Lecture 2: Approach to the Adult Patient with Anemia Flashcards
Define erythropoiesis.
The production of RBCs.
What 4 things result in erythropoiesis?
Low O2 situations (hypoxic)
EPO stimulation
RBC proliferation and maturation
Reticulocyte release
What is the progenitor cell of an RBC?
Common myeloid progenitor cell.
The binding of what to what induces RBC maturation?
Binding of EPO to marrow erythroid precursors (proerythroblasts)
What are folate and Vit B12 specifically needed for in RBCs?
Proliferation and continual maturation.
What does a lack of folate and B12 cause?
Overly large RBCs that are immature.
What is iron specifically needed for in RBCs?
Accumulation of Hgb.
What does a lack of iron cause?
Small RBCs
When is an RBC smallest and largest?
Largest when it is immature.
Smallest when it is fully matured.
What is a reticulocyte? Describe it.
An immature RBC.
It is slightly bluer than a RBC and also lacks the biconcave nature of an RBC.
What is unique about a reticulocyte vs an RBC?
It contains RNA, which is not absorbed until it becomes a fully mature RBC.
How much of our blood is typically made of reticulocytes?
0-1.5%.
This is the retic count.
In what situations would I expect retic count to increase?
Active bleeds.
Consistent blood loss.
What are the optimal conditions for erythropoiesis?
Normal EPO production
Normal erythroid marrow function
Adequate Hgb accumulation
What is anemia defined by?
A reduction in one OR more of the major RBC measurements.
Hgb, Hct, or RBC.
What are the two approaches to anemia?
Kinetic approach
Morphologic approach
Define kinetic approach to anemia.
Addressing the mechanism responsible for the fall in Hgb concentration.
Define morphologic approach to anemia.
Categorizing anemia based on alterations in RBC characteristics and reticulocyte response.
What 3 mechanisms cause anemia?
Decreased RBC production
Increased RBC destruction (hemolysis)
Blood loss (Most COMMON CAUSE)
When we are at steady state, how many RBCs are being destroyed and produced?
About 1%. Directly related to reticulocyte count.
What can cause a reduction in RBC production?
Lack of nutrients
Bone marrow disorders
Bone marrow suppression
Low levels of trophic hormones
Acute/chronic inflammation
What nutrients cause a reduction in RBC production?
Iron, Folate, and B12.
How do bone marrow disorders and bone marrow suppression reduce RBC production?
They reduce the production of the RBC precursors.
In what chronic condition is EPO commonly reduced?
Chronic renal failure.
How does acute/chronic inflammation affect RBC production?
Iron concentration is affected.
EPO reduced.
RBC life span decreased.
What 3 conditions can cause increased RBC destruction?
Inherited hemolytic anemias
Acquired hemolytic anemias
Hypersplenism
What are the two major inherited hemolytic anemias?
Sickle cell
Thalassemia major
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
What secondary condition often results when you lose a lot of RBCs?
Iron deficiency, which further exacerbates anemia.
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.
How is the morphologic approach to anemia classified?
RBC indices.
MCV, MCH, MCHC
How is MCV classified in anemia?
Microcytic, normocytic, macrocytic.
What does reticulocytosis do to MCV?
Increase it, since reticulocytes are larger than regular RBCs.
How is MCH classified in anemia?
Hypochromic, normochromic, hyperchromic.
What are the main causes of a macrocytic anemia?
Folate and B12 deficiency
Drugs that interfere with nucleic acid synthesis
Abnormal RBC maturation
Alcohol abuse (folate deficiency)
Liver disease (lipid deposits on RBC, increasing SA)
How does a folate and B12 deficiency cause macrocytic anemia?
Inadequate proliferation of erythroblasts, which result in giant, immature RBCs.
What are the main causes of a microcytic anemia?
Iron deficiency
Alpha/beta thalassemia minor
What is microcytic anemia often associated with?
Low MCHC due to low Hgb content.
What are the main causes of normocytic anemia?
Chronic kidney disease (CKD)
Anemia of chronic disease/inflammation
Mild iatrogenic anemia
How is normocytic anemia evaluated?
Peripheral blood smear.
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.
What is the core physiologic effect of anemia?
Decreased O2 delivery to tissues due to a fall in Hgb concentration.
What other condition often seen with anemia will result in hypovolemia?
Acute, moderate-severe blood loss.
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)
If the body is unable to compensate for an anemia, when can I tell?
If the symptoms persist at rest.
What are the S/S of anemia?
Fatigue
Exertional tachycardia/dyspnea
Tachycardia/dyspnea at rest.
Palpitations
Audible pulsations
Bounding pulses (3+)
Pallor
What are the S/S of anemia that is further complicated by hypovolemia?
Easily fatigued
Cramps
Dizziness/syncope
Lethargy
Hypotension/Shock/Death
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?
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.
What are some of the common medical conditions that result in anemia?
Melena
Large hematochezia
Menorrhagia
Renal failure
RA
CHF
Melena
Upper GI bleed, bleeding ulcer
Large Hematochezia
lower acute GI bleed
Menorrhagia
Dysfunctional uterine bleeding
What are two common OTCs that can cause melena?
Pepto-bismol or iron supplements.
What kind of anemias typically cause jaundicing?
Hemolytic anemias.
What am I looking for in a PE for anemia?
Skin color/tone
Eyes (conjuctiva and sclera)
Lymph nodes
Abdomen (HSM)
Bony tenderness in the sternum and anterior tibia
Stool
What are the skin conditions that may indicate anemia?
Pallor
Jaundice
Petechiae
Bruising
What are the eye conditions that may indicate anemia?
Pale conjuctiva
Scleral icterus
What abnormal abdominal organ condition would suggest anemia?
Hepatosplenomegaly
What should always be taken into account when interpreting a CBC?
Volume status
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.
If my patient has a decreased plasma volume status, what would I expect their RBC and H&H to be?
Elevated.
Is a manual or automatic assessment of reticulocytes preferred?
Automatic.
How is retic count displayed?
Percentage of RBCs.
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.
What is the preferred calculation for retic count in anemic patients?
Reticulocyte index (RI)
Retic count * (Patient Hct/normal Hct)
Normal is <3%
What does increased retic count often suggest in terms of anemia?
Hemolytic anemia.
What labs could I order to further evaluate a hemolytic anemia?
Serum LDH
Indirect bilirubin
Serum haptoglobin
What is serum LDH?
Concentration of LDH in the plasma.
RBCs contain high concentrations of LDH, so hemolysis would elevate serum LDH greatly.
What is indirect 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 bilirubin would be free floating from hemolyzed RBCs.
What is serum 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.
What is the direct Coombs test used for?
Testing for autoimmune hemolytic anemia.
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 the presence of antibodies, which will agglutinate in the presence of the Coombs reagent.
What can give a false positive on a Coombs test?
Drug sensitizations. They will trigger it, but it is not anemia.
How is iron distributed in the body?
65% Hgb
30% ferritin or hemosiderin in the spleen, bone marrow, and liver.
4% myoglobin
<1% in cells
<0.1% bound to transferrin
What is transferrin?
A taxicab for iron.
What is hemosiderin?
A storage of excess Hgb from broken down RBCs.
It has a similar function to haptoglobin.
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.
What does serum iron measure?
Circulating iron that is BOUND to transferrin.
Why do males have more serum iron?
Females menstruate, so they lose iron periodically.
If I have decreased serum iron, what organ is likely affected?
Kidneys
If I have increased serum iron, what organ is likely affected?
Liver
What makes transferrin?
Liver
What is the function of transferrin?
Transport of iron from the duodenum to the bone marrow.
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.
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.
What is ferritin?
Iron storage protein (main)
It is the most reliable indicator of total-body iron status.
What test is more reliable than a ferritin test?
Bone marrow testing.
Why is a ferritin test better than TIBC or serum iron?
Iron replaces Hgb, so decreased ferritin indicates that Hgb had to be replaced.
What labs are used to evaluate macrocytic anemia?
Retic count
B12
Folate
What labs are used to evaluate microcytic anemia?
Retic count
Serum iron
Transferrin
TIBC
Transferrin saturation
Ferritin
Peripheral blood smear
Coomb’s test
What does B12 require?
Intrinsic factor, produced by the stomach and absorbed in the ileum.
Where is excess B12 stored?
Liver. We can hold up to 6 months’ worth.
Where is B12 found in the diet?
Animal proteins.
Note:
Vegans? are generally more at risk for B12 deficiency as a result.
Where is folate absorbed and stored?
Absorbed in the upper 1/3 of the SI.
Stored in the liver.
Where does folate come from?
Leafy greens
Fruit
Eggs
Why can serum folate be elevated in a B12 deficiency?
B12 is required to move folate into the cells.
What labs are used to evaluate normocytic anemia?
Retic count
Workup based on Ddx
