Hematology Exam 3 Flashcards
What is one of the largest organs in the body?
Bone marrow
What percentage of our body weight is bone marrow?
4%
Where is bone marrow found in infants?
All bones
Where is bone marrow found in adults?
Flat bones
Where are RBCs located in bone marrow?
Inside the sinus around a macrophage
Where are megakaryocytes located in bone marrow?
Near the sinus wall
Ratio of fat to tissue in normal bone marrow
50:50
Job of macrophages in bone marrow
To incorporate iron into the red cells
What forms the foundation or support of bone marrow?
Meshwork of stromal cells
Cells unique to bone marrow
Osteoclasts - bone destroying/breakdown
Osteoblasts - bone forming
Name the cells
Osteoblasts
Name the cells
Osteoclasts
What is circled? (BM)
Spicules in bone marrow
What does seeing spicules tell you?
You have a good aspirate
Where does the core biopsy go in the lab?
Histology
Lifespan of RBCs
120 days
Lifespan of WBCs
anywhere from 7 hours to 20 days depending on the type of WBC
Function of bone marrow
Supplies mature cells for circulation in steady state or for increased demand
What maintains the self-renewal of bone marrow?
Pluripotential stem cells
What are some examples of stimuli received to create cells in the bone marrow?
- Thrombopoietin
- Erythropoietin
- Colony stimulating factors
- Interleukins
What is produced by stromal cells, fibroblasts, endothelial cells, and macrophages?
Growth factors
What colony stimulating factors go in to the myeloid line?
- CSF-Spleen
- CSF-GEMM
Anemia, polycythemia, leukopenia, and thrombocytopenia are all diseases that affect what in bone marrow?
Blood production of bone marrow
How do the following systemic diseases affect bone marrow?:
- Solid metastasizing tumors that spread to the marrow such as cancer and Hodgkin’s lymphoma
- Fever of Unknown Origin (FUO)
They affect blood production in bone marrow
Type of hereditary diseases that can affect bone marrow
Storage pool diseases such as Gauchers
Usual location a bone marrow aspirate is performed on adults
Posterior superior iliac crest
Usual location a bone marrow aspirate is done on children and infants
Top of tibia below the knee
Type of needle used for bone marrow aspirate
Jamshidi needle
Amount needed for bone marrow aspirate
0.5 - 1.5mL for hematology and an additional 5cc for other departments
2 diseases that could cause a “dry tap” (no aspirate)
- Myelofibrosis
- Aplastic anemia
Reasons an aspirate may not be collected
- Dry tap (Myelofibrosis or aplastic anemia)
- Not in the bone marrow
- Tumor
Preservative used for biopsy
Formalin
Marrow slide examination:
Childhood cellularity percentage
80%
Marrow slide examination:
Age 30-70 cellularity percentage
50%
Marrow slide examination:
How do you calculate the cellularity percentage for ages >70?
100 - patient age = cellularity +/- 10%
Bone marrow cellularity
What would be the expected cellularity for an 82 year old patient?
100 - 82 = 18
8 - 28%
(18 +/-10%)
Under oil immersion, how many cells are counted during a bone marrow differential? What cells are counted?
500 to 1000 both red and white cells
What cells are not included in the M:E ratio?
Lymphs, monos, and plasma cells
What percentage of the bone marrow differential count will be comprised of neutrophilic myelocytes, metamyelocytes, bands, and segmented neutrophils?
50%
M:E Ratio:
350 neutrophilic blasts >segs, eos, baso
75 lymphs, monocytes, and plasma cells
75 erythroid cells (blasts>meta)
What is the M:E ratio?
350 / 75 = 4.7:1
Normal M:E ratio
3:1
How would myeloid hypoplasia effect the M:E ratio?
Myeloid cells would be decreased causing the M:E to be < 3:1
How would erythroid hyperplasia effect the M:E ratio?
Erythroid hyperplasia would increase the red cells count causing the M:E ratio to be 1:1
What stains are performed on each bone marrow aspirate?
- Wright’s stain
- Iron stain
Iron that is stored in the bone marrow is in what form?
Hemosiderin
What is hemosiderin composed of?
Iron and protein
Stain used to stain iron
Prussian Blue
Symptoms of anemia
- Tachycardia
- Shortness of breath
- Headaches
- Pallor
- Fatigue
TRUE or FALSE
Typical CBC results in anemia include:
-Decreased hemoglobin, hematocrit, and RBC count
TRUE
TRUE or FALSE
With most anemia, the M:E ratio is 1:1
TRUE
What MCV classifies as microcytic anemia?
< 80fL
What MCV classifies as a macrocytic anemia?
> 100 fL
What MCV classifies as a normocytic anemia?
80 - 100 fL
What is the cause of Microcytic, hypochromic anemias?
Inadequate production of some part of hemoglobin (iron, heme, globin)
Thalassemias have what abnormality?
Globin abnormality
2 Etiologic categories of macrocytic anemias
- Megaloblastic
- Non-Megaloblastic
Cause of megaloblastic anemias
Abnormal DNA synthesis
Cause of non-megaloblastic anemia
Increase in membrane lipids
TRUE or FALSE
Non-megaloblastic anemia will have an MCV > 110
FALSE
Non-megaloblastic anemia will have an MCV > 100 fL but < 110 fL
This anemia is due to a slowdown in DNA synthesis in developing cells causing a shorter life span in the deficient cells
Megaloblastic anemia
What causes the defect in DNA replication that is seen in megaloblastic anemia?
A depletion of thymidine triphosphate, an immediate DNA precursor
If there is an increase in _______________ , it tells us there is possibly a B12 deficiency
Methylmalonyl Coenzyme A
(MMA)
Being deficient in this causes slowed nuclear maturation and mitosis resulting in asynchrony in cells
Thymidine triphosphate
When the nucleus of a cell is immature and the cytoplasm is matured, this is referred to as what?
Asynchrony
Another name for B12
Cyanocobalamin
How is B12 absorbed in the body?
Through the intestine by Intrinsic Factor (IF)
Where is Intrinsic Factor produced?
Parietal cells of the stomach
What do the IF-B12 complexes attach for absorption?
To receptors on the ileal mucosal cells
What does B12 attach to after being absorbed?
Transcobalamin II
Where does the B12-transcobalamin II complex go?
Bone marrow
or
Liver for storage
(large amount is stored)
Where do we get B12 from in our diet?
Meat
Eggs
Dairy products
Liver
Where does folic acid come from in our diets?
- Leafy greens
- Meat
- Some fruits
What carries folate after it is absorbed?
Albumin
Where does albumin take folate in the body?
Bone marrow
or
Liver
(only a small amount is stored)
Once absorbed and transported, what 2 cofactors play an important role in DNA synthesis?
Folate and Vitamin B12
Any cell actively dividing or replicating will have a defective nucleus when either of what 2 cofactors are deficient?
B12 and Folate
A lack of intrinsic factor causes what anemia?
Pernicious Anemia
What tapeworm can cause a B12 deficiency?
Diphyllobothium latum - fish tapeworm
TRUE or FALSE
In pernicious anemia, folate cannot be absorbed
FALSE
Vitamin B12 cannot be absorbed properly due to a lack of intrinsic factor
An autoimmune disorder with autoantibodies produced by parietal cells causes what type of anemia?
Pernicious anemia
Pernicious anemia is typically found in which descent of people?
Northern European
How is pernicious anemia treated?
Vitamin B12 injections
Which is more common and why?
B12 deficiency
or
Folate deficiency
Folate deficiency because little to none is stored in the body
Clinical features of megaloblastic anemia
- Typical signs of anemia
- Lemon-yellow pallor
-Smooth, sore tongue
Clinical features of B12 deficient megaloblastic anemia
Neurologic manifestations from degeneration of myelin:
- tingling and numbness of extremities
- gait abnormalities
- psychosis due to defective methyl group metabolism
Key diagnostic features seen in the peripheral blood smear of megaloblastic anemia
- Hypersegmented neutrophils
- Macro-ovalocytes
Identify the anemia:
- Decreased retic
- Hypercellular bone marrow
- MCV >110
- Decreased RBC, WBC, and PLT counts
- Macro-ovalocytes
- Hypersegmented neutrophils
Megaloblastic anemia
-either B12 or Folate deficiency but cannot distinguish without further testing
What is the term for a pyknotic cell causing a fragmented nucleus?
Karyorrhexis
Giant bands and giant metamyelocytes are a key findings in the bone marrow of which anemia?
Megaloblastic anemia
What is the term used to describe the cell the arrow is pointing to?
Karyorrhexis
What chemistry tests are elevated due to hemolysis with megaloblastic anemia?
LD and Bilirubin
Test that is used to differentiate between Pernicious Anemia and other B12 deficiencies
Schilling Test
Non-megaloblastic conditions (3)
- Liver disease
- Alcoholism
- Reticulocytosis
MCV will increase 1 fL for each ___% of retics
MCV will increase 1 fL for each 1% of retics
What can cause the MCV to appear macrocytic?
- Cold agglutinin
- High WBC count
- High glucose causing cells to swell
The following morphologic characteristics are seen in what class of anemia?:
- MCV <80
- MCH and MCHC are decreased
- RDW is generally normal
Microcytic, hypochromic anemia
Where does most of the iron required by the cells come from?
Broken down RBCs
How much iron is needed for each mL of RBCs?
1mg
What regulates the absorption of iron in the body?
Mucosal cells in the GI tract
How much of the daily intake of iron from diet is actually absorbed?
10%
What enhances iron absorption?
Ascorbic acid (vitamin C) and using cast iron pots/skillets
What decreases iron absorption in the body?
Antacids
All of the following affect what?
- Type of iron in the food
- Other food that is ingested
- Acidity of stomach
- Availability of iron stores
Absorption of iron
Iron is transported from mucosal cells to the blood in what state?
Ferrous state (Fe2+)
What is the dietary form of iron?
Ferric (Fe3+)
What protein transports the ferric iron?
Transferrin
Number of iron atoms that transferrin can bind to at once
2 iron atoms per 1 transferrin molecule
Where are the 2 places transferrin will transport iron?
- Bone marrow
- Liver
Iron is stored as this in the liver
Ferritin
Transferrin can bind ____ - ____ mg of iron
240 - 280 mg
About what percentage of transferrin is bound with iron?
30%
How does celiac disease cause iron deficiency?
Celiac disease doesn’t allow iron to absorb properly
What is significant about having an inherited mutation with matripase 2 protein?
It causes impaired absorption of iron leading to iron deficiency anemia
Most common cause of iron deficiency anemia
Increased blood loss
Sequence of development of iron deficient anemia
- Iron storage depleted
- Transport iron depleted
- Functional iron depletion
Iron is required for _____ synthesis
Iron is required for heme synthesis
Stage of Iron depletion:
- Normal hemoglobin
- Normal serum iron
- Normal TIBC
- Decreased ferritin
Stage 1
Storage Iron Depletion
Stage of Iron depletion:
- Normal hemoglobin
- Decreased serum iron
- Increased TIBC
- Decreased ferritin
Stage 2
Transport Iron Depletion
Stage of Iron depletion:
- Decreased hemoglobin
- Decreased serum iron
- Increased TIBC
- Decreased ferritin
Stage 3
Functional Iron Depletion
Normal range for serum iron
50 - 160 ug/dL
Normal range for TIBC
250-400 ug/dL
What is TIBC?
Total Iron Binding Capacity = transferrin related test
Normal range for % transferrin saturation
20 - 55%
Normal range for ferritin for males
40 - 400 ng/mL
Normal range for ferritin for females
12 - 160 ng/mL
Classify the type of anemia
(size and pallor)
Hypochromic, microcytic
What is iron overload also known as?
Hemosiderosis
The following may cause what?:
- Hemolytic anemia with massive transfusions
- Disorders of erythropoiesis where cells cannot be made and iron builds up
Hemosiderosis
What is the term for a more severe form of hemosiderosis
Hemochromatosis
What is the cause of Hereditary hemochromatosis?
A gene mutation (hereditary iron or transferrin receptor protein)
The following results are seen in what disorder?
- Abnormal AST and ALT (LFTs)
- Increased serum iron
- Increased % transferrin saturation
- Increased serum ferritin
- Increased hgb
- Increased HCT
Hemochromatosis
How is hereditary hemosiderosis treated?
Therapeutic phlebotomy
How is transfusion related hemosiderosis treated?
Chelation therapy
Patient is given desferrioxamine which binds to iron and gets excreted in urine
Thalassemia, Anemia of Chronic Disease/Inflammation, Lead poisoning, and Sideroblastic Anemia are all examples of what type of anemia?
Microcytic anemia
An inherited disorder in which the globin chain is not produced in adequate amounts
Thalassemia
This is the most common anemia among hospitalized patients
Anemia of Chronic Disease/Inflammation
This hormone is an acute phase reactant that regulates the absorption of iron in the intestines and also the release of iron from macrophages.
Hepcidin
What produces hepcidin?
The liver
This acute phase reactant is an iron binding protein located in the granules of neutrophils. It is involved in preventing phagocytized bacteria from using intracellular iron for their own metabolic processes
Lactoferrin
The following lab results are seen with which type of anemia?:
- Decreased serum iron
- Decreased TIBC
- Increased serum ferritin
- normal soluble transferrin receptors (sTfRs) - newer test
Anemia of Chronic Disease/Inflammation
Treatment of Anemia of Chronic Inflammation
- Treat with erythropoietin, given with iron b/c the body’s stored iron remains unavailable
- Alleviate the causative condition
Lead poisoning is caused by lead blocking the production of what in several spots?
Lead poisoning blocks heme production
This microcytic anemia causes:
-Interference in the conversion of aminolevulinic acid (ALA) to porphobilinogen (PBG)
and
-Interference in the incorporation of iron into protoporphyrin IX by ferrochetalase
Lead poisoning
This microcytic anemia will interfere with the breakdown of ribosomal RNA creating coares basophilic stippling and a low MCV
Lead poisoning
TRUE or FALSE
Basophilic stippling is diagnostic for lead poisoning
FALSE
In this microcytic anemia the following occurs:
- Cells cannot use available iron
- The iron is trapped in the cell
- Iron will form pappenheimer bodies in mature cells
Sideroblastic anemia
This picture depicts a hallmark representation of what microcytic anemia?
Sideroblastic anemia
What is considered “hallmark” for sideroblastic anemia?
Dimorphic RBCs and ringed sideroblasts
MCV, MCH, and MCHC are lowest with which microcytic anemia?
Thalassemia
Will the RDW be normal, elevated, or decreased with iron deficiency anemia?
Elevated
Will RDW be normal, elevated, or decreased with Thalassemia?
Normal
What is included in iron studies?
- Serum iron
- Total Iron Binding Capacity (TIBC)
- % Transferrin Saturation
- Serum Ferritin
What is measured in serum iron?
The amount of iron bound to transferrin in circulation
What does TIBC measure?
The amount of transferrin bound and unbound with iron
It is measuring the binding ability of transferrin
How is % transferrin saturation calculated?
Serum iron / TIBC x 100
Normal range for soluble transferrin receptors
1.15 - 2.75 mg/L
The amount measured in this test is based on intracellular iron and is an indicator of functional iron available in cells
Soluble transferrin receptors (sTfR)
TRUE of FALSE
sTfR is increased in Anemia of Chronic Inflammation
FALSE
Normal in Anemia of Chronic Inflammation
TRUE or FALSE
sTfR is increased in IDA
TRUE
When does free erythrocyte protoporphyrin accumulate?
When iron is NOT available
Free erythrocyte protoporphyrin will be increased, decreased, or normal in IDA?
Increased
With which anemia is knowing the value of free erythrocyte protoporphyrin is most valuable?
Lead poisoning due to ferrochelatase impairment