Lecture 1b Flashcards
What are some causes of erythropoiesis?
Low O2 delivery
EPO(Erythropoietin) stimulation
RBC proliferation and maturation
Reticulocyte release
How does EPO increase RBC production?
Binds to marrow erythroid precursors(pro erythroblasts) inducing cell maturation
What vitamins assist in proliferation of erythroblasts?
Folate and Vitamin B12
How does iron assist in RBC production?
Accumulation of hemoglobin
What are the characteristics of reticulocyte?
Immature RBC (non concave, slightly bluer)
Contains RNA (absorbed before maturing to a RBC)
4-5day lifespan (3 days in bone marrow 1-2days in blood)
What are the optimal conditions for erythropoiesis?
Normal EPO production
Normal erythroid marrow function
Adequate Hgb accumulation
What are the two approaches to anemia?
Kinetic approach and morphologic approach
Define kinetic approach.
Addresses the mechanism responsible for the fall in Hgb concentration
Define morphologic approach.
Categorizes anemias based on alterations in RBC characteristics and reticulocyte response
What mechanisms can cause anemia?
Decreased RBC production
Increased RBC destruction(hemolysis)
Blood loss
What is RBC production directly related to?
RBC destruction
What is the average daily RBC production amount?
1% of Red cell mass
What are common causes of decreased RBC production?
Lack of nutrients(iron, B12, folate)
Bone marrow disorders
Bone marrow suppression
Low levels of trophic hormones
Acute/chronic inflammation
What are some examples of bone marrow disorders?
Aplastic anemia
Pure RBC aplasia
Myelodysplastic syndromes
Tumor infiltration
What are some examples of bone marrow suppression?
Drugs
Chemotherapy
Irradiation
What are some causes of low levels of trophic hormones?
Chronic renal failure
Hypothyroidism
Hypogonadism
How does inflammation affect RBC production?
Decreases RBC production by affecting iron concentration, reduces EPO and decreases RBC lifespan
What are some causes of increased RBC destruction?
Inherited hemolytic anemias
Acquired hemolytic anemia
Hypersplenism(enlarged spleen)
What are some examples of inherited hemolytic anemias?
Hereditary spherocytosis
Sickle cell disease
Thalassemia major
What are some examples of acquired hemolytic anemias?
Coomb’-positive autoimmune hemolytic anemia
Thrombotic thrombocytopenia purpura(TTP)
Malaria
Paroxysmal nocturnal hemoglobinuria
What are some causes of blood loss(main cause of anemia)?
Gross blood loss
Occult blood loss
Iatrogenic blood loss
Under appreciated menstrual blood loss
What are some examples of gross blood loss?
Trauma
Surgery
Melena
Hematemesis
Severe menomotro
What are some examples of occult blood loss?
Slowly bleeding ulcer or carcinoma
What are some examples of iatrogenic blood loss?
Repeated diagnostic testing
Hemodialysis losses
Excessive blood donation
What tests do we use to classify anemia?
MCV, MCH, MCHC
What is the normal range for MCV?
80-100 fL
What can cause macrocytic anemia?
Folate and B12 Deficiency
Drugs interfering with nucleic acid synthesis(zidovudine and hydroxyurea)
Abnormal RBC maturation (myelodysplastic syndrome, acute leukemia)
Alcohol abuse(folate deficiency)
Liver Disease
What can cause microcytic anemia?
Iron deficiency
Alpha and beta thalassemia minor
Microcytic anemia is associated with what levels of MCHC?
low MCHC due to decreased HgB content in small RBC
What are the causes of normocytic anemia?
Chronic kidney diseases
Anemia of chronic disease/inflammation
Mild iatrogenic “hospital” anemia
What type of anemia is often required an evaluation by a peripheral smear?
Normocytic anemia
What are anemic symptoms related to?
Decreased O2 delivery to tissues
How does the body compensate when in an anemic state?
Increased in O2 extraction
Increase in SV and HR (maintains O2 delivery util HgB falls below 5g/dL)
How much more O2 can the body extract from HgB?
25% to 60%
25% is normal extracting
60% usually in anemia/hypoperfusion
What are the common S/S of anemia?
Fatigue
Tachycardia/dyspnea
Palpitations
Pulsations
Bounding pulses
Pallor
What are the S/S of anemia by volume depletion?
Fatigue
Muscle cramps
Dizziness/syncope
Lethargy
Hypotension/shock/death
What 4 questions do you ask when you suspect anemia?
- Is patient bleeding? Where?
- Evidence of increased RBC destruction?
- Is there bone marrow suppression? Why?
- Is Patient nutrient deficient in iron, folate, B12? Why?
What do you need to look at when a patient has an onset of symptoms?
New onset most often related to acquired d/o?
Lifelong anemia likely inherited
Compare recent to remote HgB&hematocrit/RBC indices
What recent symptoms can be a sign of anemia?
Unintentional weight loss
Loss of appetite
Fever
Night Sweats
What medical conditions are associated with anemia?
Melena (upper GI bleed, bleeding ulcer)
Large hematochezia (Lower acute GI bleed)
Menorrhagia (Dysfunctional uterine bleeding)
Renal failure
RA
CHF
What do you look for on the skin for signs of anemia?
Pallor, jaundice
Petechiae, bruising
What do you look on the eyes for signs of anemia?
Pale conjuctiva, scleral icterus
What other physical signs do you look for in anemia?
Lymph nodes
Abdomen (hepatosplenomegaly)
Bony tenderness (sternum/anterior tibia)
Stool for occult blood
How does volume affect the interpretation of a CBC?
HgB,Hct, RBC are all concentration and dependent on red cell mass(RCM)
So if RCM is decreased and/or plasma vol is increased then RBC and H&H will be low (and vice versa)
What is hemoconcentration?
Decreased plasma vol, RBC and H&H elevated
Example: Dehydration
What would an automatic reticulocyte count be preferred over manual?
More blood can be assessed
However manual used if there are errors such as blood clots
What are reticulocyte count reported as?
Percentage of RBC
What is a reticulocyte index(RI) calculation? Whats the equation?
More accurate reflection of relic count in anemia patients
RI = reticulocyte percentage × (patient’s HCT/normal HCT)
Normal RI <3%
Increased retic count is indicative of hemolysis, what other labs do we order to determine more?
Serum lactate dehydrogenase(LDH)
Indirect bilirubin(unconjucated)
Serum haptoglobin
What does an increase of LDH mean?
LDH is concentrated in RBCs so destruction of RBC will have increased LDH
What does an increase of indirect bilirubin mean? How do we calculate it?
Total bilirubin - direct bilirubin(conjugated)
From the breakdown of HgB so signs of hemolysis
What does a decrease of serum haptoglobin mean?
Binds free HgB that is released from hemolyzed RBC
So in increased hemolysis it binds to more HgB therefore low haptoglobin levels
What is the Coombs Test, Direct(Direct anti globulin test)? What is used to screen for?
Screened for autoimmune hemolytic anemia
Assess presence of antibodies on the surface of RBC’s, which ultimately causes RBC destruction
What can indicate a positive Coombs Test?
Autoimmune hemolytic anemia
Hemolytic transfusion reaction
Drug sensitizations
Hemolytic disease of newborns (erythroblastosis fetalis)
What are some drug sensitizations for a positive Coombs test?
Methyldopa
Levodopa
Cephalosporins
Penicillin
Quinidine
What do we use to test for microcytic anemia?
Retic count
Serum Iron
Transferrin
Total Iron binding capacity
Transferrin Saturation
Ferritin
Peripheral Blood smear
Coombs test
Where is iron found in the body?
65% bound to HgB
30% stored as ferritin or hemosiderin in spleen, bone marrow, and liver
4% bound up in myoglobin molecules
<1% remains in cells throughout the body
<0.1% bound to transferrin
What are ways humans lose iron?
Perspiration
Epithelial cell desquamation
Menstruation
What is serum iron a measure of?
Circulating iron bound to transferrin
What could cause decreased iron levels?
Iron-deficiency anemia
Nephrosis
Anemia of chronic disease and infection
Chronic blood loss
Malabsorption disorders
What can cause increased iron levels?
Hemochromatosis
Excessive iron intake
Hemolysis of erythrocytes
Liver necrosis
What is the function of transferrin?
Major plasma transport protein for iron
Carries iron from duodenum to marrow
Where is transferrin produced in?
Liver
What can cause decreased transferrin saturation?
Iron-deficiency anemia
What can cause increased transferrin saturation?
Hemochromatosis
Iron overload
Thalassemia
RBC transfusions
What does the total iron binding capacity(TIBC) measure?
Blood’s capacity to bind iron with transferrin
Indirectly measures transferrin
What is function of Ferritin?
Body’s major iron storage protein
Iron molecules not used in marrow bind to ferritin
What can cause in increase of ferritin?
Iron overload
Inflammation
Liver disease
What measurement is the most reliable indictor of total-body iron status? Which test is even more accurate?
Ferritin
Bone marrow is more accurate
Why is measuring ferritin better for diagnosing iron-deficiency anemia?
Its more specific and sensitive than iron concentration or TIBC
What labs to we measure for microcytic anemia?
Reticulocyte count
Vitamin B12
Folate
Where is vitamin B12 found in?
Animal proteins
Where is vitamin B12 stored?
In the liver
What else is needed for vitamin B12 to be absorbed and where is it absorbed?
Needs intrinsic factor and absorbed in ileum
Where is folic acid found in?
Eggs
Milk
Leafy vegetabels
Yeast
Liver
Fruits
Where is folate absorbed and stored?
Absorbed in upper 1/3 of intestine and stored in the liver
How does B12 affect folate?
B12 is needed to move folate into tissue cells
What is the difference between folate and folic acid?
Folate is naturally made
Folic acid is synthetic
What labs do we need to evaluate normocytic anemia?
Reticulocyte count
Workup based upon differential
