Heme Onc Lecture 1

Front 1

Where does newborn hematopoiesis occur?

Back 1

All red marrow

Front 2

Where does hematopoiesis occur in adults?

Back 2

Sternum,
Ribs,
Vertebral bodies,
Pelvis,
Proximal humerus,
Femur

Front 3

At what stage are stem cells committed to a specific type of cell?

Back 3

Blast

Front 4

In response to what does erythropoiesis occur?

Back 4

Tissue hypoxia

Front 5

Besides the kidney, where is EPO produced?

Back 5

Some in the lliver.

Front 6

What 4 things does EPO do?

Back 6

Accelerates production, differentiation, maturation

Facilitates incorp of Fe into RBC

Front 7

4 causes of inadequate erythropoiesis?

Back 7

Insufficient amt of epo (i.e. kidney disease).

BM unable to respond to epo.

BP depressed (drugs, toxic chems, ionizing radiation, cancer).

Other substances needed (B12, folate, Fe)

Front 8

Sx of acute anemia?

Back 8

Syncope,

Postural hypotension

Front 9

Sx of chronic anemia?

Back 9

Fatigue,

Weakness

Front 10

What is in Reticulocytes?

Back 10

RNA, sometimes nucleus

Front 11

What is transferrin?

Back 11

Transport protein. Largest quantity of iron-binding protein.

Regulates iron absorption.

Produced inversely w/ amounts of Fe in the liver.

Front 12

What is ferritin?

Back 12

Storage form of iron; small, soluble deposits.

Seen in BM and can be measured in serum. Decreased or absent in Fe deficiency anemia.

Front 13

**What is the most important test in early stages of Fe deficiency anemia?

Back 13

Ferritin!

Because the body will deplete storage iron before you will see a decrease in circulating iron.

Front 14

What is hemosiderin?

Back 14

Storage form of iron; large, insoluble deposit.

Decreased or absent in Fe deficiency anemai.

Front 15

Difference between Ferritin and Hemosiderin?

Back 15

Both are storage forms of iron.

Ferritin is small, soluble deposits.
Hemosiderin is large, insoluble deposit.

Front 16

What is serum iron measuring?

Normal male value?
Normal female?

Back 16

Iron bound to transferrin.

Male: 80-180 mcg/dL
Female: 60-160 mcg/dL

Front 17

What is TIBC?

Normal value?

Back 17

Measure of all proteins available for binding mobile iron.

Indirect (but accurate) measure of transferrin.

Norm: 250-460 mcg/dL

Front 18

**What is UIBC?

Normal values for male? Female?

Back 18

Unsaturated iron binding capacity.

UIBC + serum iron = TIBC.

Male: 215-365 mg/dL
Female: 250-380 mg/dL

Front 19

What does it mean that transferring is a NEGATIVE acute phase reactant protein?

Back 19

It decreases or diminishes in various acute inflammatory reactions, chronic illness, malignancy, collagen vascular disease and liver disease.

Front 20

What is the equation for Transferrin % Saturation?

Normal male?
Female?

Back 20

SI/TIBC x 100.

Male: 20-50%

Female: 15-50%

Front 21

Normal male crit?

Female?

Back 21

Male: 42-54%

Female: 37-47%

Front 22

6 Common causes (types) of anemia?

Back 22

Iron def,
Anemia of chronic disease,
Hemolytic,
Myelodysplasia,
Thalassemia
Other

Front 23

9 symptoms of anemia?

Back 23

Dizziness,
Exertional dyspnea,
Fatigue,
HA,
Loss of libido,
Mood disturbances,
Sleep disturbances,
Tinnitus
Weakness

Front 24

12 signs of anemia?

Back 24

Glossitis,
Jaundice,
Neurologic findings,
Orthostatic hypotension,
Pallor,
Periph edema,
Retinal hemorrhages,
Splenomegaly,
Systolic ejection murmur,
Tachycardia,
Tachypnea,
Venous hum

Front 25

What are you looking for in bone marrow when evaluating for anemia? (2)

Back 25

Iron storage

M:E ratio

Front 26

What constitutes megaloblastic anemia?

Back 26

>110 MCV

Front 27

2 types of microcytic anemia?

Back 27

Fe def,

Thal

Front 28

8 causes of macrocytic anemia?

Back 28

B12/ folate,
Liver disease,
Alcoholism,
Hypothyroidism,
Reticulocytosis,
Chemo,
Myelodysplastic syndromes,
Sideroblastic anemia

Front 29

6 causes of normocytic anemia?

Back 29

Blood loss,
Hemolysis,
Anemia of chronic disease,
Renal failure,
Aplastic anemia,
Bone marrow infiltration

Front 30

In microcytic hypochromic anemia, if serum iron is decreased? 2 causes?

Back 30

Iron deficiency anemia,

Anemia of chronic disease (1/3 of the time)

Front 31

In microcytic hypochromic anemia, if serum iron is normal or increased? 2

Back 31

Thal

Chronic lead poisoning (a few cases; most are normocytic normochromic)

Front 32

In microcytic hypochromic anemia, if serum iron is increased? 2

Back 32

Sideroblastic anemia (acquired/ congenital)

Pyridoxine (B6) responsive anemia

Front 33

What are the two causes of macrocytic- megaloblastic anemia?

Back 33

Vit B12 deficiency

Folic acid deficiency

Front 34

Would you see microcytic or normocytic anemia in hemorrhage/ bleeding?

Back 34

Depends!
Acutely, would see normocytic normochromic because the BM has not responded yet.
In chronic forms, would become microcytic/ hypochromic due to marked iron loss over time.

Front 35

2 causes of hemolytic anemia?

Back 35

Intracorpuscular defect (i.e. G6PD def)

Extracorpuscular defect (i.e. autoimmune hemolysis)

Front 36

2 causes of aplastic (hypoplastic) anemia?

Back 36

Idiopathic

Secondary to drugs/ chemicals/ irradiation, etc.

Front 37

3 causes of anemia of chronic disease?

Back 37

Infection

Malignancy

Liver disease

Front 38

Bone marrow causes of normocytic anemia (myelophthisic)? 5

Back 38

Carcinoma,
Leukemia,
Lymphoma,
Multiple myeloma,
Myelofibrosis

Front 39

What type of anemia would you expect to see with an increased demand of erythropoiesis (for example, in pregnancy)?

Back 39

Vit B12 & Folate deficiency.

Iron def

Front 40

What type of anemia would you expect to see with a bone marrow failure?

What might the cause of this be?

Back 40

Aplastic anemia

Drugs, Chemicals, Irradiation

Front 41

3 types of hereditary categories of hemolytic anemia?

Back 41

RBC membrane defects.

RBC enzyme deficiency.

Hemoglobinopathies.

Front 42

Types of RBC membrane defects?

Back 42

Hereditary spherocytosis

Front 43

Type of RBC enzyme deficiency?

Back 43

G6PD/ PK deficiency

Front 44

2 types of hemoglobinopathies?

Back 44

Sickle

Thal

Front 45

What is a type of mechanical acquired hemolytic anemia?

Back 45

MAHA (microangiopathic hemolytic anemia)

Front 46

What is an infection that may cause acquired hemolytic anemia?

Back 46

Malaria

Front 47

What is a physical agent that may cause acquired hemolytic anemia?

Back 47

Burns

Front 48

What is a chemical agent that may cause acquired hemolytic anemia?

Back 48

Arsenic

Front 49

How much iron is consumed daily (on average)?

How much is needed?

Back 49

10-20 mg consumed.

Only need about 1 mg.

We absorb only 10-20% from diet.

Front 50

Iron distribution in the body?

Back 50

Red cells (70% in hemoglobin).
Other 30% stored in ferritin and hemosiderin.
- liver
- circ transferrin
- bone marrow
- RE cells

Front 51

2 things that can be consumed that can lead to iron deficiency?

Back 51

Antacid (phosphates), H2 blockers, PPIs, Tetracycline.
- they complex w/ iron and --> iron deficiency.

Tea.
- Tanic acid complex w/ iron and --> iron deficiency

Front 52

2 things that can be consumed that aid in iron absorption?

Back 52

Ascorbic acid

HCl

Front 53

Do we lose iron (besides in bleeding)?

Back 53

1 mg/day lost via sloughing in intestinal tract.

Also lost in hair, fingernails, sweat, stools each day.

Front 54

What is the mucosal curtain?

Back 54

Too much Fe in body --> Fe goes to GI cells and stops there. GI cells turnover rapidly --> rid body of excess Fe.

Transferrin (UIBC) picks up 2 molecules of Fe from GI or RE cells and takes it to cells needing iron.

Front 55

What is the structure of heme?

Back 55

Fe + protoporphyrin ring + globin

Front 56

What type of hemoglobin problem is Beta thal?

Back 56

Globin synthesis problem

Front 57

What type of hemoglobin problem is iron deficiency?

Back 57

Heme synthesis problem

Front 58

What type of hemoglobin problem is siderblastic anemia?

Back 58

Protoporphyrin synthesis

Front 59

What type of hemoglobin problem is hemochromatosis?

Back 59

Fe stores

Front 60

What is the most common form of anemia in the US AND THE WORLD?

Back 60

Iron def

Front 61

What is the most common cause of iron deficiency anemia in adults?

Back 61

Chronic blood loss.

Front 62

Signs and symptoms of iron deficiency anemia?

Back 62

Fatigue,
SOB,
Pallor,
Weakness/ fatigue,
Brittle nails, koilonychia,
Atrophic tongue/ sore tongue,
Esophageal web (Plummer- Vinson syndrome) --> difficulty swallowing,
Pica

Front 63

Lab findings in iron deficiency anemia?

Back 63

Hypochromic/ microcytic,
Increased RDW,
Bone marrow: decreased iron,
Low serum ferritin,
Low serum iron,
Increased TIBC,
**Increased transferrin,
Decreased crit,
Increased platelet (in sever),
Possible occult blood,
Retics.

Front 64

Differential dx of iron deficiency?

Back 64

Anemia of chronic disease,

Thal,

Sideroblastic anemia

Front 65

Iron deficiency anemai treatment?

Back 65

Replace/ replete iron w/ oral iron in form of ferrous sulfate (FeSO4)

Liquid form also avialble

Refractory cases --> parenteral iron preps

Front 66

Problems with taking ferrous sulfate orally??

Back 66

GI distress, diarrhea, constipation, nausea.
Best absorbed on empty stomach, but to avoid SEs, give small doses w/ meals.

Turns stool black.
Liquid form stains teeth (use straw).

Follow w/ ferritin levels

Front 67

Side effects of parenteral iron dextran?

Back 67

Pain,

Fever,

HTN,

reaction.

Avoid this form if possible.

Front 68

What should you do to follow up after treating iron deficiency anemia?

Back 68

Repeat CBC 1 month. Retics may improve in 2 weeks.

Normal CBC usually 6-8 weeks. Continue therapy for 4-6 months.

Front 69

Pathophys of anemia of chronic disease?

Back 69

Iron in RE cells (storage), but is not mobilized to the body.
- **ineffective RE utilization of iron --> RE blockade.
- **IL-1 --> increased apoferritin --> trapping of iron in macrophages. Not availalble for heme synth.

Front 70

**How can you distinguish anemia of chronic disease from iron deficiency anemia?

Back 70

Fe def: Increased TIBC, decreased serum ferritin.

Anemia of chronic disease: Decreased TIBC and normal or increased serum ferritin.

Front 71

4 chronic diseases assoc w/ anemia of chronic disease?

Back 71

CHF

IBD

Liver disease

Renal disease

Front 72

2 collagen vascular diseases assoc with anemia of chronic disease?

Back 72

RA

SLE

Front 73

7 chronic infections assoc w/ anemia of chronic disease?

Back 73

Deep abscess,
Fungal/ Mycobacteria,
HIV,
Meningitis,
Osteomyelitis,
Pneumonia,
SBE

Front 74

How is diagnosis of anemia of chronic disease made?

Back 74

Associated with chronic inflammation.

Normochormic/ normocytic (sometimes hypo/micro)

MCV: 80-85
MCHC 30-32%

Front 75

Lab findings in anemia of chronic disease? (6)

Back 75

Decreased serum Fe & TIBC,
Decreased transferrin w/ decreased % sat.,
Increased iron stores,
Increased free erythrocyte protoporphyrin,
Norm or slightly increased serum ferritin,
Increased ESR

Front 76

**Treatment for anemia of chronic disease?

Back 76

**Treat underlying disease.
**Iron not effective.

If corrected, anemia usually reverses w/in 1 month.

Front 77

What is sideroblastic anemia?

Back 77

Prob w/ synth of protoporphyrin ring for Fe incorp.

**Trapped iron in mitochondria of nrbcs. "ringed sideroblasts" from excess iron deposits forming a ring around the nucleus.
Dimorphic cell population; ineffective erythropoiesis.
Hypochromic, microcytic.

Front 78

2 types of primary sideroblastic anemia?

Back 78

Hereditary: rare - abnormality in pyridoxine (B6) metabolism --> defect in enzyme delta- aminolevulinic acid synthase.

Idiopathic/ acquired - (most). Age >50-60. Refractory to treatment.

Front 79

4 types of Secondary sideroblastic anemia?

Back 79

Disease: RA, CA, myelofibrosis, leukemia, chronic alcoholism******,etc.

Drug induced: INH, cycloserine, pyrazinamide, chloramphenicol.

ETOH***** inhibits pyridoxal reaction; toxic to mitochondria.

***Lead poisoning (defective heme synth)

Front 80

**What is the name of the commonly "blocked" enzyme in siderblastic anemia?

Back 80

**Delta- ALA synthase

Front 81

**What is the hallmark of sideroblastic anemia?

Back 81

**Ringed siderblasts in the BM.

Front 82

3 types of sideroblasts?

Back 82

Normal: <4 granules

Pathologic: >4-6 granules

Ringed sideroblasts: many granules arranged in ring formation

Front 83

What hemoglobin would you expec in sideroblastic anemia?

What would you see on the smear?

Back 83

hgb: 8-10

Dimorphic cell population.
Decreased MCV

In acquired form, may se macrocytosis d/t megaloblastic (pre-leukemic state) changes w/ defective heme synth.

Front 84

What would you see in the bone marrow in sideroblastic anemia?

Back 84

Erythroid hyperplasia and **Ringed sideroblasts.

Increased RBCs but ineffective erythropoiesis d/t intramedullary destruction -->** increased serum iron.

Front 85

Lab findings in sideroblastic anemia?

Back 85

Increased serum iron,
Increased ferritin,
Increased BM storage of Fe,
Normal TIBC,
*Ringed sideroblasts,
Pappenheimer bodies,
Basophilic stip,
High serum iron w/ high transferrin sat

Front 86

What are the main differences seen in primary vs secondary sideroblastic anemia?

Back 86

Primary: rare, males. Secondary: males & females.

Primary: responds to ther. Secondary: refractory to ther.
Primary: no transfusions. Secondary: transfusions. (prob w/ iron overload).

Front 87

Other hematologic disorders that cause secondary sideroblastic anemia?

Back 87

Myelofibrosis,
Leukemia,
Hereditary and acquired hemolytic anemia,
Thal major

Therapy: treat underlying disease

Front 88

**How does alcoholism causes secondary sideroblastic anemia?

Back 88

Espec in poor diet -- decreased folic acid level (megoloblastic changes, but not pre-leukemic).

*See ringed sideroblasts.
ETOH inhibits pyridoxal phosphate reaction in heme synthesis and is directly toxic to mitochondria in cell

Front 89

Treatment of alcohol caused sideroblastic anemia?

Back 89

eliminate ETOH and treat w/ folic acid. Patient cured.

Ring sideroblasts will disappear in 1 sweek.

Front 90

How does INH and other anti-tuberculous drugs cause sideroblastic anemia?

Back 90

Inhibit phosphorylation of pyrdoxal phosphate --> decreased heme synth --> ringed sideroblasts.

Remove drugs --> problem resolves.