Anemia Flashcards
1
Q
where does erythropoiesis occur
A
- bone marrow
- Under the influence of stromal framework, cytokines, and erythropoietin
2
Q
EPO
A
- EPO is produced by the kidney in response to adequacy of tissue oxygenation
- EPO enhances growth and differentiation of the erythroid progenitors into normoblasts
- EPO=erythropoietin; The hormone tells stem cells in the bone marrow to make more red blood cells. EPO is made by cells in the kidney. These cells release more EPO when blood oxygen levels are low.
3
Q
normoblast and reticulocytes
A
- When a normoblast extrudes its nucleus to form a RBC it is called a reticulocyte
- Reticulocytes retain ribosomal network for about 4 days (3 d in marrow, 1 d in blood) then lose RNA and become mature RBC (1% total circulating RBC are reticulocytes)
- Mature RBC circulates 110-120 days in blood
4
Q
RBCs - role and breakdown
A
- Macrophages detect senescent signals in old RBCs and remove them from circulation
- RBCs carry oxygen linked to hemoglobin from the lungs to tissue capillaries
- Oxygen is then released from Hgb
5
Q
Composition of hemoglobin
A
- Hemoglobin is made of two α chains and two β chains
- Normal adult Hgb is 98% Hgb A (α2β2 chains)
- Hgb A2 is normally 1-2% of adult Hgb (α2δ2 chains)
- Hgb F is normal fetal Hgb but should be <1% of normal adult Hgb (α2γ2 chains)
6
Q
definition of anemia
A
- Hemoglobin (Hgb) measures the concentration of the major oxygen carrying pigment of whole blood
- Hematocrit (Hct) is the percent of a sample of whole blood occupied by intact red blood cells
- Red blood cell (RBC) count is the number of red blood cells in a specified volume of whole blood
- Males (Hgb < 13.5 or Hct < 41%)
- Females (Hgb <12.0 or Hct < 36%)
- Ranges can vary by laboratory or standards used; may not apply to special populations
- Volume status may affect the reported values of Hgb, Hct or RBC count
- H/H and RBC count are all concentrations and dependent on the RCM as well as plasma volume.
- In pregnancy the “normal” range changes
- Patients living at high elevations will have higher values
- Smokers will have higher Hct due to high CO exposure in cigarettes
- African Americans tend to have lower Hgb levels compared to Caucasians
7
Q
Morphologic approach to anemia
A
-Categorizing anemia by the alterations in RBC size and the reticulocyte response
-Mean corpuscular volume (MCV) measures the average RBC volume (size)
• Macrocytic anemia = MCV > 100 fL
• Microcytic anemia = MCV < 80 fL
• Normocytic anemia = MCV 80-100 fL
8
Q
kinetic approach to anemia
A
-Mechanism responsible for the fall in Hgb concentration
-Decreased RBC production
• Lack of nutrients (diet, malabsorption, blood loss)
• Bone marrow disorders or suppression
• Low levels of EPO, thyroid hormone, androgens
-Increased RBC destruction
• Hemolytic anemias
-Blood loss
9
Q
etiology of anemia
A
- Microcytic (IDA, Thalassemia)
- Normocytic (ACD)
- Macrocytic (B12/Folate deficiency, With inc retics: Hemolysis)
- These are the most common anemias by category
10
Q
signs and symptoms of anemia
A
- Symptoms occur due to decreased oxygen delivery to tissues or hypovolemia from blood loss reflecting the fall in Hgb
- Symptoms may occur at rest, with exertion, or when cardiac compensation is impaired depending on the severity and underlying condition(s)
- Do they have signs of anemia and symptoms that will help to lead me to the specific diagnosis
- When they have mild anemia, they only have sxs at rest
- When the anemia progresses, they have a harder time with lower level activity (sxs with less and less exertion)
- Exertional dyspnea, dyspnea at rest, varying degrees of fatigue, bounding pulses, palpitations, “roaring” sound in the ears
- Severe anemia may cause lethary, confusion and can lead to congestive heart failure, angina, arrhythmias, MI
- Acute bleeding with severe volume depletion may lead to fatigue, muscle cramps and can progress to postural dizziness, lethargy, syncope, hypotension, shock and death
11
Q
history needed for anemia
A
- Is the anemia acute, subacute, or chronic?
- Patient’s ethnicity and family history? (May point to inherited cause such as thalassemia or hemoglobinopathy)
- Past medical history? (PUD, RA, renal failure, CHF, liver dz, blood trx)
- Use of medications? (Aspirin, NSAIDs, hydroxyurea)
- Toxic habits or exposures?(Lead exposure, alcohol abuse, nutritional status)
- Looking for clues as to cause of anemia
- Hydroxyurea treats sickle cell anemia by helping to prevent formation of sickle-shaped red blood cells; drug class is anti-metabolite.
- Lead exposure causes microcytic anemia in children
- EtOH abuse / liver dz associated with macrocytic anemia, folate deficiency
12
Q
physical examination of anemia
A
- Organ or multisystem involvement
- Assess patient’s condition (sick or not)
- Tachycardia, dyspnea, fever, postural hypotension
- Jaundice, pallor, petechiae -> common for pts with any type of anemia to have pallor in the conjunctiva
- Lymphadenopathy, HSM, bone tenderness -> may be indicative of lymphoma or blood cancer
- Signs and symptoms of recurrent infxns
- Stool occult blood
- Looking for signs of anemia as well as signs of etiology (cancer, vitamin/mineral deficiency, heart disease, etc)
13
Q
diagnostic studies for anemia
A
- CBC with platelets and WBC differential
- Reticulocyte count -> baby RBCs (normal is 1% of the blood) (Only helpful if you look at in comparison to the other counts, If you have a person with low RBC count, you would expect the reticulocyte count to be high: If the reticulocyte count is normal with anemia, this means that something is not working)
- Peripheral blood smear
- Specific tests to narrow differential diagnosis as indicated (Iron, TIBC, transferrin saturation, ferritin, LDH, indirect bilirubin, haptoglobin, Folate, vitamin B12 levels, TSH, other specific endocrine studies)
- IDA: low serum iron, high TIBC, low transferrin, low ferritin
- Hemolysis: elevated LDH, elevated bili, low haptoglobin
- HYPOCHROMIC MICROCYTIC ANEMIA = Iron deficiency anemia!!
- Its very rare to see hyperchromic cells! Much more normal to see hypochromic or normochromic cells
14
Q
CBC includes:
A
- RBC, WBC, Hgb, Hct, MCV, MCH, MCHC, RDW, platelet count
- RDW tells you how much variation there is in the red blood cell line
15
Q
MCH, MCHC and MCV
A
- MCH and MCHC generally parallel MCV
- MCV tells the size of the RBC (Macrocytic, microcytic, normocytic)
- MCHC tells the concentration (color) of the Hgb (Hypochromic, hyperchromic, normochromic)
16
Q
reticulocyte count
A
- Reticulocyte count helps further distinguish the cause of anemia
- High retic count reflects increased erythropoietic response of bone marrow to continued hemolysis or blood loss
- Low retic count is usually evident of deficient RBC production in bone marrow (Low retic count with pancytopenia worrisome for aplastic anemia, An inappropriately normal retic count is also worrisome for bone marrow disease)
17
Q
reticulocyte shift
A
-With worsening anemia and increasing erythropoietin stimulation, bone marrow reticulocytes (left) leave the marrow at an earlier stage in their maturation. This prolongs the maturation time in the circulation from one day to as long as 2.5 days (right).
18
Q
WBC count and differential
A
- Leukopenia + anemia usually due to bone marrow suppression, hypersplenism, vitamin B12 or folate deficiencies
- Leukocytosis + anemia typically indicates infection, inflammation, or hematologic malignancy (Means high white blood cell count and anemia)
- Inc neutrophils in infxn; inc monocytes in myelodysplasia; inc eosinophils with parasites or allergic disease; dec neutrophils s/p chemo; dec lymphocytes in HIV or steroid tx
19
Q
platelet count
A
- Thrombocytopenia with anemia: DDx includes hypersplenism; malignancy involving bone marrow; autoimmune platelet destruction; sepsis; vitamin B12 or folate deficiency
- Thrombocytosis with anemia: DDx includes myeloproliferative disease; chronic iron deficiency; inflammatory, infectious, or neoplastic disorders
20
Q
peripheral blood smear
A
- Can provide information not otherwise available in a CBC with diff
- Morphology of RBC and other cells in the blood can be helpful in determining diagnosis
- High power view of a normal peripheral blood smear. Several platelets (black arrows) and a normal lymphocyte (blue arrow) can also be seen. The red cells are of relatively uniform size and shape. The diameter of the normal red cell should approximate that of the nucleus of the small lymphocyte; central pallor (red arrow) should equal one-third of its diameter.
- Normal RBCs are about the same size of a neutrophil or WBC
21
Q
approach to anemia
A
- Anemia may be the initial manifestation of a systemic disorder, and is one of the major signs of disease
- A cause for anemia should always be sought
- Use the history, physical exam, and simple laboratory tests to evaluate the potential cause of the anemia
- ANEMIA IS NEVER NORMAL!! A cause should always be figured out
- Is the patient bleeding (now or past)?
- Is there evidence for hemolysis?
- Is the bone marrow suppressed?
- Is the patient iron deficient? Why? Do they have celiac or some other issue with absorption of iron
- Is the patient deficient in folate or cyanocobalamin? Why?
- Evidence of hemolysis varies depending on etiology; ask about rash or skin changes, splenomegaly, family history, dark colored urine, recent medication use, pain, fever
- MOST COMMON cause of anemia IS GI BLEED!!!
22
Q
megaloblastic anemias
A
-are a heterogeneous group of disorders that share common morphologic characteristics. The morphological hallmark of megaloblastosis is a megaloblast. Megaloblasts are large cells with an increased nuclear/cytoplasmic ratio in which nuclear maturation is delayed, while cytoplasmic maturation is more advanced. Peripheral smears reveal that RBCs are macrocytic and occasional megaloblasts are present. Megaloblasts are usually abundant in bone marrow aspirates. Megaloblastic changes are not limited to RBCs since hypersegmented neutrophils can be seen on peripheral smears, and pancytopenia occurs in megaloblastic anemias.
23
Q
iron deficiency anemia
A
- Most common cause of anemia worldwide
- Iron is necessary for the formation of heme
- Most iron is circulating in Hgb
- Iron is stored primarily as ferritin (This is one of the first levels to decrease when looking at iron deficiency anemia)
- Iron is absorbed from the diet in the gut
- Iron is normally lost through skin/mucosal exfoliation, menstrual blood loss
24
Q
causes of iron deficiency
A
- Deficient diet
- Decreased GI absorption
- Increased iron requirements (Pregnancy and lactation)
- Blood loss (GI, menstrual, blood donation, GI bleed is the most common cause of the most common type of anemia)
- Hemoglobinuria
- Iron sequestration (Pulmonary hemosiderosis - This is extremely uncommon so you probably wont see it)
- Peripheral smear from a patient with iron deficiency shows pale small red cells with just a scant rim of pink hemoglobin; occasional “pencil” shaped cells are also present. Normal red cells are similar in size to the nucleus of a small lymphocyte (arrow); thus, many microcytic cells are present in this smear. Thalassemia can produce similar findings.
- Some of the RBCs are normal, some of them are much smaller, and many of them are very pale
25
Q
clinical presentation of iron deficiency
A
- Easy fatigability, tachycardia, palpitations, dyspnea with exertion; pica
- Skin and mucosal changes: smooth tongue, brittle nails, cheilosis (sores around the corners of the mouth)
- Dysphagia due to esophageal webs
- Stool positive for occult blood if GI bleeding is the cause of IDA
26
Q
diagnostic studies for iron deficiency
A
- Low serum ferritin is the initial abnormality
- TIBC rises as iron stores become increasingly depleted
- Serum iron and transferrin saturation levels decline as iron stores are depleted
- RBC level decreases, and RBC become microcytic and hypochromic
- Peripheral smear also may show anisocytosis and poikilocytosis
- Poikilocytosis = abnormally shaped RBC
- Anisocytosis = RBC are unequal in size
27
Q
treatment of IDA
A
- Identify and treat the cause
- Oral iron therapy: FeSO4 325mg po tid is preferred Rx (Can cause GI upset, She usually starts pts on 325 qd for a week or two and then slowly titrate up), Should see return to baseline in H/H in 2 mos, Continue 3-6 mos after achieving normal labs to replenish iron stores, Causes nausea, constipation in many pts, If they are taking their iron with milk every day then their constipation will probably actually get worse! Legumes, spinach, raisins, prunes, etc are great sources of iron, It takes a long time to replenish iron stores so that wont be normal for a long time (You monitor with H and H for a couple weeks and check iron panel and then every couple of months, you repeat these labs)
- Parenteral iron therapy (Intolerance to oral iron, refractory IDA, GI disease, uncorrectable continued blood loss)
28
Q
iron supplements
A
- Iron difficult to tolerate; constipation, GI upset, dark stools
- Ferrous sulfate 1st line; try Slow Fe or plant based iron, less absorption
29
Q
anemia of chronic disease
A
- Many chronic systemic diseases associated with mild to moderate anemia
- RBC survival is decreased – so instead of being around for 120 days, only around for 100 (for example)
- Bone marrow fails to compensate adequately for shorter RBC lifespan
- Iron is sequestered in reticuloendothelial system
- Usually this is mild anemia -> usually normocytic
- Common causes: Chronic infection or inflammation, Cancer, Liver disease, Chronic renal failure (Somewhat different pathophysiology, Decrease in EPO, More severe anemia than other chronic diseases)
