Structure and Function of
the Hematologic System
Chapter 25
1
Components of the Hematologic
System

Composition of blood



90% water and 10% solutes
6 quarts (5.5 L)
Plasma


55% to 60% of the blood volume
Organic and inorganic elements
2
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Components of the Hematologic
System

Composition of blood

Plasma proteins

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
7% of the plasma total weight
The majority are synthesized in the liver
Albumins


Globulins


Function as carriers and control the plasma oncotic pressure
Carrier proteins and immunoglobulins (antibodies)
Clotting factors

Mainly fibrinogen
3
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Components of the Hematologic
System

Composition of blood

Cellular components

Erythrocytes
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
Most abundant cell in the body
Responsible for tissue oxygenation
Biconcavity and reversible deformity
120-day life cycle
4
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Composition of Blood

Cellular components

Leukocytes (white blood cells)

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Defend the body against infection and remove debris
Granulocytes
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Membrane-bound granules in their cytoplasm
The granules contain enzymes capable of destroying
microorganisms
Inflammatory and immune functions
Capable of ameboid movement (diapedesis)
5
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Composition of Blood

Granulocytes

Neutrophils
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Polymorphonuclear neutrophil (PMN)
Phagocytes in early inflammation
Eosinophils



Eosinophils ingest antigen-antibody complexes
Induced by IgE hypersensitivity
Increase in parasitic infections
6
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Composition of Blood

Granulocytes

Mast cells



Central cell in inflammation
Found in vascularized connective tissue
Basophils


Structurally similar to mast cells
Precise function not understood
7
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Composition of Blood

Agranulocytes
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Monocytes and macrophages make up the
mononuclear phagocyte system (MPS)
Monocytes
Macrophages
Lymphocytes
Natural killer (NK) cells
8
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Composition of Blood

Platelets
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Disk-shaped cytoplasmic fragments
Formed by fragmentation of megakaryocytes
Essential for blood coagulation and control of
bleeding
9
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Lymphoid Organs

Spleen
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Largest secondary lymphoid organ
Splenic pulp
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
Masses of lymphoid tissue containing macrophages
and lymphoid tissue
Venous sinuses


Phagocytosis of old, damaged, and dead blood cells
Blood storage
10
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Lymphoid Organs

Lymph nodes

Part of the immune and hematologic systems
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Facilitates maturation of lymphocytes
Transports lymphatic fluid back to the circulation
Cleanses the lymphatic fluid of microorganisms and
foreign particles
11
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Lymphoid Organs
12
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Mononuclear Phagocyte System
(MPS)


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The MPS consists of a line of cells that
originate in the bone marrow, are transported
into the bloodstream, differentiate into
monocytes, and settle in the tissues as mature
macrophages
Cells of the MPS ingest and destroy
microorganisms and foreign material
The MPS is mostly the liver and spleen
13
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Hematopoiesis


Hematopoiesis is the process of blood cell
production
Two stages:

Mitosis


Mitosis stops before the cell enters the peripheral
blood
Maturation
14
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Hematopoiesis
15
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Hematopoiesis

Stem cell system

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
Pluripotent stem cells
Colony-stimulating factors
Bone marrow

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
Also called myeloid tissue
Red and yellow bone marrow
Adult active bone marrow

Pelvic bones, vertebrae, cranium and mandible,
sternum and ribs, humerus, and femur
16
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Colony-Stimulating Factors
17
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Erythropoiesis



Erythrocytes are derived from erythroblasts
(normoblasts)
Maturation is stimulated by erythropoietin
Sequence


Uncommitted pluripotent stem cell, committed
proerythroblast, normoblast, basophilic normoblast,
polychromatophilic normoblast, orthochromic
normoblast, reticulocyte (nucleus is lost), erythrocyte
In each step the quantity of hemoglobin increases and the
nucleus decreases in size
18
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Erythropoiesis
19
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Hemoglobin Synthesis



Oxygen carrying protein of the erythrocyte
A single erythrocyte contains as many as 300
hemoglobin molecules
Two pairs of polypeptide chains



Globulins
Four colorful iron-protoporphyrin complexes
Adult hemoglobin

Two α chains and two β chains
20
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Hemoglobin Synthesis
21
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Hemoglobin Synthesis

Nutritional requirements

Building blocks

Proteins


Vitamins


Amino acids
Vitamins B12, B6, B2, E, and C, folic acid, pantothenic acid,
and niacin
Minerals

Iron and copper
22
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Hemoglobin Synthesis

Iron cycle

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

Total body iron is bound to heme or stored bound
to ferritin or hemosiderin mononuclear
phagocytes and hepatic parenchymal cells
Less than 1 mg per day is lost in the urine, sweat,
epithelial cells, or from the gut
Transferrin
Apotransferrin
23
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Iron Cycle
24
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Regulation of Erythropoiesis

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Numbers of circulating red cells in healthy
individuals remain constant
The peritubular cells of the kidney produce
erythropoietin
Hypoxia stimulates the production and release
of erythropoietin
Erythropoietin causes an increase in red cell
production and release from bone marrow
25
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Regulation of Erythropoiesis
26
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Normal Destruction of Senescent
Erythrocytes
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Aged red cells are sequestered and destroyed
by macrophages of the MPS, primarily in the
spleen
The liver takes over if the spleen is absent
Globin chains are broken down into amino
acids
Porphyrin is reduced to bilirubin, transported
to the liver, and secreted in the bile
27
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Development of Leukocytes
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Leukocytes arise from stem cells in the bone
marrow
Granulocytes mature in the bone marrow
Agranulocytes and monocytes are released
into the bloodstream before they fully mature
Growth factors and colony-simulating factors
encourage production and maturation of
leukocytes
28
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Development of Platelets

Endomitosis

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The megakaryocyte undergoes the nuclear phase
of cell division but fails to undergo cytokinesis
The megakaryocyte expands due to the doubling
of the DNA and breaks up into fragments
Platelet levels are maintained by
thrombopoietin and IL-11
Platelets circulate for 10 days before losing
their functional capacity
29
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Hemostasis

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Hemostasis means arrest of bleeding
Requirements
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Platelets
Clotting cascade
Blood flow and shear forces
Endothelial cells
Fibrinolysis
30
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Hemostasis

Sequence
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Vasoconstriction
Formation of a platelet plug
Activation of the coagulation cascade
Formation of a blood clot
Clot retraction and clot dissolution
31
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Hemostasis

Platelet plug formation
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Activation
Adhesion
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
von Willebrand factor (vWF)
Aggregation
Secretion
32
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Hemostasis

Function of clotting factors

Intrinsic pathway


Activated when factor XII contacts subendothelial
substances exposed by vascular injury
Extrinsic pathway

Activated when tissue factor (TF) (tissue
thromboplastin) is released by damaged endothelial
cells
33
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Coagulation Cascade
34
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Control of Hemostatic Mechanisms

Antithrombotics

Antithrombin III

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Protease inhibitor; inhibits thrombin and factor Xa
Tissue factor pathway inhibitor (TFPI)
Protein C and protein S

Thrombomodulin system
35
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Control of Hemostatic Mechanisms

Clot retraction


Fibrin strands shorten; become denser and
stronger to approximate the edges of the injured
vessel and site of injury
Facilitated by large numbers of platelets within
the clot and actinlike contractile proteins in the
platelets
36
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Control of Hemostatic Mechanisms

Lysis of blood clots

Fibrinolytic system

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Plasminogen and plasmin
Tissue plasminogen activator (t-PA)
Fibrin degradation products

D-dimers
37
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Fibrinolytic System
38
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Evaluation of the Hematologic
System

Tests of bone marrow function

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Bone marrow aspiration
Bone marrow biopsy
Measurement of bone marrow iron stores
Differential cell count
Blood tests

Large variety of tests
39
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Pediatrics and the Hematologic
System

Blood cell counts increase above adult levels
at birth


The hypoxic intrauterine environment
stimulates erythropoietin production


Trauma of birth and cutting the umbilical cord
Results in polycythemia
Children tend to have more atypical
lymphocytes due to frequent viral infections
40
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Aging and the Hematologic System

Erythrocyte life span is normal but
erythrocytes are replaced more slowly

Possible causes:




Iron depletion
Decreased total serum iron, iron binding capacity, and
intestinal iron absorption
Lymphocyte function decreases with age
The humoral immune system is less
responsive
41
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