Erythrocytes Flashcards
What is an Erythron?
- All erythroid cells
- includes mature erythrocytes circulating in blood
- Immature erythroid cells in the bone marrow
What is an Erythrogram?
- A numerical or graphical representation of RBCs as seen in the CBC data
- Morphologic assessment of the RBCs
What is Erythropoiesis?
- The process of RBC production in health there is a balance between production and loss of RBCs
- Erythropoiesis is tightly regulated by what the body needs
What is Anemia?
- A deficiency of RBCs and/or hemoglobin
- In Vet med primarily determined by HCT or PCV
- RBC production < RBC loss
What is Erythrocytosis?
- An increase in RBC mass
- RBC production > RBC loss
What is sHct on the Erythrogram?
- spun Hct or PCV
- Percentage of blood volume occupied by erythrocytes
- reflects RBC mass in periferal blood
- Obtained via centrifugation of microhematocrittubes
What is Hgb on the Erythrogram?
- Blood hemoglobin concentration
- Hgb is intact & lysed with RBCs
- Obtained by spectrophotometry:
- lyse RBCs in blood
- Add reagent to bind Hgb and produce color
- Amount of color = HgB
- Should be ~⅓ the Hct in animals w/ disc-shaped RBCs
- Plasma turbidity (lipemia) can give a false increase in Hgb
What is RBC on the Erythrogram?
- RBC = Erythrocyte concentration in peripheral blood
What is MCV, MCH, and MCHC on the Erythrogram?
- MCV: mean cell volume (avg RBC volume)
- MCHC: mean cell Hgb conc (avg [Hgb] in RBC)
- MCH: mean cell Hgb (avg Hgb content in RBC)
- Changes in the MCV and MCHC for patterns that are associated with different disease processes
What does the MCV indicate?
- Tells us average volume (size) but not the distribution of sizes
- High = Macrocytic
- Normal = Normocytic
- Low = Microcytic
What is Red cell distribution width (RDW)?
- RDW is a quantitative index of RBC size and heterogeneity
- Indicates the degree of variation in RBC size
What is Anisocytosis?
- variability in RBC size
- detected by evaluation of a blood smear or by looking a a graph
What does the MCHC indicate?
- MCHC = ({Hgb] x100) / Hct
- Low = hypochromic
- Normal = normochromic
- High = hyperchromic
- used to classify the type of anemia
How can you tell if a CBC is accurate?
- cHct is calculated
- sHct = spun
- Should be within 3% of each other if handled correctly
- if the difference is >3% there is a mismatch that needs to be explained
What is the morphology of RBCs?
- Most species have a round, bi-concave shape - thinner in the middle than at the edges
- This shows as Central pallor
What are Polychromatophils?
- Occurs in young RBCs
- Released early
- Usually larger and more blue/purple (from RNA)
- Presence/absence of polyhromatophils is important in determining if anemia is regenerative or nonregenerative
- Horses are unique:
- typically do not release polychromatophilic cells
How to determine a polychromatiophilic erythrocyte vs a reticulocyte?
- Cell has polychromasia
- Blood has increased polychromasia
- “polychromatophil”
- Blood has a reticulocytosis
- “reticulocyte”
What is Rubricytosis?
- Nucleated red blood cells (nRBCs)
- Early or inappropriate release from hemic tissue
- Significance:
-
Regenerative anemias – appropriate rubricytosis
- blood loss or hemolysis
-
Nonregenerative anemias w/ or w/out anemia - inappropriate rubricytosis
- Marrow damage - inflammation, necrosis, etc
- Lead poisoning in dogs
- Extramedullary hematopoiesis, splenic contraction, splenectomy
-
Regenerative anemias – appropriate rubricytosis
What is the significance Anisocytosis?
- Anisocytosis - variation in sizes
- Depends on reason for variation of size
- Macrocytes
- incomplete maturation or skipped cell division
- Microcytes
- Decreased volume (also hypochromic)
- Spherocytes
- Normal volume
- Decreased amount of membrane
What is the significance of macrocytosis?
- Macrocyte: Increased diameter, Increased volume
- Usually means increased erythropoiesis
- release larger immature cells
- Increased MCV with anisocytosis due to macrocytosis is the best evidence of increased erythropoiesis & bone marrow response to anemia in equine CBC
How are microcytes made?
- Increased cell divisions during development
- decreased volume (⇣MCV)
- Causes:
- Iron deficiency
- Hepatic insufficiency (portosystemic shunts)
- Breed variations
What do spherocytes look like?
- Lack central pallor
- apparent hyperchromasia
What is Poikilocytosis?
- Variation in shape
- Significance - depends on the type of poikilocyte
- 2 types:
- Echinocyte
- Acanthocytes
What is an Echinocyte?
- Often regularly spaced projections
- Artifact - cell dehydration
- Envenomation (rattle snake)
- Other diseases by not consistently
What is an Acanthocytes?
- Irregularly spaced projections
- Altered lipid metabolism
- Liver disease (cats)
- Hemangiosarcoma (dogs)
What causes the projections on echinocyte/acanthocytes?
Increased cholesterol or phospholipid in outer lipid bilayer
What is a schistocytes
- Fibrin strand that breaks apart erythrocytes
- Occurs in Microangiopathic diseases
- DIC
- hemangiosarcoma
- glomerulonephritis
- myelofibrosis
What are Keratocytes?
irregularly shaped RBCs with a enlarged blister-like vesicle
What are Codocytes?
- Target cells
- Central focus of Hgb surrounded by ring of pallor
- Formation: excess membrane relative to amount of Hgb
What are Heinz bodies?
- Indicate oxidative damage
- Large, membrane bound, aggregates of denatured hemoglobin (sulfhemoglobin)
What are eccentrocytes?
- Fused, unstained, crescent-shaped region of membrane, with a shift of hemoglobin to the opposite side
- Hallmark of severe oxidative damage
- Combination of:
- Direct oxidative injury to membrane
- Force to bring membrane sides together
- Combination of:
What are Pyknocytes?
- Not spherocytes
- different pathophysiology
- Loss of fused membrane portion of eccentrocytes
What is basophilic stippling?
- Formation: ribosomal RNA not degraded
- Significance: regenerative anemia, lead poisoning
What is a Howell-jolly body?
- Nuclear remnant
- Most importantly do not call these parasites
- Significance:
- Low numbers in health
- Regenerative anemia
What are some of the RBC organisms?
- Anaplasma marginale
- Babesia sp.
- Cytauxzoon felis
- Mycoplasma sp. (Haemobartonella sp.)
What do distemper inclusions look like?
- Pink RBC inclusions with Diff quick
- Blue with Modified Wright’s Stain
How are Rouleaux and Agglutination different?
- Rouleaux is a charge attraction
- nonspecific sign of inflammation
- Normal in a horse
- Will separate with added saline
- Agglutination is antibody-related cell bridging
- Used to diagnose Immune mediated hemolytic anemia
- IgG or IgM
- Does NOT separate with added saline
What is the physiology of RBCs?
-
Function: The primary function of RBCs is to carry O2 from the lungs to the tissue
- Also transport CO2 from the tissue to the lungs and buffer H+
- Properties:
- Flexibility: In part due to the flexible membrane and shedding of the nucleus
- Strength: Strong but flexible membrane able to withstand recurrent shear forces involved in blood circulation
- Shape: Biconcavity allows for increased surface area for gas exchange
- Hemoglobin content: Unique to the red cell, hemoglobin is pivotal to the development and oxygen transport ability due to its affinity for oxygen
- Lifespan: Because the mature RBC has no nucleus, the cell cannot divide or repair itself. The lifespan is, therefore relatively short and varies between species
What is RBC deformability?
- Ability to change shape in response to stress AND recover once the stress is removed
- Allows RBCs to move through the circulation without loss of structural integrity and is a major determinant of blood viscosity
- Dependent on:
- structure of the membrane and cytoskeleton
- High surface area to volume ratio
-
Low viscosity cytoplasm
- .33% solution of hemoglobin
- Alterations in the lipid or protein composition of the membrane may result in abnormal red-cell shapes
What are the Red Cell Life spans?
- Mouse - 40 days
- Rat - 65 days
- Cat 75 days
- Dog 120 days
- Human 130
- Cow 140
- Horse 150
What is Erythropoiesis?
- Production of erythrocytes form stem cell to circulating RBC
- Complex process that occurs in the bone marrow
- Most effective, other tissues (spleen) too
- Before a RBC arrives in the blood stream it must develop from a stem cell and progress through a number of stages.
What is the main regulator of erythropoiesis?
- Tissue oxygenation
- Renal peritubular interstitial cells produce erythropoietin (Epo) in response to renal hypoxia
- Anemia
- Poor oxygenation of blood
- Poor renal perfusion
- Renal peritubular interstitial cells produce erythropoietin (Epo) in response to renal hypoxia
What happens when [Erythropoietin] is high?
- Erythroid hyperplasia
- Shortened erythroid maturation time
- Increased hemoglobin synthesis in dividing cells
- Decreased apoptosis of progenitor cells in the bone marrow (CFU-E, rubriblasts, prorubricytes)
What happens when [Erythropoietin] is persistently low
- Erythroid hypoplasia
- RBC production < RBC loss
- Gradual onset of anemia
- Causes:
- Decreased functional renal tissue
- Inflammation
What is the other regulator of erythropoiesis?
- Iron
- A deficiency in iron can result in anemia through impaired red cell production within the bone marrow (causes hypochromasia)
- Iron is at the center of a heme molecule in Ferrous (Fe2 = reduced) state
- reversibly binds oxygen
What is the other regulator of erythropoiesis?
- Iron
- A deficiency in iron can result in anemia through impaired red cell production within the bone marrow (causes hypochromasia)
- Iron is at the center of a heme molecule in Ferrous (Fe2 = reduced) state
- reversibly binds oxygen
What is the rate-limiting step for erythropoiesis?
Hemoglobin concentration
Why is carbon monoxide so dangerous?
200x greater affinity for Hgb than O2
What are the 2 iron pools?
- 25-40% of body iron is in storage
- Stored as:
- Ferritin
- Hemosiderin
How is Ferritin stored?
- A small amount of ferritin can be detected in the circulation
- indirectly reflects how much iron is in the storage pool
- Serum ferritin
- ⇣ in iron deficiency
- ⇡ for many reasons
What is Hemosiderin?
- Stable form of stored iron
- Aggregate of denatured ferritin
- Less readily available for use than ferritin
- Dark grey to black with routine stains
- Prussian blue stain can detect this form of storage iron
- Not seen in the bone marrow of healthy cats
What is Heme synthesis?
- Occurs in RBC precursors
- Can only occur in cells that have mitochondria
- ALA synthase is major rate-limiting enzyme
- Requires Vit B
How does lead poisoning affect heme synthesis?
- Inhibits 4 enzymes in the pathway
- ALA-Synthase
- ALA Dehydratase
- Coproporphyrinogen oxidase
- Ferrochelatase
What happens to Bilirubin in health?
- Product of hemoglobin breakdown
- Senescent red cells are phagocytized by macrophages
- Hemoglobin ⇢ Heme and globin
- Globin ⇢ AA
- Heme ⇢ Fe and protoporphyrin ⇢ bilverdin ⇢bilirubin
- Hemoglobin ⇢ Heme and globin
- Bilirubin released from macrophages, binds to plasma proteins, transported to liver
- Taken up by hepatocytes via membrane carriers
- Attaches to a binding protein- ligandin (y and z proteins) - in hepatocyte cytoplasm - prevents efflux back into blood
- Conjugated with glucuronic acid (glucose in horses) - now is water soluble
- Secreted into biliary system, stored in gall bladder
- Excreted into small intestine as part of bile
- Bacterial reduction ⇢ urobilinogen which can be passively absorbed and recirculates to be excreted in bile or urine
- Recirculates in portal system or renal excretion
- Some degraded to stercobilnogen and excreted in feces
- Bacterial reduction ⇢ urobilinogen which can be passively absorbed and recirculates to be excreted in bile or urine