CHAPTER 28
Know function and life span of RBCs and platelets.
RBCs or erythrocytes: the most abundant cells of the blood – primarily
responsible for tissue oxygenation
Contains hemoglobin (carries the gases and electrolytes) regulates
diffusion through a cell’s plasma membrane.
Mature erythrocyte lacks a nucleus and cytoplasmic organelles (e.g.,
mitochondria), cannot synthesize protein or carry out oxidative
reactions (CANNOT UNDERGO MITOTIC DIVISION)
Has a limited life span of about 100 to 120 days
Erythrocyte’s size and shape biconcave with the capacity to be
reversibly deformed – functions great as a gas carrier)
Platelets or thrombocytes: not true cells (irregularly-shaped cytoplasmic
fragments)
Essential for blood coagulation and control of bleeding
Formed by fragmentation of very large cells known as
megakaryocytes
A platelet circulates for about 10 days, ages, and is removed by
macrophages of the MPS, mostly in the spleen
Contain cytoplasmic granules injury to blood vessel release
biochemical mediators (contents are pro-inflammatory)
Know the process of hemoglobin synthesis. What is methemoglobin?
Hemoglobin (Hb) the oxygen-carrying protein of the erythrocyte (approximately 90% of the cell's dry weight; erythrocytes can
contain as many as 300 hemoglobin molecules)
Hb-packed blood cells take up oxygen lungs (exchange it for carbon dioxide in the tissues)
Hb increases the oxygen-carrying capacity of blood by 100-fold
Hb is responsible for blood's ruby red color
Each Hb molecule composed of two (2) pairs of polypeptide chains (the globins)
Four (4) colorful complexes of iron plus protoporphyrin (the hemes)
Polypeptide chains consist of alpha, beta, gamma, delta, epsilon, or zeta
Hemoglobin A is the most common type in adults
Hemoglobin F is the most common in fetal hemoglobin
Heme: is a large, flat, iron-protoporphyrin disk (synthesized in the mitochondria; carry one molecule to oxygen)
An individual hemoglobin molecule with its four hemes can carry four oxygen molecules [all four oxygen binding sites occupied
by oxygen molecule is saturated]
1. Protoporphyrin: series of complex biochemical reactions
complex four-ringed molecule produced bound with ferrous iron
o It is crucial that the iron be correctly charged; reduced
ferrous iron (Fe²+) can bind oxygen in the lungs and release
it in the tissues (where oxygen concentration is less),
whereas ferric iron (Fe³+) cannot
2. Oxyhemoglobin: binding of oxygen to ferrous iron temporally
oxidizes Fe²+ to Fe³+, after the release of oxygen body reduces
the iron to Fe²+ (BINDS OXYGEN)
3. Deoxyhemoglobin (reduced hemoglobin): reactivates the
hemoglobin’s capacity to bind oxygen
4. Methemoglobin: form of the oxygen-carrying
metalloprotein hemoglobin (iron in the heme group is in the Fe3+
(ferric) state, not the Fe2+ (ferrous) of normal hemoglobin);
cannot bind oxygen without reactivation by methemoglobin
reductase (Fe³+- containing hemoglobin cannot bind oxygen)
(CARRIES OXYGEN)
, Know function of all granulocytes and agranulocytes
CELLULAR COMPONENTS OF BLOOD
Granulocytes
Granulocytes are phagocytes; have many membrane-bound granules in their cytoplasm containing enzymes capable of killing microorganisms and
catabolizing debris ingested during phagocytosis and biochemical mediators with inflammatory / immune functions neutrophils, basophils, and
eosinophils; capable of amoeboid movement (migrate through vessel walls (diapedesis) sites where their action is needed)
Formation: stem cells in the bone marrow
Lifespan: short-lived and highly motile; normally takes 14 days to develop from early precursors but
accelerated by infection.
Types of neutrophils:
a. Immature neutrophils bands or stabs
b. Mature neutrophils segmented neutrophils (because of their nucleus)
Neutrophils Neutrophils may be subdivided into:
(most numerous – constitute about 55% of the a. Segmented neutrophils (or segs)
total leukocyte count in adults) b. Banded neutrophils (or bands).
They form part of the polymorphonuclear cell family (PMNs) together with
basophils and eosinophils
Job Function: chief phagocytes of early inflammation
Soon after invasion go to site of inflammation ingest and destroy die in 1 to 2 days
Dead neutrophils release enzymes dissolve debris and prepare for healing
Function: stimulation induces synthesis of vasoactive lipid molecules and cytokines Composition:
cytoplasmic granules that have an abundant mixture of biochemical mediators, including
Basophils histamine, chemotactic factors, proteolytic enzymes, and an anticoagulant (heparin)
(least common) Rich source of the cytokine IL4 guides B cell differentiation toward plasma cells that
secrete IgE
Increased during allergic inflammatory reactions and parasitic reactions / infections
(exoparasites; ticks)
Large, coarse granules
Function: ingest antigen antibody complexes and viruses and are induced by mast cell chemotactic
Eosinophils factors attack parasites (phagocytosis response to parasites & control of allergic reactions)
(only 1%-4% of the normal leukocyte count in Eosinophil secondary granules toxic chemicals highly destructive to parasites and
adults) viruses
Eosinophil granules enzymes (histamines) help control the inflammatory process
High numbers of eosinophils type 1 hypersensitivity allergic reactions and asthma.
Formation: different set of precursors cells in the bone marrow
Location: connective tissue beneath body epithelial surface (including submucosal tissues of the GI
Mast cells
and respiratory tract and the dermal layer that is just below the skin)
(similar to basophils) Function: central role in inflammation and healing activation increased permeability of
blood vessels and smooth muscle contractions
Agranulocytes
monocytes (phagocytes), macrophages (phagocytes), and lymphocytes (immunocytes); contain fewer granules in cytoplasm than granulocytes
Formation: formed and released by the bone marrow into the bloodstream.
Composition: amoeboid in shape, clear cytoplasm and horse shoe-shaped nucleus
Monocytes are unilobar makes them one of the types of mononuclear leukocytes (agranulocytes)
Location: half of them are stored in the spleen (except in people who have undergone splenectomy).
Monocytes are usually identified in stained smears by their large kidney shaped or notched
nucleus.
Monocytes
(largest of all leukocytes and constitute 2% to Function: migrate into a variety of tissues fully mature into tissue macrophages and myeloid
10% of all leukocytes in the human body) dendritic cells
type of white blood cell (leukocyte) Part of the innate immune system and play multiple roles:
1. Replenishing resident macrophages under normal states
2. In response to inflammation signals move quickly (approximately 8–12 hours) to sites
of infection in the tissues divide/differentiate into macrophages and dendritic cells
elicit an immune response
Lifespan: survive for many months, even years.
Function: to remove old and damaged cells and large molecular substances from the blood;
remove and kill contaminating microorganisms in the blood (liver and spleen) and at sites of
infection; initiate wound healing and tissue remodeling by T cells
Macrophages
, (larger and more active phagocyte) Target cells include:
circulating senescent or damaged erythrocytes and platelets, dead neutrophils
cells undergoing apoptosis
A type of white blood cell that
Engulfs and digests cellular debris, foreign substances, microbes, and cancer cells in a
process called phagocytosis.
They play a critical role in non-specific defense (innate immunity)
Help initiate specific defense mechanisms (adaptive immunity) by recruiting other immune
cells such as lymphocytes.
Lymphocytes Function: the primary cells of the immune response
(constitute approximately 36% of the total Location: reside in secondary lymphoid tissues as mature T cells, B cells, or plasma cells.
leukocyte count) Lifespan: days, months, or years depending on their type
Composition: do not contain enzyme-filled digestive vacuoles
Formation: predominant form develops in the bone marrow and circulates in the blood
Natural Killer Cells Location: found mainly in the peripheral blood and spleen.
(resemble lymphocytes) NK cells develop independent of thymus, although some NK precursors are found in the thymus and
may develop into NKT cells
Function: to kill some types of tumor cells in vitro and virus infected cells.
Have the capacity to activate T cells and phagocytes and produce a variety of cytokines
that can regulate immune responses
*Note: monocytes and macrophages make up the mononuclear phagocyte system (active phagocytes participate in immune and inflammatory
response ingest dead or defective host cells, particularly blood cells).
, Know hematopoiesis-the process and where does it occur in the fetus, neonate, child and adult
Define: blood cell production, termed hematopoiesis
Location: constantly ongoing throughout life;
occurring in the liver and spleen of the fetus and
only the bone marrow (medullary hematopoiesis)
after birth.
a. Prenatally occurs in the yolk sack, then in
the liver (8th week of gestation), and lastly in
the bone marrow (5th month of gestation).
By the time of delivery, the marrow is the
only significant site of hematopoiesis.
b. Adults occurs in the bone marrow and
lymphatic tissues. This process involves the
biochemical stimulation of populations of
relatively undifferentiated cells to undergo
mitotic division (i.e., proliferation) and
maturation (i.e., differentiation) into
mature hematologic cells.
Function: to replace blood cells increasing in
response to a need to replenish destroyed circulating
cells that grow old and die, are killed by disease, or
are lost through bleeding; (i.e. hemorrhage, hemolytic
anemia [peripheral destruction of erythrocytes],
consumptive thrombocytopenia) or infection.
Chronic diseases greater increase in hematopoiesis
then acute condition (i.e. hemorrhage)
Bone marrow confined to the cavities of the
bones and is the primary site of residence of
hematopoietic stem cells.
Adults two kinds of bone marrow
a. Red marrow (active or hematopoietic
marrow; also called myeloid tissues)
Located in the pelvis, vertebrae, cranium, and mandible, sternum / rib, and proximal portions of humerus / femur
b. Yellow marrow (inactive marrow) – large quantity of fat responsible for yellow color
Two populations of stem cells found in bone marrow niches
1. hematopoietic stem cells (HSCs) progenitors of all hematologic cells - undergo continuous proliferation and self-renewal
so that additional HSCs are produced to replace those undergoing differentiation
2. Mesenchymal stem cells (MSCs) stomal cells and have role of in maintaining HSCs; differentiate into a variety of cells
(osteoblasts – produce bone marrow; adipocytes – store fat; chondrocytes – produce cartilage)
The hematologic compartment of the bone marrow consists of a
variety of cellular microenvironments, called niches; contain
stem cells, precursor cells, and terminally differentiated cells –
provide coordinated signaling network regulates self-renewal,
differentiation, and maintained of HSCs
There are two distinct types of niches:
1. Osteoblastic niche: centralized around osteoblasts, which
lines the surface of the bone. Contains osteoblasts, CAR
cells, and nestin-expressing cells.
2. Vascular niche: organized around the sinusoidal
endothelial cells. Contains endothelial cells, as well as
nestin-expressing cells and larger numbers of perivascular
CAR cells.
Know function and life span of RBCs and platelets.
RBCs or erythrocytes: the most abundant cells of the blood – primarily
responsible for tissue oxygenation
Contains hemoglobin (carries the gases and electrolytes) regulates
diffusion through a cell’s plasma membrane.
Mature erythrocyte lacks a nucleus and cytoplasmic organelles (e.g.,
mitochondria), cannot synthesize protein or carry out oxidative
reactions (CANNOT UNDERGO MITOTIC DIVISION)
Has a limited life span of about 100 to 120 days
Erythrocyte’s size and shape biconcave with the capacity to be
reversibly deformed – functions great as a gas carrier)
Platelets or thrombocytes: not true cells (irregularly-shaped cytoplasmic
fragments)
Essential for blood coagulation and control of bleeding
Formed by fragmentation of very large cells known as
megakaryocytes
A platelet circulates for about 10 days, ages, and is removed by
macrophages of the MPS, mostly in the spleen
Contain cytoplasmic granules injury to blood vessel release
biochemical mediators (contents are pro-inflammatory)
Know the process of hemoglobin synthesis. What is methemoglobin?
Hemoglobin (Hb) the oxygen-carrying protein of the erythrocyte (approximately 90% of the cell's dry weight; erythrocytes can
contain as many as 300 hemoglobin molecules)
Hb-packed blood cells take up oxygen lungs (exchange it for carbon dioxide in the tissues)
Hb increases the oxygen-carrying capacity of blood by 100-fold
Hb is responsible for blood's ruby red color
Each Hb molecule composed of two (2) pairs of polypeptide chains (the globins)
Four (4) colorful complexes of iron plus protoporphyrin (the hemes)
Polypeptide chains consist of alpha, beta, gamma, delta, epsilon, or zeta
Hemoglobin A is the most common type in adults
Hemoglobin F is the most common in fetal hemoglobin
Heme: is a large, flat, iron-protoporphyrin disk (synthesized in the mitochondria; carry one molecule to oxygen)
An individual hemoglobin molecule with its four hemes can carry four oxygen molecules [all four oxygen binding sites occupied
by oxygen molecule is saturated]
1. Protoporphyrin: series of complex biochemical reactions
complex four-ringed molecule produced bound with ferrous iron
o It is crucial that the iron be correctly charged; reduced
ferrous iron (Fe²+) can bind oxygen in the lungs and release
it in the tissues (where oxygen concentration is less),
whereas ferric iron (Fe³+) cannot
2. Oxyhemoglobin: binding of oxygen to ferrous iron temporally
oxidizes Fe²+ to Fe³+, after the release of oxygen body reduces
the iron to Fe²+ (BINDS OXYGEN)
3. Deoxyhemoglobin (reduced hemoglobin): reactivates the
hemoglobin’s capacity to bind oxygen
4. Methemoglobin: form of the oxygen-carrying
metalloprotein hemoglobin (iron in the heme group is in the Fe3+
(ferric) state, not the Fe2+ (ferrous) of normal hemoglobin);
cannot bind oxygen without reactivation by methemoglobin
reductase (Fe³+- containing hemoglobin cannot bind oxygen)
(CARRIES OXYGEN)
, Know function of all granulocytes and agranulocytes
CELLULAR COMPONENTS OF BLOOD
Granulocytes
Granulocytes are phagocytes; have many membrane-bound granules in their cytoplasm containing enzymes capable of killing microorganisms and
catabolizing debris ingested during phagocytosis and biochemical mediators with inflammatory / immune functions neutrophils, basophils, and
eosinophils; capable of amoeboid movement (migrate through vessel walls (diapedesis) sites where their action is needed)
Formation: stem cells in the bone marrow
Lifespan: short-lived and highly motile; normally takes 14 days to develop from early precursors but
accelerated by infection.
Types of neutrophils:
a. Immature neutrophils bands or stabs
b. Mature neutrophils segmented neutrophils (because of their nucleus)
Neutrophils Neutrophils may be subdivided into:
(most numerous – constitute about 55% of the a. Segmented neutrophils (or segs)
total leukocyte count in adults) b. Banded neutrophils (or bands).
They form part of the polymorphonuclear cell family (PMNs) together with
basophils and eosinophils
Job Function: chief phagocytes of early inflammation
Soon after invasion go to site of inflammation ingest and destroy die in 1 to 2 days
Dead neutrophils release enzymes dissolve debris and prepare for healing
Function: stimulation induces synthesis of vasoactive lipid molecules and cytokines Composition:
cytoplasmic granules that have an abundant mixture of biochemical mediators, including
Basophils histamine, chemotactic factors, proteolytic enzymes, and an anticoagulant (heparin)
(least common) Rich source of the cytokine IL4 guides B cell differentiation toward plasma cells that
secrete IgE
Increased during allergic inflammatory reactions and parasitic reactions / infections
(exoparasites; ticks)
Large, coarse granules
Function: ingest antigen antibody complexes and viruses and are induced by mast cell chemotactic
Eosinophils factors attack parasites (phagocytosis response to parasites & control of allergic reactions)
(only 1%-4% of the normal leukocyte count in Eosinophil secondary granules toxic chemicals highly destructive to parasites and
adults) viruses
Eosinophil granules enzymes (histamines) help control the inflammatory process
High numbers of eosinophils type 1 hypersensitivity allergic reactions and asthma.
Formation: different set of precursors cells in the bone marrow
Location: connective tissue beneath body epithelial surface (including submucosal tissues of the GI
Mast cells
and respiratory tract and the dermal layer that is just below the skin)
(similar to basophils) Function: central role in inflammation and healing activation increased permeability of
blood vessels and smooth muscle contractions
Agranulocytes
monocytes (phagocytes), macrophages (phagocytes), and lymphocytes (immunocytes); contain fewer granules in cytoplasm than granulocytes
Formation: formed and released by the bone marrow into the bloodstream.
Composition: amoeboid in shape, clear cytoplasm and horse shoe-shaped nucleus
Monocytes are unilobar makes them one of the types of mononuclear leukocytes (agranulocytes)
Location: half of them are stored in the spleen (except in people who have undergone splenectomy).
Monocytes are usually identified in stained smears by their large kidney shaped or notched
nucleus.
Monocytes
(largest of all leukocytes and constitute 2% to Function: migrate into a variety of tissues fully mature into tissue macrophages and myeloid
10% of all leukocytes in the human body) dendritic cells
type of white blood cell (leukocyte) Part of the innate immune system and play multiple roles:
1. Replenishing resident macrophages under normal states
2. In response to inflammation signals move quickly (approximately 8–12 hours) to sites
of infection in the tissues divide/differentiate into macrophages and dendritic cells
elicit an immune response
Lifespan: survive for many months, even years.
Function: to remove old and damaged cells and large molecular substances from the blood;
remove and kill contaminating microorganisms in the blood (liver and spleen) and at sites of
infection; initiate wound healing and tissue remodeling by T cells
Macrophages
, (larger and more active phagocyte) Target cells include:
circulating senescent or damaged erythrocytes and platelets, dead neutrophils
cells undergoing apoptosis
A type of white blood cell that
Engulfs and digests cellular debris, foreign substances, microbes, and cancer cells in a
process called phagocytosis.
They play a critical role in non-specific defense (innate immunity)
Help initiate specific defense mechanisms (adaptive immunity) by recruiting other immune
cells such as lymphocytes.
Lymphocytes Function: the primary cells of the immune response
(constitute approximately 36% of the total Location: reside in secondary lymphoid tissues as mature T cells, B cells, or plasma cells.
leukocyte count) Lifespan: days, months, or years depending on their type
Composition: do not contain enzyme-filled digestive vacuoles
Formation: predominant form develops in the bone marrow and circulates in the blood
Natural Killer Cells Location: found mainly in the peripheral blood and spleen.
(resemble lymphocytes) NK cells develop independent of thymus, although some NK precursors are found in the thymus and
may develop into NKT cells
Function: to kill some types of tumor cells in vitro and virus infected cells.
Have the capacity to activate T cells and phagocytes and produce a variety of cytokines
that can regulate immune responses
*Note: monocytes and macrophages make up the mononuclear phagocyte system (active phagocytes participate in immune and inflammatory
response ingest dead or defective host cells, particularly blood cells).
, Know hematopoiesis-the process and where does it occur in the fetus, neonate, child and adult
Define: blood cell production, termed hematopoiesis
Location: constantly ongoing throughout life;
occurring in the liver and spleen of the fetus and
only the bone marrow (medullary hematopoiesis)
after birth.
a. Prenatally occurs in the yolk sack, then in
the liver (8th week of gestation), and lastly in
the bone marrow (5th month of gestation).
By the time of delivery, the marrow is the
only significant site of hematopoiesis.
b. Adults occurs in the bone marrow and
lymphatic tissues. This process involves the
biochemical stimulation of populations of
relatively undifferentiated cells to undergo
mitotic division (i.e., proliferation) and
maturation (i.e., differentiation) into
mature hematologic cells.
Function: to replace blood cells increasing in
response to a need to replenish destroyed circulating
cells that grow old and die, are killed by disease, or
are lost through bleeding; (i.e. hemorrhage, hemolytic
anemia [peripheral destruction of erythrocytes],
consumptive thrombocytopenia) or infection.
Chronic diseases greater increase in hematopoiesis
then acute condition (i.e. hemorrhage)
Bone marrow confined to the cavities of the
bones and is the primary site of residence of
hematopoietic stem cells.
Adults two kinds of bone marrow
a. Red marrow (active or hematopoietic
marrow; also called myeloid tissues)
Located in the pelvis, vertebrae, cranium, and mandible, sternum / rib, and proximal portions of humerus / femur
b. Yellow marrow (inactive marrow) – large quantity of fat responsible for yellow color
Two populations of stem cells found in bone marrow niches
1. hematopoietic stem cells (HSCs) progenitors of all hematologic cells - undergo continuous proliferation and self-renewal
so that additional HSCs are produced to replace those undergoing differentiation
2. Mesenchymal stem cells (MSCs) stomal cells and have role of in maintaining HSCs; differentiate into a variety of cells
(osteoblasts – produce bone marrow; adipocytes – store fat; chondrocytes – produce cartilage)
The hematologic compartment of the bone marrow consists of a
variety of cellular microenvironments, called niches; contain
stem cells, precursor cells, and terminally differentiated cells –
provide coordinated signaling network regulates self-renewal,
differentiation, and maintained of HSCs
There are two distinct types of niches:
1. Osteoblastic niche: centralized around osteoblasts, which
lines the surface of the bone. Contains osteoblasts, CAR
cells, and nestin-expressing cells.
2. Vascular niche: organized around the sinusoidal
endothelial cells. Contains endothelial cells, as well as
nestin-expressing cells and larger numbers of perivascular
CAR cells.
