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Heme - Strom > Pathophysiology of Anemias I > Flashcards

Pathophysiology of Anemias I Flashcards

1
Q

What are the 3 most basic reasons for why a patient would be anemic?

A
  • Red cells are being lost from the bloodstream
  • Red cells are not being produced
  • Both
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2
Q

What is MCV?

- what does a low MCV imply in an anemic patient?

A

Mean Corpuscular Volume

  • Low MCV means Red cells are smaller than they should be. This implies that PRODUCTION of Red cells defective
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3
Q

When evaluating ANY hematologic disease, where is the first place to start?

A
  • Peripheral Blood Smear
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4
Q

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?

A

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

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5
Q

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?
A

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

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6
Q

T or F: Microcytosis, Hypochromia, Anisocytosis, Poikilocytosis are diagnostic of an Iron Deficiency.

A

False, while these characteristics strongly suggest iron deficiency, additional lab tests are needed to confirm the Dx.

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7
Q

• 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?

A

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.

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8
Q

If these tests give ambiguous findings what less common test might you used to Dx the iron deficiency?
- what does it measure?

A

Soluble Transferrin Receptor

  • Measures the number of Transferrin Receptors on macrophages, they will UPREGULATE in the ABSENCE of iron
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9
Q

Chronic Blood loss in what areas leads to BOTH RBC loss and impaired production?

A

GI tract
Urinary Tract
Dysfunctional Uterine bleeding

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10
Q

What is a Thalassemia?

- causes?

A

Reduced Globin Production (alpha or beta)

  • There are many genetic causes of thelassemia
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11
Q

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) ?

A

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

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12
Q

Is an MCV below 70 pL specific to thalassemia?

  • are target forms specific?
  • if not, explain.
A

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

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13
Q

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?
A

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
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14
Q

What defect leads to most Thalassemias?

A
  • Reduced or Absent expression of One or Both BETA globulin genes
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15
Q

What is normal Hbg made of in an adult?

A

MOSTLY:
alpha(2)beta(2)

TRACES of:
alpha(2)delta(2)

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16
Q

What result is most commonly seen when you do Electrophoresis on a patient with BETA thalassemia?
- Severe cases?

A

**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)

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17
Q

What does the severity of a ß-thalassemia depend on?

A
  1. Severity of Mutations

2. Homozygosity and Heterozygosity

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18
Q

What chromosome holds the globin genes (with the exception of alpha and zeta)?
- what are these genes?

A

Chromosome 11

  1. Epsilon
  2. g-Gamma
  3. a-Gamma
  4. (psi-beta) - pseudogene
  5. Delta
  6. Beta
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19
Q

What are the 3 types of Beta Thalessemia?

  • treatment?
  • Genotype?
A

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
20
Q

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?
A

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

21
Q

What tissues are most likely to be affected by a BETA globulin gene defect?
- explain why these defects occur.

A

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

22
Q

What chromosome is the alpha globin locus found on?

- what genes are found here?

A

Chromosome 16

4 Genes:

  • Zeta 2, Zeta 1 (fetal)
  • Alpha 2, Alpha 1 (adult)
23
Q

T or F: a person may have Alpha 2 and Alpha 1 gene defects and never present clinically with any symptoms.

A

True, while it depends on the nature of the defect, the patient may be asymptomatic if their OTHER HAPLOTYPE is NORMAL

24
Q

Differentiate between an alpha thalassemia 1 trait and an alpha thalassemia 2 trait.

A

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

25
Q

How would you Diagnose Alpha Thalassemia 2 trait?

  • how do most clinicians diagnose it?
  • what ethnic group is this most prevalent in?
A

Dx:
• PCR based electrophoresis and/or sequencing

Most Clinicians just rule out 3/4 top causes of microcytic anemia

**3% of African Americans have this

26
Q

What is Hemoglobin H disease caused by?

  • Peripheral Smear Findings?
  • Lab Finding?
  • Dx?
A

Hemoglobin H:
• 3 Defective Alpha Globin Alleles
• Beta x 4 (beta tetramer) is formed

Smear:
• Micocytic Anemia

Lab/Dx:
• 15-30% Hbg H

27
Q

What is Hemoglobin H disease often misdiagnosed as?

A

Hbg H disease is often mistaken for Iron Deficiency

28
Q

T or F: ALPHA globlin can form a functional tetramer just as BETA globin can form a tetramer to make Hbg H.

A

FALSE, in beta thalessemia ALPHA globin does NOT form a tetramer as BETA globlin does in alpha thalessemia

29
Q

A baby is born in Southeast Asia and Dies shortly after birth. Electrophoresis shows presence of Hgb Bart’s (gamma) x4. What is the most likely Dx?

A

4 defective alpha globin alleles
- death typically occurs in utero or right after birth

**Apparently there is not enough time for the Beta tetramers to kick in as they do with 3 defective alpha globin genes

30
Q

What aspect of RBC synthesis is B12 important to?

- what do you expect to see in the bone marrow of someone with this deficiency?

A

B12 is needed as cofactor needed in the process of Methylating UMP to TMP

  • Megablastic Appearance in Bone marrow - cell production gets halted after 1 or 2 divisions and cytoplasm becomes eosinophilic
  • Macrocytic Appearance in Peripheral blood - larger MCV (mean cell volume) - large RBCs (bigger than lymphocytes)
  • Hypersegmented Neutrophils - 5 or more lobes
31
Q

What should be on your differential when considering why marrow would have a Megaloblastic Appearance?

A

DDx:

  • Impaired B12 uptake (pernicious anemia)
  • Impaired Folate Uptake (malabsorption, malnutrition)
  • Drug Effect (Nucleoside Analogues - HAART therapy, Hydroxyurea - Ribonucleotide Reductase Inhibitor)
  • Intrinsic Bone Marrow Dysfunction (Myelodysplastic Syndromes)
32
Q

What is the difference between Macrocytic Anemia and Megaloblastic Anemia?

A

Macrocytic Anemia
- Refers to large RBCs

Megaloblastic
- Refers to Bone Marrow with the halted cell division and increased eosinophilia in cytoplasm

***Most Macrocytic Anemias Turn out to be megaloblastic

33
Q

What is the major exception to the rule that most macrocytic anemias are also megaloblastic?
- how do they present in lab values/smears?

A

Acute EtOH Toxicity:
- Very high MCV

Recovery From Acute Anemia:
- Increased Reticulocyte Count

Ab-Induced RBC clumping:
- artificially increased MCV

34
Q

What binding proteins are important to B12 absorption?

- what cells produce these proteins/where are they found?

A

Haptocorrin (HC) - found in the saliva and is the predominant protein bound to B12 all the way down to the jejunum

Intrisic Factor (IF) - Released from PARIETAL cells in the stomach, but does not bind until HC is dissolved in the Jejunum

35
Q

What are some problems that could result in Intrinsic Factor Deficiency?

A
  • Pernicious Anemia (lack of IF)
  • Gastrectomy/ Gastric Bypass
  • Acid Blocking drugs
  • Atrophic Gastritis
36
Q

What problems could impair IF-B12 uptake?

A
  • Ileum Resection
  • Crohn’s Disease

*Others exist - see lecture diagram (don’t know if these are important)

37
Q

Compare the time it takes for B12 deficiency to cause problems vs. a folate deficiency.

A

B12 - takes years for clinical problems
Folate - takes months
**Folate Def. common with Alcoholics, can also happen with bowel diseases like B12 def.

38
Q

What would you expect to see in the bone marrow of a patient that was on MTX?

A
  • Megaloblastic Anemia because MTX is a DHFR inhibitor

**Hydroxyurea (Ribronucleotide Reductase Inhibitor) can also cause this

39
Q

Where does EPO production occur?

- in response to what?

A
  • Peritubular Cells in the Renal Cortex

- In Response to LOW O2

40
Q

T or F: Hepicidin Reduces the Availability of Stored Iron

A

True

41
Q

What are some common reasons for Hepcidin production to be inappropriately Up-regulated?
- what cells does this affect and how?

A

Chronic Inflammatory Conditions Lead to Hepcidin Getting Ramped Up
- e.g. Cancer, Autoimmune Conditions, Hard-to-cure infections, Chronic Hepatitis

Ferroportin is Down Regulated:

  • Iron is Trapped in Gut Epithelium
  • Iron also Trapped in Macrophages

**Our bodies might be doing this to keep iron out of the bloodstream in the case that its a bacterial infection

42
Q

What happens to TIBC in anemia of chronic inflammation?

  • Transferrin?
  • Trasferrin Saturation
A

TIBC Decreases

Transferrin bound to Iron is pulled out of the BS

Transferrin Saturation = Serum Iron/TIBC increases

**Net Effect is Less Iron, Less RBC production –> Anemia

43
Q

T or F: even macrophages that are filled with iron in the bone marrow lack the ability to provide iron for RBC synthesis in chronic inflammatory states

A

True, because Hepcidin is upregulated in chronic inflammatory anemia ferroportin is down regulated and cells cannot release iron

44
Q

What lab Values should you expect in chronic inflammatory Anemia?
- what should you do to confirm chronic inflammatory anemia?

A
  • Normocytic Cells on Smear
  • INCREASED Ferritin (Increased Bone Marrow Iron Stores)
  • Reduced or Normal Serum Iron

**Bone Marrow biopsy needed to rule out Lymphomas, Leukemias, Metastasis, Granulomas

45
Q

How do you calculate a corrected Reticulocyte Count?

**How do you know if bone marrow is responding appropriately?

A

Corrected = (Ret. Count%)*(hct/45)

**Appropriate Response: 
• Divide Corrected count by the Reticulocyte maturation time which can be determined looking at Hct. 
Hct = 45, RMT = 1
Hct = 35, RMT = 1.5
Hct = 25, RMT = 2.0
Hct =  15, RMT = 2.5
46
Q

What lab values are likely to be elevated if a patient is hemolyzing RBCs?
• What values will be depressed?

A 
Elevated: 
• LDH
• Indirect Bilirubin
• Plasma Free Hemoglobin (elevated in extravascular hemo.)
• Urine Hemosiderin

Depressed:
• Serum Haptoglobin

47
Q

What are the indications for doing a bone marrow biopsy?

A
  • Multiple Cell lines Affected (Anemic but also neutropenic and thrombocytopenic)
  • Unresolved Hyporegenerative Anemia
  • Abnormal Cells in Peripheral Blood

Heme - Strom (13 decks)

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