absolute when there is an increase in the total red cell mass
An elevated hematocrit is a hematocrit value that is
greater than the 97.5 percentile value of the reference range for normal individuals and reference range must account for:
Altitude of residence of the individual
Age
Sex
Relative polycythemia
results from dehydration, such as occurs with deprivation of water, prolonged vomiting or diarrhea, or excessive use of diuretics
Absolute polycythemia : primary vs secondary
is primary when it results from an intrinsic abnormality of hematopoietic precursors and secondary when the red cell progenitors are responding to increased levels of erythropoietin
The most common cause of primary polycythemia
is polycythemia vera, a myeloproliferative disorder associated with mutations that lead to erythropoietin-independent growth of red cell progenitors.
Secondary polycythemias are caused by
compensatory or pathologic increases in erythropoietin secretion.
Causes of the latter include erythropoietin-secreting tumors and rare, but illustrative, inherited defects that lead to the stabilization of HIF-1α, a hypoxia-induced factor that stimulates the transcription of the erythropoietin gene
Elevated hematocrit should be called
erythrocytosis, implying an increase in red blood cell count, hemoglobin, and hematocrit
Erythrocytosis refers to
an increase in erythroid values without an accompanying increase in the leukocyte or platelet values
the interchanging of polycythemia and erythrocytosis.
Term polycythemia used interchangeably with erythrocytosis. This is an improper use of the term. Polycythemia implies an increase in all three myeloid cell lines in the peripheral blood:
Erythrocytosis
Leukocytosis
Thrombocytosis
Increased Red Cell Mass – ErythrocytosisClinical Consequences
Hematocrit greater than 50% is associated with:
Increasing blood viscosity
Increasing cardiovascular complications
Increased risk of thrombosis and hemorrhage
