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Pathophysiology of Blood Disorders

Pathophysiology of Blood Disorders by Howard Franklin Bunn
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Table of Contents

Chapter 1 – Overview of Blood and Hematopoietic Tissues

(Aster and Bunn)

Impact of blood in health and disease

Red blood cell

White blood cells


Blood clotting proteins

The bone marrow

The spleen

The thymus

Lymph nodes

Chapter 2 – Hematopoiesis and the Bone Marrow


Hematopoietic cell diffrerentiation

Myeloid lineage

Erythroid lineage

Megakaryocyte-platelet lineage

Lymphoid lineages – B, T, and NK cells

The biology of the stem cell


Stem cell ontogeny

Stem cell trafficking

The regulation of blood cell formation

The bone marrow niche and cell-cell interactions

Cytokines in early hematopoietic differentiation

Lineage specific cytokines

Cytokine therapy

Stem cell therapy

Section I – Anemias and Disorders of the Red Blood Cell

Chapter 3 – Overview of the Anemias


(See full sample chapter)

Definition of anemia

Adaptations to anemia

Alterations in blood flow

Changes in oxygen unloading

Stimulation of erythropoiesis

Signs and symptoms of anemia

Pathophysiology of anemia

Anemia due to blood loss

Anemia due to decreased red cell production




Anemia due to increased red cell destruction

Chapter 4 - Anemias due to Bone Marrow Failure or Infiltration


Congenital causes of bone marrow failure

Acquired aplastic anemia and pure red cell aplasia




(Myelodysplasia and the leukemias will be covered in detail in Chapters 21 and 22).

Chapter 5 – Iron Homeostasis: Deficiency and Overload


Normal iron homeostasis

Iron binding proteins: transferrin; ferritin

The iron cycle

Role of hepcidin in iron regulation

Iron utilization in erythropoiesis

Laboratory evaluation of iron status

Serum iron and transferrin saturation

Serum ferritin

Bone marrow and liver iron stores

Serum transferrin receptor

Iron deficiency


Clinical features – signs and symptoms

Hematological features


Iron overload

Primary – inherited mutations in proteins regulating iron homeostasis

Secondary – transfusional hemosiderosis

Chapter 6 - Megaloblastic Anemias


Biochemistry of vitamin B12 and folate


Megaloblastic marrow and peripheral blood morphology

Vitamin B12 and folate absorption

B12 deficiency


Clinical presentation (signs and symptoms)

Laboratory evaluation


Folate deficiency


Clinical presentation (signs and symptoms)

Laboratory evaluation


Chapter 7 - Anemias associated with Chronic Disease

(Heeney and Bunn)

Anemia of chronic inflammation



Connective tissue disorders

Pathophysiology – role of hepcidin

Lab features


Anemia of renal insufficiency


Erythropoietin levels

Treatment with erythropoietin and iron

Anemia of chronic liver disease

Anemia of endocrine hypofunction

Chapter 8 – Thalassemia


Ontogeny of globin gene expression

Organization of alpha and beta globin genes

Definition and classification of the thalassemias

Mutations responsible for the thalassemias

Beta thalassemia

Beta+ versus beta0

Beta thal major

Cellular pathogenesis

Clinical presentation

Laboratory evaluation



Red cell transfusion

Iron chelation

Stem cell transplant

Prevention – prenatal diagnosis

Beta thal intermedia

Beta thal minor

Interacting beta thalassemias – Hb S and Hb E

Alpha thalassemia

Four degrees of gene deletion – correlate with clinical presentation

Three alpha gene deletion - Hb H disease

Four alpha gene deletion – Hydrops fetalis

Prevention – prenatal diagnosis

Chapter 9 – Sickle Cell Disease and other Disorders of Hemoglobin Structure


Inheritance – beta globin structural mutation: b6 Glu ® Val

The sickling disorders: SS, Sb0Thal, Sb+Thal, SC, AS

Molecular pathogenesis

Structure of the sickle fiber

Kinetics of fiber formation

In vivo significance of polymer formation

Cellular aspects of in vivo sickling and vaso-occlusion

Contribution of Hb F

Sickle cell – endothelial cell adhesion

Clinical manifestations

Constitutional: growth, development and susceptibility to infections

Hemolytic anemia


Acute pain crises

Acute chest syndrome

Chronic organ damage


Bone – aseptic necrosis

Renal: impaired concentrating ability; impaired glomerular function

Pulmonary hypertension


Supportive – analgesia, oxygen, fluid and pH balance

Prophylaxis: penicillin and vaccinations

Hydroxyurea – induction of Hb F

Novel therapeutic strategies

Chapter 10 – Other Inherited Hemolytic Anemias


Disorders of the red cell membrane

Molecular anatomy of the red cell membrane

Hereditary spherocytosis – mutations in spectrin, band 4.1, band 3

Other inherited membrane disorders

Disorders of red cell metabolism

Hexose monophosphate shunt and G6PD deficiency

Glycolytic pathway – pyruvate kinase deficiency

Chapter 11 – Acquired Hemolytic Anemias


Acquired membrane disorders

Paroxysmal nocturnal hemoglobinuria

Spur cell anemia

Traumatic hemolytic disorders

Thrombotic thrombocytopenic purpura (Covered in detail in Chapter 14)

Hemolytic uremic syndrome

Disseminated intravascular coagulation (Covered in detail in Chapter 16)

Heart valve hemolysis

Immune hemolytic anemias

Pathophysiologic principles

Clinical presentation and course

Warm antibody hemolysis

Cold antibody hemolysis

Lab diagnosis


Chapter 12 - Erythrocytosis (Polycythemia)


Pathophysiologic principles: Algorithm for evaluating patients with erythrocytosis

Primary erythrocytosis – polycythemia vera

(See Chapter 20 for coverage of molecular pathogenesis, Chapter 22 for clinical presentation and course, diagnosis and treatment)

Secondary erythrocytosis

Appropriate erythropoietin production

High altitude hypoxemia

Pulmonary hypoxemia

Cardiac hypoxemia (right to left shunt)

Mutant hemoglobin with high oxygen affinity

Inapproriate erythropoietin production

Tumors: renal, hepatic

Von Hippel Lindau syndrome

Inherited disorders of oxygen sensing HIF pathway

McGraw-Hill Education; January 2011
342 pages; ISBN 9780071713771
Read online, or download in secure EPUB or secure PDF format
Title: Pathophysiology of Blood Disorders
Author: Howard Franklin Bunn; Jon C. Aster
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