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what percent of our weight is our blood volume (in liters)
7%
how many liters of blood does a 70 kg pt have
4.9 L
what are the two components of blood volume
RBCs and plasma
how does acute blood loss affect the components of blood volume (and hematocrit)
- low plasma
- low RBCs
the hematocrit is still considered normal
how does chronic anemia affect the components of blood volume (and hematocrit)
- low RBCs (body is unable to produce them for whatever reason (most commonly iron deficiency))
- extra plasma (body can still produce it and is compensating for low RBCs)
the hematocrit is low
how does volume-overload affect the components of blood volume (and hematocrit)
- normal amount RBCs
- too much plasma (due to lots of salt and water)
the hematocrit is low
how to write fishbone diagram for a CBC
write hemoglobin over hematocrit, WBC on the left and platelets on the right
what is hemoglobin (and what is the normal range)
molecule that carries O2 in the blood
- units are g/dL
- 14 - 17.5 g/dL for men (less for women)
what is hematocrit (and what is the normal range)
percentage of blood volume made up of RBCs
- % of RBCs/blood
- if half of our BV is RBCs and the other half is plasma, hematocrit should be around 50%
- 42 - 50% (less for women)
what is RBC count (and what is the normal range)
estimation of how many RBCs are in the body
- units are millions/uL
- 4.5 - 6 mill/uL (less for women)
relationship between hemoglobin and hematocrit
hemoglobin x 3 = hematocrit
normal WBC range
4,000-11,000 per microliter
normal range of neutrophils (PMN)
45-75%
normal range of lymphocytes
15-45%
normal range of monocytes
0-15%
normal range of eosinophils
0-5%
normal range of basophils
0-3%
normal platelet range
150,000-450,000 per microliter
how can aggregated platelets affect the RBC and platelet count
clumps of plts may be counted as RBCs
- falsely elevated RBC count
- falsely lowered platelet count
what does a neutrophil look like
numerous lobes
what does a lymphocyte look like
large round nucleus
what does a monocyte look like
kidney bean shaped nucleus
what does an eosinophil look like
pink, bi-lobed cell
what does a basophil look like
purple and granulated
two ways to count the number of cells in a CBC
- light impedance
- manually (looking at a peripheral smear under microscope--morphologic changes may be helpful in diagnosis)
proper definition of anemia
functional inability of blood to supply tissue with adequate oxygenation for proper metabolic function
real-life definition anemia
decrease in the circulating red cell mass
what is mean corpuscular volume (and what is the normal range)
average size of the circulating RBCs
- units are femtoliters
- 80 - 96 fL
what is red cell volume distribution width
how big is the range in RBC sizes (are they all around the same size or are some big and some small)
- even if MCV is normal, the sizes could be off
- 11.5 - 14.5
microcytosis
cells are small
- MCV <80 fL
macrocytosis
cells are large
- MCV >100 fL
anisocytosis
variation in RBC size
- RDW >14.5
anisochromia
variation in color of RBCs
poikilocytosis
abnormal cell shapes
- examples: spherocytes, acanthocytes
schistocytes
fragments of RBCs
what does a peripheral blood smear look like for a pt with iron deficiency
- microcytic (they should be similar size to nucleus of lymphocyte)
- hypochromic (little pigmentation- white area within RBC is more than 1/3 of size of cell)
- poikilocytosis (some cells may have weird pencil shape)
megaloblastic vs microcytic
- microcytic- large RBCs
- megaloblastic- large AND too many lobes in nucleus
causes of megaloblastic anemia
b12 or foalte deficiency
what are reticulocytes
immature RBCs
what does the reticulocyte count tell us
can the bone marrow produce new RBCs in response to anemia?
what does it mean if the reticulocyte count is low
bone marrow does not have the materials or ability to make more RBCs
- iron, vitB12, or folate deficiency
- anemia of inflammation (can't put RBCs together)
what does it mean if the reticulocyte count is high
bone marrow CAN make RBCs and its not a supply or ability issue
- high bc BM is trying to compensate for RBC loss
- hemolytic anemia
- anemia d/t acute blood loss
what does it mean if reticulocytes have ribosomal RNA in them
they are VERY immature
- body is trying SO hard to increase RBC count and is releasing blood cells well before they are ready
what labs should you order if you suspect missing substrate as cause of anemia
- iron studies
- vit B12 levels
- folate levels (serum and RBC folate levels)
(suspected with low retic count)
what labs should you order if you suspect hemolysis as cause of anemia
- bilirubin (would go up)
- lactate dehydrogenase (would go up)
- haptoglobin (would go down)
- direct antiglobulin test
- UA
what labs should you order if you suspect abnormal hemoglobin production as cause of anemia
- hemoglobin electrophoresis
functional approach to anemia diagnosis
think about WHY someone became anemic
- blood loss (acute or chronic)
- impaired production
- increased destruction (hereditary or inherited)
morphologic approach to anemia diagnosis
- determine MCV (are cells small, normal, or large)
what are the microcytic anemias
- iron deficiency
- thalassemias
- anemia of inflammation (chronic disease)
- heavy metal poisoning
- hereditary sideroblastic
what are the normocytic anemias
- acute blood loss
- EARLY iron deficiency anemia
- anemia of inflammation (chronic disease)
- renal insufficiency
what are the macrocytic anemias
- folate deficiency
- ethanol abuse
- vitB12 deficiency
- AML
- reticulocytosis
CBC abnormalities consistent with iron deficiency
- decreased RBCs, Hgb, and HCT
- microcytic (low MCV)
- increased RDW (anisocytosis)
- hypochomia
- poikilocytosis
iron studies (and when would you get each one)
- serum Fe/total iron binding capacity ratio (percent that transferrin is saturated with Fe)
- ferritin (under normal circumstances, ferritin is a DIRECT reflection of body iron stores; ferritin rises during inflammation)
ferritin is best, but you can't get it if pt is sick
normal serum Fe/total iron binding capacity ratio
25-40%
how do the labs change as patient develops Fe deficiency
- ferritin begins to decrease early
- anisocytosis (high RDW)- more small cells than large
- MCV and MHC decrease
- hypochromia, low Hgb, tranferrin sat <16%
why is a retic count so important
- if high, it implies there is hemolysis or blood loss- these are URGENT kinds of anemia
- if retic count is low or inappropriately normal, lab workup is done based on MCV
if the patient has macrocytic anemia and you suspect folate deficiency, what tests do you do
- START with serum folate (cheap and easy, but can easily be affected by outside factors [eating])
- if normal or high, do RBC folate level
tests for vitB12 deficiency (due to malabsorption)
Schilling test
- radiolabeled vitB12 ingested
- check urine (if low, it suggests malabsorption of B12)
- to figure out WHY give: intrinsic factor (pernicious anemia), abx (bacterial overgrowth), pancreatic enzymes (pancreatic dysfunction)
what do you do if CBC shows normocytic anemia
- check all iron studies to rule out early Fe deficiency
- differentiate anemia of chronic disease from Fe deficiency
how does anemia of chronic disease affect iron
- iron storage in organs increases and iron gets trapped in macrophages (serum Fe is LOW)
- ferritin increases
- transferrin is normal/low (body still detects iron so it doesn't increase transferrin)
lab values for Fe deficiency vs chronic disease
- transferrin: increased in Fe, decreased in chronic D
- % saturation: decreased in Fe D, normal in chronic D
- ferritin: decreased in Fe D, increased in chronic D
how do chronic diseases cause anemia
- trapped iron --> less utilization
- decreased EPO (kidney disease)
- inflammatory disease --> cytokines decrease iron utilization
etiologies of anemia of chronic disease
- infections (HIV, chronic viral infections, fungal, bacterial)
- connective tissue disorders
- systemic malignancy
- renal failure
- liver disease
- alcoholism
- endocrine disorders
hallmark of anemia of chronic disease
high ferritin
what does it mean if retic count is high but there is no sign of acute blood loss
hemolysis is likely
- drug and family history
- check haptoglobin, LDH, bilirubin, and Coombs test
- do hemoglobin electrophoresis if indicated
what is haptoglobin
- protein that binds to free hemoglobin from RBC breakdown (or hemolysis)
- delivers hemoglobin to liver to convert it to bilirubin
- if low- think LOTS of free hemoglobin --> hemolysis
what is considered very low haptoglobin
< 7 mg/dL
what happens if there is too much free hemoglobin and not enough haptoglobin
- free hemoglobin in plasma
- gets filtered by kidneys --> urine or some is reabsorbed
increased serum LDH and decreased haptoglobin is a sign of
hemolysis
how is bilirubin affected in hemolysis
- breakdown of RBCs causes release of unconjugated bilirubin
- indirect/unconjugated bilirubin is elevated
how do you measure indirect bilirubin
order total bilirubin and direct bilirubin
- then calculate indirect
which form of bilirubin is water-soluble (and may be excreted in urine if liver becomes damaged and it back-leaks)
conjugated/direct bilirubin
why is it that if the liver is damaged, the main sign is conjugated hyperbilirubinemia
when liver becomes damaged, all steps of bilirubin conjugation are affected (uptake of bili by hepatocytes, conjugation, and excretion into bile) but excretion is affected the MOST and the EARLIEST
- later on in the disease course, it will be a mixed hyperbilirubinemia
etiologies of unconjugated hyperbilirubinemia
overproduction of bilirubin in blood d/t hemolysis
- hemolytic drugs
- autoimmune rxn
- sickle cell
- infections like malaria and babesiosis
can unconjugated bilirubinemia cause urine darkening
no
what is the direct Coombs test
direct antiglobulin test
- used to see if RBCs have antibodies already bound to them (and causing hemolysis)
- examples: autoimmune (body made antibodies binding to own RBCs), drug-induced (drug made body make antibodies binding to own RBCs)
how to do direct Coombs test
- take sample of blood from pt
- remove pts serum (we want JUST the RBCs)
- combine RBCs with Coombs reagent (anti-human globulin)
- if RBCs are coated with antibodies, reagent will bind to antibodies and cause RBCs to clump
intravascular vs extravascular hemolysis (what is it, what are examples, and how to tell difference)
- intravascular: occurs in circulation, releasing Hgb into plasma; causes: trauma, DIC, toxic damage; produces schistocytes
- extravascular: RBCs are phagocytized by macrophages in spleen and liver; causes: RBC membrane or structure abnormalities; produces spherocytes
what to do if intravascular hemolysis is suspected
- measure plasma Hb concentration (looking for hemoglobinemia)
- measure free Hb in urine (looking for hemoglobinuria)
what happens if a patient has anemia with pancytopenia
this means ALL cell lines are affected (RBCs, WBCs, platelets)
- this is a bone marrow issue!- aplastic anemia