Anemias/Leukemias Flashcards

1
Q

Describe the sites of hematopoiesis in various age groups

A
  • *Embryo** = fetal yolk sac
  • *Fetus** = bones, liver, spleen
  • *Child** = long and short bones
  • *Adult** = all bones, but bone marrow biopsy only performed the iliac crest of the pelvis and sternum)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How is hematopoiesis regulated?

A

Development potential is only realized in the presence of colony-stimulating factors. Most CSF’s produced in bone marrow. Interleukins produced by macrophages and T lymphocytes stimulate as well as erythropoietin (kidney).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Describe the pathways of differentiation of pluripotent hematopoietic stem cells.

A

All cell lineages originate from a developmentally pluripotent stem cell. This common precursor gives rise to developmentally restricted stem cells: erythromyeloid stem cells and lymphoid stem cells.

The descendants of these intermediated stem cells are mature T and B lymphocytes, erythrocytes, neutrophils, monocytes, eosinophils, basophils, and megakaryocytes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Compare serum and plasma and explain which one you would collect for various blood tests.

A
  • *Serum** = defibrinated plasma (contains all proteins except fibrinogen, prothrombin, coag factors)
  • *Plasma** = typically used for the study of clotting disturbances
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Explain the molecular structure of hemoglobin.

A

Heme = oxygen binding part (must have iron), has four pyrrole rings held together by iron in the ferrous form. On degradation, iron and globin are reutilized, while pyrrole gives rise to bilirubin.

Hemoglobin consists of four heme groups and four globins. Globin has four polypeptide chains (alpha, beta, gamma, and delta).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe the major events in the life of erythrocytes.

A

Live in circulation for 120 days.

  • nucleated RBC precursors, stimulated by erythropoietin, form erythroctes in the bone marrow.
  • normal synthesis of hemoglobin occurs only in the presence of nutrients, iron, b12, and folic acid
  • mature RBCs released into circulation
  • old and defective RBCs are degraded in the spleen
  • iron and globin reutilized stat, bilirubin released in bile
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Explain the significance of various erythrocytic parameters such as MCV, MCH, and MCHC, and describe how they are measured.

A
  • *MCV =** mean volume of each RBC, calculated by HCT/RBC count, Nl 83-99 fL
    • lo = < 80** microcytic anemia
    • hi = >100** macrocytic anemia

MCH = denotes content of hemoglobin per each RBC, HGB conc. divided by RBC count, Nl 28-32 pg/cell

MCHC = concentration of hemoglobin in red blood cells, HGB/HCT, Nl 32-36 g/dL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the normal values for a white blood cell count?

A

Neutrophils 60-70%
Eosinophils 1-3%
Basophils 1%
Monocytes 4-8%
Lymphocytes 40%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Compare neutrophils and lymphocytes

A
  • *Neutrophils** - short-lived and survive no more than 4 days in peripheral circulation. Bone marrow contains three times more WBC precursors than erythroid precursors
  • *Lymphocytes** - long-lived
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the function of platelets

A

Essential clotting factors. Derived from megakaryocytes, have no nuclei. 8-10 days in circulation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is anemia?

A

= the reduction of hemoglobin in RBCs below normal
females = < 11.5 g/dL
males = <13 g/dL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Provide an etiologic and a morphologic classification of anemias

A

Etiology =

  1. decreased hematopoiesis
  2. abnormal hematopoiesis
  3. increased loss or destruction of RBC

**Morphologic = **

  1. size
  2. color
  3. shape
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Which anemias are caused by decreased hematopoiesis?

A
  1. aplastic anemia (bone marrow failure)
  2. myelofibrosis
  3. myelophthisic anemia secondary to BM replacement with TUMOR cells
    - leukemia
    - multiple myeloma
    - mets
  4. deficiency disorders
    - iron
    - B12
    - folic acid
    - protein
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Which anemias are caused by abnormal hematopoiesis?

A

Genetic hemoglobinopathies
sickle cell anemia
thalassemia

Structural protein defects
spherocytosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Which anemias are caused by increased loss or destruction of RBCs?

A

Bleeding
prolonged menstruation
peptic ulcer

**Immune hemolytic anemia

Hypersplenism

Infection**

malaria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

List typical examples of normocytic, microcytic, and macrocytic anemia.

A

normocytic, normochromic
massive blood loss

microcytic, hypochromic
iron-deficiency
thalassemia

macrocytic, normochromic
chronic liver disease
B12/folic acid deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

List typical examples of anemias that present with abnormal red blood cell shapes.

A

elliptocytosis
spherocytosis
sickle cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Explain the pathogenesis and pathology of aplastic anemia.

A

**aplastic anemia = pancytopenia **(generalized bone marrow failure)

Two forms: idiopathic, secondary (drugs, radiation, virus)
BM is depleted of hematopoietic cells, and consists of fibroblasts, fat cells, scattered lymphocytes

Clinical features: uncontrollable infections, bleeding tendency *most patients dies of overhwelming infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

List the causes of iron deficiency anemia.

A

iron deficiency = most common form of anemia
more prevalent among women

depletion of body iron (chronic blood loss)
Can be caused by

  1. increased iron loss
  2. inadequate iron intake/absorption
  3. increased iron requirements (growth, PG)

Note: the bone marro shows normal hematopoiesis but contain reduced number of hemosiderin laden macrophages

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Terminology

A
  • *anisocytosis = **variation in size
  • *poikilocytosis = **variation in shape
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the critical events in the metabolism of iron in the human body

A
  1. Uptake of heme or ferrous iron occurs in the intestine.
  2. Iron transported on transferrin to the liver or bone marrow.
  3. Transferrin binds to RBC precursors in the BM and delivers iron for incorporation into hemoglobin.
  4. RBC in the circulation contain 60-80% of body iron.
  5. Old RBCs are destroyed in the spleen.
  6. The iron is bound to transferrin for recirculation.
  7. 20-30% of iron is stored in the form of hemosiderin in the spleen, liver, BM. *esp stroma, can see with Prussian blue
  8. Remaining iron is in the respiratory ezymes of somatic cells.
    Iron is lost by desquamation of skin and intestinal cells.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Explain the pathogenesis of megaloblastic anemia

A

B12 or folic acid = 2 essential cofactors for DNA synthesis

RBCs do not mature, but transform to megaloblasts.
Diagnosis:
BM hypercellular, many megaloblasts
Hypersegmented neutrophils
Decreased RBCs

Clinical: destruction of posterior and lateral columns in the SC result in loss of vibration, proprioception, DTR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Compare anemia caused by vitamin B12 with anemia caused by folic acid deficiency.

A

B12
- binds to IF in the terminal ileum
- treated with IV
Folic Acid
- abosrbed in the duodenum and jejunum
- treated with oral

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Compare hemolytic anemia caused by intracorpuscular defects with anemia caused by extracorpuscular factors.

A

Intracorpuscular
sickle cell
thalassemia
hereditary spherocytosis

Extracorpuscular
antibodies
infectious agents
mechanical factors

Common to all the conditions = anemia, compensatory erythroid hyperplasia of the BM, hyperbilirubinemia, jaundice

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

When does jaundice appear?

A

When bilirubin in serum exceend 2-3 mg/dL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Explain the pathogenesis of sickle cell anemia.

A

formation of abn hemoglobin S d/t genetic defect in the beta chain (subs. of valine for glutamine)
- <40% HbS asymptomatic
- 40-80% HbS mild/moderate
- >80% HbS typical disease
* symptoms only occur in homozygotes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Pathogenenisis of Sickle Cell

A

Hbs >> polymerization at low O2 tension

Symptoms noticed at 1-2 years of age b/c fetal hgb replaced by HbA.

Sickling crisis: anoxic situations, avoid mountain climbing, strenuous exercise, pregnancy, respiratory disease, fever

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Sickle Cell Pathology

A

Multiple infarcts in various organs

Spleen: repeated infarcts, becomes fibrotic and shrinks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Sickle Cell Clinical Features

A

repeated sickling

  • retarded IQ and neurologic deficits
  • cardiopulmonary insufficiency
  • recurrent infections
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Explain the pathogenesis of thalassemia

A

In contrast to sickle cell, defect is quantitative, not qualitative.
HbA has four chains: 2 alpha, 2 beta

2 genes >> beta chains
4 genes >> alpha chains

** Note: b/c there are only 2 beta genes, these anemias are MORE SEVERE. Beta is more common, and thalasessemia minor.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Compare thalassemia minor and thalassemia major.

A

Thalassemia minor = 1 deletion, mild anemia (trait)
microcytic, hypochromic
*note: looks like iron deficiency!!

Thalassemia major = hemolysis accompanied by splenomegaly, hemosiderosis, hepatomegaly, BM compensatory hyperplasia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Why are RBCs round in hereditary spherocytosis?

A

There are mutations in the genes encoding that proteins that make up the membrane skeleton.

33
Q

What is immune hemolytic anemia?

A

Recall: four blood groups = A, B, AB, O

Autoimmune hemolytic anemias develop as a consequence of an immune reaction to RBC autoantigens or neoantigens formed between the body’s own proteins and hapten.

34
Q

Explain the pathogenesis of immune hemolytic anemia.

A

Hemolytic anemias:

  1. Autoantigens present on RBCs are normally not recognized as foreign by the body. In some persons the body produces antibodies to its own antigens on RBCs. This occurs for no obvious reasons.
  2. Alloantigens are foreign antigens. For example, blood group B RBCs are recognized as foreign by group A persons.
  3. Neoantigens are from from the body’s own protein’s linked to a non-immunologic hapten. IgG, immunoglobulin G.
35
Q

Compare primary and secondary polycythemia.

A

Primary = clonal proliferation of hematopoietic stem cells and increased total RBC mass (neoplastic)

Secondary = increased RBC volume as a result of erythroid bone marrow hyperplasia caused by erythropoietin

36
Q

What is leukopenia, and what are its causes?

A

leukopenia = reduction in the WBC count

Can be caused by:

drugs

chemicals

radiation

aplastic anemia

37
Q

What is leukocytosis, and what are its causes?

A

leukocytosis = increased WBCs (>10,000)

Causes:

reactive luekocytosis (splenomegaly in response to bacterial infection)

lymphoma

leukemia

38
Q

What are the possible causes of lymph node enlargement?

A
  • common in children with URI
  • with EBV
  • early stages of AIDs
  • most common presenting symptom of lymphoma
39
Q

What is the difference between lymphoma and leukemia?

A

Lymphoma = lymphoid cell malignant disease prodominantly involving the lymph nodes

Leukemia = increased number of malignant WBC in the peripheral blood due to WBC precursors in the BM

40
Q

What causes lymphomas and leukemias?

A

Most causes are unknown.

viruses = HTLV-1, EBV

oncogenes = translocation (Burkitts), philadelphia chromosome (CML), hybrid BCR, ABL

41
Q

What are the common features of all leukemias?

A
  1. BM is infiltrated with malignant cells
  2. Peripheral blood contains increased immature cells
  3. Chromosomal and genetic changes specific for each disease
  4. Complications: anemia, recurrent infections, uncontrollable bleeding

_**INFECTION_ = most common cause of death in all forms of leukemia

42
Q

What distinguishes acute from chronic leukemia and lymphocytic from myelogenous leukemia?

A
43
Q

List the most important features of acute lymphoblastic leukemia and correlate the pathologic findings with the clinical features of this disease.

A
  • massive BM infiltration with immature lymphoid cells (blasts = T and B precursors)
  • most common form of leukemia in children, and most common malignant disease in children <5yrs
  • rapid course, marked recurrent infections, generalized weakness, bleeding into the skin and internal organs
  • remission can be induced, 2/3 are CURED
44
Q

List the most important features of acute myelogenous leukemia.

A

**Clonal proliferation of myeloblasts in the bone marrow. **Must find 20% in the BM biopsy!

  • Most common form of acute leukemia in adults.
  • Treatment: high dose radiation and chemo.
45
Q

List the most important features of chronic myelogenous leukemia.

A

Malignant disease of **pluripotent stem cells capable of differentiating into neutrophilic leukocytes. **

  • Mostly affects ADULTS
  • SLOW onset; anemia, SM, thrombosis
  • Tx: radiation + chemo = 70% 3 yr survival
46
Q

3 phases of CML

A
  1. chronic phase: marked leukocytosis, increased eosinophils and basophils. BM <10 % blasts
  2. accelerated phase: BM >10% blasts, >20% basophils in peripheral blood.
  3. blast crisis: BM >20% blasts
47
Q

90% of patients have the Philadelphia chromosome with BCR-ABL gene arrangement . . . for which leukemia???

A

CML

48
Q

Do you have worse or better prognosis when you have the Philadelphia chromosome?

A

BETTER!!!

49
Q

List the most important features of chronic lymphocytic leukemia.

A

Malignant disease of lymphoid cells.

  • Disease of OLDER age (>50)
  • SLOW course
  • Sx = lymphadenopathy and peripheral leukocytosis
  • Tx: cells do not grow rapidly, therefore NO CHEMO
  • can TRANSFORM into more aggressive form
50
Q

How do you diagnose CLL?

A

CLL cells look **NORMAL **on a smear!! Suspect if lymphocytes >5000 (Nl = <4000). **BM Biopsy **confirms diagnosis.

51
Q

How are non-Hodgkin’s lymphomas classified?

A

Two categories:

  • B-cell
  • **T-cell and NK cell **
52
Q

True or False:

All lymphomas are malignant

A

True

53
Q

True or False:

Most lymphomas have a B-cell phenotype

A

TRUE

54
Q

**Extranodal **sites for lymphomas are . . .

A

can be outside of the lymph nodes, like **eyes, brain, skin. **

Most common is the GI system!

55
Q

Immunohistochemistry

A

Uses **antibodies **to analyze tissues for tumor cells.

Can help determine B and T cell and zones of the lymph node (cortical, mantle, germinal center)

56
Q

What method is used to determine maturation and phenotype of lymphocytes?

A

flow cytometry

57
Q

List the most common symptoms and clinical findings of non-Hodgkin’s lymphomas.

A
  • painless lymphadenopathy
  • systemic constitutional symptoms
  • extranodal spread
58
Q

What are systemic constitutional symptoms?

A
  • fatigue
  • malaise
  • fever
  • weight loss
  • pruritis
  • sweating
59
Q

What is the most common form of lymphoma in the UNited states?

A

Follicular lymphoma

60
Q

Follicular Lymphoma

A

**The follicular structure of lymph nodes is preserved. **

  • SLOW growing
  • Sx: long term lymphadenopathy, mild constitutional sx
  • Tx: does not response well to chemo
61
Q

What is the most common **aggressive **form of NHL?

A

Diffuse large B-cell lymphoma

62
Q

Diffuse large B-cell lymphoma

A

Lymphocyte tissue is infiltrated with large lymphoid cells that have irregular outlines and prominent nucleoli.

  • commonly spread into parenchyma of major organs
  • Tx: CHEMO!!!! 75% remission
63
Q

True or False:

Burkitt’s lymphoma can be cured

A

TRUE

Responds to CHEMO

64
Q

Burkitt’s lymphoma

A

Highly malignant, with small B cells that divide rapidly

  • cells prone to apoptosis, “starry sky”
  • originates in BM or lymph nodes
  • endemic in children with EBV
  • common in subsaharan Africa
65
Q

How does Burkitt’s lymphoma present outside of endemic areas?

A

abdominal masses

66
Q

What does in mean that Hodgkin’s lymphoma is BIMODAL?

A

It peaks at 25 yrs and also at **55 yrs. **

67
Q

What is a Reed Sternberg cell?

A

Binucleated and multinucleated.

68
Q

Classical Hodgkin’s Lymphoma Divisions

A
  1. Lymphocyte-rich classical
  2. Nodular sclerosis
  3. Mixed-cellularity
  4. Lymphocyte-depleted
69
Q

Non-classical HL

A

Nodular lymphocyte predominant HL

“popcorn cell”

70
Q

Clinical features of HL

A
  1. lymph node enlargement
    - neck nodes
    - mediastinal
    - central nodes
  2. High rate of CURE with CHEMO!
71
Q

Involvement of single node or group of nodes

A

Stage 1

HL

72
Q

Involvement of 2 or more sites of same side of diaphragm

A

Stage 2

HL

73
Q

Disease on both sides of diaphragm; may include spleen or localized extranodal disease

A

Stage 3

HL

74
Q

Widespread extralymphatic involvement (liver, bone marrow, lung, skin)

A

Stage 4

HL

75
Q

What is multiple myeloma?

A

Malignant disease of plasma cells

76
Q

With what disease do you find Bence Jones proteins in the urine?

A

Multiple Myeloma

77
Q

What is the most common cause of death in multiple myeloma?

A

kidney failure

78
Q

Which disease process do you find “punched out” lesions in radiographs of the skull, ribs, and vertebrae?

A

Multiple myeloma

79
Q

Multiple Myeloma

A

Begins with single malignant plasma cell.

  • secrete all the same form of Ig! = monoclonal “spike” on electrophoresis
  • Old age
  • punched out holes in blood forming bones
  • hypercalcemia
  • anemia, leukopenia, thrombocytopenia
  • CHEMO is INEFFECTIVE