Anemia: Dec RBC production Flashcards
Describe some of the major causes for underproduction anemia
ACD: chronic infection or inflammation, malignant disease, renal insufficiency, endocrine disorders, lead intoxication, and malnutrition
Sideroblastic (congenital or acquired disorders)
Vitamin B12 and folate deficiency
Clinical & lab findings for: chronic infection/inflamm
Fever, arthritis, arthralgia or symptoms involved with an infected or inflamed area - depends on underlying cause)
Hgb 8-12
normocytic/normochrom OR normocytic/hypochromic
All have reticulocytopenia
low serum Fe
low to normal TIBC
normal to high Ferritin
EPO levels are inappropriately low [for the degree of anemia].
Treat: (1) underlying disease to reduce cytokines/interleukins, (2) treat co-morbid, (3) EPO SOMETIMES
Clinical & lab findings for: Pb intox
personality changes, irritability, and headache; abdominal pain and vomiting
Decreased retic count
microcytosis
basophilic stippling (smear)
Increase in zinc protoporphyrin (watch for concurrent iron deficiency)
Treatment: chelation
Clinical & lab findings for: Renal insuff
“insidious onset” consistent w/ the Dx; not seen until kidney fund < 40%.
normo/normo
Low EPO
Other contributors: iron and other nutritional deficiencies)
Treatment: EPO!!!! & treat co-morbid
Clinical & lab findings for: Endocrine (thyroid) disorders
Changes in skin, hair, nails, activity, tone of voice, and vital signs
normo/normo
microcytosis (both) or macrocytosis (hypothyroidism) can be seen
Treat w/ hormone replacement
Clinical & lab findings for: adrenal insuff
normo/normo
Describe the pathophysiology of the anemia of chronic disease.
TNF decreases Fe availability from stores and decreases production of EPO, and INF-β inhibits erythropoiesis. In chronic infection or inflammation, IL-1 diminishes iron mobilization and EPO production, and INF-γ inhibits proliferation of erythroid precursors.
Result = inability to use Fe stores, diminished EPO production, and decreased erythropoiesis.
With renal insufficiency, the lack of EPO causes anemia.
Finally, in lead intoxication, lead inhibits synthesis of protoporphyrin and the enzyme that ligates iron to the porphyrin ring.
Describe the rationale and indications for the use of erythropoietin in the management of underproduction anemia.
EPO is used where there is:
- absolute deficiency or
- EPO levels are decreased out of proportion to the degree of anemia, and administration is known to induce a response (cancer & HIV?)
Pretty much: renal insuff and sometimes ACD
Explain the biochemical basis for B12 and folate deficiency leading to a macrocytic anemia.
Folic acid and vitamin B12 (cobalamin) are critical co-factors for normal hematopoiesis.
Methyl group gets transferred from THF to B12 to Homocysteine –> Methionine
Rxn generates THF which is a substrate for purine and pyrimidine synthesis and the conversion of deoxyuridylate to thymidylate (required for normal DNA synthesis).
Deficiencies of either impact maturation process of red cell precursors in the marrow. “One less division” The cells increase in size, arrest in S phase of mitosis, and then undergo destruction, resulting in ineffective erythropoiesis and anemia.
B12: sources, absorption, transport, storage, and deficiency
Source: meat, eggs, & milk
B12 cleaved off animal protein via amylase
B12 binds to R-binder
R-binder is cleaved off by panc enz in duos
B12 binds IF, made by parietal cell in stomach
IF-B12 absorbed in ileum
B12 released and bound to TcII then transported to liver for storage or marrow for use
Cause of def:
- Pernicious anemia - AI destruction of IF-producing gastric parietal cells
- Fail to produce (gastritis, gastrectomy, congenital)
- Malabsorption
- Transport/storage def (TcII def)
- Metabolic defect in paths that use B12
Folate: sources, absorption, transport, storage, and deficiency
Source: cereals/bread, fruits/veg, meats/fish. Human milk = good, goats milk = bad
Absorbed in jejunum
Hydrolyzed, reduced, methylated then distributed to tissues or liver as THF
Liver stores undergo turnover
Secretion in bile
Reabsorption (enterhepatic) = const supply
Cause of def:
- Poor diet
- Malabsorption (tropical sprue/parasite infection which disrupts enterohepatic circulation)
- Inborn error of folate metal
- Inc demand (hemolysis, preg/lac, rapid growth, psoriasis, myeloprolif disorder)
- EtOH consumption disrupts cycling from liver stores to tissues
Describe the findings in the peripheral blood and bone marrow in a patient with B12 or folate deficiency.
BM: erythroid hyperplasia –> M:E shifts from H:L to L:H
Megaloblastic changes are seen in both M&E
Cytoplasmic maturation is normal, but marrow precursors show large, immature nuclei (termed nuclear-cytoplasmic asynchrony).
Peripheral: anemia is variable.
Macrocytosis (MCV > 97 in adults).
Retic count is decreased, RI < 1.0
On the smear, macro-ovalocytes and hyper-set neuts
As the anemia progresses, poikilocytes and fragmentation may be seen.
SEVERE cases:
- neutropenia and thrombocytopenia
- increases in bilirubin and LDH levels (due to intramedullary [in BM] destruction of red cells)
B12 vs. Folate: time to development, presence of neurologic abnormalities, and laboratory studies used to make a diagnosis.
Folate def takes MONTHS to develop, B12 takes years. However, onset of symptoms can be rapid w/i weeks (esp in malabsorption or alcoholism)
Neuro: B12, rarely folate.
Sensory abnormalities occur first (numb, ting)
Loss of proprioception
Ataxia, spasticity, gait disturbances
Sometimes cerebral: cognitive dysfunction and emotional changes
Anemia may be absent in 28% of patients with neurologic problems
Labs: look for low B12 of Folate (but not accurate)
Homocysteine low in both
In B12, HIGH MMA!!! (B12 used as cofactor to convert MMA to SCoA). Schilling can confirm
Describe the appropriate therapies for B12 deficiency and folate deficiency.
B12: IM or SC injections - daily for 2 weeks, weekly until Hct is normal, monthly for life. If absorption isn’t an issue, can go orally. In some pernicious anemia, large dose oral can overcome
Folate def: 1mg/day orally or parenterally
DO NO MIX UP!! If pt w/ B12 def is given folic acid, neuro damage can be exacerbated
