POD 3450 Hematology - RBCs

Lectures 2.1 -

What cytokine is responsible for red blood cell production? What is the source of this cytokine? What is the stimulus that causes release?

erythropoietin (Epo); kidneys; hypoxia, cells sensing low O2 tension

At what progenitor stage do red blood cells stop dividing and start differentiating?

Rubricytes

What is the longest living cell in circulation? What differences are there between species?

Red blood cells; smaller species have shorter lifespans for RBCs

What happens when a RBC reaches the end of its lifespan?

When no longer able to perform their duties, RBC are phagocytized by macrophages in the spleen

What tube is used for a complete blood count (CBC)?

EDTA lavender top tubes

Hct stands for:

Hematocrit

Hb stands for:

Hemoglobin

MCV stands for _______. What terms are used to describe anemia?

Mean corpuscular volume; high = macrocytic, normal = normocytic, low = microcytic

MCHC stands for _______. What terms are used to describe anemia?

Mean corpuscular hemoglobin concentration; high = hyperchromic, normal = normochromic, low = hypochromic

Reference intervals are based on:

the average mature animal; meaning that even a number within reference intervals may not be “normal”

Term used to describe lipid build up in hematocrit tube:

Lipidemia

Term used to describe hemoglobin build up in hematocrit tube:

Hemoglobinemia

Term used to describe bilirubin build up in hematocrit tube:

Bilirubinemia

If you saw autoagglutination in a tube or on a slide, it would indicate:

antibody/antigen complex → immune mediated hemolytic anemia

What is a rouleaux pattern in blood smear?

RBCs clumped in a line

What is the difference visually between a rouleaux pattern and agglutination?

Agglutination groups RBC in grape-like clumps, rouleaux groups RBC in lines

What might it mean to see a rouleaux pattern on the blood smear of a dog or ruminant?

indicates increased protein (normal in horses and cats)

If unclear whether rouleaux or agglutination is present, what should be added to the blood slide? What does this do?

saline; saline interrupts the rouleaux pattern but not the antibody/antigen clumping present in agglutination

What cells are present in a regenerative anemia?

Polychromatophils/reticulocytes (name stain dependent)

What is a poikilocyte?

a general term for shape changes in RBCs

What is crenation? What can these cells mask?

RBCs with spiky projections; mask acanthocytes with similar shape changes

What is an acanthocyte? What diseases might these indicate?

RBCs with more round-ended projections; liver or spleen disease

What is a Howell-Jolly body? What disease might these indicate?

it is the remnant of the nucleus; disease involving the spleen, indicating that the spleen is too busy to destroy cells containing HJ bodies (cats may have occasionally, even without disease)

What is a target cell? What disease might might these indicate?

cells with a circle at the center; indicator of liver disease

What is a hypochromic erythrocyte? What disease might these indicate?

cells with extreme central pallor (dogs have central pallor normally but this is more significant); Iron deficiency

What is a spherocyte? What disease might these indicate?

Smaller rounded RBCs, most notably in dogs where they differ from normal RBCs which have central pallor; indicator of IMHA, may also be seen in transfused blood due to storage method

What is a schistocyte? What diseases might these indicate?

RBCs that have been fragmented, due to increased turbulence or caught on fibrin in vessels; often indicator of disseminated intravascular coagulopathy (DIC), can also been seen in relation to hemangiosarcoma

Anemia generally means decrease in:

RBC, Hgb, and Hct; usually decrease together unless very mild

Give 7 possible causes for anemia:

iron deficiency, blood loss, inflammation, neoplasia, endocrine, hemolysis, and renal failure

What are the 2 general pathophysiological mechanisms for anemia?

1. decreased red blood cell production

2. increased red blood loss

What are the 2 general causes for regenerative anemia?

1. Hemorrhage → lost from body (external) or not (internal)

2. Hemolysis → body destroying RBCs

What are the 2 general causes for nonregenerative anemia?

1. Primary marrow disorders

2. Secondary marrow disorders

What is a regenerative anemia generally going to look like on CBC?

• increased polychromasia/reticulocytes

• increased neutrophils, platelets

• increased anisocytosis (shape change), RDW

• increased MCV (macrocytosis)

• decreased MCHC (hypochromia)

Why do we see increased MCV in regenerative anemia?

larger, immature cells are released early, increasing the mean corpuscular volume

Why do we see decreased MCHC in regenerative anemia?

polychromatophils are being released immaturely and don’t have enough hemoglobin, decreasing the overall hemoglobin in RBCs

Why do we see increased anisocytosis and RDW in regenerative anemia?

immature cells are being released from the bone marrow into circulation are larger than mature RBC

What might changes in protein mean in a regenerative anemia?

Normal or high: suspect hemolysis (because blood is staying in the body)

Low: suspect hemorrhage (because blood is being lost from the body; may not be as clear if internal hemorrhage, as protein not lost and may be reabsorbed)

Why does hydration status affect significance of total protein?

dehydration will increase concentration of the protein in the blood

Hemorrhage at a single site may indicate:

local trauma/problem

Hemorrhage at multiple sites may indicate:

issues with platelets and clotting factors

What are some causes of acute hemorrhage?

• trauma

• thrombocytopenia (must be severe to have spontaneous bleeding)

  • causes include: immune, infectious, drug-related, DIC, or bone marrow failure

• Coagulation factor deficiency

• Neoplasia (where cytokines stop clotting, masses enter vessels, ex hemangiosarcoma)

What are the stages of chronic external hemorrhage?

• Iron deficient erythropoiesis

  • RBC still made, but struggling to make hemoglobin due to low iron levels

• Iron deficient anemia

  • poorly to no longer regenerative anemia, too little iron to make more RBCs

What on a CBC and blood smear might indicate iron deficient erythropoiesis?

• MCHC (hypochromic) and MCV (microcytic) decreased because of decreased hemoglobin content

• Additional mitoses to try to divide into smaller cells with enough hemoglobin

• Delayed nuclear degeneration, staying in the bone marrow longer to make more hemoglobin

• RBC on slide have large, pale center (larger than central pallor in dogs would usually appear)

What on a CBC and blood smear might indicate iron deficient anemia?

• poor regenerative to lack of regenerative ability

• very low MCHC (hypochromic) and MCV (microcytic)

• increased anisocytosis (shape change) and RDW (changes both with larger and smaller RBCs)

• increased red cell fragility (resulting in shape change and fragments)

• lack of marrow or serum iron

What is a Heinz body? When might this change be seen?

small projection on RBC; often seen as result of oxidative injury, for example from onion/garlic in dogs, red maple in horses, or heavy metals

Small basophilic inclusion in a cat RBC, “rods and rings,” might indicate what bacterial infection?

M. hemofelis

How does a primary bone marrow disease usually present?

generalized depression of multiple cell lines, multiple cytopenias to pancytonpenia

What are a few reasons for nonregenerative anemia with depression of multiple cell lines?

• hypoplasia/aplasia of bone marrow

• myelodysplasia

• leukemia

What are some causes of hypoplasia/aplasia of bone marrow?

• infectious (ex. FeLV, ehrlichiosis)

• drug/chemical toxicity (ex. estrogen, phenobarbital, griseofulvin, cephalosporins, chemo-therapeutic agents)

• Immune-mediated (going after mature or progenitor cells)

Reasons for estrogen toxicity:

• exogenous administration (ie for cycle manipulation)

• Sertoli cell tumors (in cryptorchid males with testicle left within the body)

• Persistent estrus in ferrets

• Polycystic kidney (rarely)

What is myelodysplasia, aka myelodysplastic syndrome?

Hematopoietic neoplasm, resulting in abnormal maturation of one or more cell line

What are the criteria for diagnosis of myelodysplasia?

• peripheral blood cytopenia(s)

• normal to hypercellular bone marrow (cells not leaving the marrow though, resulting in cytopenia; but more active than expected for cytopenia)

• dysplastic (abnormal maturation) changes

Leukemia (aka lympho/myeloproliferative disease) definition:

tumor of developing red cells, white cells (not lymphocytes), or platelets; replaces normal marrow with neoplastic cells

What is myelofibrosis? What are some possible causes?

increased fibrocytes/collagen in the bone marrow, replacing marrow, end-stage lesion; possibly related to FeLV, neoplasia, chronic hemolytic anemia, marrow necrosis, or idiopathic

What cell might you see in circulation in myelofibrosis?

Dacryocyte (tear-drop shaped RBC)

How might you tell that a nonregenerative anemia is primary vs secondary bone marrow disease?

• primary: multiple cytopenias to pancytopenia

• secondary: RBC decreased, but WBC and platelets are normal to increased.

What are some causes of secondary bone marrow disease?

• chronic inflammation

• endocrine disease

• FeLV related

• metastatic neoplasia

• renal disease

Anemia of chronic disease:

• due to inflammation (infectious or not) & neoplasia

• often due to poor iron availability due to suppressive cytokines (iron sequestered in macrophages to keep from infectious agents)

• usually mild to moderate

• normocytic, normochromic nonregenerative anemia

Anemia of endocrine disease:

Deficiency in one of the hormones required for erythropoiesis; usually mild as it is not effecting EPO production. Hormones include:

• cortisol

• androgens

• thyroxine

• growth hormone

Anemia due to FeLV infection:

• can be normocytic of macrocytic

• can cause nonregenerative anemia in 3 different ways

  • anemia of chronic disease due to predisposition to secondary infection

  • myelophthisis from hematologic neoplasia (destruction of bone marrow; primary!)

  • pure red blood cell aplasia (PRCA; hypoplastic changes in

Anemia of chronic kidney disease:

• usually moderate, though can be worse if bleeding or with decrease platelet function

• due to:

  • decreased red cell life span

  • decreased Epo production

  • decreased marrow responsiveness to Epo

What does pure red cell aplasia look like in a hematocrit tube? On a blood smear?

• in hematocrit - almost more platelets than red blood cells

• on smear - chronically, tube appears nearly empty

What is polycythemia? What’s another name for it?

increased RBC, Hgb, and Hct; aka erythrocytosis

What characterizes absolute primary polycythemia?

• absolute - increased RBC mass

• primary - decreased to normal Epo; normal PO₂

What disease is considered absolute primary polycythemia? What might this disease present as?

polycythemia vera (aka a myeloproliferative disease); Hct will be very high, resulting in a thick blood consistency, blood so thick that it cannot easily oxygenate the brain and periphery

What characterizes absolute secondary polycythemia?

• absolute - increased RBC mass

• secondary - increased Epo and low PO₂

What are some possible causes of absolute secondary polycythemia?

cardiopulmonary disease, high altitude, hormone excess, renal masses, paraneoplastic, etc.

What characterizes a relative polycythemia? What are the possible causes?

• relative - normal RBC mass, no change in Epo or PO₂

• causes - dehydration or splenic contraction