Red Cells and Bleeding Disorders - Chapter 14

Question 1

Briefly discuss the embryogenesis of the bone marrow and blood.

Answer 1

In the human embryo, clusters of stem cells, called blood islands, appear in the yolk sac in the 3rd week of fetal development. Germ cells may also give rise to hematopoietic stem cells. At about the 3rd month of embryogenesis, some of the cells migrate to the liver, which then becomes the chief site of blood cell formation until shortly before birth. In the 4th month of development, hematopoiesis commences in the bone marrow. At birth, all the marrow throughout the skeleton is active and virtually the sole source of blood cells. (Not in Robbins)

Question 2

In adults, approximately _____ % of the marrow space is actively involved in hematopoiesis.

Answer 2

50 (Not in Robbins)

Question 3

In the premature infant, foci of hematopoiesis are frequently evident in the ___, ___, and____.

Answer 3

Liver, spleen, lymph nodes or thymus (Not in Robbins)

Question 4

List the five types of formed elements in the circulating blood and give their common origin cell.

Answer 4

Erythrocytes, granulocytes, monocytes, platelets, and lymphocytes
Origin – pluripotent hematopoietic stem cell (Not in Robbins)

Question 5

Normally the marrow contains about 60%______, 20%______, 10%______, and 10% _______.

Answer 5

60% granulocytes, 20% erythroid precursors, 10% lymphocytes and monocytes and their precursors, and 10% unidentified or disintegrating cells (Not in Robbins)

Question 6

The normal myeloid/erythroid ratio is_____.

Answer 6

0.125694444444444 (Not in Robbins)

Question 7

The dominant cell types in the myeloid compartment include _____, _____, and ______.

Answer 7

Myelocytes, metamyelocytes, and granulocytes (Not in Robbins)

Question 8

Define anemia from a clinical perspective.

Answer 8

A reduction of the total circulating red cell mass below normal limits, measured by hematocrit and hemoglobin concentrations. (p. 629)

Question 9

List the three major mechanisms associated with the development of anemia.

Answer 9

Blood loss, increased red cell destruction (hemolysis), decreased red cell production (p. 630)

Question 10

Define and differentiate the two types of blood loss anemia.

Answer 10

Acute blood loss –loss of intravascular volume which if massive can lead to cardiovascular collapse and death.
Chronic blood loss induces anemia only when the rate of loss exceeds the regenerative capacity of the marrow or when iron reserves are depleted. (p. 631)

Question 11

The hemolytic anemias are characterized by _______.

Answer 11

1) shortened red cell life span and premature destruction of red cells
2) accumulation of hemoglobin degradation products released by red cell breakdown derived from hemoglobin
3) Elevated erythropoietin levels and a compensatory increase in erythropoiesis (p. 631)

Question 12

In the great majority of hemolytic anemias,the premature destruction of red cells occurs within____, referred to as _____.

Answer 12

Phagocytes
Extravascular hemolysis (p. 631)

Question 13

List the two main mechanisms associated with the development of hemolytic anemia and list examples of each.

Answer 13

Intravascular hemolysis – mechanical injury (mechanical heart valves), complement fixation to red cells, exogenous toxic factors, intracellular parasites
Extravascular hemolysis – hereditary spherocytosis, sickle cell anemia (p. 631)

Question 14

List three major causes of hereditary hemolytic anemias.

Answer 14

Red cell membrane disorders – hereditary spherocytosis
Red cell enzyme deficiencies – Glucose-6-phosphate dehydrogenase deficiency Disorders of hemoglobin synthesis – Thalassemia syndromes (p. 633-639)

Question 15

Briefly differentiate the hemoglobin changes seen in the homozygote and heterozygote sickle cell patient.

Answer 15

About 8-10% of African Americans are heterozygotes for HbS. If an individual is homozygous for the sickle cell mutation, almost all the hemoglobin in the erythrocyte is HbS. In the heterozygote, only about 40% is HbS, the remainder is HbA. (p. 635)

Question 16

Define autosplenectomy.

Answer 16

Autosplenectomy – erythrostasis in the spleen leads to infarction and fibrosis. Continued scarring causes progressive shrinkage of the spleen so that by adolescence or early adulthood, only a small nubbin of fibrous tissue may be left. (p. 647)

Question 17

The four factors which affect the rate and degree of sickling in Hb S are_____.

Answer 17

1) Interaction of HbS with the other types of hemoglobin in the cell
2) Mean cell hemoglobin concentration
3) Intracellular pH
4) Transit time of red cells through microvascular beds (p. 635-636)

Question 18

In the spleen, focal fibrous scars containing deposits of hemosiderin and calcium are known as___________.

Answer 18

Gandy-Gamna nodules (bodies) (Not in Robbins)

Question 19

The classification of immunohemolytic anemia is based upon which three antibody types?

Answer 19

Warm antibody type
Cold agglutinin type
Cold hemolysin type (p. 643-644)

Question 20

Briefly define megaloblastic anemia, and list the two principal types.

Answer 20

The megaloblastic anemias constitute a diverse group of entities, having in common impaired DNA synthesis and distinctive morphologic changes in the blood and bone marrow.
Two principal types – pernicious anemia, the major form of vitamin B12 deficiency anemia, and folate deficiency anemia (p.645)

Question 21

The feature that sets pernicious anemia apart from other vitamin B12 deficiency megaloblastic anemias is ____________.

Answer 21

Autoimmune gastritis with failure of production of intrinsic factor (p. 645)

Question 22

Pernicious anemiais believed to result from__________.

Answer 22

An autoimmune attack on the gastric mucosa (p. 645)

Question 23

The principle alteration in the central nervous system in cases of pernicious anemiais _______.

Answer 23

Involvement of the spinal cord, where there is demyelination of the dorsal and lateral tracts, sometimes followed by loss of axons. (p. 648)

Question 24

The three most common laboratory findings in cases of aplastic anemia are _____, ____, and ___.

Answer 24

Anemia, neutropenia, thrombocytopenia (pancytopenia) (p. 653)

Question 25

List some causes of aplastic anemia. Which is the most common?

Answer 25

Acquired: Idiopathic, chemical agents, idiosyncratic, physical agents, viral infection
Inherited: Fanconi anemia, telomerase defects
Most cases of aplastic anemia of known etiology follow exposure to chemicals and drugs. 65% of all cases are considered idiopathic. (p. 653)

Question 26

Define myelophthisic anemia.

Answer 26

Space occupying lesions that replace normal marrow; the most common cause is metastatic cancer. (p. 655)

Question 27

Define and differentiate relative vs. absolute polycythemia.

Answer 27

Polycythemia denotes an abnormally high red cell count, usually with a corresponding increase in hemoglobin level. Such an increase may be relative, when there is hemoconcentration due to decreased plasma volume, or absolute, when there is an increase in total red cell mass. (p. 656)

Question 28

What are major causes of thrombocytopenia?

Answer 28

1) decreased production of platelets
2) decreased platelet survival 3) sequestration
4) dilution (p.658)

Question 29

The most common inherited bleeding disorder of humans is __________.

Answer 29

Von Willebrand Disease (p. 662)

Question 30

Define and differentiate petechiae and purpura.

Answer 30

Petechiae – minute 1-2 mm hemorrhages into skin, mucous membranes, or serosal surfaces. Associated with locally increased intravascular pressure, low platelet counts, or defective platelet function.

purpura -Slightly larger (3 or >3 mm) hemorrhages. may be associated with similar pathologies as well as trauma, vascular inflammation or increased vascular fragility. (p. 658)

Question 31

Briefly discuss the pathophysiology of disseminated intravascular coagulation (DIC), and list some of the major disorders associated with DIC.
DIC is an acute, subacute, or chronic thrombohemorrhagic disorder characterized by the excessive activation of coagulation, which leads to the formation of thrombi in the microvasculature of the body.
Two major mechanisms trigger DIC: 1) release of tissue factor or thromboplastic substances into the circulation, 2) widespread injury to the endothelial cells.
Major disorders associated with DIC: obstetric complications, sepsis, neoplasms, major trauma (p. 663)