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195 Cards in this Set

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Microcytic anemias: Definition
Mean Corpuscular Volume less than 80 cubic micrometers
Macrocytic anemias: Definition
Mean Corpuscular Volume more than 100 cubic micrometers
Normocytic anemias: Definition
Mean Corpuscular Volume between 80 and 100 cubic micrometers
Corrected reticulocyte count less than 3%: Bone marrow status
Ineffective erythropoiesis
Corrected reticulocyte count greater than or equal to 3%: Bone marrow status
Effective erythropoiesis
Regular hematocrit level
45%
Stimuli for erythropoietin
-hypoxemia
-left-shifted oxygen binding curve
-high altitude
Where is erythropoietin made?
Endothelial cells of peritubular capillaries
Corrected reticulocyte count: Definition
(Actual hematocrit/45) * reticulocyte count

If polychromasia, divide by 2.
Reticulocyte count: What does it measure?
-Effective erythropoiesis
-Must be corrected for degree of anemia
How long does it take for reticulocyte count to increase after blood loss?
5-7 days.
Microcytic (less than 80 cubic micrometers) anemias: List
-Iron deficiency
-Anemia of chronic disease
-Thalassemia (alpha and beta)
-Sideroblastic anemia
Sideroblastic anemias: List
-Chronic alcoholism (most common)
-Pyridoxine (B6) deficiency
-Lead poisoning
Anemias of chronic disease: List
-Chronic inflammation (eg rheumatoid arthritis, TB)
-Alcoholism
-Malignancy
Type of anemia: Iron deficiency
Early-stage: Normocytic with a low reticulocyte count.

Later-stage: Microcytic
Type of anemia: Anemia of chronic disease
Early-stage: Normocytic with a low reticulocyte count.

Later-stage: Microcytic
Type of anemia: Thalassemia
Microcytic
Sign: Dark blue iron granules around the nucleus of developing normoblasts
Ringed sideroblasts, indicating sideroblastic anemia
Type of anemia: Sideroblastic
Microcytic
Type of anemia: Pyridoxine deficiency
Sideroblastic, so Microcytic
Type of anemia: Lead poisoning
Sideroblastic, so microcytic
Type of anemia: Alcoholism
Either sideroblastic, or anemia of chronic disease. Either way, microcytic.
Type of anemia: Rheumatoid arthritis
Chronic inflammation, so anemia of chronic disease, so microcytic
Type of anemia: TB
Chronic inflammation, so anemia of chronic disease, so:

Early: Normocytic with low reticulocyte count

Later: Microcytic
Type of anemia: Malignancy
Anemia of chronic disease, so microcytic
Type of anemia: Vitamin B12 deficiency
B12 deficiency or metabolism defect means megaloblastic macrocytic
Type of anemia: Vitamin B12 metabolism defect
B12 deficiency or metabolism defect means megaloblastic macrocytic
Type of anemia: Folate deficiency
Folate deficiency or metabolism defect means megaloblastic macrocytic
Type of anemia: Folate metabolism defect
Folate deficiency or metabolism defect means megaloblastic macrocytic
Type of anemia: DNA synthesis defect
Macrocytic megaloblastic
Type of anemia: Liver disease
non-megaloblastic macrocytic

or

normocytic with a normal reticulocyte count and an extrinsic RBC defect
Type of anemia: Cytotoxic drugs
Macrocytic non-megaloblastic
Type of anemia: Hypothyroidism
Macrocytic non-megaloblastic
Type of anemia: Stress erythropoiesis
Macrocytic non-megaloblastic
Type of anemia: Blood loss
Normocytic

Reticulocyte count
-Less than one week: low
-More than one week: normal
Type of anemia: Aplastic anemia
Normocytic with a low reticulocyte count
Type of anemia: Renal disease
Normocytic

Reticulocyte count
-low
-normal: extrinsic defect hemolytic anemia
Type of anemia: Absence of erythropoietin
Normocytic with a low reticulocyte count
Type of anemia: Replacement of bone marrow
Normocytic with a low reticulocyte count
Type of anemia: Hereditary spherocytosis
Membrane defect, so:

Normocytic hemolytic anemia with normal reticulocyte count
Type of anemia: Hereditary elliptocytosis
Membrane defect, so:

Normocytic with normal reticulocyte count
Type of anemia: South-East Asian Ovalocytosis
Membrane defect, so:

Normocytic with normal reticulocyte count
Type of anemia: Paroxysmal Nocturnal Hemoglobinuria
Membrane defect, so:

Normocytic with normal reticulocyte count
Type of anemia: G6PD deficiency
Metabolism defect so:

Normocytic hemolytic anemia with normal reticulocyte count
Type of anemia: Glutathione deficiency
Metabolism defect so:

Normocytic hemolytic anemia with normal reticulocyte count
Type of anemia: Pyruvate kinase deficiency
Metabolism defect so:

Normocytic hemolytic anemia with normal reticulocyte count
Type of anemia: Sickle cell disease
Hemoglobin defect so:

Normocytic hemolytic anemia with normal reticulocyte count
Type of anemia: Drugs
Normocytic hemolytic anemia with normal reticulocyte count
Type of anemia: Chemical/Physical agents
Normocytic hemolytic anemia with normal reticulocyte count
Type of anemia: Snake bite venom
Toxin so:

Normocytic hemolytic anemia with normal reticulocyte count
Type of anemia: Clostridial toxin
Toxin so:

Normocytic hemolytic anemia with normal reticulocyte count
Type of anemia: Burns
Injury so:

Normocytic hemolytic anemia with normal reticulocyte count
Type of anemia: Fresh water drowning
Injury so:

Normocytic hemolytic anemia with normal reticulocyte count
Type of anemia: Hypersplenism
Normocytic hemolytic anemia with normal reticulocyte count
Type of anemia: Cold antibody type
Autoimmune so:

Normocytic hemolytic anemia with normal reticulocyte count
Type of anemia: Warm antibody type
Autoimmune so:

Normocytic hemolytic anemia with normal reticulocyte count
Type of anemia: Alloimmune
Immune so:

Normocytic hemolytic anemia with normal reticulocyte count
Type of anemia: Drug induced immune hemolytic anemia
Drug-induced and/or immune so:

Normocytic hemolytic anemia with normal reticulocyte count
Type of anemia: Vasculitis
Red cell fragmentation syndrome so:

Normocytic hemolytic anemia with normal reticulocyte count
Type of anemia: Mechanical devices
Red cell fragmentation syndrome so:

Normocytic hemolytic anemia with normal reticulocyte count
Type of anemia: Microangiopathic hemolytic anemia
Red cell fragmentation syndrome so:

Normocytic hemolytic anemia with normal reticulocyte count
Type of anemia: Macroangiopathic hemolytic anemia
Red cell fragmentation syndrome so:

Normocytic hemolytic anemia with normal reticulocyte count
Type of anemia: March hemoglobinuria
Normocytic hemolytic anemia with normal reticulocyte count
How do you identify a reticulocyte?
-Supravital stain (new methylene blue)
-RNA filaments
How do you get hemoglobin from hematocrit?
hb = (1/3)hct
For every unit of packed red blood cells, you increase:
hemoblobin by 1
hematocrit by 3
Most common cause of anemia in the world
iron deficiency
Most common cause of iron deficiency
GI bleed
RDW: Definition
RBC Distribution Width

Checks uniformity of size.
Low MCV with Increased RDW
-Increases variation in size: Mixture of normocytic and microcytic RBCs
-Iron deficiency
Spherocyte: membrane defect
Too little membrane
Target cell: membrane defect
Too much membrane so more hemoglobin can collect in the middle
Target cell: markers for what?
-Alcoholism
-Hemoglobinopathy
How to identify a microcytic cell
Too much central pallor
How to identify a spherocyte
-No central pallor
-Small and red
Spoon nails: Sign of?
Iron deficiency
Cheilosis: Sign of?
-Iron deficiency
-Riboflavin deficiency
Pale conjunctiva: Sign of?
Low hemoglobin
No red in palmar creases: Sign of?
Iron deficiency
Discoloration of gum margin: Sign of?
Known as "lead lines". A sign of lead poisoning.
Normal serum iron
About a 100 (like the alveolar oxygen)
Serum ferritin: what is it?
Soluble circulating form of iron storage
Serum ferritin: what does it represent?
Amount of iron in bone marrow
-Best overall screening test
Carrying protein for iron
Transferrin (Carries iron)
TIBC: What does it measure?
Transferrin
What does increased TIBC indicate?
Increased transferrin synthesis by liver, so decreased iron stores in the bone marrow.
What does decreased TIBC indicate?
Decreased transferrin synthesis by liver, so increased iron stores in the bone marrow.
Define: % iron saturation
Serum iron/TIBC
Normal TIBC
300
Normal % iron saturation
33%

=normal serum iron/ normal TIBC = 100/300
Hemoglobin type: 2 alpha chains and 2 beta chains
HbA
Hemoglobin type: 2 alpha chains and 2 delta chains
HbA2
Hemoglobin type: 2 alpha chains and 2 gamma chains
HbF
Mechanism of pathogenesis in Anemia of Chronic Disease
Bugs increase reproduction with iron, so body assumes there is a bacterial infection, and keeps iron away from bacteria.

Iron is normally stored in macrophages in bone marrow. It's kept away from RBCs.
Where does Hemoglobin synthesis begin?
Mitochondria of RBC
First reaction of Hemoglobin synthesis
Succinyl CoA + Glycine (catalyzed by ALA synthetase) yields delta-ALA

all in the mitochondria
What kind of neurotransmitter: Glycine
Inhibitor of muscle.
What toxin blocks glycine?
Tetanus
Rate limiting step in Heme synthesis
delta-ALA synthesis
What enzyme does heme inhibit?
ALA synthase
Why does alcoholism cause sideroblastic anemia?
Alcohol is a mitochondrial toxin.
What are sideroblasts?
Overloaded mitochondria
Why does B6 deficiency cause sideroblastic anemia?
Can't form CoA, so can't form succinyl CoA, so can't do first reaction of heme synthesis.
Mechanism of lead poisoning
Lead denatures ferrochelatase --> Can't form heme
Test for lead poisoning
Blood lead levels
What are the main groups that we see alpha-thalassemia?
-Southeast asians
-Black Americans
What are the main populations we see beta-thalassemia in?
-black Americans
-Greeks
-Italians
% of Hb that is: HbA
95%
% of Hb that is: HbA2
2%
% of Hb that is: HbF
1%
alpha-thalassemia: mode of inheritance
Autosomal recessive
alpha-thalassemia: pathogenesis
problem making alpha chains
alpha-thalassemia: electropheresis results
all normal proportions (all Hbs decreased)
alpha-thalassemia: one gene deletion
Silent carrier
alpha-thalassemia: two gene deletions
alpha-thalassemia minor

-mild anemia (microcytic because globin is decreased)
alpha-thalassemia: three gene deletions
Four beta chains form making HbH. Found in electropheresis.
Called HbH disease
alpha-thalassemia: four gene deletions
Four gamma chains form making Hb Bart. Found in electropheresis. Called hydrops fetalis.
Why is choriocarcinoma increased in far east?
1. Increased alpha thalassemia rates
2. Increased spontaneous abortions due to Hb Bart
3. Increased choriocarcinoma
alpha-thalassemia: treatment
None
beta-thalassemia: permutations of problems
beta by itself: normal number of beta chains

beta with a + sign: not making enough, but are making

beta with a 0: not making it at all
beta-thalassemia: mode of inheritance
autosomal recessive
beta-thalassemia: what is the genetic association with severe anemia?
Nonsense mutation with formation of a stop codon
beta-thalassemia: what hemoglobin will decrease
HbA
beta-thalassemia: what hemoglobins will increase
HbA2 and HbF
beta-thalassemia: electropheresis results
Will show increased HbA2 and HbF with decreased HbA
beta-thalassemia: treatment
none
Cooley's anemia: disease type
Not making any beta chains (beta 0)
Cooley's anemia: Prognosis
Will not live past 30
Main way to tell Anemia of chronic disease from Iron deficiency
Ferritin levels

Low: Iron deficiency
High: Anemia of chronic disease
Stain used to find Ringed Sideroblasts
Prussian Blue
Histologic sign associated with Lead poisoning
Coarse basophilic stippling
Where does stippling come from?
Inability to break down ribosomes.
Classic presentation of lead poisoning in children
-Severe abdominal colic
-Cerebral edema (convulsions, etc)
-Severe microcytic anemia
-Failure to thrive
What is seen on a flat plate?
-Iron (if kid took iron tablets)
-Lead (from intestine)
-Mercury
Mechanism of lead poisoning
Buildup of delta-ALA, leading to neuronal toxicity
Presentation of lead poisoning in adults
-Workers from automobile factory or moonshine makers or pottery painters
-Abdominal colic
-Diarrhea
-Neuropathy (slapping gait, drops (radial, ulnar palsies), claw hand
What is the disease: Serum Iron (low), TIBC (high), % iron saturation (low), Serum ferritin (low)
Iron deficiency
What is the disease: Serum Iron (low), TIBC (low), % iron saturation (low), Serum ferritin (high)
Anemia of Chronic Disease
What is the disease: Serum Iron (normal), TIBC (normal), % iron saturation (normal), Serum ferritin (normal)
Thalassemia
Sideroblastic anemias: Iron status
Iron overload
Hemochromatosis: Iron status
Iron overload
Hemosiderosis: Iron status
Iron overload
What is the disease: Serum Iron (high), TIBC (low), % iron saturation (high), Serum ferritin (high)
Iron overload (Sideroblastic anemia, hemochromatosis, hemosiderosis)
What do B12 and folate deficiencies most immediately not allow production of?
dTMP (using Thymidylate synthase) leading to lack of DNA production
What is the size of immature nuclei?
Nucleus gets smaller and more condensed due to increased DNA?
What are cells called with immature nuclei?
Megaloblasts
Why is B12 called Cobalamin?
It has cobalt in it.
What is the circulating form of Folate?
N5-methyl-Tetrahydrofolate
What does B12 do in folate metabolism?
B12 removes methyl group from N5-methyl-THF to make THF
What happens when you add a methyl group to homocysteine?
Methionine
Which amino acid is used for one-carbon transfers?
Methionine
What are serum homocysteine levels in B12 or THF deficiency?
High
Why do high homocysteine levels produce thromboses?
It damages endothelial cells predisposing them to thrombosis.
What is the most common cause of high homocysteine levels?
Folate deficiency
Drugs which inhibit folate metabolism
5-fluorouracil (which inhibits thymidylate synthase),
Methotrexate and TMP-SMX (which both inhibit DHF reductase), Phenytoin (which inhibits intestinal conjugase), Oral contraceptives and alcohol (which both inhibit of uptake of monoglutamate in jejunum, but alcohol also inhibits the release of folate from the liver)
What happens if B12 is missing to Methylmalonyl-CoA?
It builds up, because it cannot form succinyl-coA
Sensitive test for B12 deficiency
Methylmalonic acid
What is methylmalonic acid level a test for?
B12 deficiency
What is the mechanism of B12 deficiency leading to neurologic deficiencies?
Propionyl CoA builds up, and myelin production is deficient.
What are the neurologic effects of B12 deficiency?
Dementia, demyelination of posterior columns (proprioception and vibratory sensation) and lateral corticospinal tract (upper motor neuron problems)
Serum levels to order in dementia
TSH to rule out hypothyroidism and B12 to rule out B12 deficiency
Where is B12 gotten from?
Animal products
What is the first factor B12 binds to?
R factor
What does R factor do?
It protects B12 from being destroyed?
Where does intrinsic factor come from?
Parietal cells in the gastric body and fundus.
Where is vitamin B12 absorbed?
Terminal ileum
What deficiencies are found in Crohn's disease?
Bile salts and vitamin B12 (both due to reabsorption problems in terminal ileum)
Most common cause of B12 deficiency
Pernicious anemia
What is the mechanism in pernicious anemia?
Autoimmune destruction of parietal cells and intrinsic factor
What is achlorhydria?
Atrophic gastritis of the body and fundus leading to :

lack of acid which leads to gastric adenocarcinoma

AND

bacterial overgrowth from stasis
Causes for achlorhydria
Tapeworms, pernicious anemia, folate deficiency
Eaten form of folate
Polyglutamate
What converts polyglutamate to monoglutamate?
Intestinal conjugase
What drug blocks intestinal conjugase?
Phenytoin
What is the mechanism of Phenytoin?
Blocks intestinal conjugase
What blocks absorption of monoglutamate from jejunum?
Alcohol and oral contraceptives
What are hypersegmented neutrophils with neurologic deficiency diagnostic for?
Vitamin B12 deficiency
What are hypersegmented neutrophils without neurologic deficiency diagnostic for?
Folate deficiency
What is a characteristic CBC finding in macrocytic anemia?
Pancytopenia
Schilling's test
1. Give radioactive B12 by mouth
2. 24 hour urine collection
3. If nothing comes out, can't reabsorb B12.
4. Then give radioactive B12 and intrinsic factor together by mouth.
5. 24 hour urine collection. If something comes out, it's pernicious anemia. If not, go to step 6.
6. Give broad-spectrum anti-biotic. If you see B12 in the urine, you have bacterial overgrowth. If not, go to step 7.
7. Take pancreatic extract with radioactive B12. If you get B12 in the urine, they have chronic pancreatitis. If not, it could be Crohn's disease, a worm, or some other cause.
Stages of iron deficiency
1. Ferritin goes down
2. Iron decreases, TIBC increases, % iron sat decreases
3. Mild normocytic anemia
4. Microcytic anemia
What test must be ordered to confirm aplastic anemia?
Bone marrow study
Most common cause of aplastic anemia
Idiopathic
Most common known cause of aplastic anemia
Drugs (Indomethacin, Phenylbutazone, Thyroid-related drugs, Chloramphenicol)
Second most common known cause of aplastic anemia
Hepatitis C
Most common infective cause of pure RBC aplasia
Parvovirus
Mechanisms of hemolysis
1) Intravascular hemolysis
2) Extravascular hemolysis which is more common
What is the mechanism of extravascular hemolysis?
Macrophages kill them at the Cords of Bilroth
What are some causes of RBCs being phagocytosed at the cords of Bilroth?
IgG or c3b on the surface,
or Howell-Jolly bodies inside, or an abnormal shape (such as spherical or sickle cell)
End product of phagocytosing an RBC
Unconjugated bilirubin
Clinical finding in extravascular hemolysis
Jaundice, which is due to unconjugated bilirubin due to macrophages phagocytosing red blood cells.
Causes of intravascular hemolysis
1) Congenital bicuspid aortic valve.
2) IgM binding to surface and activating complement system
End product of intravascular hemolysis
Hemoglobin
Name of protein which binds free hemoglobin in blood
Haptoglobin
Clinical findings in intravascular hemolysis
1) Hemoglobinuria
2) Low haptoglobin levels