Hematology 14: Anemias Pt 2 (Normocytic-Normochromic, Macrocytic)

function: Three Pathophysiological Mechanisms of anemia

production

ability to survive

maturation

Morphology: erythrocyte indices of anemia

MCV - cell size

MCHC - color (hemoglobin content)

Normocytic-Normochromic Anemia

Normocytic normochromic anemia is the type of anemia characterized by RBCs that are of normal size (normocytic) and have a normal hemoglobin content (normochromic)

•Most cases result from impaired RBC production.

Normocytic-Normochromic Anemia etiology

Most cases are consequences of other diseases such as •Chronic disease

•Hemolytic anemia

also depends on anemia type *hypo/hyperproliferative

Hypoproliferative Anemia

corrected reticulocyte count <2%

Hyperproliferative Anemia

corrected reticulocyte count >2%

normocytic-normochromic anemia pathophysiology

decreased rbc count, underlying disease or condition affects RBC production or lifespan

Pathogenesis Varies Depending on the Underlying Causes - 3 listed

Reduced Erythropoietin (EPO) levels:

Impaired kidney function affects the production of EPO

Increased proinflammatory cytokines:

Chronic inflammation (e.g., rheumatoid arthritis, lupus, inflammatory bowel disease) disrupts normal bone marrow function.

Bone marrow Infiltration/Invasion/RBC destruction:

Certain infections can invade the bone marrow or directly destroy RBCs

clinical presentation of normo anemia

same as anemia part 1 - fatigue, pallor and shortness of breath - need to look at underlying disease

reticulocyte count of normo anemia

May vary depending on the specific underlying condition

hemolytic anemias

Hemolytic anemia is a type of normocytic anemia characterized by an increased rate of red blood cell (RBC) destruction, which leads to low hemoglobin levels and increased bone marrow activity to regenerate RBCs.

Hemolysis: definition and lifespan of hemolytic cells

•Premature or increased rate of destruction of circulating RBCs

The lifespan of normal RBCs is approximately 120 days; in hemolytic anemias, it is reduced to 10-15 days

consequences of hemolysis

•Loss of RBCs

•Increased RBC production resulting in reticulocytosis

Damaged RBCs result in microspherocytes (hemolysis sign), elliptocytes, sickle cells, and red cell fragments (hemolysis sign)

Hemolytic anemias etiology

are broadly categorized into hereditary and acquired defects

•Hereditary or inherited: Examples include sickle cell anemia and thalassemia

•Acquired: Examples include autoimmune hemolytic anemia and infections

hemolytic anemia pathophysiology

•Increased RBC destruction, leading to a shorter lifespan

•Bone marrow compensates by increasing RBC production

clinical presentation of hemolysis

•Symptoms of anemia: shortness of breath, weakness, fatigue, etc.

•Jaundice, hematuria, and splenomegaly

•Fatigue and pallor

Hemoglobin Catabolism

•Once taken up by macrophages, RBCs are degraded, releasing hemoglobin.

•The globins are further broken down into amino acids and then used for protein synthesis.

•The Heme group (porphyrin + Fe) gets oxidized, producing biliverdin and releasing Fe.

•Biliverdin is reduced to unconjugated bilirubin.

•Unconjugated bilirubin is released into the plasma, where it binds albumin and is taken up by hepatocytes.

•Once released from heme, Fe has one of 3 fates.

Peripheral blood smear of Hemolytic Anemia

•Poikilocytosis

•Spherocytes

•Sickle cells

•Elliptocyte

bite cells

Hemolytic Anemia reticulocyte count

elavated

Hemolytic Anemia lactate dehydrogenase and indirect bilirubin

increased and increased

types of hemolytic anemia

G6PD Hemolytic Anemia and hereditary spherocytosis

G6PD Hemolytic Anemia

Caused by a deficiency in the enzyme Glucose 6 phosphate dehydrogenase (G6PD).

G6PD is a key enzyme in protection against oxygen radicals.

In its absence, RBCs are vulnerable to oxidative stress and damage, hb acumulation

Inclusion body: Heinz body

G6PD Hemolytic Anemia

cell bitten off, inclusion bodies (heinz) bitten off by spleen

G6PD Hemolytic Anemia

G6PD Hemolytic Anemia

sickle cell anemia

•Homozygous state caused by β-globin gene mutation. HbS

•This mutation causes the Hgb to become abnormally soluble and stable, resulting in SICKLING.

Why does sickling occur?

•HbS aggregates and polymerizes

Factors affecting sickling

Oxygen

HbA & HbF

Factors decreasing sickling

Oxygenation

HbA & HbF

Factors favoring sickling

•HbC & HbS

•Acidosis, fever, infections

sickle cell anemia

clinical features of sickle cell anemia

Symptoms appear after 6 months as HbF is protective in the first 6 months of life.

•Chronic hemolysis – anemia

•Ischemic tissue damage resulting from occlusion of small blood vessels.

•Chronic hyperbilirubinemia- Jaundice

what is Sickle Cell “CRISIS

it is a sickle cell event where cells undergo sickling

what types is sickle cell crisis affected

Vasoocclusive/Pain crisis

aplastic crisis (bone marrow)

hemolytic crisis

Vasoocclusive/Pain crisis:

Episodes of hypoxic injury and infarction associated with severe pain in the affected region. The most commonly involved sites are the Bone, lungs, liver, brain, spleen, and penis.

what organs do sickle cell anemia affect (

Chronic Organ Damage

Spleen – Initially splenomegaly, Gradual loss of splenic function due to infarct- AUTOSPLENECTOMY (after overuse of spleen)

Bone - Osteomyelitis

Kidney – Renal infarcts/papillary necrosis, might need kidney transplant

Skin - Ulcers

Heart – Ischemia , cardiomegaly after long time of low o2 CCF due to long standing anemia