L26 - RBC Disorders Flashcards
True endocrine hormone produced in the kidney
• Enhances the growth and differentiation of the two erythroid progenitors: burst forming units-erythroid (BFUE) and colony forming units-erythroid (CFU-E) into normoblasts of increasing maturity.
Erythropoietin (EPO)
enucleate red blood cell still capable of a limited amount of hemoglobin and protein synthesis
reticulocyte
Helps with hemoglobin production which helps carry out maturation of RBC
Fe
Which is false regarding Hepcidin:
A. Peptide hormone made in the liver, is the principal regulator of systemic iron homeostasis.
B. Controls plasma iron concentration and tissue distribution of iron by inhibiting intestinal iron absorption
C. inc iron recycling by macrophages
D. Dec iron mobilization from hepatic stores.
E. elevated during infections and inflammation
C. dec iron recycling
ultimate cause of most forms of hemochromatosis, either due to mutations in this gene itself or due to mutations in the regulators of this molecule’s synthesis.
Hepcidin deficiency
A. How does chronic inflammation affect EPO and hepcidin?
B.What happens to hepcidin in Fe deficiency?
A. EPO decreases –> no mature RBC –> anemia
Hepcidin inc –> dec Fe absorption –> fe deficient
B. hepcidin dec –> inc Fe absorption
3 parts of the RBC life cycle
- Produce RBC (BM, EPO, Fe, vit b12 and folic acid)
- Eliminated RBC (life span 120 days)
- Steady state (1% RBC eliminated and equal # made each day)
hemoglobin in whole blood, gm/dL
Hemoglobin
% blood vol in RBCs
hematocrit • Hct = Hb x 3
low Hb or Hct
anemia
high Hb or Hct
Erythrocytosis
Why do elderly have lower EPO levels –> dec RBC/Hb
Low androgens
Why do women have lower Hb than men
Low levels of androgens, Fe loss during menses, pregnancy and lactation
T/F Hb varies by race, tobacco smoke exposure and inc altitude
• Black - lower Hb
• Smoker/high altitude - RBC goes up to inc oxygenation
○ Secondary erythrocytosis
○ Baseline higher Hb than normal (Hb 15-16)
- Diagnostic criteria for anemia
- need to use age-adjusted tables
- adult men – Hb ___ g/dL, Hct ___
adult women – Hb ___ g/dL, Hct ____
adult men – Hb 13 g/dL, Hct 40%
adult women – Hb 12 g/dL, Hct 35%
why does alcoholism or being vegan increase your risk of anemia?
- alcohol - folate
- veagn - lack vit B12
Review of systems in anemias
1. T/F : Generally, symptoms are non-specific.
2. T/F: Infants: poor feeding, irritability, tachycardia
3. T/F: Compensation – Cardiovascular & Hematologic
• weakness, dyspnea, palpitations, angina
• heart failure or shock
• SX usually at Hb
- True
- True
- True
- False - Neurologic: drowsiness, syncope, headache, seeing spots, tinnitus, vertigo
- True
T/F a complete physical exam is necessary for anemia
True: vitals, skin, LN, cardiopulm, GI, musc, neuro
Hypoproliferative erythropoiesis indicates what about the BM?
Not working well
Hyperproliferative erythropoiesis indicates what about the BM?
BM is working but there is some peripheral destruction
How do you determine if erythropoiesis is hypo or hyperproliferative?
Reticulocyte index - normally RBC form in marrow and mature for 3 days then spend 1 day in circulation bf maturing to RBC
• RI = (measured retic %) x (Hct/45) x (1/Correction Factor)
- How does the reticulocyte index assess adequacy of BM response to anemia?
- RI less than ___ indicates inadequate marrow response
• e.g. if hematocrit is low (15%), then the bone marrow tries to push the reticulocytes into peripheral circulation to help compensate for anemia
○ In BM shorter (1.5 days) and in peripheral blood longer (2.5 days)
○ Correction factor is the number of days the reticulocytes stay in the blood - here it would be 2.5
• RI less than 2.0 indicates inadequate marrow response
What approach to classification of anemia addresses the mechanism(s) responsible for the fall in hemoglobin concentration
• Blood loss, production problem, destruction problem
Kinetic approach
What approach to classification of anemia categorizing anemias via alterations in red blood cell (RBC) size (i.e., mean corpuscular volume) and the reticulocyte response
morphologic approach
Blood loss can
- Result in retic count (decrease/increase) generally less striking than in hemolysis
- T/F: Obvious vs occult
- T/F: Iatrogenic: daily CBC, surgical, hemodialysis, excessive blood donation
- T/F: Menstrual blood loss - uncommon cause
- increase
- true
- true
- false
What results from the following?
- Deficiency of iron, B12, folate
- Marrow is dysfunctional from myelodysplasia, tumor infiltration, aplastic anemia, etc.
- Bone marrow is suppressed by chemotherapy or radiation
- Low levels of erythropoietin, thyroid hormone, or androgens
Decreased RBC production hypoproliferative anemia( RI low)
What results from the following?
- Acquired: autoimmune hemolytic anemia, TTP-HUS, DIC, malaria
- Inherited: spherocytosis, sickle cell, thalassemia
- Anemia occurs when the BM is unable to keep up with the need to replace more than approximately 5% of the RBC mass/day= RBC survival of 20 days or less
Increased RBC destruction hyperproliferative anemia (RI high)
What morphological appearance do these result in?
- Fe deficiency anemia
- Thalssemic disorders/hemoglobinopathies
- anemia of inflammation/chronic idsease
- sideroblastic anemia (congenital, lead, alcohol, drugs)
- copper deficiency
Microcytic anemia (MCV less than 80fL)
What morphological appearance do these result in?
- acute blood loss
- Fe deficiency (early)
- anemia of inflammation/chronic disease
- BM suppression (aplastic anemia, pure red cell aplasia)
- endocrine dysfunction
- combined deficiency
Normocytic anemia (MCV 80-100fL)
What morphological appearance do these result in?
- alcohol abuse
- hemolytic anemia
- BM disorders such as MDS
- Drugs (chemotherapy agents)
- liver disease
Macrocytic anemia (MCV greater than 100 fL)
Which is not a clinical feature of Fe deficiency?
A. Pagophagia (eating ice)
B. Delayed growth, motor dev, behavior, cog fcn in children
C. koilonychia (spoon nails), pale, glossitis
D. paresthesia in the legs
E. Evidence of blood loss (menorrhagia, epistaxis, melenic stool, hematemesis)
D. restless leg syndrome not paresthesia
When diagnosing Fe deficiency
- blood testing for Fe saturation will be (low/high)
- blood testing for ferritin (low/high)
- BM Fe stain (is recommended/not needed)
- T/F these tests can be confound by inflammation
- low
- low
- not needed
- T
What are the stages of Fe deficiency?
- normal
- Fe deficiency w/o anemia
- Fe deficiency w/mild anemia
- severe Fe deficiency w/severe anemia
Which is false regarding Fe deficiency treatment?
A. Oral iron is expensive but effective when taken as prescribed, it can be considered front line therapy
B. Oral iron therapy may take up to 6 months to replete stores
C. Gastrointestinal side effects are extremely common and may result in poor adherence to therapy
D. If intolerant to oral therapy, may need to consider iron infusions
A. inexpensive
What is this RBC disorder?
- history: autoimmune, GI surgery, diet (vegan), paresthesia (stocking-glove)
- PE: glossitis, lingual papillae atrophy, jaundice
- Neuro: gait ataxia, babinski/Romberg signs, depression, dementia
Vitamin B12 Deficiency
What is this RBC disorder?
- history: diet poor in folic acid, malnourished, alcoholic, Crohn’s, diarrhea, anticonvulsants, preg
- PE: no glossitis, no neuro features
Folate Deficiency
What are the risks of Folic Acid / Cobalamin – Management?
- replacing only folate may mask pernicious anemia & worsen neuropathy
- interacting metabolism
- deficit of one may effect other
If methylmalonate & homocysteine are both normal, this indicates
folate or B12 deficiency is NOT involved
If methylmalonate & homocysteine are both high, this indicates
B12 deficiency
Solely homocysteine indicates
folate
What is this condition?
- Cytokine mediated process which inhibits RBC production or interferes with action of EPO
- Decreased iron utilization/mobilization
- Seen with rheumatologic diseases, chronic infections, malignancy
- Indices: Low Fe, Low TIBC, N/increased Ferritin
- May be seen in conjunction with Fe-deficiency
Anemia of chronic disease - common and often very hard to treat unless the underlying disorder can be treated
- subset of “anemia of chronic disease”
- renal disease – dialysis patients
- therapy: replacement
- common challenge: determining if there is concomitant iron deficiency, esp. if inflammation
EPO deficiency
Which is not a feature of hemolysis? A. dark urine B. B12 deficiency C. Skin: jaundice, petechiae, ecchymoses D. spleen/liver enlargement, lymphadenopathy E. Bone/chest pain (sickle cell dz)
B
What is seen on smear on hemolysis
Schistocytes - hemolytic process
spherocytes - autoimmune
sickle
bite cells - G6P def
Why do you do the Coomb’s test?
To determine if the hemolytic anemia is immune or non-immune
Which is false regarding thalassemia?
A. Decreased production of either α-globin or β- globin chains
B. Normal hemoglobin electrophoresis
C. Microcytic anemia with increased RBC mass
D. Polychromasia (dark staining retics), target cells, basophilic stippling
B. Abnormal
Alpha or beta thalassemia?
- 4 genes
- 1/4: silent carrier
- 2/4: (alpha/beta)-Thalassemia trait, microcytosis and mild anemia
- 3/4: excess (alpha/beta)-chains form tetramers, results in severe anemia and microcytosis
- 4/4: hydrops fetalis
- Most common in SE Asian populations
Alpha
- alpha
- beta
Alpha or beta thalassemia?
- 2 genes
- 1/2 mutation: (alpha/beta)-Thal trait, increased Hgb A2, rarely anemic, mild microcytosis
- 2/2 mutation: (alpha/beta)-Thalassemia major, Hgb F increased, microcytosis, anemia
- Usually found in people of African or Mediterranean descent but has world-wide distribution
- beta
3. beta
These are clinical manifestations of what condition?
A. pulmonary HTN
B. angina
C. splenomegaly
D. Skeletal changes (facial abnormalities, osteopenia/porosis)
E. hepatomegaly, gallstones
F. endocrine problems
thalassemia
T/F BM transplant is curative for thalassemia
True - chronic transfusions, Fe chelation, splenectomy, drugs, gene therapy are also possible
Which is false regarding sickle cell disease?
A. deoxygenation leads to polymerization of Hb, causing sicking of red cells
B. Sickle cells damage the endothelium and adhere to it leading to vasoconstriction
C. caused by a frame shift on chrom 11
D. recessively inherited chronic hemolytic anemia
C. single nucleotide substitution in the beta globin gene on chrom 11
Sickle cell anemia
- T/F shortens erythrocyte survival from 120 days to 10-25 days
- T/F multiple organs are involved
- T/F mild hemolysis
- T/F treatment mainly supportive (hydration and analgesia for painful crisis)
- True
- True
- False - Hb around 8
- True
What kind of anemia is this?
- Myelodysplastic syndrome
- BM infiltration: nucleated RBC found in circulation
- Might see “rouleaux” formation in multiple myeloma
- WBC, plts often abnormal
Anemia due to Primary Bone Marrow Disorder
