Flashcards in Quiz #1 - Benign Deck (16):
Causes of microcytic anemia
1) iron deficiency
2) anemia of chronic disease
3) siderblastic anemia
Red blood cells: 2.4 million new erythrocytes/second 100-120 day life span
Neutrophils: The most abundant WBCs (50-70% of all WBCs) 5 billion neutrophils are produced every hour of the day 8 hour life span
Platelets: 10 billion are produced per day. One megakaryocyte can give rise to 5000 platelets. 7 day life span.
Stem Cell -->
- lymphoid progenitor -->
*lymphocytes --> B and T cells
- myeloid progenitor -->
*Red Blood Cells (from erythroid progenitors)
*monocytes and neutrophils (from monocyte progenitors)
* platelets (from megakaryocyte progenitors)
Types of Hemoglobin:
A: α2β2 (96.5%)
A2: α2δ2 (2.5%)
Fetal: α2γ2 (<1%)
Others (not present in adults -- relevant in thalassemia)
A RBC that normally exits the bone marrow is still enriched with ribosomes and slightly larger than other RBCs. The ribosomes give it a blueish color on a Wright Giemsa stain and special stains (Methylene blue for example) will be positive and allow clear idenfication of reticulocytes. Reticulocytes last for 24 h in the periphery before they become indistinguishable from other mature RBCs.
When the marrow is stressed because of an increased erythroid production requirement, reticulocytes may be released in to the periphery a little earlier and may thus persist in the periphery for a longer period.
corrected reticulocyte count
Retic ct x patient Hct/normal Hct. Correction only necessary when Retic Ct. is reported as a percentage of all RBCs.
reticulocyte proliferation index
A 2nd correction is due to the prolonged survival of retics in the periphery when the marrow is stressed (see above): Divide corrected retic ct by:
1 if Hct is normal (45%)
1.5 if Hct is 35%
2 if Hct is 25%
2.5 if Hct is 15%
For example if the Hct 25% and the retic ct is 4% the corrected retic count is 4 x 25/40 = 2.5 And the reticulocyte proliferation index is 2.5/2 = 1.25%
Ddx for normocytic anemia
• hemolytic anemias
• Anemia of chronic disease
• Anemia of chronic renal failure
• Aplastic anemia (drugs, chemotherapy, radiation, toxins (benzene), alcohol)
Ddx for microcytic anemia
- Iron deficiency (common)
- Thalassemia (common, except in people of Germanic, Slavonic, Baltic, Native American, Han Chinese, Japanese descent)
- Anemia of chronic disease (uncommonly microcytic) - Sideroblastic anemia (uncommon; acquired forms more often macrocytic)
- Lead poisoning (uncommon)
- Hemoglobin E trait or disease (common in Thai, Khmer, Burmese,Malay, Vietnamese, and Bengali groups)
Hepcidin and Iron Regulation
Hepcidin puts on a “brake” on the iron uptake system: it signals that the body has sufficient iron and more might lead to toxicity. Iron overload is to be avoided because of its toxicity. Hepcidin inhibits GI uptake through the mucosa, but also inhibits export of iron from cells (intestinal mucosa, macrophages, hepatocytes, etc).
When there is anemia, hepcidin needs to be turned off! The hepcidine gene (HAMP) is transcriptionally regulated as follows: (-) low PO2, low erythropoiesis, low EPO (+) high amounts of serum iron and high transferrin sat (+) high amounts of cellular iron (-) low O2 > HIF1a > inhibiton of hemojuvelin, a coreceptor for cellular iron stores (+) inflammation, cytokines (IL-1, IL-6)
Ddx for macrocyic anemia
- Folate deficiency (common)
- Vit B12 deficiency (common)
- Myelodysplastic syndromes (not uncommon, especially in older individuals)
- Hypothyroidism (rare)
neuro consequences of B12 deficiency
Severe B12 deficiency causes progressive neuropathy of peripheral sensory nerves due to degeneration of the posterior and lateral columns - usually tingling in feet
Due to increased D-adenosyl homocysteine and reduced S-adenosyl methionine in nervous tissue resulting in defective methylation of myelin.
Ddx for pancytopenia
1. Drugs: chloramphenicol, phenylbutazone, anticonvulsants, sulfonamides, gold, chemotherapy
2. Toxins: ethanol, benzene, insecticides, solvents
3. Infections: hepatitis, EBV, influenza
4. Radiation exposure
5. Immune disorders
7. Neoplastic disorders replacing the bone marrow parenchyma: acute leukemia, chronic leukemia, malignant lymphoma, multiple myeloma, metastatic carcinoma, sarcoma.
8. Disorders/therapy causing bone marrow fibrosis: agnogenic myeloid metaplasia, metabolic bone disorders, endocrine abnormalities, post-chemotherapy, post-toxin
9. Miscellaneous disorders: storage diseases, other histiocytic disorders, angioimmunoblastic lymphadenopathy, mast cell disease.
significance of ringed sideroblasts and vacuoles in the erythroblasts
Sideroblastic changes: accumulation of siderotic granules in the mitochondria surrounding the nucleus, gives the characteristic ringed appearance on Prussian blue stains. They are thought to result from defective iron utilization for hemoglobin synthesis. It can be a toxic effect of alcohol. They can reverse within days to weeks of alcohol withdrawal. The role of pyridoxine deficiency in producing these changes remains controversial. The vacuoles in the erythroblasts are a non-specific sign of marrow toxicity
anemia in alcoholics
(1) toxic suppression: hypocellular bone marrow with vacuolated erythroid precursors; alcohol is toxic to hematopoeitic precursors
(2) chronic disease: normocytic, normochromic anemia; failed erythropoeisis, decreased iron for hemoglobin synthesis
(3) folate deficiency: megaloblastic anemia with oval macrocytes and hypersegmented neutrophils; decreased ingestion, impaired absorption and antagonistic action of alcohol against folate
(4) iron deficiency: hypochromia present, microcytosis often masked by concurrent folate deficiency; decreased ingestion of iron and chronic blood loss via the gastrointestinal tract
(5) decreased red blood cell survival: target cells, spherocytes, spur cells, microspherocytes; extracorpuscular red blood cell defects due to congestive splenomegaly and portal hypertension; lipoprotein abnormalities causing target and spur shapes; severe hypophosphatemia
(6) abnormal iron metabolism: ringed sideroblasts in bone marrow; complex etiology; caused in part by decreased functional pyridoxine and inhibition of enzymes involved in hemoglobin synthesis
(7) hemodilution: portal hypertension associated with fluid overload leading to dilutional anemia
(8) chronic blood loss.