Anemias- Lecture Flashcards
Purple blotches in the background that look like dirt are platelets
What does hematocrit (Hct) represent?
Hematocrit (Hct) is the percentage of blood composed of RBCs
MCH vs MCHC
Mean cell hemoglobin (MCH) is the average weight of hemoglobin per RBC
Mean cell hemoglobin concentration (MCHC) is the average concentration of hemoglobin per RBC
Relative erythrocytosis occurs due to _
Absolute erythrocytosis occurs due to _
Relative erythrocytosis occurs due to decreased plasma volume
Absolute erythrocytosis occurs due to increased RBC mass
(True/ False) Anemia is a decrease in red blood cell mass
True; this comes with decreased oxygen and carbon dioxide transport
(True/ False) All anemias will have decreased hemoglobin, hematocrit, and RBC count
True; All anemias will have decreased hemoglobin, hematocrit, and RBC count
Normal sized RBCs are _
Large RBCs are _
Small RBCs are _
Normal sized RBCs are normocytic
Large RBCs are macrocytic
Small RBCs are microcytic
Anisocytosis
Anisocytosis means the RBCs vary in size
If RBCs vary in shape we call this _
If RBCs vary in shape we call this poikilocytosis
“Normochromic, hypochromic, and hyperchromic” reflect the amount of _ and is measured with _ or _
“Normochromic, hypochromic, and hyperchromic” reflects the amount of hemoglobin and is measured with MCH or MCHC
Classify as normocytic, microcytic, or macrocytic
Normocytic: normal RBCs are the size of a lymphocyte nucleus
When might you see the following?
Acanthocyte (spur cell): seen with liver disease
When might you see the following?
Bite cell: seen in G6PD deficiency
When might you see the following?
Target cell (aka codocyte): thalassemia
When might you see the following?
Echinocyte (burr cell): kidney disease
When might you see the following?
Schistocyte: microangiopathic hemolytic anemia
When might you see the following?
Sickle cell: sickle cell anemia
When might you see the following?
Spherocyte: either warm autoimmune hemolytic anemia or hereditary spherocytosis
_ are younger RBCs that have not yet ejected all of their genetic material
Reticulocytes are younger RBCs that have not yet ejected all of their genetic material
* They are visualized using a supravital stain
Supravital stain (for reticulocyte count) will highlight _
Supravital stain (for reticulocyte count) will highlight rRNA
* Uses crystal violet and brilliant cresyl blue
How can the reticulocyte count be interpreted?
Increased reticulocyte: bone marrow is responding to the anemia
Normal or decreased reticulocyte: bone marrow is not responding to anemia (hypoproliferative anemia)
What are the general symptoms of anemia?
- Dyspnea (short of breath)
- Fatigue
- Dizziness
- Tachycardia
- Conjunctival pallor
Jaundice is a sx that is exclusive to _ anemias
Jaundice is a sx that is exclusive to hemolytic anemias
Megaloblastic anemia falls into the (decreased production/ increased destruction) category
Megaloblastic anemia falls into the decreased production category
Sideroblastic anemia falls into the (decreased production/ increased destruction) category
Sideroblastic anemia falls into the decreased production category
Name the 3 microcytic anemias
- Iron-deficiency anemia
- Thalassemia
- Sideroblastic anemia
Name the two macrocytic anemias
- Megaloblastic anemia
- Nonmegaloblastic anemia (alcohol related)
Megaloblastic anemias result from decreased RBC production due to the missing _ which is caused by a deficiency in _ or _
Megaloblastic anemias result from decreased RBC production due to the missing building blocks of DNA synthesis which is caused by a deficiency in folate (B9) or vitamin B12
Megaloblastic anemia can be caused by medications like _ , _ , _
Megaloblastic anemia can be caused by medications like chemo , anti-retroviral drugs , hydroxyurea
Cells in our bone marrow rapidly turn over –> this means they require a lot of _ and _ to constantly synthesize DNA
Cells in our bone marrow rapidly turn over –> this means they require a lot of folate and B12 to constantly synthesize DNA
* A deficiency in these will decrease cell division
Megaloblastoid changes occur in the bone marrow including cytoplasmic assynchrony, which means _
Megaloblastoid changes occur in the bone marrow including cytoplasmic assynchrony, which means cytoplasm continues to grow while the nucleus is stunted –> ineffective erythropoiesis
To get from homocysteine –> methionine we need THF to _ and we need the presence of _
To get from homocysteine –> methionine –> DNA we need THF to donate a methyl group and we need the presence of B12 and folate
Methylmalonyl CoA –> Succinyl CoA –> myelin requires only _
Methylmalonyl CoA –> Succinyl CoA –> myelin requires only B12
* Therefore only B12 deficiency is associated with neuro deficits
B12 deficiency will result in an accumulation of _
B12 deficiency will result in an accumulation of homocysteine and methylmalonic acid
Folate deficiency will result in an accumulation of _
Folate deficiency will result in an accumulation of homocysteine only
Vitamin B12 gets absorbed in the _
Vitamin B12 gets absorbed in the ileum (last part of the small intestine)
* Needs to be bound to intrinsic factor (IF)
_ occurs when there is a lack of intrinsic factor which inhibits the absorption of B12 in the small intestine and leads to megaloblastic anemia
Pernicious anemia occurs when there is a lack of intrinsic factor which inhibits the absorption of B12 in the small intestine and leads to megaloblastic anemia
* Begins with auto-antibodies destroying gastric parietal cells
Three causes of vitamin B12 AND folate deficiency
- Intestinal malabsorption (example crohn’s disease affects the terminal ileum and celiacs affects the duodenum)
- Alcohol (general lack of nutrients)
- Diet (poor diet)
What is non-megaloblastic anemia?
Non-megaloblastic anemia is a macrocytic anemia without B12 or folate deficiency
* Causes: liver disease, medications, hypothyroidism, copper deficiency
Vitamin B12 in our diet comes from sources like _
Vitamin B12 in our diet comes from sources like animal liver, meat, fish, cheese, dairy, eggs
Folate in our diet comes from _
Folate in our diet comes from dark leafy green vegetables
How long does it take to deplete our stores of vitamin B12 vs. folate?
Vitamin B12: stored in the liver; takes months-years to deplete
* Strict vegans can eventually become deficient
Folate: takes months to deplete
Name 5 causes specific to B12 deficiency
- Pernicious anemia
- Pancreatic insufficiency
- Medications
- Diphyllobotrium latum
- Surgically absent ileum
How does pancreatic insufficiency lead to B12 deficiencies?
Trypsin (enzyme produced in the pancreas) is needed to cleave transcobalamin and release B12
_ is a fish tapeworm that is known to cause vitamin B12 deficiency leading to megaloblastic anemia
Diphyllobotrium latum is a fish tapeworm that is known to cause vitamin B12 deficiency leading to megaloblastic anemia
What are 3 causes specific to folate deficiency?
- Rapid cell turnover states (pregnancy, cancer)
- Medications
- Gastric bypass surgery (shortened jejunum)
Megaloblastic anemias can be diagnosed by the presence of _ or _ on peripheral blood smear
Megaloblastic anemias can be diagnosed by the presence of macrocytic erythrocytes or hypersegmented neutrophils on peripheral blood smear
Megaloblastic anemia can be diagnosed on a bone marrow biopsy by the presence of _
Megaloblastic anemia can be diagnosed on a bone marrow biopsy by the presence of immature-appearing nuclei with mature cytoplasm
Anemia of chronic disease:
Iron _
Ferritin _
TIBC _
Transferrin saturation percentage _
Anemia of chronic disease:
Iron low
Ferritin normal/high
TIBC low
Transferrin saturation percentage low
_ is an inability to form the protoporphyrin ring
Sideroblastic anemia is an inability to form the protoporphyrin ring (problem with heme synthesis pathway)
Heme synthesis occurs in the _ of the immature erythroid cells in the _
Heme synthesis occurs in the mitochondria of the immature erythroid cells in the bone marrow
In sideroblastic anemia, what happens when iron is sent to the mitochondria?
Iron cannot be incorporated into the ring –> build up of iron in the mitochondria –> leads to ring sideroblast in the bone marrow
Pappenheimer bodies: iron deposits in the peripheral blood on a prussian blue stain
* Indicative of sideroblastic anemia
Explain the relationship with free radicals in sideroblastic anemia
When iron stores in the bone marrow are increased this increases the production of free radicals –> increased RBC hemolysis –> further increasing iron –> iron overload
Aplastic anemia occurs from damage to _ stem cell progenitors
Aplastic anemia occurs from damage to myeloid hematopoietic stem cell progenitors
Aplastic anemia
Fanconi anemia is an autosomal recessive _ defect
Fanconi anemia is an autosomal recessive DNA repair defect (cannot repair DNA cross-links)
* Diagnosed with chromosome breakage analysis
Sickle cell disease is a point mutation in the _ globin and exchanges _ for _ at position _
Sickle cell disease is a point mutation in the beta globin and exchanges valine for glutamic acid at position 6(Glu –> Val)
* Valine is hydrophobic –> formation of rods
Conditions that shift the oxygen dissociation curve to the _ promote sickling; explain
Conditions that shift the oxygen dissociation curve to the right promote sickling
* Conditions include increased lactic acid, CO2, 2-3BPG, altitude, temperature
* These promote the taut state of Hb which exposes the abnormal hydrophobic valine residues –> causes Hb to polymerize to hide valine
What causes sickle cell to be so painful?
Sickle cells are not flexible like normal cells and they can polymerize into rods –>
Get trapped in capillaries throughout body and spleen –> vaso-occlusive crises –> pain and ischemia
The lifespan of a sickle RBC is _
The lifespan of a sickle RBC is 10-30 days
* They lyse easier and get removed by splenic macrophages
Identify the Hb alleles on the hemoglobin electrophoresis
What unique features will be present on PBS for sickle cell?
Target cells (nonspecific) and Howell-Jolly bodies (DNA remnants that are usually removed by the spleen)
We have a total of _ alpha globin genes and they are found on chromosome _
We have a total of 4 alpha globin genes and they are found on chromosome 16
Patients with G6PD deficiency cannot produce NADPH to regenerate reduced glutathione –> leads to _ and _
Patients with G6PD deficiency cannot produce NADPH to regenerate reduced glutathione –> leads to oxidative stress and lysis
G6PD deficiency is mainly (intravascular/ extravascular) hemolysis and we often see _ haptoglobin
G6PD deficiency is mainly intravascular hemolysis and we often see low haptoglobin
What two findings may be seen on G6PD deficiency PBS?
Heinz bodies (denatured hemoglobin chains) and Bite cells (spleen takes a bite out of these cells)
Hereditary spherocytosis is a genetic defect that leads to abnormal formation of _
Hereditary spherocytosis is a genetic defect that leads to abnormal formation of
* Cytoskeletal proteins: ankyrin, spectrin
* Anchoring protein (holds cytoskeleton to RBC membrane): band 3, band 4.1, band 4.2
Triad of symptoms for hereditary spherocytosis
- Jaundice
- Anemia
- Splenomegaly
Hereditary spherocytosis:
MCV:
RDW:
MCHC:
Other:
Hereditary spherocytosis:
MCV: normocytic
RDW: high
MCHC: high
Other: elevated bilirubin, LDH, positive osmotic fragility test
