Hematology Exam 2 Flashcards
Stain used to view blood smears and bone marrow
Wright’s Stain
Stain to view reticulocytes
New Methylene Blue
What type of stain is New Methylene Blue?
Supravital
Stain used to view iron
Prussian Blue
A normocytic, normochromic erythrocyte typically measures at how many microns?
7 microns
Central pallor of erythrocytes is typically __/__ of the cell
1/3
TRUE or FALSE
Even if only one or two cells are seen to have abnormalities (ex. echinocyte), you will make note of it on the differential.
FALSE
In order to be clinically significant, MOST abnormal morphology needs to be seen in every field.
DEFINITION:
Variation in size
Anisocytosis
DEFINITION:
Variation in shape
Poikilocytosis
DEFINITION:
Size of RBC
(indices)
Mean Cell Volume
(MCV)
DEFINITION:
Average weight of hemoglobin in red blood cell
(indices)
Mean Cell Hemoglobin
(MCH)
DEFINITION:
Average concentration of hemoglobin in each red blood cell
(indices)
Mean Cell Hemoglobin Concentration
(MCHC)
TRUE or FALSE
Spherocytosis is the only case that a smear would be called hyperchromic
TRUE
Otherwise it doesn’t ‘really’ exist (misnomer)
DEFINITION:
Pale blue-gray erythrocytes (Wright’s Stain)
Polychromasia
DEFINITION:
Pale blue-gray erythrocytes (New Methylene Blue Stain)
Reticulocytes
What is the size of most erythrocytes?
6-8 microns
What is the normal range for MCV?
80-100 fL
What do we typically compare RBCs to for reference on size?
The nucleus of a normal ‘resting’ lymphocyte
MCV>100 should typically show what type of RBCs under a microscope?
Macrocytes
What intracellular issue typically causes Macrocytes?
Impaired DNA synthesis in the nucleus
What is typically happening to cause macrocytes in the blood?
>1% of RBCs are being destroyed
Changes in membrane lipids causing the cell to spread-out (macrocytes) can be seen in which disease?
Liver disease
MCV<80fL should show what type of RBCs in a peripheral smear?
Microcytes
Intracellular cause of microcytes
Impaired hemoglobin synthesis
-Any deprivation of hemoglobin molecules will cause an increase in cell division, decreasing cell size.
Examples of impaired hemoglobin synthesis that will cause microcytes
(3)
-Thalassemia - involves globin chain
-Iron deficiency anemia (IDA)
-Lead poisoning - interferes with heme synthesis
RBC Shape:
- Rod or oval
- oval shape increases as cell matures
- Hereditary or acquired condition
- Defect in spectrin affecting the horizontal linkage of cell cytoskeleton
Ovalocytes
(Elliptocytes)
You can see ovalocytes (elliptocytes) for many reasons.
How many can you remember?
(6 given in lecture)
-Hereditary ovalocytosis (if majority are oval)
-Sickle cell anemia
-Iron deficiency anemia
-RBC enzyme deficiences
-Pernicious anemia as macro-ovalocytes
-Miscellaneous anemia (non-specific)
Another name for ovalocytes
Elliptocytes
Another name for sickle cells
Drepanocytes
Abnormal hemoglobin S causes this type of RBC shape
Sickle cell
This form of hemoglobin can cause the following:
- Decreased solubility
- Homozygous causes severe hemolytic anemia
- Heterozygous have both normal and abnormal hemoglobin
- Sickling occurs when oxygen tension decreases
Hemoglobin S
Drepanocytes are specific for which disease?
Sickle Cell Disease
TRUE or FALSE
You WILL report drepanocytes even if only a small number of them are seen
TRUE
Drepanocytes = Sickle cells
RBC Shape:
- Small spherical cells with pointed irregular spaced projections radiating from cell tips
- Tips may be bent back or are bulb-like
- 3 or more blunt spicules of uneven length
- Cells have no central pallor
Spur cells
AKA
Acanthocytes
An altered lipid content (increased cholesterol) can cause this RBC shape
Acanthocytes
AKA
Spur cells
When are acanthocytes most often observed in peripheral smears?
(4 given in lecture)
-Liver disease
-Congenital Abetalipoproteinemia (rare)
-Alcoholic liver disease
-Post-splenectomy
RBC Shape:
- “Sea urchin”
- 10-30 rounded spicules evenly placed over the surface of the erythrocyte
- Spicules may be even, sharp, and random
Echinocytes
AKA
Burr/Crenated cells
When are echinocytes observed?
(5 ways given in lecture)
-Liver disease
-Uremia (increased blood urea due to kidney disease)
-Dehydration
-Peptic ulcers
-Pyruvate Kinase Deficiency
TRUE or FALSE
Burr cells are caused due to a change in the tonicity of the cell when there is an anion imbalance
FALSE
Burr cells occur due to a cation imbalance (sodium and potassium)
TRUE or FALSE
It isn’t necessary to call schistocytes unless you see a lot of them
FALSE
Always make note of schistocytes
RBC Shape:
- Fragments are formed as RBC is abnormally desrtoyed
- RBC may become damaged as it squeezes through small damaged vessel
Schistocytes
What were the 5 reasons given in lecture for why we might see schistocytes in a peripheral smear?
-Coagulation defects such as DIC
-Microangiopathic hemolytic anemia
-Heart-valve hemolysis
-Severe burns (heat damages spectrin in membrane)
-Uremia
The helmet cell, aka keratocyte, is a variant form of which abnormal RBC shape?
Schistocyte
Another name for Dacryocyte
Tear Drop Cell
RBC Shape:
- Round cell with a single elongated or pointed extremity
- Pear-shaped
Dacryocytes
AKA
Tear Drop Cell
What would cause us to see dacryocytes?
(4 ways given in lecture)
-Myelofibrosis (fibrous material in bone marrow)
-Extra-medullary hematopoiesis
-Enlarged spleen or removal of inclusion from a cell by the spleen (macrophages try to grab RBC but RBC escapes)
-Megaloblastic Anemia
RBC Color:
- Central pallor >3microns
- Due to impaired hemoglobin synthesis
- Usually observed alongside microcytosis
- Can be measured with MCH and MCHC
- May be observed due to water artifact
Hypochromasia
RBC Color:
- Term used to describe the blue-gray RBCs observed on Wright Stain
- Normally will observe ~1% of RBCs looking this way
- If increased number is observed, indicates the bone marrow is increasing output of cells
Polychromasia
Where are the highest number of polychromatic cells is observed?
(4 given in lecture)
-Post hemorrhage
-Hemolytic anemia
-Significant loss of RBCs
-Following treatment of iron deficiency anemia
- Increased production of RBCs with no central pallor
- Defect in membrane protein causing vertical disruption between transmembrane proteins and underlying cytoskeleton
- Only cell described as hyperchromic
- Decreased surface area to volume ratio
- Causes extravascular hemolysis
- MCHC >36%
- MCV ~80fL
Spherocytosis
RBC Shape:
- Cell loses part of its membrane from antibody or genetic defect
- May be hereditary or due to an immune hemolytic anemia
- ANY observed is considered clinically significant
Spherocytes
What is always considered clinically significant in a peripheral blood smear?
-Parasites
-Sickle cells
-Schistocytes
-Spherocytes
Abnormal RBC:
- Bell shaped
- Appear very thin and flat on smear
- “Bull’s eye”
Target Cell
AKA
Codocyte
Another name for Target Cell
Codocyte
What causes codocytes?
A rearrangement of hemoglobin
This abnormal RBC has an increased cell membrane and surface area due to lipid alteration causing the cells to expand.
Codocytes
AKA
Target Cells
TRUE or FALSE
Codocytes cause decreased hemoglobin leading to thalassemia and severe cases of iron deficiency anemia
TRUE
What are some disorders that can cause an increase in membrane lipids leading to viewing codocytes on a peripheral smear?
(4 given in lecture)
-Liver disease (aquired)
Hemoglobinopathies such as:
-Sickle cell anemia
-Hemoglobin C disease
-Thalassemia
Abnormal RBC:
- Cup shaped
- “Kiss cell”
- Often is an artifact
- Central pallow is slit-shaped or rectangular
Stomatocytes
TRUE or FALSE
An electrolye imbalance causing potassium to be increased and sodium to be decreased can produce stomatocytes in a peripheral smear
False
the imbalance is from increased sodium and decreased potassium
TRUE or FALSE
Stomatocytes are observed in alcoholism
TRUE
RBC inclusion:
- Remnants of nuclear material (DNA)
- Small deep blue, round granule typically in the periphery of the cell
Howell-Jolly Body
Cause of Howell-Jolly Bodies
(2 reasons given in lecture)
-Accelerated or abnormal erythropoiesis
-Spleen not removing (pitting) piece of nucleus
Non-functioning spleen is the most common reason
Howell-Jolly Bodies are observed in which type of Megaloblastic anemias?
-B12 deficiency
-Folic acid deficiency
Faulty maturation of RBC precursors
TRUE or FALSE
Splenomegaly or splenectomy can cause Howell-Jolly bodies to be seen in peripheral blood smears
TRUE
non-functioning spleen is the most common reason we see Howell-Jolly Bodies
RBC inclusion:
- Aggregates or clumped ribosomes containing RNA (denatured RNA)
- Indicates altered or impaired hemoglobin synthesis
- Granules are distributed throughout the RBC (either fine or coarse)
Basophilic stippling
What causes basophilic stippling granules to appear fine/small?
Thalassemia
What causes basophilic stippling granules to appear coarse?
Lead poisoning
RBC inclusion:
- Collection of mitochondria and ribosomes that contain iron
- Contain non-heme iron (Fe3+) that was not utilizedin hemoglobin production (due to ineffective iron metabolism)
Pappenheimer Bodies
RBC inclusion:
- on Wright’s stain - subtle pale dots near periphery of cell
- Typically appear in doublets or triplets
Pappenheimer Bodies
Confirmation stain for Pappenheimer bodies
Prussian Blue
or
Iron Stain
RBC inclusion:
This inclusion is seen in sideroblastic anemia
Pappenheimer bodies
Type of anemia:
- Iron overload
- Overabundance of iron metabolism causing iron to be stored in other places besides the liver and bone marrow
Sideroblastic anemia
When would we see pappenheimer bodies?
(3 possibilities discussed in lecture)
-Sideroblastic anemia
-Thalassemia
-Splenectomy
When using Prussian Blue stain, pappenheimer bodies are called ________________
Siderocytes
Definition:
Non-nucleated red blood cell in which particles of iron are visible with Prussian Blue stain
Siderocyte
Definition:
Nucleated red blood cell precursor that shows excessive iron granules with Prussian Blue stain
Sideroblast
Definition:
Nucleated red blood cell precursor with at least five granules that circle at least one third of the nucleus with Prussian Blue stain
Ringed Sideroblast
RBC inclusion:
- Not seen with Wright Stain
- Must use Supravital stain
Heinz Bodies
Types of supravital stains (2)
-New Methylene Blue
-Crystal Violet
RBC inclusion:
- Composed of denatured or precipitated hemoglobin
- Large round masses lying under or attached to the cell membrane
Heinz Bodies
RBC inclusion:
Observed in:
- G6PD deficiency
- Unstable hemoglobin, causing iron to be unprotected
- Oxidizing drugs
- Alpha thalassemia
Heinz Bodies
RBC inclusion:
- Ring or figure 8 forms
- Contain arginine-rich histone and non-hemoglobin iron
- Thought to be remnants of spindle fibers, which form during mitosis
- Very rare
Cabot Rings
RBC inclusion:
Observed in:
- Severe anemias
- Pernicious anemia
- Dyserythropoiesis
Cabot Rings
RBC inclusion:
- Oblong dark crystal
- Not normally present in normal adult blood
- Diagnostic
- Abnormal hemoglobin crystallizes
Hemoglobin C Crystals
RBC inclusion:
- Indicaties infectin with one of four species of parasite
- Stages observed is dependent on type with ring forms being most common
- Must be careful to not confuse with platelet on top of RBC
- Always clinically significant even if only 1 is seen
Malaria
4 different species of Malaria
-P. malariae
-P. falciparum
-P. vivax
-P. ovale
(P = Plasmodium)
RBC inclusion:
- Always abnormal in adult peripheral blood
- Few are normally observed in newborn blood (2-24/100 WBC on newborn)
- Typically a metarubricyte
Nucleated Red Blood Cell
-NRBC-
2 situations that would cause RBCs to clump
-Agglutination
-Rouleaux
Red Cell Distribution:
- Random clumping of RBCs
- Usually due to a cold antibody
- MCV increases, RBC count decreases, MCHC >38%
-Agglutination
Red Cell Distribution:
These antibodies will stop agglutinating at 37C (Body temp)
IgG
Red Cell Distribution:
These antibodies will stop agglutinating at 25C (Room temp)
IgM
Red Cell Distribution:
What is suggested for agglutination?
Warm specimen to 37C
Red Cell Distribution:
- Red blood cells look like stacks of coins
- Due to elevated antibodies (globulins) or improper balance of proteins in serum
- Thick parts of normal peripheral smears can look this way
Rouleaux
Red Cell Distribution:
An improper balance of these globulins/proteins would likely cause rouleaux on a peripheral smear
(3)
-IgG
-IgA
-Fibrinogen
Red Cell Distribution:
When could you encounter rouleaux?
(3)
-Multiple myeloma
-Liver disease
-Chronic inflammation
Types of RBCs that are diagnostic even if only a few are seen
(7)
-Schistocytes
-Sickle cells
-C crystals
-Malaria/other blood parasites
-Target cells if anemia is present
-Tear drops cells in some settings
-Spherocytes in some settings (severe burn)
- Simple, non-specific screen for inflammation in hematology
- Anticoagulated blood stands undisturbed for 1 hour
- Distance in millimeter that RBCs will fall in one hour in a vertical tube of defined length
ESR
Erythrocyte Sedimentation Rate
Determines presence of anemia
Hemoglobin
and
Hematocrit
Cloud of negative charges found on RBC cell membrane
Zeta
- Increased fibrinogen
- In vivo rouleaux formation of cells
- Anemia
- Macrocytosis
- Hypercholesterolemia
- Hyperfibrinogenemia
- Hypergammaglobulinemia
- Leukemia
- Diabetes Mellitus
How would all of the above affect an ESR?
Increase fall-out
(Settle faster)
- Polycythemia
- Sickle cells
- Spherocytes
- Leukocytosis
How would all of the above affect an ESR?
-Decrease Fall-Out
(settle slower)
Normal ESR values for Females and children
0-20 mm/hr
Normal ESR values for males
0-15 mm/hr
2 commonly used methods for ESR
Wintrobe
Westergren
ESR method:
- Utilizes a 100mm column
- Allows for increased sensitivity in detecting mildly elevated ESRs
Wintrobe method
ESR method:
- Considered universal reference method
- Uses 200mm column with 2.55mm internal diameter
- Allows for the detection of highly elevated ESR
Westergren method
Increase or Decrease ESR:
Vertical slant
Falsely increase
Increase or Decrease ESR:
Temperature higher that room temp (25C)
Falsely increase
Increase or Decrease ESR:
Temperature lower than room temperature (25C)
Falsely decrease
Increase or Decrease ESR:
Bubbles
Falsely decrease
Increase or Decrease ESR:
Abnormal shapes such as sickle cell or spherocytes
Falsely decrease
(won’t rouleaux)
Increase or Decrease ESR:
Improper anticoagulants
(Sodium oxalate, potassium oxalate, and heparin)
Falsely increase
(causes RBCs to shrink)
Increase or Decrease ESR:
Concentration of anticoagulant
-tube not properly filled
Falsely increases
(causes cells to alter shape - spherocytes)
ESRs may be increased which cancers?
(2)
-Multiple myeloma
-Leukemia
Increase or Decrease ESR:
Hypercholesterolemia
Increased
Increase or Decrease ESR:
Viral or bacterial infection
Increased
Increase or Decrease ESR:
Rheumatoid arthritis
Increased during flare up
Increase or Decrease ESR:
Osteoarthritis
Increased
Increase or Decrease ESR:
Hyperfibrinogenemia
Increased
-Large pigmented protein that gives red cells their color
Hemoglobin
Components of hemoglobin
(3)
-Protoporphyrin Ring IX
-Tetramer of four polypeptide chains
-Ferrous iron
Function:
-Carries oxygen to tissue and brings CO2 back
Hemoglobin
Reference method for measuring hemoglobin
Cyanmethemoglobin
Measures all forms of hemoglobin except for sulfhemoglobin
Cyanmethemoglobin
This form of hemoglobin can occur from antibiotics or pesticides
Sulfhemoglobin
TRUE or FALSE
When measuring hemoglobin, Fe3+ is oxidized to Fe2+ by potassium ferricyanide to methemoglobin
FALSE
Fe2+ (ferrous iron) is oxidized to Fe3+ (ferric)
Fe3+
Ferric iron
Fe2+
Ferrous iron
Normal reference range of hemoglobin for females
12 - 15 g/dL
Normal reference range of hemoglobin for males
13.5 - 18 g/dL
Normal reference range of hemoglobin for newborns
16.5 - 21.5 g/dL
Normal reference range of hemoglobin for children
11 - 14 g/dL
- Non-specific turbidity
- High WBC
- Lipemia
- Hemoglobin C and S
What do these do to hemoglobin measurement?
Falsely elevate
Definition:
- Expressed as a % of RBC of the whole blood volume
- Percentage of whole blood occupied by red cells after packing by centrifugation
Hematocrit
AKA
Hct
AKA
PCV (packed cell volume)
Calculation for automated hematocrit
Indirect Hct =
RBC x MCV
_____________
10
What is the Rule of Three?
Hematocrit should be 3 times the hemoglobin +/- 3%
Hct = 3 x Hgb
Reference range for hematocrit for females
35 - 49%
Reference range for hematocrit for males
40 - 54%
Reference range for hematocrit for newborns
48 - 68%
Indice that tells us the size or volume of an RBC
MCV
-Higher the number, larger the cell
TRUE or FALSE
Agglutination can cause a falsely decreased MCV
FALSE
agglutination would falsely elevate the MCV
In order to calculate MCV, you need to know what indices?
RBC and Hct
MCV calculation
MCV (fL) =
Hct x 10
___________
RBC
- Average weight of hemoglobin per red blood cell
- Usually 1/3 of MCV
- Measured in pg (picograms)
Mean Cell Hemoglobin
MCH
Reference range for MCH
26 - 34 pg
Indices needed in order to calculate MCH
Hemoglobin and RBC
Calculation for MCH
MCH (pg) =
Hgb x 10
__________
RBC
How would hypochromasia affect MCH?
Decreased cellular hemoglobin content
How would hyperchromasia affect MCH?
Increased cellular hemoglobin content
What are 2 ways an MCH value could be altered?
Lipemic specimen
or
Cold agglutinin
- Indice that tells us the average hemoglobin concentration of each individual red blood cell in a sample
- Usually corresponds with MCH
MCHC
Mean Cell Hemoglobin Concentration
Reference range for MCHC
32 - 36 %
How would hypochromasia affect MCHC?
Decreased MCHC
How would hyperchromasia affect MCHC?
Increased MCHC
-too much hemoglobin for size of cell
Indices needed in order to calculate MCHC
Hemoglobin
and
Hematocrit
Calculation for MCHC
MCHC (%) =
Hgb x 100
____________
Hct
Main function of RBCs
-Carry oxygen to tissues
-Bring CO2 back from tissues
What part of an RBC is responsible for the transportation of O2 and CO2?
Hemoglobin
What part of the RBC is responsible for making the ATP to be used for energy?
Mitochondria
What do RBCs rely heavily on to produce ATP?
Anaerobic glycolysis
4 pathways used to provide ATP for red blood cells
-Embden-Meyerhof Glycolytic Pathway
-Hexose Monophosphate Shunt aka Phosphogluconate (Oxidative Pathway)
-Methemoglobin Reductase Pathway
-Rapaport-Leubering Shunt/Pathway
This pathway provides RBCs with 90% of their ATP
Embden-Meyerhof Glycolytic Pathway
Pathway that maintains erythrocyte shape, flexibility, and membrane integrity
Embden-Meyerhof Glycolytic Pathway
Enzyme utilized in Embden-Meyerhof Glycolytic Pathway
Pyruvate kinase
This pathway provides RBCs 5-10% energy and is an oxidative pathway
Hexose Monophosphate Shunt
What enzyme does the Hexose Monophosphate Shunt utilize?
Glucose-6-Phosphate-Dehydrogenase
G6PD
This pathway protect against oxidative injury from toxic reducing oxidants such as certain antimalarial drugs or infections
Hexose Monophosphate Shunt
If this pathway were defective, globin chains in the hemoglobin molecule would denature and precipitate as aggregates (Heinz bodies)
Hexose Monophosphate Shunt
This pathway is an “off-shoot” of Embden-Meyerhof
-Maintains heme in the reduced ferrous (Fe3+)state which carries oxygen
Methemoglobin Reductase Pathway
Enzyme utilized in the Methemoglobin Reductase Pathway
Methemoglobin reducatase
If this pathway is defective/decreased, cyanosis occurs due to lack of oxygen binding
Methemoglobin Reductase Pathway
This pathway uses 1 ATP and produces 2,3-DPG (aka 2,3-BPG) which affects the oxygen affinity of hemoglobin
Rapaport-Leubering Shunt/Pathway
Enzymes utilized in the Rapaport-Leubering Pathway
Biphosphoglycerate mutase
and
Biphosphoglycerate kinase
Composition of RBC
52% protein
40% lipid
8% carbohydrate
What is responsible for providing strength to the lipid bilayer of an RBC?
Cholesterol
TRUE or FALSE
Cholesterol and lecithin affect the surface area of RBCs which in turn affect their ability to carry oxygen
TRUE
These determine a red blood cells fluidity by maintaining differences in osmotic pressure, cation concentrations, and gas concentrations between external plasma and cytoplasm
Phospholipids
Glycolipids embedded in the membrane that carry several important RBC antigens (A, B, H, and Lewis - blood bank)
Lipid matrix/ Phospholipids
Predominant cytoskeletal (peripheral) protein in erythrocytes
Spectrin
Protein that extends from outer surface to inner side of erythrocytes
Integral proteins
Major glycoprotein that accounts for most of the sialic acid that gives erythrocytes their negative charge
Glycophorin
Proteins that are limited to the cytoplasmic surface of erythrocytes
Peripheral proteins
Major peripheral protein that:
- Binds to other peripheral proteins and integral proteins
- Forms skeleton and strengthens membrane to protect against shear forces
Spectrin
TRUE or FALSE
The peripheral and integral proteins network for erythrocytes requires ATP
TRUE
Permeability of RBCs:
Intracellular- to - extracellular ratio for sodium
1 : 12
1 sodium inside for ever 12 outside
Permeability of RBCs:
Intracellular - to - extracellular ratio for potassium
25 : 1
25 potassium inside for every 1 outside
Increased amounts of this ion will cause cell rigidity, shrunken cells with membrane protrusions (echinocytes) and reduced deformability
Calcium
Purpose of sialic acid found on the surface of glycophorin A of red blood cell membrane
Produces a negative cell charge that causes the cells to repel each other (zeta potential)
Molecule consisting of four globin protein chains containing a heme component nestled in a hydrophobic crevice
Hemoglobin
A tetrapyrrole ring with ferrous iron in the center
Heme
What percent of hemoglobin synthesis occurs during the nucleated stages of RBC maturation?
65%
What percent of hemoglobin synthesis occurs during the reticulocyte stage of RBC maturation?
35%
Tetramer of two pairs of unlike polypeptide chains
Globin
How many globin chains does a hemoglobin molecule have?
4 chains
-each with its own heme group
How many groups of heme are in a hemoglobin molecule?
4
-Each containing a protoporphyrin ring plus ferrous iron (Fe2+)
Most common disease caused by defective hemoglobin development
Iron deficiency anemia (lack of iron)
Diseases caused by defective hemoglobin (3)
-Thalassemia (defective globin chains)
-IDA (lack of iron)
-Sideroblastic anemia (lack of heme)
__/__ of the body’s iron is bound to heme
2/3
How much iron is needed daily for erythropoiesis?
20 - 25 mg
__/__ of total body iron content is present as hemoglobin
2/3
__/__ of total body iron content is present as tissue iron
1/3
90% of tissue iron is storage iron known as?
Ferritin
- Partially degraded ferritin
- Less metabolically available than ferritin
Hemosiderin
Where is hemosiderin seen?
Liver
Spleen
Bone marrow
When is hemosiderin increased?
Hemachromatosis
and
Iron Overload
What percent of tissue iron is non-available?
10%
Iron that is lost each day, is replaced by the diet through which organ?
Intestines
What is the average blood volume for a healthy adult?
4500 - 5000 mL
Foods high in iron (4)
-Organ meats
-Wheat germ
-Brewer’s yeast
-Legumes
Foods with a moderate level of iron (6)
-Muscle meats
-Fish
-Fowl
-Prunes
-Some green vegetables (spinach)
-Cereals (fortified)
Low molecular weight compounds that can increase iron absorption
(3)
-Amino acids
-Fructose
-Ascorbic acid (Vitamin C)
What decreases absorption of iron? (2)
-Phosphates
-Milk products (contains calcium phosphate)
Ex. Antacids
What populations are most prone to iron deficiency anemia?
Women and children
Where in the intestine is iron absorbed?
Duodenum of the jejunum
This part of the cell produces heme
Mitochondria
What influences the enzymatic steps of heme synthesis?
Erythropoietin and Vitamin B6
Porphyrin synthesis starts with what 2 components?
Glycine and Succinyl Coenzyme A
Protoporphyrin synthesis:
What does the combination of Glycine and Succinyl Coenzyme A form?
Aminolevulinic acid (ALA)
Protoporphyrin synthesis:
What does Aminolevulinic acid become?
Porphobilinogen
Protoporphyrin synthesis:
What does porphobilinogen become?
Coproporphyrinogen
Protoporphyrin synthesis:
What does Coproporphyrinogen become?
Protoporphyrin synthesis from start to finish
(be able to recognize)
Glycine + Succinyl Coenzyme A
→
Aminolevulinic Acid (ALA)
→
Porphobilinogen
→
Coproporphyrinogen
→
Protoporphyrinogen IX
What does Protoporphyrinuria cause?
Werewolf sundrome
Protoporphyrin IX + Ferrochelatase = ?
Heme
Any block in the enzymatic pathway will result in the excess formation of a particular porphyrin. What is this referred to as?
Porphyrias
Where will porphyrin accumulate in the body?
Brain
Liver
Bone marrow
(very toxic if in the brain)
Protoporphyrin synthesis impairment will result in the accumulation of iron in the cytoplasm in the form of ________ aggregates
Ferritin
Protoporphyrin synthesis impairment can cause the mitochondria to become encrusted with iron that will be visible around the nucleus of the RBC precursor.
If we saw these cells stained with Prussian Blue, what would they be called?
Ringed sideroblast
Globin synthesis is directed by how many genetic loci per haploid genome?
8
What are the 7 different types of globin chains?
Zeta
Epsilon
Gamma-A
Gamma-G
Delta
Beta
Alpha

Alpha

Beta

Delta

Epsilon

Gamma
-Remember Gamma has A and G

Zeta
Which globin-like genes are on chromosome 16?
Zeta
Alpha-1
Alpha-2
Which globin-like genes are on chromosome 11?
Epsilon
Gamma-G
Gamma-A
Delta
Beta
Which globin genes are considered embryonic?
Zeta
Gamma
Epsilon
These globin chains are produced up to 3 months following conception
Zeta and Epsilon
Embryonic Hemoglobins:
Zeta2, Epsilon2
Hemoglobin Gower 1
Embryonic Hemoglobins:
Alpha2, Epsilon2
Hemoglobin Gower 2
Embryonic Hemoglobins:
Zeta2, Gamma2
Hemoglobin Portland
Embryonic Hemoglobins:
Hemoglobin Portland
Zeta2, Gamma2
Embryonic Hemoglobins:
Hemoglobin Gower 2
Alpha2, Epsilon2
Embryonic Hemoglobins:
Hemoglobin Gower 1
Zeta2, Epsilon2
Fetal hemoglobin contains which globin chains?
Alpha2, Gamma2
This hemoglobin type has a high affinity for oxygen and by age 2 is less than 2% of total hemoglobin
Hemoglobin F
(Fetal hemoglobin)
When does Beta chain production reach adult percentages?
Between 3-6 months postnatally
Make up of normal adult hemoglobins
2 Alpha chains
2 non-Alpha chains - Beta, Delta, or Gamma
Hydrogen bonds
Salt bridges
Polypeptide for Hemoglobin A
Alpha2, Beta2
Alpha2, Beta2 makes what hemoglobin?
Hemoglobin A
Polypeptide for Hemoglobin A2
Alpha2, Delta2
Alpha2, Delta2 forms which hemoglobin?
Hemoglobin A2
Polypeptide for Hemoglobin F
Alpha2, Gamma2
Alpha2, Gamma2 forms which hemoglobin?
Hemoglobin F
AKA
Fetal Hemoglobin
Normal % of Hemoglobin A in adults
>95%
Normal % of Hemoglobin A in newborn - 2 years?
10 - 40 %
Normal % of Hemoglobin A2 in adults
< 3.5%
Normal % of Hemoglobin A2 in newborns
< 1%
Normal % of Hemoglobin F in adults
1 - 2%
Normal % of Hemoglobin F in newborn to 2 years
60 - 90%
At birth, Hemoglobin F levels are what %?
60 - 90%
At 12 weeks, Hemoglobin F is at what %?
7%
Between 4-5 months, Hemoglobin F reaches what %?
1.1 - 5.3%
As an adult, Hemoglobin F is found at what %?
1 - 2%
This comprises 33% of an RBC
Hemoglobin
One of the most important controls of hemoglobin affinity for oxygen is which RBC organic phosphate?
2,3-diphosphoglycerate
AKA
2,3-biphosphoglycerate
What does 2,3-DPG (2,3-BPG) do when part of the hemoglobin molecule?
Widens the space between beta chains, forming an anionic salt bridge and creating deoxyhemoglobin
What happens to the hemoglobin molecule when 2,3-DPG (2,3-BPG) is absent?
The salt bridge is broken and the hemoglobin molecule will carry more oxygen - creating oxyhemoglobin
Location that oxyhemoglobin occurs
In the lungs
Amount of iron needed each day to replace iron lost by senescent RBCs
18.5 - 21 mg
TRUE or FALSE
Increased oxygen affinity means the hemoglobin more readily gives up the oxygen
FALSE
Increased oxygen affinity means the hemoglobin does NOT readily give up oxygen
TRUE or FALSE
Decreased oxygen affinity means hemoglobin releases oxygen more readily (hemoglobin has a low affinity for oxygen)
TRUE
If the Hemoglobin-Oxygen Dissociation Curve shows a more BASIC pH, it is noted as what type of shift?
Left Shift
If the Hemoglobin-Oxygen Dissociation Curve shows a more ACIDIC pH, it is noted as what type of shift?
Right shift
How is oxygen tension measured?
mmHg
millimeters of Mercury
TRUE or FALSE
Oxygen affinity being decreased causes more oxygen to be released to the tissues. This causes a right shift.
TRUE
What causes a right shift in the hemoglobin-oxygen dissociation curve?
Hypoxia
Increased 2,3-DPG
Anemia
Acidosis
Fever
TRUE or FALSE
Oxygen affinity being increased causes decreased amounts of oxygen being delivered to tissues. This causes a left shift.
TRUE
TRUE or FALSE
An increase in oxygen affinity causes a decrease in oxygen delivery
TRUE
What causes a left shift on the hemoglobin-oxygen dissociation curve?
Decreased 2,3-BPG
Alkalosis
Increased quantity of abnormal hemoglobin
Multiple transfusions (new blood/not as oxygenated)
Fetal hemoglobin (higher affinity for oxygen, so holds on to it)
Definition:
Inadequate amount of oxygen at tissue level
Hypoxia
Definition:
Bluish color of skin due to presence of high amounts of deoxyhemoglobin in blood
Cyanosis
3 acquired nonfunctional hemoglobins
Carboxyhemoglobin
Methemoglobin
Sulfhemoglobin
This acquired nonfunctional hemoglobins oxygen affinity is 200x greater than that of normal hemoglobin.
It can be fatal.
Smokers can have up to 12%
Carboxyhemoglobin
This nonfunctional hemoglobin is incapable of combining with oxygen due to the iron being in the ferric state.
Increased levels are formed when exposed to certain oxidizing drugs or chemicals.
Infants are more susceptible due to HbF more readily converting to it.
Methemoglobin
This nonfunctional hemoglobin is irreversible
Sulfhemoglobin
This returns iron to bone marrow or liver
Transferrin
What is the protoporphyrin ring broken down to?
Toxic bilirubin
What carries toxic bilirubin from the breakdown of the protoporphyrin ring to the liver?
Albumin
What % of aged erythrocyte destruction occurs extravascularly?
90%
What % of erythrocyte destruction occurs intravascularly?
10%
Approximately what % of the total red cells are removed from circulation on a daily basis?
~1%
TRUE or FALSE
Oxygen affinity is dependent on 2,3-BPG
TRUE
When are enzymes made in RBCs
When RBCs still have a nucleus
Size of reticulocytes
9 microns
Purpose of haptoglobin
Prevents kidney damage by binding hemoglobin dimers after intravascular hemolysis occurs
Hemoglobin synthesis occurs here
Nucleated red blood cells in the bone marrow
What is involved in protein synthesis?
Transcription
Translation
and Codons
Automated instruments use what indices to calculate hematocrit?
MCV and RBC
What is urobilinogen the final breakdown product of?
Hemoglobin
This abnormal RBC shape has an MCHC >36
Spherocytes
Iron is stored as _______
Ferritin
Iron is carried by __________ to the liver and bone marrow
Transferrin
(b/c trans = across or to the other side)
Defective hemoglobin synthesis causes this disease
Porphyria
Rule of 3
Hemoglobin x 3
+/-3
= Hematocrit
Normal RDW range
11.5 - 14.5%