Lecture 4: Anemias - Disorders of Iron and Heme

100 vocabulary-based flashcards covering the definition, clinical findings, lab diagnosis, mechanisms, and specific types of anemias including IDA, ACD, and sideroblastic anemias.

Anemia (Functional Definition)

Decreased oxygen carrying capacity of blood due to either insufficient Hb or abnormally functioning Hb.

Anemia (Operational Definition)

Reduction in the Hb content of blood caused by a decrease in RBC count, Hb concentration, and HCT below the reference interval for individuals based on age, sex, and race.

Pagophagia

Cravings for unusual substances like ice, which is a helpful clue in diagnosing Iron deficiency anemia (IDA).

Classical physical symptoms of anemia

Fatigue and shortness of breath.

Skin findings in anemia

Presence of petechiae.

Eye findings in anemia exam

Pallor, jaundice, or hemorrhage.

Mouth findings in anemia exam

Mucosal bleeding.

Heart findings in anemia exam

Cardiac murmurs and arrythmias.

Hepato-splenomegaly

Enlargement of the liver and spleen which may be found during a physical examination for anemia.

Tachycardia in anemia

A vital sign indicating a rapid Hb fall, whereas heart rate may be normal in compensated anemia.

Moderate anemia Hb level

$$7-10\,g/dL$$

Moderate anemia clinical signs

May cause pallor; may not be clinically apparent if onset is slow, depending on age and cardiovascular state.

Severe anemia Hb level

$$<7\,g/dL$$

Severe anemia clinical symptoms

Tachycardia, hypotension, and association with volume loss.

Ineffective erythropoiesis

A mechanism where defective erythroid precursors undergo apoptosis in the bone marrow before maturing into reticulocytes.

Examples of ineffective erythropoiesis

Megaloblastic anemia, thalassemia, and sideroblastic anemia.

Insufficient erythropoiesis

A mechanism where the number of erythroid precursors produced in the BM is low, resulting in low RBC production.

Factors in insufficient erythropoiesis

Iron, EPO, antibody, infection, leukemia, or metastatic tumor.

Causes of hemolysis

Intrinsic defects in RBC membrane, enzymes, or Hb structure, or extrinsic factors like antibodies, prosthesis, and infections.

RBC indices

MCV, MCH, MCHC, and RDW.

Clinical significance of Reticulocyte count

An important tool to assess the bone marrow’s ability to increase RBC production in response to anemia.

Reticulocyte RI for an adult

$0.5-2.5\%$, or $20$ to $115 \times 10^{9}/L$.

Absolute reticulocyte count formula

$$\text{Absolute reticulocyte count } (\times 10^{9}/L) = [\text{reticulocytes (\%)}/100] \times \text{RBC count } (\times 10^{12}/L)$$

Corrected reticulocyte count formula

$$\text{Corrected reticulocyte count (\%)} = \text{reticulocytes (\%)} \times \frac{\text{patient’s HCT (\%)}}{45}$$

Reticulocyte production index (RPI) formula

$$\text{RPI} = \frac{\text{corrected reticulocyte count}}{\text{maturation time}}$$

RPI value in anemic patients

$$>3$$

Mean cell volume (MCV) formula

$$\text{MCV (fL)} = \frac{\text{HCT (\%)} \times 10}{\text{RBC count } (\times 10^{12}/L)}$$

MCV Adult Reference Interval

$$80–100\,fL$$

Mean cell hemoglobin (MCH) formula

$$\text{MCH (pg)} = \frac{\text{HGB (g/dL)} \times 10}{\text{RBC count } (\times 10^{12}/L)}$$

MCH Adult Reference Interval

$$26–32\,pg$$

Mean cell hemoglobin concentration (MCHC) formula

$$\text{MCHC (g/dL)} = \frac{\text{HGB (g/dL)} \times 100}{\text{HCT (\%)}}$$

MCHC Adult Reference Interval

$$32–36\,g/dL$$

Maturation time for HCT 15-24%

$$2.5\,days$$

Maturation time for HCT < 15%

$$3\,days$$

Maturation time for HCT 25-34%

$$2\,days$$

Maturation time for HCT 35-39%

$$1.5\,days$$

Normocyte

A red blood cell of normal size and shape.

Stomatocyte

An RBC with a mouth-like or slit-like area of central pallor.

Drepanocyte

A sickle-shaped red blood cell.

Elliptocyte

An oval or cigar-shaped red blood cell.

Schistocyte

A fragmented red blood cell resulting from physical damage.

Spherocyte

A spherical red blood cell lacking central pallor.

Acanthocyte

Also called a spur cell; an RBC with irregular spikes on the surface.

Echinocyte

Also called a burr cell; an RBC with blunt, evenly spaced projections.

Dacryocyte

A tear-drop shaped red blood cell.

Codocyte

A target cell with a bullseye appearance.

Degmacyte

A bite cell where a portion of the cell has been removed.

Basophilic stippling

Presence of small blue granules (ribosomal RNA) distributed throughout the RBC.

Polychromatic RBC

A young RBC that appears slightly blue-gray on Wright stain, representing reticulocytes.

Howell-Jolly (HJ) bodies

Nuclear remnants containing DNA within the RBC.

Siderotic granules

Iron-containing granules visible in red cells using iron stains like Prussian blue.

Ring sideroblast

An erythroid precursor in the BM with iron-containing mitochondria encircling at least one-third of the nucleus.

Pappenheimer bodies

Iron-containing inclusions in RBCs visible on a Wright-stained peripheral blood smear (PBS).

Microcytic anemia definition

Anemia characterized by an MCV $<80\,fL$.

Macrocytic anemia definition

Anemia characterized by an MCV $>100\,fL$.

Hypochromic anemia definition

Anemia often associated with microcytosis where MCHC is $<32\,g/dL$.

Examples of Microcytic Anemia

Iron deficiency anemia, Thalassemia, Sideroblastic anemia, and Anemia of chronic inflammation.

Megaloblastic macrocytic anemia causes

Vitamin $B_{12}$ or folate deficiency.

Non-megaloblastic macrocytic anemia causes

Chronic liver disease, alcohol abuse, or bone marrow failure.

Pathophysiologic: Disorders of DNA synthesis

Megaloblastic anemia.

Pathophysiologic: BM failure

Aplastic anemia.

Examples of intrinsic RBC membrane defects

Hereditary spherocytosis.

Examples of intrinsic RBC enzyme deficiencies

$G6PD$ deficiency.

Immune mechanisms of destruction

WAIHA, PCH, CAD, and HDFN.

Non-immune MAHA examples

DIC, TTP, and HUS.

Three iron compartments

Storage (ferritin), transport (transferrin), and functional (Hb and myoglobin).

IDA Pathogenesis Stage 1

Storage iron depletion; ferritin decreases, while Hb and serum iron remain normal.

IDA Pathogenesis Stage 2

Transport iron depletion (Latent Iron Deficiency); serum iron decreases and TIBC increases, while Hb remains normal.

IDA Pathogenesis Stage 3

Functional iron depletion (Iron Deficiency Anemia); Hb decreases alongside lowered ferritin and serum iron.

High risk groups for IDA

Menstruating women, pregnant women, and breastfeeding women.

Low risk groups for IDA

Men and postmenopausal women due to enough iron storage.

Necator americanus and Ancylostoma duodenale

Hookworms that cause intestinal infection leading to chronic blood loss and IDA.

IDA Screening tests

Abnormal CBC and blood smear abnormalities.

IDA Diagnostic tests

Serum iron, Total iron-binding capacity (TIBC), transferrin saturation, and ferritin.

Total Iron Binding Capacity (TIBC) formula

$$\text{TIBC} = \text{Unsaturated Iron Binding Capacity (UIBC)} + \text{Serum Iron (S.I.)}$$

Transferrin Saturation percentage formula

$$\%\text{ Transferrin Saturation} = \left(\frac{\text{Serum Iron Concentration}}{\text{TIBC}}\right) \times 100$$

Soluble transferrin receptor (sTfR) in IDA

Levels are increased in iron deficiency anemia.

Free erythrocyte protoporphyrin (FEP)

A specialized test used to evaluate heme synthesis; levels increase when iron is unavailable.

Anemia of Chronic Inflammation (ACD) Etiology

Underlying conditions involving chronic inflammation.

Impaired ferrokinetics in ACD

Iron stores are abundant but sideropenia (low serum iron) develops because iron cannot be released.

ACD degree of anemia

Mild anemia with Hb usually $8$ to $10\,g/dL$.

ACD Classification

Usually normocytic and normochromic, though microcytosis and hypochromia can occur with co-existent IDA.

ACD Iron studies profile

Low serum iron, low TIBC, and normal or low transferrin saturation.

sTfR in Anemia of Chronic Inflammation

Remains normal because intracellular iron is sufficient.

Sideroblastic Anemias primary feature

Abnormality in heme synthesis caused by interference in the incorporation of iron into protoporphyrin.

Sideroblastic Anemia iron studies

High serum iron, high ferritin, high transferrin saturation, and abundant iron in BM.

Lead poisoning sources

Wall painting in old houses built before the $1970s$; toddlers are mostly vulnerable.

Lead interference with ALA dehydratase

Inhibits the conversion of aminolevulinic acid (ALA) to porphobilinogen (PBG), leading to ALA accumulation.

Lead interference with ferrochelatase

Inhibits the incorporation of iron into protoporphyrin IX, causing iron and protoporphyrin to accumulate in mitochondria.

Treatment for lead poisoning

$CaNa_2EDTA$ and/or dimercaprol.

Serum ferritin in IDA

Decreased ($\downarrow$).

Serum ferritin in Anemia of Chronic Inflammation

Increased or Normal ($\uparrow/N$).

TIBC in Anemia of Chronic Inflammation

Decreased ($\downarrow$).

TIBC in Iron Deficiency Anemia

Increased ($\uparrow$).

FEP/ZPP in Lead Poisoning

Markedly increased ($\uparrow$).

Basophilic stippling in lead poisoning

A laboratory feature characterized by blue-staining granules in RBCs on a blood smear.

BM iron staining (Prussian blue) in IDA

No stainable iron.

Sideroblasts in BM for IDA

None.

Sideroblasts in BM for Sideroblastic Anemia

Increased, specifically ring sideroblasts.

Hb A2 significance in thalassemia minor

Levels are increased ($\uparrow\,Hb\,A_2$) as a special diagnostic test.