Lecture 2: Approach to the Adult Patient with Anemia (enochs) Flashcards

1
Q

Define erythropoiesis.

A

The production of RBCs.

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2
Q

what is the four steps of Erythropoiesis

A

Low O2 situations (hypoxic)
EPO stimulation
RBC proliferation and maturation
Reticulocyte release

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3
Q

What is the progenitor cell of an RBC?

A

Common myeloid progenitor cell.

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4
Q

The binding of what to what induces RBC maturation?

A

Binding of EPO to marrow erythroid precursors (proerythroblasts)

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5
Q

What are folate and Vit B12 specifically needed for in RBCs?

A

Proliferation and continual maturation.

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6
Q

What does a lack of folate and B12 cause?

A

Overly large RBCs that are immature.

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7
Q

What is iron specifically needed for in RBCs?

A

Accumulation of Hgb.

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8
Q

What does a lack of iron cause?

A

Small RBCs

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9
Q

When is an RBC smallest and largest?

A

Largest when it is immature.
Smallest when it is fully matured.

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10
Q

What is a reticulocyte? Describe it.

A

An immature RBC.

It is slightly bluer than a RBC and also lacks the biconcave nature of an RBC.

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11
Q

What is unique about a reticulocyte vs an RBC?

A

It contains RNA, which is not absorbed until it becomes a fully mature RBC.

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12
Q

How much of our blood is typically made of reticulocytes?

A

0-1.5%.

This is the retic count.

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13
Q

In what situations would I expect retic count to increase?

A

Active bleeds.

Consistent blood loss.

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14
Q

What are the optimal conditions for erythropoiesis?

A

Normal EPO production
Normal erythroid marrow function
Adequate Hgb accumulation

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15
Q

What is anemia defined by?

A

A reduction in one OR more of the major RBC measurements.

Hgb, Hct, or RBC.

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16
Q

What are the two approaches to anemia?

A

Kinetic approach
Morphologic approach

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17
Q

Define kinetic approach to anemia.

A

Addressing the mechanism responsible for the fall in Hgb concentration.

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18
Q

Define morphologic approach to anemia.

A

Categorizing anemia based on alterations in RBC characteristics and reticulocyte response.

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19
Q

What 3 mechanisms cause anemia?

A

Decreased RBC production
Increased RBC destruction (hemolysis)
Blood loss (Most COMMON CAUSE)

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20
Q

When we are at steady state, how many RBCs are being destroyed and produced?

A

About 1%. They are are directly related.

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21
Q

What can cause a reduction in RBC production?

A

Lack of nutrients (iron, B12, folate)
Bone marrow disorders
Bone marrow suppression
Low levels of trophic hormones (decrease stim for RBC production such as EPO)
Acute/chronic inflammation (affects iron conc, reduces EPO and decreases RBC life span)

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22
Q

What nutrients cause a reduction in RBC production?

A

Iron, Folate, and B12.

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23
Q

How do bone marrow disorders and bone marrow suppression reduce RBC production?

A

They reduce the production of the RBC precursors.

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24
Q

In what chronic condition is EPO commonly reduced?

A

Chronic renal failure.

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25
How does acute/chronic inflammation affect RBC production?
Iron concentration is affected. EPO reduced. RBC life span decreased.
26
What 3 conditions can cause increased RBC destruction?
Inherited hemolytic anemias Acquired hemolytic anemias Hypersplenism
27
What are the two major inherited hemolytic anemias?
Sickle cell Thalassemia major
28
What are the 4 conditions that can cause blood loss?
Gross blood loss (aka visible blood loss) Occult blood loss (aka hidden blood loss) Iatrogenic blood loss (aka healthcare-induced) Underappreciated menstrual blood loss
29
What secondary conditions often results when you lose a lot of RBCs?
Iron deficiency, which further exacerbates anemia.
30
What happens to retic count in an active bleed? Decreased RBC production? Increased RBC destruction?
Increased in an active bleed. Decreased in decreased RBC production. Increased in increased RBC destruction.
31
How is the morphologic approach to anemia classified?
RBC indices. MCV, MCH, MCHC
32
How is MCV classified in anemia?
Microcytic, normocytic, macrocytic.
33
What does reticulocytosis do to MCV?
Increase it, since reticulocytes are larger than regular RBCs.
34
How is MCH classified in anemia?
Hypochromic, normochromic, hyperchromic.
35
What are the main causes of a macrocytic anemia?
Folate and B12 deficiency Drugs that interfere with nucleic acid synthesis (lack of RNA degredation) Abnormal RBC maturation Alcohol abuse (folate deficiency) Liver disease (lipid deposits on RBC, increasing SA)
36
How does a folate and B12 deficiency cause macrocytic anemia?
Inadequate proliferation of erythroblasts, which result in giant, immature RBCs.
37
What are the main causes of a microcytic anemia?
Iron deficiency Alpha/beta thalassemia minor
38
What is microcytic anemia often associated with?
Low MCHC due to low Hgb content.
39
What are the main causes of normocytic anemia?
Chronic kidney disease (CKD) Anemia of chronic disease/inflammation Mild iatrogenic (hospital) anemia (recurrent venipuncture, blood loss from surgery, dilution w IV fluids
40
How is normocytic anemia evaluated?
Peripheral blood smear.
41
How does iron deficiency affect MCV acutely and chronically?
An acute iron deficiency anemia would result in normocytic anemia. A chronic iron deficiency anemia would result in microcytic anemia.
42
What is the core physiologic effect of anemia?
Decreased O2 delivery to tissues due to a fall in Hgb concentration.
43
What other condition often seen with anemia will result in hypovolemia?
Acute, moderate-severe blood loss.
44
In what two ways does the body compensate for anemia?
Increased O2 extraction, aka tissues will extract even more O2 from Hgb. Increased SV and HR. (overall increasing CO)
45
If the body is unable to compensate, when can I tell?
If the symptoms persist at rest.
46
What are the S/S of anemia?
Fatigue Exertional tachycardia/dyspnea Tachycardia/dyspnea at rest. Palpitations Audible pulsations Bounding pulses (3+) Pallor
47
What are the S/S of anemia that is further complicated by hypovolemia?
Easily fatigued Cramps Dizziness/syncope Lethargy Hypotension/Shock/Death
48
What 4 questions will help determine the etiology of anemia?
Is the patient bleeding? Where? Is there evidence of increased RBC destruction? Is there bone marrow suppression? Is the patient nutrient deficient in iron, B12, or folate?
49
Why is the onset of anemia important in determining its etiology?
New onsets are most commonly linked to an acquired disorder. Lifelong anemia is most commonly linked to an inherited disorder.
50
What are some of the common medical conditions that result in anemia?
Melena - upper GI bleed Large hematochezia - lower acute GI bleed Menorrhagia - dysfunctional uterine bleeding Renal failure RA CHF
51
What are two common OTCs that can cause melena?
Pepto-bismol or iron supplements.
52
What kind of anemias typically cause jaundicing?
Hemolytic anemias.
53
What am I looking for in a physical exam regarding anemia?
Skin color/tone Eyes (conjuctiva and sclera) Lymph nodes Abdomen (Hepatospenomegaly) Bony tenderness in the sternum and anterior tibia Stool for occult blood
54
What are the skin conditions that may indicate anemia?
Pallor Jaundice Petechiae Bruising
55
What are the eye conditions that may indicate anemia?
Pale conjuctiva Scleral icterus
56
What abnormal abdominal organ would suggest anemia?
Hepatosplenomegaly
57
What should always been taken into account when interpreting a CBC?
Volume status
58
If my patient has low Red cell mass (RCM) but increased plasma volume, what would I expect their RBC and H&H to be?
Low. H&H is a concentration, so increased plasma volume lowers the concentration.
59
If my patient has a decreased plasma volume status, what would I expect their RBC and H&H to be?
Elevated.
60
Is a manual or automatic assessment of reticulocytes preferred?
Automatic.
61
How is retic count displayed?
Percentage of RBCs.
62
What condition can elevate retic count artificially?
Hemolysis. The lower volume of RBCs with the same number of reticulocytes will result in an elevated retic count with no real change in the absolute number of reticulocytes.
63
What is the preferred calculation for retic count in anemic patients?
Reticulocyte index (RI) Retic count * (Patient Hct/normal Hct) Normal is <3%
64
What does increased retic count often suggest in terms of anemia?
Hemolytic anemia.
65
What labs could I order to further evaluate a hemolytic anemia?
Serum LDH- LDH is highly concentrated in RBCs - therefore destruction of the RBC will increase LDH Indirect bilirubin - Bilirubin is the orange-yellow pigment derived from the breakdown of hgb Serum haptoglobin - Haptoglobin binds free hgb that is released from hemolyzed RBC
66
What is serum LDH? When would we see a change in LDH?
Concentration of LDH in the plasma. RBCs contain high concentrations of LDH, so hemolysis would elevate serum LDH greatly.
67
What is indirect bilirubin? When would we see a change in bilirubin?
It is the unconjugated bilirubin in the serum. Bilirubin comes from the breakdown of Hgb. Increased indirect bilirubin is suggestive of hemolytic anemia because Hgb would be free floating from hemolyzed RBCs.
68
What is serum haptoglobin? When would we see a change in haptoglobin?
Haptoglobin is a molecule that binds free Hgb from hemolyzed RBCs. Decreased haptoglobin is suggestive of hemolytic anemia because it only captures free haptoglobin.
69
What is the direct Coombs test used for?
Testing for autoimmune hemolytic anemia.
70
What is the Coombs test?
AKA the direct antiglobulin test. Assess the presence of antibodies on the RBC's surface. A negative result indicates lack of antibody, which is NORMAL. A positive result indicates presences of antibodies, which will agglutinate in the presence of the Coombs reagent.
71
What can give a false positive on a Coombs test?
Drug sensitizations. They will trigger it, but it is not anemia.
72
How is iron distributed in the body?
65% boung to hgb 30% stored as ferritin or hemosiderin in the spleen, bone marrow, and liver. 4% bound to myoglobin <1% in cells <0.1% bound to transferrin
73
What is transferrin?
A taxicab for iron.
74
What is hemosiderin?
A storage complex that binds to free iron released from hemolyzed RBCs
75
How is iron lost?
Perspiration Epithelial cell desquamation Menstruation Note: This means taking iron supplements is potentially dangerous since the body does not get rid of excess iron easily.
76
What does serum iron measure?
Circulating iron that is BOUND to transferrin.
77
Why do males have more serum iron?
Females menstruate, so they lose iron periodically.
78
If I have decreased serum iron, what organ is likely affected?
Kidneys
79
If I have increased serum iron, what organ is likely affected?
Liver
80
What makes transferrin?
Liver
81
What is the function of transferrin?
Transport of iron from the duodenum to the bone marrow.
82
What is transferrin saturation?
Measures how much of our transferrin is bound to iron. Decreases when we lack iron. Increases when we have excess iron.
83
What is TIBC?
Total iron binding capacity. Measures blood's capacity to bind iron with transferrin, which also indirectly measures transferrin. Essentially, it measures how much transferrin is available for binding.
84
What is ferritin?
Iron storage protein (main) It is the most reliable indicator of total-body iron status.
85
What test is more reliable than a ferritin test?
Bone marrow testing.
86
Why is a ferritin test better than TIBC or serum iron?
Iron replaces Hgb, so decreased ferritin indicates that Hgb had to be replaced.
87
What labs are used to evaluate macrocytic anemia?
Retic count B12 Folate
88
What labs are used to evaluate microcytic anemia?
Retic count Serum iron Transferrin TIBC Transferrin saturation Ferritin Peripheral blood smear Coomb's test
89
What does B12 require?
Intrinsic factor, produced by the stomach and absorbed in the ileum.
90
Where is excess B12 stored?
Liver. We can hold up to 6 months' worth.
91
Where is B12 found in the diet?
Animal proteins. Note: Vegans? are generally more at risk for B12 deficiency as a result.
92
Where is folate absorbed and stored?
Absorbed in the upper 1/3 of the SI. Stored in the liver.
93
Where does folate come from?
Leafy greens Fruit Eggs
94
Why can serum folate be elevated in a B12 deficiency?
B12 is required to move folate into the cells.
95
What labs are used to evaluate normocytic anemia?
Retic count Workup based on Ddx