Anemias Flashcards
1
Q
Hypoproliferative anemia
A
- Based on the reticulocyte count and bilirubin levels
- In hypoproliferative (decreased total production), there is low blood levels of all blood cells (RBCs, platelets, WBCs)
- Will have a decrease in retics, normal bill
- An example is aplastic anemia (check BM under LM for Dx), Fe deficiency (microcytic), and chronic inflammation anemia (ACD)
- ACD is normocytic or microcytic
2
Q
Ineffective production
A
- RBCs developing in BM die before reaching maturity, releasing their contents into the blood
- Results in an decreased retic count and elevated (or normal) bill, elevated LDH
- Can be due to many things: cobalamin, folate deficiencies, or thalassemia
- Can lead to microcytic (Hb production problem; thalassemia) or macrocytic (DNA production problem; cobalamin, folate deficiency) anemias
3
Q
Hemolysis
A
- RBCs are destroyed either intravascularly or extravascularly (spleen, BM, liver), releasing their contents into the blood stream (intravascular) or into macrophages (extravascular)
- Results in elevated retic count, LDH, and bili
- The Hb that is released will either go to the kidney (high Hb/hemosiderin in urine/tubules, only in intravascular), or will be broken down into bilirubin in macrophages (only extravascular)
- In both, there will be Hb in the blood (some leaks out in extravascular) which is picked up by haptoglobin and taken to liver for conversion to bili
- Therefore haptoglobin is a marker to check for hemolysis, since it will be low
- Can be due to SCD, thalassemia, hereditary spherocytosis, paroxysmal nocturnal hemoglobinuria
4
Q
Acute blood loss
A
- Hemorrhage leads to anemia, also the only major cause of Fe deficiency anemia
- Results in elevated retic count but normal bili
- Fe deficiency more common in women (menses)
- Most bleeding is in GI tract (occult blood) due to polyps
5
Q
RBC indices
A
- Hb: 13-16g/dl (males), 11.5-14g/dl (females)
- Hct: 37 (F), 39 (M)
- RBC: 4.5-5E6 (M), 4-5E6 (F)
- MCV: mean corpuscular volume (macro or microcytic), is the (Hctx10)/RBC integer
- Normal: 80-100
- MCH: Mean cell Hb (hypo of hyper chromic)
- Normal is 28-33
- MCHC: mean cell Hb concentration (spherocytes or normal), elevated = spherocytes
- Normal: 31-35%
- Normal retic count: 1% (.5% w/ shift cells), also 50,000 (out of 5,000,000 RBCs)
- Normal granulocyte:erythrocyte is 4:1
- Normal bili: ≤1.2 mg/dl (ind. ≤.9, dir. ≤.3)
- LDH <250
- RDW≤14 (higher is variability in size= anesocytosis), poikilocytosis: change in shape (only via smear)
6
Q
Aplastic anemia
A
- Do not produce any blood cells (hypoproliferative)
- Distinct in that there will be anemia along w/ low WBCs (<150,000)
- Causes are hereditary (Fanconi anemia) or acquired
- Acquired aplastic anemia can be due to direct toxicity (radiation, chemo, toxins), or indirect toxicity (drugs like chloramphenicol, infections, pregnancy)
7
Q
Fe deficiency anemia
A
- Due to low Fe (drained the stores) and inability to produce Hb (microcytic, hypoproliferative) leads to decreased retic and bili
- Almost always from hemorrhage (usually GI bleeds), can also be increased requirements (growth, pregnancy), decreased intake/absorption
- Normally lose 1mg of Fe daily (from RBC destruction), have 300mg in storage
- 3.4mgFe/1gHb, 14gHb/dL (#dL is 65mL/Kg female, 70mL/Kg male)
- Fe absorbed in duodenum by DMT1 transporter on apical surface (same transporter used in macrophages for Fe influx)
- Fe released into blood via ferroportin on basolateral side of duodenal epithelia (ferroportin also on macrophages for efflux)
8
Q
Hepcidin and Fe regulation
A
- Hepcidin regulates release of Fe from stores/GI
- When hepcidin levels rise (during times of high Fe, infection, ect), hepcidin down regulates DMT1 in GI epithelia and up regulates DMT1 in macrophages (to absorb less and store more, respectively)
- Hepcidin internalizes ferroportin (in both GI and macs) to decrease efflux from the cells
- During this, there will be a lower transferrin level and a higher ferritin level (since Fe was high)
- Overall hepcidin will lower serum Fe levels
9
Q
Other regulation of transferrin/ferritin
A
- IRP (Fe regulating protein) binds to response element (IRE) on transferrin gene when there is low Fe (otherwise Fe would bind to IRP and prevent it from binding to IRE)
- IRP+IRE binding means an increase of transferrin and DMT1 (need more Fe) via mRNA stabilization
- IRP+IRE binding means no ferritin is translated (no Fe to store)
10
Q
Regulation of hepcidin
A
- Produced in the liver
- Increasing hepcidin levels: IL6 (inflammation), Fe overload (HFE)
- Decreasing hepcidin levels: EPO, HIF1a (hypoxia/anemia)
11
Q
Extravascular hemolysis 1
A
- Due to hemolysis in tissue macrophages such as in the spleen, liver, BM
- RBCs are phagocytosed by macrophages, leading to hemolysis inside the cell
- Some Hb does leak out of the RBC during this process, and free Hb in the blood is picked up mainly by haptoglobin (also hemopexin and albumin)
- The remaining Hb in macrophages is converted to bilirubin by heme oxygenase (releasing Fe and CO2) and biliverdin reductase
12
Q
Extravascular hemolysis 2
A
- The bilirubin is released into the blood and binds to albumin for transport to the liver (indirect bili)
- In the liver the bili is conjugated w/ glucuronic acid to direct bili (water soluble) to be excreted in bile (stercobilinogen) and urine (urobilinogen). Both will be elevated in either kinds of hemolysis
- There will not be an elevation in urine hemosiderin or Hb (or plasma Hb) in extravascular hemolysis because all of the Hb is picked up by haptoglobin or sent to liver in form of bili
- Will get a reduced serum haptoglobin b/c haptoglobin levels decrease as Hb leaks out during extravascular hemolysis and is picked up by haptoglobin
- Indirect bili will be high, direct bili will be normal
13
Q
Intravascular hemolysis
A
- The RBCs are lysing directly in the blood stream, releasing their contents into the blood
- The Hb and Fe2+ is picked up by haptoglobin, the Hb and Fe3+ is picked up by hemopexin and albumin, all of which is taken to the liver to be converted into bili
- Since there is more Hb being released into the blood, some Fe2+ heme (pink) and Fe3+ metheme (brown) are not picked up and therefore are filtered by the kidney
- Urine hemosiderin and hemoglobin often are elevated in intravascular hemolysis
- The heme that is sent to the liver is converted to direct bili and excreted in the same fashion as in extravascular hemolysis (urobilinogen in urine and stercobilinogen in bile)
- Indirect bili will be high, direct will be normal
14
Q
Intra vs extravascular hemolysis
A
- Best way to distinguish extra vs intra is looking at urine Hb and hemosiderin
- Urine Hb and hemosiderin will be high in intravascular but normal in extravascular
- Also look at blood smears; intravascular RBCs usually show schistocytes (fragmented, due to lysis by IgM binding-> complement activation) whereas extravascular RBCs usually show spherocytes (due to IgG/complement binding-> macrophages phagocytose)
- Both will have increased bili and LDH
- Extravascular often due to IgG binding to RBCs, causing the macrophages to eat them
15
Q
Acquired/hereditary, extrinsic/intrinsic
A
- Almost always, acquired hemolysis is due to extrinsic factors (autoimmune, toxins, drugs, ect)
- Whereas hereditary hemolysis is due to intrinsic factors (gene mutations leading to linkage problems, nz deficiencies, ect)
- Examples of hereditary defects: eliptocytosis (horizontal linkage defect) and hereditary spherocytosis (spectrin defect, vertical linkage)
