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17. Blood. Blood Composition. Blood: a fluid connective tissue composed of Plasma Formed elements Erythrocytes (red blood cells, or RBCs) Leukocytes (white blood cells, or WBCs) Platelets. Blood Composition. Hematocrit Percent of blood volume that is RBCs 47% ± 5% for males

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17

17

Blood


Blood composition

Blood Composition

  • Blood: a fluid connective tissue composed of

    • Plasma

    • Formed elements

      • Erythrocytes (red blood cells, or RBCs)

      • Leukocytes (white blood cells, or WBCs)

      • Platelets


Blood composition1

Blood Composition

  • Hematocrit

    • Percent of blood volume that is RBCs

    • 47% ± 5% for males

    • 42% ± 5% for females


17

Formed

elements

Plasma

• 55% of whole blood

• Least dense component

Buffy coat

• Leukocytes and platelets

• <1% of whole blood

Erythrocytes

2

• 45% of whole blood

• Most dense

component

1

Centrifuge the

blood sample.

Withdraw

blood and place

in tube.

Figure 17.1


Physical characteristics and volume

Physical Characteristics and Volume

  • Sticky, opaque fluid

  • Color scarlet to dark red

  • pH 7.35–7.45

  • 38C

  • ~8% of body weight

  • Average volume: 5–6 L for males, and 4–5 L for females


Functions of blood

Functions of Blood

  • Distribution of

    • O2 and nutrients to body cells

    • Metabolic wastes to the lungs and kidneys for elimination

    • Hormones from endocrine organs to target organs


Functions of blood1

Functions of Blood

  • Regulation of

    • Body temperature by absorbing and distributing heat

    • Normal pH using buffers

    • Adequate fluid volume in the circulatory system


Functions of blood2

Functions of Blood

  • Protection against

    • Blood loss

      • Plasma proteins and platelets initiate clot formation

    • Infection

      • Antibodies

      • Complement proteins

      • WBCs defend against foreign invaders


Blood plasma

Blood Plasma

  • 90% water

  • Proteins are mostly produced by the liver

    • 60% albumin

    • 36% globulins

    • 4% fibrinogen


Blood plasma1

Blood Plasma

  • Nitrogenous by-products of metabolism—lactic acid, urea, creatinine

  • Nutrients—glucose, carbohydrates, amino acids

  • Electrolytes—Na+, K+, Ca2+, Cl–, HCO3–

  • Respiratory gases—O2 and CO2

  • Hormones


Formed elements

Formed Elements

  • Only WBCs are complete cells

  • RBCs have no nuclei or organelles

  • Platelets are cell fragments

  • Most formed elements survive in the bloodstream for only a few days

  • Most blood cells originate in bone marrow and do not divide


17

Platelets

Erythrocytes

Monocyte

Neutrophils

Lymphocyte

Figure 17.2


Erythrocytes

Erythrocytes

  • Biconcave discs, anucleate, essentially no organelles

  • Filled with hemoglobin (Hb) for gas transport

  • Contain the plasma membrane protein spectrin and other proteins

    • Provide flexibility to change shape as necessary

  • Are the major factor contributing to blood viscosity


17

2.5 µm

Side view (cut)

7.5 µm

Top view

Figure 17.3


Erythrocytes1

Erythrocytes

  • Structural characteristics contribute to gas transport

    • Biconcave shape—huge surface area relative to volume

    • >97% hemoglobin (not counting water)

    • No mitochondria; ATP production is anaerobic; no O2 is used in generation of ATP

  • A superb example of complementarity of structure and function!


Erythrocyte function

Erythrocyte Function

  • RBCs are dedicated to respiratory gas transport

  • Hemoglobin binds reversibly with oxygen


Erythrocyte function1

Erythrocyte Function

  • Hemoglobin structure

    • Protein globin: two alpha and two beta chains

    • Heme pigment bonded to each globin chain

  • Iron atom in each heme can bind to one O2 molecule

  • Each Hb molecule can transport four O2


17

bGlobin chains

Heme

group

a Globin chains

(a) Hemoglobin consists of globin (two

alpha and two beta polypeptide

chains) and four heme groups.

(b) Iron-containing heme pigment.

Figure 17.4


Hemoglobin hb

Hemoglobin (Hb)

  • O2 loading in the lungs

    • Produces oxyhemoglobin (ruby red)

  • O2 unloading in the tissues

    • Produces deoxyhemoglobin or reduced hemoglobin (dark red)

  • CO2 loading in the tissues

    • Produces carbaminohemoglobin (carries 20% of CO2 in the blood)


Hematopoiesis

Hematopoiesis

  • Hematopoiesis (hemopoiesis): blood cell formation

    • Occurs in red bone marrow of axial skeleton, girdles and proximal epiphyses of humerus and femur


Hematopoiesis1

Hematopoiesis

  • Hemocytoblasts (hematopoietic stem cells)

    • Give rise to all formed elements

    • Hormones and growth factors push the cell toward a specific pathway of blood cell development

  • New blood cells enter blood sinusoids


Erythropoiesis

Erythropoiesis

  • Erythropoiesis: red blood cell production

    • A hemocytoblast is transformed into a proerythroblast

    • Proerythroblasts develop into early erythroblasts


Erythropoiesis1

Erythropoiesis

  • Phases in development

    • Ribosome synthesis

    • Hemoglobin accumulation

    • Ejection of the nucleus and formation of reticulocytes

  • Reticulocytes then become mature erythrocytes


17

Stem cell

Committed

cell

Developmental pathway

Phase 1

Ribosome

synthesis

Phase 2

Hemoglobin

accumulation

Phase 3

Ejection of

nucleus

Reticulo-

cyte

Erythro-

cyte

Proerythro-

blast

Early

erythroblast

Late

erythroblast

Normoblast

Hemocytoblast

Figure 17.5


Regulation of erythropoiesis

Regulation of Erythropoiesis

  • Too few RBCs leads to tissue hypoxia

  • Too many RBCs increases blood viscosity

  • Balance between RBC production and destruction depends on

    • Hormonal controls

    • Adequate supplies of iron, amino acids, and B vitamins


Hormonal control of erythropoiesis

Hormonal Control of Erythropoiesis

  • Erythropoietin (EPO)

    • Direct stimulus for erythropoiesis

    • Released by the kidneys in response to hypoxia


Hormonal control of erythropoiesis1

Hormonal Control of Erythropoiesis

  • Causes of hypoxia

    • Hemorrhage or increased RBC destruction reduces RBC numbers

    • Insufficient hemoglobin (e.g., iron deficiency)

    • Reduced availability of O2 (e.g., high altitudes)


Hormonal control of erythropoiesis2

Hormonal Control of Erythropoiesis

  • Effects of EPO

    • More rapid maturation of committed bone marrow cells

    • Increased circulating reticulocyte count in 1–2 days

  • Testosterone also enhances EPO production, resulting in higher RBC counts in males


17

IMBALANCE

Homeostasis: Normal blood oxygen levels

1

Stimulus:

Hypoxia (low blood

O2- carrying ability)

due to

• DecreasedRBC count

• Decreased amountof hemoglobin

• Decreasedavailability of O2

5

O2- carryingability of bloodincreases.

IMBALANCE

4

Enhancederythropoiesisincreases RBCcount.

2

Kidney (and liver toa smaller extent)releaseserythropoietin.

3

Erythropoietinstimulates redbone marrow.

Figure 17.6


17

IMBALANCE

Homeostasis: Normal blood oxygen levels

1

Stimulus:

Hypoxia (low blood

O2- carrying ability)

due to

• DecreasedRBC count

• Decreased amountof hemoglobin

• Decreasedavailability of O2

IMBALANCE

Figure 17.6, step 1


17

IMBALANCE

Homeostasis: Normal blood oxygen levels

1

Stimulus:

Hypoxia (low blood

O2- carrying ability)

due to

• DecreasedRBC count

• Decreased amountof hemoglobin

• Decreasedavailability of O2

IMBALANCE

2

Kidney (and liver toa smaller extent)releaseserythropoietin.

Figure 17.6, step 2


17

IMBALANCE

Homeostasis: Normal blood oxygen levels

1

Stimulus:

Hypoxia (low blood

O2- carrying ability)

due to

• DecreasedRBC count

• Decreased amountof hemoglobin

• Decreasedavailability of O2

IMBALANCE

2

Kidney (and liver toa smaller extent)releaseserythropoietin.

3

Erythropoietinstimulates redbone marrow.

Figure 17.6, step 3


17

IMBALANCE

Homeostasis: Normal blood oxygen levels

1

Stimulus:

Hypoxia (low blood

O2- carrying ability)

due to

• DecreasedRBC count

• Decreased amountof hemoglobin

• Decreasedavailability of O2

IMBALANCE

4

Enhancederythropoiesisincreases RBCcount.

2

Kidney (and liver toa smaller extent)releaseserythropoietin.

3

Erythropoietinstimulates redbone marrow.

Figure 17.6, step 4


17

IMBALANCE

Homeostasis: Normal blood oxygen levels

1

Stimulus:

Hypoxia (low blood

O2- carrying ability)

due to

• DecreasedRBC count

• Decreased amountof hemoglobin

• Decreasedavailability of O2

5

O2- carryingability of bloodincreases.

IMBALANCE

4

Enhancederythropoiesisincreases RBCcount.

2

Kidney (and liver toa smaller extent)releaseserythropoietin.

3

Erythropoietinstimulates redbone marrow.

Figure 17.6, step 5


Dietary requirements for erythropoiesis

Dietary Requirements for Erythropoiesis

  • Nutrients—amino acids, lipids, and carbohydrates

  • Iron

    • Stored in Hb (65%), the liver, spleen, and bone marrow

    • Stored in cells as ferritin and hemosiderin

    • Transported loosely bound to the protein transferrin

  • Vitamin B12 and folic acid—necessary for DNA synthesis for cell division


Fate and destruction of erythrocytes

Fate and Destruction of Erythrocytes

  • Life span: 100–120 days

  • Old RBCs become fragile, and Hb begins to degenerate

  • Macrophages engulf dying RBCs in the spleen


Fate and destruction of erythrocytes1

Fate and Destruction of Erythrocytes

  • Heme and globin are separated

    • Iron is salvaged for reuse

    • Heme is degraded to yellow the pigment bilirubin

    • Liver secretes bilirubin (in bile)) into the intestines

    • Degraded pigment leaves the body in feces as stercobilin

    • Globin is metabolized into amino acids


17

1

Low O2levels in blood stimulate

kidneys to produce erythropoietin.

2

Erythropoietin levels rise

in blood.

3

Erythropoietin and necessary

raw materials in blood promote

erythropoiesis in red bone marrow.

4

New erythrocytes

enter bloodstream;

function about 120 days.

5

Aged and damaged

red blood cells are

engulfed by macrophages

of liver, spleen, and bone

marrow; the hemoglobin

is broken down.

Hemoglobin

Heme

Globin

Bilirubin

Amino

acids

Iron stored

as ferritin,

hemosiderin

Iron is bound to

transferrin and released

to blood from liver as

needed for erythropoiesis.

Bilirubin is picked up from blood

by liver, secreted into intestine in

bile, metabolized to stercobilin by

bacteria, and excreted in feces.

Circulation

Food nutrients,

including amino acids,

Fe, B12, and folic acid,

are absorbed from

intestine and enter

blood.

6

Raw materials are

made available in blood

for erythrocyte synthesis.

Figure 17.7


17

1

Low O2levels in blood stimulate

kidneys to produce erythropoietin.

Figure 17.7, step 1


17

1

Low O2levels in blood stimulate

kidneys to produce erythropoietin.

2

Erythropoietin levels rise

in blood.

Figure 17.7, step 2


17

1

Low O2levels in blood stimulate

kidneys to produce erythropoietin.

2

Erythropoietin levels rise

in blood.

3

Erythropoietin and necessary

raw materials in blood promote

erythropoiesis in red bone marrow.

Figure 17.7, step 3


17

1

Low O2levels in blood stimulate

kidneys to produce erythropoietin.

2

Erythropoietin levels rise

in blood.

3

Erythropoietin and necessary

raw materials in blood promote

erythropoiesis in red bone marrow.

4

New erythrocytes

enter bloodstream;

function about 120 days.

Figure 17.7, step 4


17

Hemoglobin

5

Aged and damaged red

blood cells are engulfed by

macrophages of liver,

spleen, and bone

marrow; the

hemoglobin is

broken down.

Heme

Globin

Bilirubin

Amino

acids

Iron stored

as ferritin,

hemosiderin

Bilirubin is picked up from blood

by liver, secreted into intestine in

bile, metabolized to stercobilin by

bacteria, and excreted in feces.

Circulation

Figure 17.7, step 5


17

Hemoglobin

5

Aged and damaged red

blood cells are engulfed by

macrophages of liver,

spleen, and bone

marrow; the

hemoglobin is

broken down.

Heme

Globin

Bilirubin

Amino

acids

Iron stored

as ferritin,

hemosiderin

Iron is bound to

transferrin and released

to blood from liver as

needed for erythropoiesis.

Bilirubin is picked up from blood

by liver, secreted into intestine in

bile, metabolized to stercobilin by

bacteria, and excreted in feces.

Circulation

Food nutrients,

including amino acids,

Fe, B12, and folic acid,

are absorbed from

intestine and enter

blood.

6

Raw materials are

made available in blood

for erythrocyte synthesis.

Figure 17.7, step 6


17

1

Low O2levels in blood stimulate

kidneys to produce erythropoietin.

2

Erythropoietin levels rise

in blood.

3

Erythropoietin and necessary

raw materials in blood promote

erythropoiesis in red bone marrow.

4

New erythrocytes

enter bloodstream;

function about 120 days.

5

Aged and damaged

red blood cells are

engulfed by macrophages

of liver, spleen, and bone

marrow; the hemoglobin

is broken down.

Hemoglobin

Heme

Globin

Bilirubin

Amino

acids

Iron stored

as ferritin,

hemosiderin

Iron is bound to

transferrin and released

to blood from liver as

needed for erythropoiesis.

Bilirubin is picked up from blood

by liver, secreted into intestine in

bile, metabolized to stercobilin by

bacteria, and excreted in feces.

Circulation

Food nutrients,

including amino acids,

Fe, B12, and folic acid,

are absorbed from

intestine and enter

blood.

6

Raw materials are

made available in blood

for erythrocyte synthesis.

Figure 17.7


Erythrocyte disorders

Erythrocyte Disorders

  • Anemia: blood has abnormally low O2-carrying capacity

    • A sign rather than a disease itself

    • Blood O2 levels cannot support normal metabolism

    • Accompanied by fatigue, paleness, shortness of breath, and chills


Causes of anemia

Causes of Anemia

  • Insufficient erythrocytes

    • Hemorrhagic anemia: acute or chronic loss of blood

    • Hemolytic anemia: RBCs rupture prematurely

    • Aplastic anemia: destruction or inhibition of red bone marrow


Causes of anemia1

Causes of Anemia

  • Low hemoglobin content

    • Iron-deficiency anemia

      • Secondary result of hemorrhagic anemia or

      • Inadequate intake of iron-containing foods or

      • Impaired iron absorption


Causes of anemia2

Causes of Anemia

  • Pernicious anemia

    • Deficiency of vitamin B12

    • Lack of intrinsic factor needed for absorption of B12

    • Treated by intramuscular injection of B12 or application of Nascobal


Causes of anemia3

Causes of Anemia

  • Abnormal hemoglobin

    • Thalassemias

      • Absent or faulty globin chain

      • RBCs are thin, delicate, and deficient in hemoglobin


Causes of anemia4

Causes of Anemia

  • Sickle-cell anemia

    • Defective gene codes for abnormal hemoglobin (HbS)

    • Causes RBCs to become sickle shaped in low-oxygen situations


17

(a) Normal erythrocyte has normal

hemoglobin amino acid sequence

in the beta chain.

1

2

3

4

5

6

7

146

(b) Sickled erythrocyte results from

a single amino acid change in the

beta chain of hemoglobin.

1

2

3

4

5

6

7

146

Figure 17.8


Erythrocyte disorders1

Erythrocyte Disorders

  • Polycythemia: excess of RBCs that increase blood viscosity

  • Results from:

    • Polycythemia vera—bone marrow cancer

    • Secondary polycythemia—when less O2 is available (high altitude) or when EPO production increases

    • Blood doping


Leukocytes

Leukocytes

  • Make up <1% of total blood volume

  • Can leave capillaries via diapedesis

  • Move through tissue spaces by ameboid motion and positive chemotaxis

  • Leukocytosis: WBC count over 11,000/mm3

    • Normal response to bacterial or viral invasion


17

Differential

WBC count

(All total 4800–

10,800/l)

Formed

elements

Platelets

Granulocytes

Neutrophils (50–70%)

Leukocytes

Eosinophils (2–4%)

Basophils (0.5–1%)

Erythrocytes

Agranulocytes

Lymphocytes (25 – 45%)

Monocytes (3 – 8%)

Figure 17.9


Granulocytes

Granulocytes

  • Granulocytes: neutrophils, eosinophils, and basophils

    • Cytoplasmic granules stain specifically with Wright’s stain

    • Larger and shorter-lived than RBCs

    • Lobed nuclei

    • Phagocytic


Neutrophils

Neutrophils

  • Most numerous WBCs

  • Polymorphonuclear leukocytes (PMNs)

  • Fine granules take up both acidic and basic dyes

  • Give the cytoplasm a lilac color

  • Granules contain hydrolytic enzymes or defensins

  • Very phagocytic—“bacteria slayers”


Eosinophils

Eosinophils

  • Red-staining, bilobed nuclei

  • Red to crimson (acidophilic) coarse, lysosome-like granules

  • Digest parasitic worms that are too large to be phagocytized

  • Modulators of the immune response


Basophils

Basophils

  • Rarest WBCs

  • Large, purplish-black (basophilic) granules contain histamine

    • Histamine: an inflammatory chemical that acts as a vasodilator and attracts other WBCs to inflamed sites

  • Are functionally similar to mast cells


17

(a) Neutrophil;

multilobed

nucleus

(b) Eosinophil;

bilobed nucleus,

red cytoplasmic

granules

(c) Basophil;

bilobed nucleus,

purplish-black

cytoplasmic

granules

Figure 17.10 (a-c)


Agranulocytes

Agranulocytes

  • Agranulocytes: lymphocytes and monocytes

    • Lack visible cytoplasmic granules

    • Have spherical or kidney-shaped nuclei


Lymphocytes

Lymphocytes

  • Large, dark-purple, circular nuclei with a thin rim of blue cytoplasm

  • Mostly in lymphoid tissue; few circulate in the blood

  • Crucial to immunity


Lymphocytes1

Lymphocytes

  • Two types

    • T cells act against virus-infected cells and tumor cells

    • B cells give rise to plasma cells, which produce antibodies


Monocytes

Monocytes

  • The largest leukocytes

  • Abundant pale-blue cytoplasm

  • Dark purple-staining, U- or kidney-shaped nuclei


Monocytes1

Monocytes

  • Leave circulation, enter tissues, and differentiate into macrophages

    • Actively phagocytic cells; crucial against viruses, intracellular bacterial parasites, and chronic infections

  • Activate lymphocytes to mount an immune response


17

(d) Small

lymphocyte;

large spherical

nucleus

(e) Monocyte;

kidney-shaped

nucleus

Figure 17.10d, e


17

Table 17.2 (1 of 2)


17

Table 17.2 (2 of 2)


Leukopoiesis

Leukopoiesis

  • Production of WBCs

  • Stimulated by chemical messengers from bone marrow and mature WBCs

    • Interleukins (e.g., IL-1, IL-2)

    • Colony-stimulating factors (CSFs) named for the WBC type they stimulate (e.g., granulocyte-CSF stimulates granulocytes)

  • All leukocytes originate from hemocytoblasts


17

Stem cells

Hemocytoblast

Lymphoid stem cell

Myeloid stem cell

Committed

cells

Myeloblast

Myeloblast

Myeloblast

Monoblast

Lymphoblast

Developmental

pathway

Promonocyte

Promyelocyte

Promyelocyte

Promyelocyte

Prolymphocyte

Eosinophilic

myelocyte

Basophilic

myelocyte

Neutrophilic

myelocyte

Basophilic

band cells

Eosinophilic

band cells

Neutrophilic

band cells

Monocytes

Neutrophils

Eosinophils

Basophils

Lymphocytes

(a)

(e)

(b)

(c)

(d)

Agranular leukocytes

Some

become

Granular leukocytes

Some become

Figure 17.11


Leukocyte disorders

Leukocyte Disorders

  • Leukopenia

    • Abnormally low WBC count—drug induced

  • Leukemias

    • Cancerous conditions involving WBCs

    • Named according to the abnormal WBC clone involved

    • Myelocytic leukemia involves myeloblasts

    • Lymphocytic leukemia involves lymphocytes

  • Acute leukemia involves blast-type cells and primarily affects children

  • Chronic leukemia is more prevalent in older people


Leukemia

Leukemia

  • Bone marrow totally occupied with cancerous leukocytes

  • Immature nonfunctional WBCs in the bloodstream

  • Death caused by internal hemorrhage and overwhelming infections

  • Treatments include irradiation, antileukemic drugs, and stem cell transplants


Platelets

Platelets

  • Small fragments of megakaryocytes

  • Formation is regulated by thrombopoietin

  • Blue-staining outer region, purple granules

  • Granules contain serotonin, Ca2+, enzymes, ADP, and platelet-derived growth factor (PDGF)


Platelets1

Platelets

  • Form a temporary platelet plug that helps seal breaks in blood vessels

  • Circulating platelets are kept inactive and mobile by NO and prostacyclin from endothelial cells of blood vessels


17

Stem cell

Developmental pathway

Hemocyto-

blast

Promegakaryocyte

Megakaryoblast

Megakaryocyte

Platelets

Figure 17.12


Hemostasis

Hemostasis

  • Fast series of reactions for stoppage of bleeding

    • Vascular spasm

    • Platelet plug formation

    • Coagulation (blood clotting)


Vascular spasm

Vascular Spasm

  • Vasoconstriction of damaged blood vessel

  • Triggers

    • Direct injury

    • Chemicals released by endothelial cells and platelets

    • Pain reflexes


Platelet plug formation

Platelet Plug Formation

  • Positive feedback cycle

    • At site of blood vessel injury, platelets

      • Stick to exposed collagen fibers with the help of von Willebrand factor, a plasma protein

      • Swell, become spiked and sticky, and release chemical messengers

        • ADP causes more platelets to stick and release their contents

        • Serotonin and thromboxane A2 enhance vascular spasm and more platelet aggregation


17

1

Step Vascular spasm

•Smooth muscle contracts,

causing vasoconstriction.

2

Step Platelet plug

formation

•Injury to lining of vessel

exposes collagen fibers;

platelets adhere.

Collagen

fibers

•Platelets release chemicals

that make nearby platelets

sticky; platelet plug forms.

Platelets

3

Step Coagulation

•Fibrin forms a mesh that traps

red blood cells and platelets,

forming the clot.

Fibrin

Figure 17.13


Coagulation

Coagulation

  • A set of reactions in which blood is transformed from a liquid to a gel

  • Reinforces the platelet plug with fibrin threads


Coagulation1

Coagulation

  • Three phases of coagulation

    • Prothrombin activator is formed (intrinsic and extrinsic pathways)

    • Prothrombin is converted into thrombin

    • Thrombin catalyzes the joining of fibrinogen to form a fibrin mesh


17

Phase 1

Intrinsic pathway

Extrinsic pathway

Tissue cell trauma

exposes blood to

Vessel endothelium ruptures,

exposing underlying tissues

(e.g., collagen)

Platelets cling and their

surfaces provide sites for

mobilization of factors

Tissue factor (TF)

XII

Ca2+

XIIa

VII

XI

XIa

VIIa

Ca2+

IX

IXa

PF3

released by

aggregated

platelets

VIII

VIIIa

TF/VIIacomplex

IXa/VIIIacomplex

X

Xa

Ca2+

V

PF3

Va

Prothrombin

activator

Figure 17.14 (1 of 2)


17

Prothrombin

activator

Phase 2

Prothrombin (II)

Thrombin (IIa)

Phase 3

Fibrinogen (I)

(soluble)

Ca2+

Fibrin

(insoluble

polymer)

XIII

XIIIa

Cross-linked

fibrin mesh

Figure 17.14 (2 of 2)


Coagulation phase 1 two pathways to prothrombin activator

Coagulation Phase 1: Two Pathways to Prothrombin Activator

  • Initiated by either the intrinsic or extrinsic pathway (usually both)

    • Triggered by tissue-damaging events

    • Involves a series of procoagulants

    • Each pathway cascades toward factor X

  • Factor X complexes with Ca2+, PF3, and factor V to form prothrombin activator


Coagulation phase 1 two pathways to prothrombin activator1

Coagulation Phase 1: Two Pathways to Prothrombin Activator

  • Intrinsic pathway

    • Is triggered by negatively charged surfaces (activated platelets, collagen, glass)

    • Uses factors present within the blood (intrinsic)

  • Extrinsic pathway

    • Is triggered by exposure to tissue factor (TF) or factor III (an extrinsic factor)

    • Bypasses several steps of the intrinsic pathway, so is faster


Coagulation phase 2 pathway to thrombin

Coagulation Phase 2: Pathway to Thrombin

  • Prothrombin activator catalyzes the transformation of prothrombin to the active enzyme thrombin


Coagulation phase 3 common pathway to the fibrin mesh

Coagulation Phase 3: Common Pathway to the Fibrin Mesh

  • Thrombin converts soluble fibrinogen into fibrin

  • Fibrin strands form the structural basis of a clot

  • Fibrin causes plasma to become a gel-like trap for formed elements

  • Thrombin (with Ca2+) activates factor XIII which:

    • Cross-links fibrin

    • Strengthens and stabilizes the clot


17

Figure 17.15


Clot retraction

Clot Retraction

  • Actin and myosin in platelets contract within 30–60 minutes

  • Platelets pull on the fibrin strands, squeezing serum from the clot


Clot repair

Clot Repair

  • Platelet-derived growth factor (PDGF) stimulates division of smooth muscle cells and fibroblasts to rebuild blood vessel wall

  • Vascular endothelial growth factor (VEGF) stimulates endothelial cells to multiply and restore the endothelial lining


Fibrinolysis

Fibrinolysis

  • Begins within two days

  • Plasminogen in clot is converted to plasmin by tissue plasminogen activator (tPA), factor XII and thrombin

  • Plasmin is a fibrin-digesting enzyme


Factors limiting clot growth or formation

Factors Limiting Clot Growth or Formation

  • Two homeostatic mechanisms prevent clots from becoming large

    • Swift removal and dilution of clotting factors

    • Inhibition of activated clotting factors


Inhibition of clotting factors

Inhibition of Clotting Factors

  • Most thrombin is bound to fibrin threads, and prevented from acting elsewhere

  • Antithrombin III, protein C, and heparin inactivate thrombin and other procoagulants

  • Heparin, another anticoagulant, also inhibits thrombin activity


Factors preventing undesirable clotting

Factors Preventing Undesirable Clotting

  • Platelet adhesion is prevented by

    • Smooth endothelial lining of blood vessels

    • Antithrombic substances nitric oxide and prostacyclin secreted by endothelial cells

    • Vitamin E quinine, which acts as a potent anticoagulant


Disorders of hemostasis

Disorders of Hemostasis

  • Thromboembolytic disorders: undesirable clot formation

  • Bleeding disorders: abnormalities that prevent normal clot formation


Thromboembolytic conditions

Thromboembolytic Conditions

  • Thrombus: clot that develops and persists in an unbroken blood vessel

    • May block circulation, leading to tissue death

  • Embolus: a thrombus freely floating in the blood stream

    • Pulmonary emboli impair the ability of the body to obtain oxygen

    • Cerebral emboli can cause strokes


Thromboembolytic conditions1

Thromboembolytic Conditions

  • Prevented by

    • Aspirin

      • Antiprostaglandin that inhibits thromboxane A2

    • Heparin

      • Anticoagulant used clinically for pre- and postoperative cardiac care

    • Warfarin

      • Used for those prone to atrial fibrillation


Disseminated intravascular coagulation dic

Disseminated Intravascular Coagulation (DIC)

  • Widespread clotting blocks intact blood vessels

  • Severe bleeding occurs because residual blood unable to clot

  • Most common in pregnancy, septicemia, or incompatible blood transfusions


Bleeding disorders

Bleeding Disorders

  • Thrombocytopenia: deficient number of circulating platelets

    • Petechiae appear due to spontaneous, widespread hemorrhage

    • Due to suppression or destruction of bone marrow (e.g., malignancy, radiation)

    • Platelet count <50,000/mm3 is diagnostic

    • Treated with transfusion of concentrated platelets


Bleeding disorders1

Bleeding Disorders

  • Impaired liver function

    • Inability to synthesize procoagulants

    • Causes include vitamin K deficiency, hepatitis, and cirrhosis

    • Liver disease can also prevent the liver from producing bile, impairing fat and vitamin K absorption


Bleeding disorders2

Bleeding Disorders

  • Hemophilias include several similar hereditary bleeding disorders

    • Hemophilia A: most common type (77% of all cases); due to a deficiency of factor VIII

    • Hemophilia B: deficiency of factor IX

    • Hemophilia C: mild type; deficiency of factor XI

  • Symptoms include prolonged bleeding, especially into joint cavities

  • Treated with plasma transfusions and injection of missing factors


Transfusions

Transfusions

  • Whole-blood transfusions are used when blood loss is substantial

  • Packed red cells (plasma removed) are used to restore oxygen-carrying capacity

  • Transfusion of incompatible blood can be fatal


Human blood groups

Human Blood Groups

  • RBC membranes bear 30 types glycoprotein antigens that are

    • Perceived as foreign if transfused blood is mismatched

    • Unique to each individual

    • Promoters of agglutination and are called agglutinogens

  • Presence or absence of each antigen is used to classify blood cells into different groups


Blood groups

Blood Groups

  • Humans have 30 varieties of naturally occurring RBC antigens

  • Antigens of the ABO and Rh blood groups cause vigorous transfusion reactions

  • Other blood groups (MNS, Duffy, Kell, and Lewis) are usually weak agglutinogens


Abo blood groups

ABO Blood Groups

  • Types A, B, AB, and O

  • Based on the presence or absence of two agglutinogens (A and B) on the surface of the RBCs

  • Blood may contain anti-A or anti-B antibodies (agglutinins) that act against transfused RBCs with ABO antigens not normally present

  • Anti-A or anti-B form in the blood at about 2 months of age


17

Table 17.4


Rh blood groups

Rh Blood Groups

  • There are 45 different Rh agglutinogens (Rh factors)

  • C, D, and E are most common

  • Rh+ indicates presence of D


Rh blood groups1

Rh Blood Groups

  • Anti-Rh antibodies are not spontaneously formed in Rh– individuals

  • Anti-Rh antibodies form if an Rh– individual receives Rh+ blood

  • A second exposure to Rh+ blood will result in a typical transfusion reaction


Homeostatic imbalance hemolytic disease of the newborn

Homeostatic Imbalance: Hemolytic Disease of the Newborn

  • Also called erythroblastosis fetalis

  • Rh– mother becomes sensitized when exposure to Rh+ blood causes her body to synthesize anti-Rh antibodies

  • Anti-Rh antibodies cross the placenta and destroy the RBCs of an Rh+ baby


Homeostatic imbalance hemolytic disease of the newborn1

Homeostatic Imbalance: Hemolytic Disease of the Newborn

  • The baby can be treated with prebirth transfusions and exchange transfusions after birth

  • RhoGAM serum containing anti-Rh can prevent the Rh– mother from becoming sensitized


Transfusion reactions

Transfusion Reactions

  • Occur if mismatched blood is infused

  • Donor’s cells

    • Are attacked by the recipient’s plasma agglutinins

    • Agglutinate and clog small vessels

    • Rupture and release free hemoglobin into the bloodstream

  • Result in

    • Diminished oxygen-carrying capacity

    • Hemoglobin in kidney tubules and renal failure


Blood typing

Blood Typing

  • When serum containing anti-A or anti-B agglutinins is added to blood, agglutination will occur between the agglutinin and the corresponding agglutinogens

  • Positive reactions indicate agglutination


Abo blood typing

ABO Blood Typing


17

Serum

Blood being tested

Anti-A

Anti-B

Type AB (contains

agglutinogens A and B;

agglutinates with both

sera)

RBCs

Type A (contains

agglutinogen A;

agglutinates with anti-A)

Type B (contains

agglutinogen B;

agglutinates with anti-B)

Type O(contains no

agglutinogens; does not

agglutinate with either

serum)

Figure 17.16


Restoring blood volume

Restoring Blood Volume

  • Death from shock may result from low blood volume

  • Volume must be replaced immediately with

    • Normal saline or multiple-electrolyte solution that mimics plasma electrolyte composition

    • Plasma expanders (e.g., purified human serum albumin, hetastarch, and dextran)

      • Mimic osmotic properties of albumin

      • More expensive and may cause significant complications


Diagnostic blood tests

Diagnostic Blood Tests

  • Hematocrit

  • Blood glucose tests

  • Microscopic examination reveals variations in size and shape of RBCs, indications of anemias


Diagnostic blood tests1

Diagnostic Blood Tests

  • Differential WBC count

  • Prothrombin time and platelet counts assess hemostasis

  • SMAC, a blood chemistry profile

  • Complete blood count (CBC)


Developmental aspects

Developmental Aspects

  • Fetal blood cells form in the fetal yolk sac, liver, and spleen

  • Red bone marrow is the primary hematopoietic area by the seventh month

  • Blood cells develop from mesenchymal cells called blood islands

  • The fetus forms HbF, which has a higher affinity for O2 than hemoglobin A formed after birth


Developmental aspects1

Developmental Aspects

  • Blood diseases of aging

    • Chronic leukemias, anemias, clotting disorders

    • Usually precipitated by disorders of the heart, blood vessels, and immune system


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