2-04 Exam 12 Anemia Intro And Cont'd

Front 1

Know the definition for anemia

Back 1

reduction of hemoglobin concentration in blood and/or RBC count

Anemia is not a diagnosis, it is a manifestation of an underlying disorder

Front 2

Understand the general causes of anemia and consequence/symptoms

Back 2

Causes
-Excessive destruction of red blood cells
-Blood loss
-Inadequate production of red blood cells

Acute onset:
rapid heartbeat
lightheadedness
shortness of breath

Chronic:
irritability, fatigue, weakness
headache, vertigo
pallor of mucous membrane (e.g. under eye), skin color is

less reliable
sensitivity to cold
loss of appetite

Sxs:

Front 3

How do adaptations that occur mask anemia?

Back 3

SPEED OF ONSET: Rapid onset causes more symptoms (less time for adaptation)

SEVERITY: Mild anemia often no
symptoms

AGE: Anemia is less well tolerated by elderly (cardiovascular compensation impaired); however, very common among elderly

Hb O2 DISSASSOC CURVE:
Rise in 2,3 BPG (2,3-Bisphosphoglycerate) yields in more oxygen released

Front 4

Know what: Hct, Hgb, and RBC tests mean.

Back 4

Hct (hematocrit) = percent volume of blood contributed by red blood cells
Hgb = total Hb
RBC = RBC count

Front 5

7. Understand what red blood cell indices are.

Back 5

REALIZE THESE ARE PER-CELL CALCULATIONS

Measures hemoglobin volume/concentration and red blood cell size.
The relationships between the hematocrit, the hemoglobin level, and the RBC are converted to red blood cell indices through mathematical formulas.

Front 6

Define mean corpuscular hemoglobin (MCH)

What do we call low, normal, and high hemoglobin levels?

what's the eqn for MCH?

Back 6

amount of hemoglobin per red blood cell.

Hgb/RBC

hypochromic anemia: MCH low
normochromic anemia: MCH normal
hyperchromic anemia: MCH high

Front 7

9. Define Mean corpuscular hemoglobin concentration (MCHC)

Back 7

calculation of the concentration of hemoglobin inside the red blood cells (takes size into account)
Hgb/Hct

Front 8

Define mean corpuscular volume (MCV)

What do we call low, normal, and high volume levels?

what's the eqn for MCV?

Back 8

10. Define mean corpuscular volume (MCV)
average single red blood cell size
Hct/RBC

normocytic anemia: MCV
normal
microcytic anemia: MCV low
macrocytic anemia: MCV high

Front 9

What type of anemia (red blood cell indices) would you expect in thalassemia? Explain why

Back 9

Hypochromic, microcytic anemia (low MCH, low MCV)

Understand that b-thalasemia cells have less Hb and are this affects RBC development = smaller cell.

Front 10

Understand the different clinical aspects/techniques used to look at anemia (what are they, what do they look for, and what does it determine?)

Back 10

1. ANALYZER:
hematocrit (Hct) = packed RBC volume (percent blood vol made up of RBCs)
total hemoglobin (Hgb) = total Hb
number of red blood cells = #RBCs

2. CALCULATE RBC INDECES
red blood cell indices (MCH and MCV)
i. Mean Corpuscular Volume
1. normocytic anemia: MCV normal
2. microcytic anemia: MCV low
3. macrocytic anemia: MCV high

ii. Mean Corpuscular Hb
1. normochromic anemia: MCH normal
2. hypochromic anemia: MCH low
3. hyperchromic anemia: MCH high

MICROSCOPY of BLOOD FILM
1. sickles - SCA
2. pencil shapes - FE deficiency

WHOLE BLOOD CELL EVALUATION
1. Includes leukocyte (white blood cell) and platelet counts:
2. Helps to distinguish “pure” anemia from pancytopenia (drop in number of all blood cells)
3. If all cell numbers are low: marrow hypoplasia or infiltration, general destruction of cells (e.g. hypersplenism)
4. If leukocytes and platelet count is high: infections, leukemias, hemolysis, hemorrhage

RETICULOCYTE COUNT
immature RBCs - meas of how fast RBCs are made
i. The reticulocyte count rises when there is a lot of blood loss or in certain diseases or where red blood cells are destroyed prematurely, such as hemolytic anemia.

BONE MARROW EXAM
Aspiration: liquid of bone marrow. Morphological information on developing cells (more information on hematopoiesis)

Trephine biopsy: solid cores of bone marrow which is examined microscopically (sometimes with the aid of immunohistochemistry) for cellularity and infiltrative processes.

Front 11

Define whole blood cell evaluation.
What do we use it for?
What does it mean if all cell numbers are low?
What does it mean if leukocytes and platelets are high?
What do high

Back 11

1. Includes leukocyte (white blood cell) and platelet counts:
2. Helps to distinguish “pure” anemia from pancytopenia (drop in number of all blood cells)
3. If all cell numbers are low: marrow hypoplasia or infiltration, general destruction of cells (e.g. hypersplenism)
4. If leukocytes and platelet count is high: infections, leukemias, hemolysis, hemorrhage

Front 12

What is microscopy?
What diseases can we identify using it? (there may be more than what I have here)

Back 12

Microscopy = analysis of blood film (microscopy)
1. sickles = sickle cell anemia
2. pencil shapes = Fe deficiency

Front 13

What does a reticulocyte count help us determine?

Back 13

The reticulocyte count rises when there is a lot of blood loss or in certain diseases or where red blood cells are destroyed prematurely, such as hemolytic anemia.

Front 14

Name and describe the (2) types of bone marrow exams.

Back 14

i. ASPIRATION: liquid of bone marrow
Morphological information on developing cells (more information on hematopoiesis)
ii. TREPHINE BIOPSY: solid cores of bone marrow which is examined microscopically (sometimes with the aid of immunohistochemistry) for cellularity and infiltrative processes.
FYI-Blood Panel

Front 15

Know that... anemia is the most common anemia. What is the consequence for the synthesis of heme and hemoglobin, what is the consequence for the red blood cell size?

Back 15

Iron deficiency (sideropenic anemia)
microcytic

Front 16

What are the possible causes of iron deficiency and what is the treatment?

Back 16

What are the possible causes of iron deficiency and what is the treatment?

Causes
loss of blood (including from heavy menstrual bleeding, ulcers, pregnancy, nursingdiet low in iron
poor absorption of iron

Treatment:Oral iron supplements (ferrous (Fe2+) sulfate), in extreme cases, parenteral

Front 17

Explain the iron cycle in the body:

Back 17

b. Absorption of dietary iron as either:
i. iron (transporter DMT-1)
ii. Intact heme (transporter HCP-1) (digested to release Fe)
c. Transferrin xports Fe to marrow cell (free Fe is toxic!)
i. Ferritin stores Fe ("ferret it away")
ii. Neg-fb, if XS Fe (no xferrin receptor made)
d. Delivered to mitochondria & incorporated into heme
e. Heme combines with globin chains (a2b2) to form hemoglobin
f. Circulation of Fe
g. Some secretion, mostly recycling of Fe after RBC destroyed

Front 18

Know that. . . is the most commonly used as diagnostic tool to measure iron levels in body

Back 18

a. SERUM FERRITIN - Amt of ferritin rel into blood is prop to amt of tot Fe stored

Front 19

How does iron overload (hemochromatosis) occur and why is this a problem?

Back 19

No physiological mechanism for XS Fe elimination (e.g. thalassemia victims get xfusions but can't get rid of XS iron)

Overload:
Damage to organs, especially heart, liver, endocrine organs
Abnormal deposition of an iron-containing compound (hemosiderin) in tissues

Usually caused by genetic disease (common ~1/300): HFE (HEMOCHROMATOSIS) gene (iron absorption & regulation)

Front 20

What type of anemia (red blood cell indices) does iron deficiency cause?

Back 20

Hypochromic, microcytic anemia

Front 21

What could cause high Fe levels?

Back 21

HFE (hemochromatosis) gene (Fe abs + reg)

Resulting in Organ damage (heart, liver, endocrine) and/or abnormal deposit of Fe in tissues

Front 22

Which proteins transport and store iron in the body?

Back 22

Xferrin, ferretin

Front 23

What are the treatments for Fe overdose?

Back 23

phlebotomy or iron chelating therapy

Front 24

What do thalassemia and iron deficiency anemia have in common?

Back 24

Result in smaller, less numerous RBC's: hypochromic (MCH), hypovolemic (MCV).

Front 25

briefly describe sideroblastic anemia

Back 25

Failure of protoporphyrin synthesis due to a lack of Fe (usually)

Front 26

Describe lead poisoning

Back 26

Lead poisoning inhibits both HEME --AND-- GLOBIN synthesis Interferes with ALAD, zinc binding protein impt in syth of hemeInterferes w/ferrochelatase which catalyzes binding of protoporphrin and Fe2+ to form hemeResult: microcytic, hypchromic anemia

Front 27

Be able to explain why iron deficiency, sideroblastic anemia, thalassemia, and lead poisoning cause microcytic, hypochromic anemia.

Back 27

all three of these retard hemoglobin synthesis. Hb is necessary for proper RBC development, as a result cells are small (microcytic) and have less Hb (hypochromic)

Front 28

Describe sideroblastic anemia

Back 28

Genetic or acquired cause leading to Fe deficiency; Adequate iron but unable to incorporate iron into hemoglobin (protoporphoryn synthesis). Iron accumulates in mitochondria of erythroblasts in bone marrow.

Front 29

Understand that ____ and vitamin ____ deficiencies are common causes for megaloblastic anemias. What is the molecular basis for this?

Back 29

folate , B12Folic acid (Vitamin B9):Required for several steps of DNA synthesisVitamin B12:Required to convert methyltetrahydrofolate into tetrahydrofolate

Front 30

Be able to briefly outline vitamin B12 absorption.

Back 30

meat is best source (not in plants) initially binds to salivary R-protein vitamin B12 then binds to intrinsic factor (IF) in stomach uptake of B12-IF across intestinal wall into circulationtranscobalamin II xports to marrowstored in liver

Front 31

Know what causes pernicious anemia. Understand the main causes for vitamin B12 deficiencies.

Back 31

pernicious anemia: autoimmune destruction of gastric parietal cells, lack of IF production = B12 deficiency (can't absorb)

Causes congenital lack or abnormality of intrinsic factortotal or partial gastrectomy

Intestinal causes
-Crohn’s disease
-Surgical removal of intestine or part of it
-Stagnant loop syndrome (obstruction of part of intestine, bacterial overgrowth)
-chronicle tropical sprue (malabsorption disease caused by infections)
-fish tapeworm

Front 32

What are the main causes for folate deficiencies?

Back 32

Excess utilization
-increased need during pregnancy (dividing cells), lactation
-hematological or malignant diseases
-inflammatory diseases

Nutritional
-poor diet, famine, old age

Intestinal causes
-Crohn’s disease surgical -removel of intestine or part of it
-stagnant loop syndrome (obstruction of part of intestine, bacterial overgrowth)
-chronical tropical sprue (malabsorption disease caused by infections)

Front 33

What are the treatments for folate and vitamin B12 deficiencies?

Back 33

Folate = folic acid, PO, 5mg
B12 = hydroxycobalamin, IM, 1000ug

Front 34

What is the definition for hemolytic anemia?

Back 34

anemias that result from an increase in red blood cell destruction

Front 35

Know how red blood cells are normally disposed of. What organ is most important and what cell type removes the RBC's? What other organs besides the major one can perform this task?

Back 35

Removed by macrophages of the reticuloendothelial system in spleen, liver, marrow

Front 36

Be able to list and briefly define the three main genetic defects for intrinsic anemia.

Back 36

Membrane-hereditary spherocytosis, elliptocytosis

Metabolism-G6PD deficiency, pyruvate kinase deficiency

Hemoglobin-genetic abnormalities (sickle cell anemia, thalassemia)

Front 37

Be able to LIST the two cases of red blood cell membrane disorders. Why do they cause hemolytic anemia?

Back 37

Spherocytosis and elliptocytosis

sphere shaped rather than doughnut shaped

Diag by microscopy

Front 38

Be able to briefly describe G6PD (Glucose-6-phosphate dehydrogenase) deficiency (molecular cause, metabolic problem).

Back 38

pentose-phosphate pathway - gens NADPHgens reduced glutathione, to defend vs oxidative stress reduce Fe3+ to Fe2+)Deficiency renders cell susceptible to oxidative stress

Front 39

Why is this G6PD deficiency -based anemia such a problem for the use of anti-malaria drugs?

Back 39

Antimalarials like primaquine: mechanism of action not well understood but they may produce reactive oxygen species…this is what's causing our hemolytic crisis to begin w

Front 40

Be able to very briefly define pyruvate kinase deficiency.

Back 40

Metab defect, Reduction in ATP generation:pyruvate kinase: phosphoenolpyruvate to pyruvate

RIGID, RBCs as result of ATP lack

Front 41

How does the malaria parasite cause hemolytic anemia?

Back 41

Plasmodium invades, multiplies in and destroys red blood cells, Hemoglobin used as nutrient source by parasite

Front 42

Know what chronic anemia is.

Back 42

Repetitive, long-lasting anemias, usually disease caused

ommon causes Chronic infections
Tuberculosis
HIV
Osteomyelitis
Chronic inflammation (e.g. rheumatoid arthritis, systemic lupus erythematosus, chronic inflammatory liver diseases)
Malignancies (carcinoma, lymphoma, leukemia)

Front 43

Be able to describe aplastic anemia. Understand how serious this type of anemia is.

Back 43

Bone marrow does not prod enough blood cells (total blood cells not just red)Leads to rapid death <6mos

Front 44

Know what primary and secondary polycythemia (erythrocytosis) is.

Back 44

Polycythemia (erythrocytosis): overproduction of red blood cells

Primary polycythemia: no increase in erythropoietin, myeloproliferative disease (polycythaemia ruba vera)

Secondary polycythemia: increase in erythropoietin (tumors, low oxygen levels, heart disease, heavy smoking, kidney disease)

Front 45

Categorize the following anemias

hemolytic anemia
pernicious anemia
lead poisoning
alcohol, liver disease
anemias of chronic disease
sideroblastic anemia
myelodysplasia
thalassemias
renal disease
acute hemorrhage
folate deficiency

Back 45

NN: decr #rbc but normal size and Hb content

HypoMicro: anything affecting Hb development = retard cell dev
HyperMicro: Lg size, little replication

chromic/cytic
hemolytic anemia - N/N
pernicious anemia - N/Mac
lead poisoning - Hypo/Mic
alcohol, liver disease - N/Mac
anemias of chronic disease - N/N
sideroblastic anemia - Hypo/Micro
----------------------------------
myelodysplasia - N/Macro
----------------------------------
thalassemias - Hypo/Micro
renal disease - NN
acute hemorrhage - NN
folate deficiency - N/Macro

Front 46

What test do we use to ID microcytic hypochromic anemia?

Back 46

serum ferrtin most common

Lead poisening
Thalassemia
Sideroblastic anemia
Vitamin deficiencies:
Lack of transferrin due to vitamin A (pyridoxine) deficiency
Lack of heme synthesis due to B6 deficiency

Front 47

Describe megaloblastic anemia and how we test for it.

Back 47

Megaloblastic (macrocytic) anemia - cell grows but doesn't divide, prob w/dna synth (high MCV + direct meas of folate/b12)

Vitamin B12: direct measurement of serum B12 levels measurement of homocysteine or methylmalonic acid serum levels shilling test (absorption test using radioactive B12) IF and gastric parietal cell antibodies

Folate: serum folate levels red blood cell folate levels

Front 48

Effects of megaloblastic anemia

Back 48

Effects:Resulting in unbalanced cell growth, impaired cell division

Mature cytoplasm, immature nucleus, larger cell volume

Large but less red blood cells produced

Front 49

Causes of megaloblastic anemia

Back 49

Vitamin B12 deficiency
Folate deficiency
Other defects of DNA synthesis

Front 50

Why would you give vitamin B12 as an injection and not orally?

Back 50

Pt missing part of stomachPernicious anemia = no IF, thus can't abs through stomach = need iv

Front 51

What type of anemia (red blood cell indices) would occur in hemolytic anemia?

Back 51

normocytic, normochromic

Front 52

Could thalassemia or sickle cell anemia lead to hemolytic anemia?

Back 52

SHAPE is critical!Sickle cell: RBCs are shaped strangely = identified by macrohages and destroyedExcess of a-chains precipitate = change in RBC structure and thus shorter lifespan

Front 53

What causes elliptocytosis and spherocytosis

Back 53

RBC membr disorder = eliptica/sphere shape vs donut

Front 54

What metabolic pathway is affected in G6PD deficiency and why does that cause hemolytic anemia?

Back 54

PPP pathway, oxidative stress

Front 55

What is the difference between intrinsic and extrinsic hemolytic anemia?

Back 55

Genetic vs acquired (malaria)

Infections Autoimmune disorders Some medications

Front 56

Anemia can be difficult to identify because:

Early symptoms may be mild Early on, it is not symptomatic
There are no definite tests to confirm the condition
All of the above

Back 56

early symptoms may be mild

Front 57

What tests are used in the diagnosis of anemia?

a. White blood cell (WBC) count
b. Hemoglobin
c. Hematocrit
d. Red blood cell (RBC) count
e. b, c, and d

Back 57

b, c, d...all but WBC

Front 58

1) A 40-year old female visits her physician and complains about fatigue. She has had strong menstrual blood flow during the last year.Her blood analysis reveals the following:

CBC Patient Normal
MCH 8.0 g/dL (12-15.6g/dL)
MCV 45.4 (fL) 82.0-100.0 (fL)

Which of the following do these values suggest:

(choose a -chromic, -cytic diagnosis of the anemia)

Back 58

hypochromic, microcytic

Front 59

Identify the morphology that matches the syndrome

Iron deficiency anemia
Anemia of chronic disease
Thalassemia
Sideroblastic anemia
Pernicious anemia
Folate deficiency
Vitamin B12 deficiency

Back 59

Macro/micro -cytic / hypo/hypo -chromic

Iron def = (- / -)
chronic disease = (N / N)
Thalassemia = (- / -)
Sideroblastic anemia (- / -)
Pernicious anemia (+ / N)
Folate deficiency (+ / N)
Vitamin B12 deficiency (+ /N)

Front 60

What are the two most commonly encountered anemias.

Back 60

Iron deficiency and anemia of chronic disease

Front 61

Select true and false of the following statements about thalassemia

1. Increased Hgb A2 suggests alpha thalassemia.
2. Increased Hgb A2 suggests
beta thalassemia
3. Genetic testing can be used to diagnose thalassemia

Back 61

1. False, Hb A2 is (a2 b2); alpha thalssemia has less alpha globin, no effect on this
2.True, since there is less beta globin around, more of the normally unsual Hb A2 (a2 d2) is made
3. True, since it is an inherited disease

Front 62

A patient is anemic with microcytic hypochromic indices. A source of blood loss has not been identified. Would it be safe to start iron therapy if the patient’s insurance would not cover any additional lab studies?

What test would you order if you could?

Back 62

No. 20% of patients with anemia of chronic disease have a microcytic anemia and their serum iron levels can be decreased. Therefore, iron therapy would not be indicated and if given over a prolonged period could contribute to iron overload. Additional iron studies, particularly serum ferritin levels should be ordered to confirm a need for iron therapy.

Front 63

Why would people with kidney disease develop anemia

Back 63

Because the kidney produces erythropoietin

Front 64

Define megaloblastic anemia (cause).

Back 64

Defect in DNA synthesis, Resulting in unbalanced cell growth, impaired cell division, Mature cytoplasm, immature nucleus, larger cell volume

Front 65

What is the role of vitamin B12 and folic acid in megaloblastic anemia?

Back 65

Both are important for DNA synthesis, Vitamin B12is required to convert methyltetrahydrofolate into tetrahydrofolate. Folate is required at several steps of DNA synthesis. Folate is a donor of single carbon units, also important for amino acid synthesis

Front 66

Why would you give vitamin B12 as an injection and not orally?

Back 66

If the problem is vitamin B12 absorption due to lack of intrinsic factor (pernicious anemia) then it would not be absorbed if given orally

Front 67

Why would vegans be at risk for megaloblastic anemia?

Back 67

Vitamin B12 is produced by bacteria, found in animals

Front 68

Could thalassemia or sickle cell anemia lead to hemolytic anemia?

Back 68

thalassemia: to some extend because red blood cells are small and have a short half-life, sickle cell anemia for sure, deformed red blood cells

Front 69

What causes elliptocytosis and spherocytosis

Back 69

inherited membrane defects. Elliptocytosis: defect usually in spectrin, destabilizes the cytoskeletal scaffold of cells, spherocytosis: Defects in cytoskeleton (ankyrin or spectrin)

Front 70

What is the difference between intrinsic and extrinsic hemolytic anemia?

Back 70

Intrinsic is caused by endogenous factors, e.g. elliptocytosis, spherocytosis, or metabolism defects; extrinsic is due to external factors: e.g. infections, drug-induced

Front 71

A patient of Mediterranean descent shows symptoms of mild anemia. What type of disorder do you suspect?

Back 71

Thalassemia – minor Beta

Front 72

A patient complaining about feeling tired and pale has a blood sample taken. The red blood cells appear microcytic and hypochromic. What type of anemia could explain these values? Explain why. What further tests would you suggest?

Back 72

Iron deficiency anemia (Fe deficiency)
Test for serum ferritin

Front 73

Which of the conditions discussed in class would lead to normocytic, normochromic red blood cells that are reduced in numbers? Explain why.

Back 73

hemolytic anemias

Front 74

A patient has an overall reduced blood cell count. You suspect aplastic anemia. Which tests would you like to perform to confirm your diagnosis?

Back 74

RBC count, reticulocyte count