Pathophysiology of Anemias I Flashcards
What are the 3 most basic reasons for why a patient would be anemic?
- Red cells are being lost from the bloodstream
- Red cells are not being produced
- Both
What is MCV?
- what does a low MCV imply in an anemic patient?
Mean Corpuscular Volume
- Low MCV means Red cells are smaller than they should be. This implies that PRODUCTION of Red cells defective
When evaluating ANY hematologic disease, where is the first place to start?
- Peripheral Blood Smear
What term is used to describe Red Cells that are small?
- lightly colored/larger than normal central pallor?
***What Anemia most often results in small, lightly colored RBCs on the peripheral blood smear?
Small: Microcytosis
Lightly Colored: Hypochromia (central pallor larger than 1/3 of central area)
*Small lightly colored RBCs implies IRON deficiency (via blood loss, chronic disease), SIDEROBLASTIC anemia, or THALASSEMIA
In severe Iron deficiency a patients blood may show the following:
- Anisocytosis
- Hypochromia
- Poikilocytosis
- Define these terms and determine which one would show up first.
- What indication do Automatic analyzers give that this is happening?
Hypochromia - cells with central pallor that is greater than 1/3 the diameter
*This feature will show up 1st on a peripheral blood smear
Anisocytosis - variation in size between RBCs
Poikilocytosis - variation in shape between RBCs
***Automatic Analyzer will report a HIGH RDW (red cell distribution width) - this correlates well with ANISOCYTOSIS
T or F: Microcytosis, Hypochromia, Anisocytosis, Poikilocytosis are diagnostic of an Iron Deficiency.
False, while these characteristics strongly suggest iron deficiency, additional lab tests are needed to confirm the Dx.
• What is the more reliable and important test you can run in a person who has an iron deficiency?
- What findings would you expect and why?
• What other tests should you also consider?
- What findings would you expect and why?
**Which two tests CONFIRM the iron deficiency?
Serum Ferritin
- Ferritin is the Iron present in the STORAGE pools, some leaks out into the serum raising the serum ferritin conc. Serum Ferritin will be LOW.
Serum Iron
- Measures Fe+++/Transferrin, this is LOW because iron is rapidly being transported to Iron Stores in BONE MARROW
TIBC (total iron binding capacity)
- Transferrin production is ramped UP to get more Iron to Bone Marrow, this will be INCREASED
***TIBC (high) and Serum Ferritin (low) is diagnostic of iron def.
If these tests give ambiguous findings what less common test might you used to Dx the iron deficiency?
- what does it measure?
Soluble Transferrin Receptor
- Measures the number of Transferrin Receptors on macrophages, they will UPREGULATE in the ABSENCE of iron
Chronic Blood loss in what areas leads to BOTH RBC loss and impaired production?
GI tract
Urinary Tract
Dysfunctional Uterine bleeding
What is a Thalassemia?
- causes?
Reduced Globin Production (alpha or beta)
- There are many genetic causes of thelassemia
What Features would you expect to see on the peripheral blood smear of a person who is thalassemic?
- how would you differentiate this from a person with an iron deficiency (including lab values) ?
These Cells Lack Hbg so they are Small (microcytic) and Pale (hypochromic)
Distinguishing Features:
• MCV (mean corpuscular volume) under 70 pL
• Target Forms
Most Reliable Clue:
• NUMBER of RBCs - RBCs are usually Reduced in Iron Deficiency, but in Thalessemia they will be NORMAL or ELEVATED
Is an MCV below 70 pL specific to thalassemia?
- are target forms specific?
- if not, explain.
MCV less than 70 pL and Target forms are NOT specific
MCV - could be lower than 70 pL in iron deficiency (but not common)
Target Forms - seen in pts. with liver disease
A patient has Very Microcytic Anemia and Normal or Increased numbers of RBCs.
- how do you confirm the Dx?
- How does it work?
- What does it detect?
Hemoglobin Electrophoresis (usually done w/ HPLC)
- Will detect sequence abnormalities (such as those in SICKLE cell)
- Separates and Quantifies intact Hbg (tetramer) vs. any other types that might be present
What defect leads to most Thalassemias?
- Reduced or Absent expression of One or Both BETA globulin genes
What is normal Hbg made of in an adult?
MOSTLY:
alpha(2)beta(2)
TRACES of:
alpha(2)delta(2)
What result is most commonly seen when you do Electrophoresis on a patient with BETA thalassemia?
- Severe cases?
**INCREASED Hbg A2 - consists of 2 DETLA units bound to 2 ALPHA units
Severe:
- Hemoglobin F - consisting of 2 GAMMA units bound to 2 ALPHA units (fetal Hbg)
What does the severity of a ß-thalassemia depend on?
- Severity of Mutations
2. Homozygosity and Heterozygosity
What chromosome holds the globin genes (with the exception of alpha and zeta)?
- what are these genes?
Chromosome 11
- Epsilon
- g-Gamma
- a-Gamma
- (psi-beta) - pseudogene
- Delta
- Beta
What are the 3 types of Beta Thalessemia?
- treatment?
- Genotype?
Thalassemia Minor:
- Heterozygous
- Asymptomatic, NO transfusion Required
Thalassemia Major:
- Homozygous
- SEVER anemia, TRANSFUSION Required
Thalassemia Intermedia:
- NOT DETERMINED GENOTYPE (could be severe Heterozygote, Mild Homozygote, or COMPOUND heterozygote)
- Characterized by Mutations that do not require transfusion, but are complicated by other Clinical Manifestations
What is the responsible for the most severe clinical manifestations of Thalessemia Intermedia and Major?
- what is the under lying process?
- Why are RBCs numbers not reduced and sometimes elevated?
Ineffective Erythropoiesis:
• NO regulatory System for ALPHA globin in the absence of BETA globin
• ALPHA globlin accumulates inside RBC precursors causing severe cell damage
Why No Reduced Numbers:
• O2 sensors in Kidney detect low O2 and Release EPO
• EPO ramps up production but the Hbg packed into the RBCs is largely ineffective
What tissues are most likely to be affected by a BETA globulin gene defect?
- explain why these defects occur.
Skeletal Deformities:
- Constant EPO stimulation creates ENLARGED BONE MARROW SPACES that can lead to Bone Deformities
Liver Damage
Myocardial Damage
Endocrine Organ Damage:
- Results from REDUCED Hepacidin (strom not sure why it gets red., ERFE?) that results INCREASED Ferroportin and iron transport.
- INCREASE iron uptake due to REDUCTION in Hepcedin production affects liver, myocardium, and endocrine organs
What chromosome is the alpha globin locus found on?
- what genes are found here?
Chromosome 16
4 Genes:
- Zeta 2, Zeta 1 (fetal)
- Alpha 2, Alpha 1 (adult)
T or F: a person may have Alpha 2 and Alpha 1 gene defects and never present clinically with any symptoms.
True, while it depends on the nature of the defect, the patient may be asymptomatic if their OTHER HAPLOTYPE is NORMAL
Differentiate between an alpha thalassemia 1 trait and an alpha thalassemia 2 trait.
Alpha Thalassemia 1:
- loss of one alpha allele
- may never be detected clinically
Alpha Thalassemia 2:
2 defective alpha alleles
CLINICALLY SIGNIFICANT
• Mild Microcytic Anemia
• Excess Hgb Bart’s (gamma)x4 at Birth
• NORMAL Hgb Electrophoresis as Adults
