Blood And Lymph- Hypochromic Microcytic Anemia By Turnicky

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Blood and Lymph- Hypochromic Microcytic Anemia by Turnicky

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Blood and Lymph- Hypochromic Microcytic Anemia by Turnicky

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Hypochromic Microcytic Anemia is

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-Deficiency in either heme or globin chain synthesis resulting in decreased hemoglobin production resulting in hypochromic/microcytic anemia
-Deficiency in heme synthesis: Iron deficiency
-Deficiency in globin synthesis: Thalassemia

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What are 2 causes of decreased hemoglobin production?

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-defective synthesis of heme secondary to decreased iron availability (iron deficiency)
-hypochromic/microcytic
-abnormal iron utilization (anemia of chronic disease)
-normachromic/normacytic

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Disorders of heme synthesis:
Sideroblastic Anemias.. 3 types

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Acquired idiopathic (Myelodysplasia)
-macrocytic

Acquired toxic
-(lead –microcytic/normo, alcohol-macrocytic)

Hereditary (x-linked or autosomal)
-Rare
-Often macrocytic

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Hypochromic Microcytic Anemia Causes: What are the disorders of iron metabolism (iron deficiency)?

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-Dietary
-Blood loss
-Increased requirements with growth or pregnancy
-Malabsorption
-Neoplasia

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What are the disorders of globin synthesis?

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Thalassemia syndromes:
-Alpha thalassemia
-Beta thalassemia

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What are the causes of Iron Deficiency Anemia per age?

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Infants and children:
Inadequate intake; Growth spurts with increased iron requirements

Pre-menopausal women:
Menstrual blood loss; Pregnancy with inadequate intake

Adult men and post-menopausal women:
Blood loss due to tumor, peptic ulcer , gastrointestinal or genitourinary bleeding; Malabsorption; Gastric surgery; Intestinal Malabsorption syndromes

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Pica

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eating of clay, dirt and starch. body is craving metal proteins for heme synthesis if iron isn't there.

rare clinical feature of IDA.

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concavity of the nails

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Kiolonychia

clinical feature of IDA.

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Ferritin is the

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-Major storage from of iron, predominately in BM, spleen and liver
-Water soluble and can not be visualized by microscopy and does not stain with iron stains.
-Synthesis is directly proportional to total iron stores

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Hemosiderin

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-Heterogeneous iron-protein complex
-The long term storage form of iron
-Water insoluble, thus stains blue with iron stain (Prussian blue)
(as compared to ferritin which is water soluble so you can't see it on stains)

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What is the carrier protein of iron called? What is needed for iron absorption?

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transferrin. mediates iron exchange between tissues; recycled.

For Iron absorption, you need the appropriate gastric acidity and morphology of duodenum
-Released to blood stream, oxidized to Ferric form (+3) and taken up by transferrin for release to red cell precursor or stored (ferritin/hemosiderin)

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Iron Absorption Impairment: alterations in the gastric environment and duodenum...

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Alterations of the gastric environment
-Achlorhydria
-gastrectomy

Alterations of the duodenum
-Crohn’s disease
-Celiac disease

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What do RBCs look like in IDA? What is the reticulocyte count in true hypoproliferative anemia?

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-Insufficient iron results in rbcs that are small and pale (MCV, MCHC) or hypochromic microcytic.

-If a true hypoproliferative anemia expect a low reticulocyte count.

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What are the four stages of IDA development?

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1. Depletion of Fe stores, decreased ferritin, no anemia
2. Increased transferrin levels, no anemia
3. Fall in serum Fe, no anemia (notice ferritin falls before serum Fe)
4. Initial N/N anemia followed by classic Hypochromic/Microcytic anemia.

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If you have increased platelets and an occult bleeding site, this is one of the first signs...

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that you may be dealing with an occult cancer, usually a primary colon cancer. the reason for this is the platelets are elevated because there is chronic bleeding

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TIBC is always _____ in iron deficiency anemia.

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increased. If there's no iron there, the transferrin receptors are vacant and the lab throws in iron into the test. so if there's a lot of iron bound to the vacant receptors, the TIBC is elevated. Or the iron concentration necessary to bind those sites is going to be elevated.

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What does serum iron measure?

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the transferrin-bound iron. all iron transported in the plasma is bound to the specific iron-binding protein transferrin.

TIBC is the Fe concentration necessary to saturate the iron-binding sites of transferrin

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What is % saturation?

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-Saturation of transferrin is calculated as a %
-% Transferrin Saturation = Serum Iron / TIBC
-Normal transferrin Saturation is 30%

The serum iron and % sat. is low in both IDA and microcytic ACD, but usually much more so in IDA (<10% in IDA; >10% in ACD)

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**How does the TIBC change in iron deficiency anemia? How about TIBC in anemia of chronic disease?

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increased in IDA

decreased in ACD

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What is often a first indication of developing IDA?

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Decreased serum ferritin in all stages.

-Serum Ferritin is an acute phase reactant (may be falsely elevated if there is ongoing inflammation)
-Increased in ACD, unless complicated by iron deficiency anemia
-Increased in iron over-load conditions such as sideroblastic Anemia and hemochromatosis

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What is free erythrocyte protoporphyrin? When FEP is elevated, what can we suspect?

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When insufficient iron is available for the developing red cell, excess protoporphyrin that was destined to be converted to heme accumulates as FEP.

Elevations of FEP in:
-Iron deficiency
-Conditions associated with a block in iron utilization such as ACD, lead poisoning and sideroblastic anemia.

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Free Erythrocyte Protoporphyrin or Zinc Protoporphyrin can be used as a screening test to differentiate types of hypo-micro anemia. What do these values look like in IDA, ACD, lead poisoning, thalassemia?

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IDA: Increased
ACD: Increased
Lead Poisoning: Increased
Thalassemia: Normal**

*there's no abnormality in heme synthesis, there's an abnormality in globin synthesis, therefore thalassemia levels will be normal.

omg won't be tested on, but this is practical. thanks for wasting my time.

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Lab Summary: Iron Deficiency

Serum ferritin quantitation
Serum Iron
TIBC
% Saturation

increased or decreased?

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Serum ferritin quantitation (decreased)
Serum Iron: (decreased)
TIBC: (Increased)---always**
%Saturation: (decreased)

Free erythrocyte protoporphyrin (increased)
Zinc protoporphyrin (increased)
more cost effective.
**use these in a differential to exclude thalassemia

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What is the normal ratio of erythroid to myeloid cells?

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1 erythroid to 3 myeloid cells.

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Anemias due to Abnormal Iron Metabolism. 2 types.

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1. Sideroblastic anemia (myelodysplasia)- block in the incorporation of iron into the protoporphyrin ring to form heme
2. Anemia of chronic disease- defective iron reutilization

*end result for either one is a lack of iron for Hb synthesis within the developing red cell within the setting of:
-Increased storage hemosiderin (storage form of iron) in spleen, liver & BM
-Elevated serum ferritin (storage form of iron)

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Sideroblastic Anemia

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1. Hereditary; Sex-linked and Autosomal recessive
2. Acquired
-Refractory Anemia with ringed sideroblasts
-Secondary to drugs (alcohol), toxins, lead
-Secondary to malignancy
-Leukemia, lymphoma, multiple myeloma suggesting a stem cell disorder

*Diverse biochemical and pathogenic mechanisms, but all characterized by:
-Increase in total body iron
-Presence of ringed sideroblasts
-Anemia

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Hereditary Sideroblastic Anemia

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Heme enzyme abnormality:
-Decreased erythopoietic delta aminolevulinic acid synthetase (ALA synthase)
-Uncommon compared to acquired Sideroblastic Anemia

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RARS

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“Refractory Anemia with Ringed Sideroblasts” (Myelodysplastic Syndrome); an acquired sideroblastic anemia.
-Abnormality of mitochondrial Fe metabolism
-10% terminate in acute myelogenous leukemia
-A stem cell disorder

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Acquired Sideroblastic Anemia, Secondary to drugs/toxins... which are the main players.

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Interference with the activity of heme enzymes
-alcohol*
-lead*
-Chemotherapeutic drugs
-Antituberculosis drugs
-Chloramphenicols

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Lead Poisoning

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Plumbism (mental concentration disorders, low IQ, impaired development)
Abnormality of heme synthesis
-Inhibit Delta aminolevulinic acid dehydrase
-Inhibit ferrocheletase
-Increased ZPP or FEP
Direct lead measurements (CDC)
Microcytic hypochromic anemia is NOT characteristic of elevated lead levels in children
-Likely a complication of Iron Deficiency
-Or co-existence of thalassemia trait.

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Anemia of Chronic Disease

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-In chronic infections, inflammatory disorders, neoplastic disorders
-Not related to any nutritional deficiency.
-Anemia with renal, endocrine or hepatic insufficiency are usually excluded from ACD.
-Second only to iron deficiency anemia in frequency (exception Tertiary care centers)
-Results from a normal physiologic immune response to protect the host from microorganisms and/or tumor cells
-Cytokines release results in iron deprivation to proliferating cells (organisms/tumor cells)
-When this physiologic response is sustained ACD is the consequence

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Cytokines and ACD

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-Inhibitory cytokines (TNF-B, IL-1/6, INF-gamma, hepcidin) adversely impact erythropoiesis
-Cytokines effect disturbances in iron homeostasis
-Shunting of iron into macrophages compounded by decreased macrophage release of iron (impaired iron recycling)
-Inhibition of erythroid progenitor cell proliferation and differentiation
-Decreased erythrocyte survival time

Associations include chronic inflammatory disorders and chronic infection (viral, bacterial)

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What do you see in the iron studies of ACD?

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-Increased ferritin, a storage form of iron, (remember low in IDA); ferritin is a measure of total body iron stores
-Decreased serum iron (defect in recycling; Fe trapped in macrophage)
-Decreased % saturation
-Decreased TIBC always (and always elevated in IDA)
-Increased FEP or ZPP (doesnt help)

-Usually Normochromic Normocytic (normal MCV, MCH, MCHC)
-Long standing may be microcytic
-Decreased “corrected” Reticulocyte Count non-corrected usually in normal range
-Normal RDW (little anisopoikilocytosis)

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What do you see in the bone marrow examination of ACD?

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-Normal morphology, without erythroid hyperplasia.

seen on BM Iron Stain for hemosiderin:
-Increased storage iron in macrophages
-Decreased sideroblastic iron

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Multifactorial AnemiaAnemia in Neoplasia

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-Anemia of chronic disease
-Blood loss
-Nutritional deficiencies (iron)
-BM replacement by tumor/fibrosis
-BM suppression by chemotherapy
-Chemotherapy-related myelodysplasia
-Hypersplenism
-Hemolytic anemias
-Microangiopathic (DIC),
-Autoimmune (autoantibodies in B cell tumors)

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Anemia in HIV

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-Anemia of chronic disease
-BM suppression by virus (HIV-1, or parvo)
-Ineffective heme regulation (T cell defects)
-Secondary to infections and neoplasms
-Drug treatments
-Autoimmune
-Nutritional
-Advanced serous fat atrophy from inanition

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Anemia in Chronic Renal Disease

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-Multifactorial, but shares characteristics of ACD
-Generally Normochromic/Normocytic
-The primary mechanism is decreased erythropoiesis due to decreased or nonfunctional erythropoietin (EPO)
-Bone Marrow shows erythroid hypoplasia

Patients on hemodialysis:
-Become folate deficient
-Prone to fluid overload which can further decrease the hematocrit
-Red cell toxins introduced from dialysis
-(aluminum, copper, chlorine, formaldehyde)

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Anemia associated with endocrine disease. who is this common in?

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common in patients with DM and hypothyroidism

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Anemia Associated with Liver Disease.. is associated prototypically with...

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-Prototypic liver disease linked to alcoholism and anemia is very common
-Anemia is mild to moderate, but may be severe
-Multifactorial

-Anemia of Chronic Disease (hepatitis)
-Direct toxic effects of alcohol
-Nutritional deficiencies
-Folate and iron deficiency
-B12 deficiency with pancreatitis

-The typical morphologic feature is that of macrocytic anemia, however, these changes are often masked by concurrent RBC abnormalities from iron deficiency.