Physiology of Blood

Lect 1
 Composition of Blood
 Blood is the body’s only fluid tissue
 It is composed of liquid plasma and formed elements
 Formed elements include:
 Erythrocytes, or red blood cells (RBCs)
 Leukocytes, or white blood cells (WBCs)
 Platelets
 Hematocrit – the percentage of RBCs out of the total blood
volume
Physical Characteristics and Volume
 Blood is a sticky, opaque fluid with a metallic taste
 Color varies from scarlet to dark red
 The pH of blood is 7.35–7.45
 Temperature is 36.6-37.2 Co
 Blood accounts for approximately 8% of body weight
 Average volume:
 4–5 L for females
 5–6 L for males
 Functions of Blood
1. Substance distribution
 Oxygen from the lungs and nutrients from the digestive tract
 Metabolic wastes from cells to the lungs and kidneys for elimination
 Hormones from endocrine glands to target organs
2. Regulation of conditions by maintaining
 Appropriate body temperature by absorbing and distributing heat
 Normal pH in body tissues using buffer systems
 Adequate fluid volume in the circulatory system
3. Body protection
 From blood loss by:
 Activating plasma proteins and platelets
 Initiating clot formation when a vessel is broken
 From infection by:
 Synthesizing and utilizing antibodies
 Activating complement proteins
 Activating WBCs to defend the body against foreign invaders
Blood Plasma
 Blood plasma contains over 100 solutes, including:
 Proteins – albumin, globulins, clotting proteins, and others
 Non-protein by-products of metabolism, e.g. lactic acid,
urea, creatinine
 Organic nutrients – glucose, amino acids, lipids
 Electrolytes – sodium, potassium, calcium, chloride,
bicarbonate
 Respiratory gases – oxygen and carbon dioxide
Plasma
 Liquid part of blood
 Contains:
 Water
 Proteins
 Hormones
 Nutrients
 Electrolytes
 Respiratory Gases
 Wastes
 Plasma Proteins
 Include:
 Albumin (60%)
 Globulins (36%)
(Antibodies &
transport proteins)
 Clotting Proteins (4%)
Plasma
 Enzymes & Hormones
 Serum
Liquid part of blood without clotting proteins

 Albumin (60%)
 Globulins (36%)
(Antibodies &
transport proteins)

X
 Clotting Proteins (4%)
Plasma
Serum
 Enzymes & Hormones

Clot
Formed Elements
 3 Types
1) Erythrocytes (RBC),
2) Leukocytes (WBC), and
3) Platelets make up the formed elements

 Only WBCs are complete cells

 RBCs have no nuclei or organelles, and platelets are just cell
fragments
 Most formed elements survive in the bloodstream for only a few
days
 Most blood cells do not divide but are renewed by cells in bone
marrow
Components of Whole Blood

Figure 17.2
 1) Erythrocytes (RBCs)
 Biconcave discs, anucleated, essentially no
organelles
 Filled with about 97% hemoglobin (Hb), a
protein that functions in gas transport
 ATP is generated anaerobically, so the
erythrocytes do not consume the oxygen they
transport
 Contain the plasma membrane protein spectrin
and other proteins that:
 Give erythrocytes their flexibility

 Allow them to change shape as necessary

1) Erythrocytes (Continued): Function
 RBCs are dedicated to respiratory gas transport
 Hb reversibly binds with oxygen
 Most oxygen in the blood is bound to Hb

 Hb is composed of the protein globin, made up of

 2 alpha & 2 beta chains, each bound to a heme group

 Each heme group bears an atom of iron (Fe), which can bind to
one oxygen molecule
 Each Hb molecule can transport four molecules of oxygen
1) Erythrocytes (continued): Production
 Hematopoiesis – blood cell formation
 Hematopoiesis occurs in the red bone marrow of the:
 Axial skeleton and girdles

 Epiphyses of the humerus and femur

 Hemocytoblasts give rise to all formed elements

 Specifically, production of erythrocytes: erythropoiesis
1) Erythrocytes (continued): Erythropoiesis
 A hemocytoblast (the stem cell that gives rise to all of the formed
elements) is transformed into
 A proerythroblast, which develops into
 An early erythroblast, which is characterized by the ribosome synthesis
phase
 A late erythroblast is characterized by Hb accumulation
 A normoblast continues the Hb accumulation phase. Ejection of the
nucleus leads to
 A reticulocyte which matures into
 An erythrocyte
1) Erythrocytes (continued):
Regulation and Requirements for Erythropoiesis
 Circulating erythrocytes – the number remains constant and reflects a
balance between RBC production and destruction
 Too few RBCs leads to tissue hypoxia
 Too many RBCs causes undesirable blood viscosity
 Erythropoiesis is hormonally controlled and depends on adequate supplies
of iron, amino acids, and B vitamins
 Intracellular iron is stored in protein-iron complexes such as ferritin and hemosiderin
 Circulating iron is loosely bound to the transport protein transferrin
 Erythropoietin (EPO) release by the kidneys is triggered by:
 Hypoxia due to decreased RBCs
 Decreased oxygen availability
 Increased tissue demand for oxygen
1) Erythrocytes (continued): Erythropoietin
Mechanism
Im b Start
ala
nce
Stimulus: Hypoxia due to
decreased RBC count,
Increases Homeostasis: Normal blood oxygen levels decreased amount of
O2-carrying hemoglobin, or decreased
I mb
ability of blood ala availability of O2
nce

Reduces O2 levels
in blood

Enhanced Kidney (and liver to a smaller

erythropoiesis Erythropoietin extent) releases erythropoietin
increases stimulates red
RBC count bone marrow

Figure 17.6
 1) Erythrocytes (continued):
Life and death of Erythrocytes
 The life span of an erythrocyte is approximately120 days
 Old RBCs get rigid & fragile, and Hb begins to degenerate
 Dying RBCs are engulfed by macrophages
 Heme and globin are separated and the iron is salvaged
 Heme is degraded to a yellow pigment called bilirubin
 The liver secretes bilirubin into the intestines as bile

 The intestines metabolize it into urobilinogen

 This degraded pigment leaves the body in feces, in a pigment called stercobilin
 Globin (polypeptide chains) is metabolized into amino acids and is released
into the circulation
 Hb released into the blood is captured by haptoglobin and phagocytized
 1 Low O2 levels 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

Bilirubin
Heme

Iron stored
as ferritin,
Globin

Amino
acids
Life and Death of
Erythrocytes
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
6 Raw materials are
are absorbed made available in
from intestine blood for erythrocyte
and enter blood synthesis.

Figure 17.7
 1) Erythrocytes (continued): Disorders
 Anemia – blood has abnormally low oxygen-carrying capacity
 It is a symptom rather than a disease itself

 Blood oxygen levels cannot support normal metabolism

 Signs/symptoms include:

 fatigue, paleness, shortness of breath, and chills

 Types
 Hemorrhagic anemia – result of loss of blood

 Hemolytic anemia – prematurely ruptured RBCs

 Aplastic anemia – destruction/inhibition of red bone marrow

 Iron-deficiency anemia results from lack of iron

 Pernicious anemia results from either deficiency of vitamin B or lack of intrinsic factor needed for
12
absorption of B12 Treatment is intramuscular injection of B12
 Thalassemias – absent or faulty globin chain in Hb
 Sickle-cell anemia – results from a defective gene & causes RBCs to become sickle-shaped in low
oxygen situations
 Erythrocytes (continued): Disorders -
Polycythemia
 Polycythemia – excess RBCs increase blood viscosity
 Three main polycythemias are:
1. Polycythemia vera, bone marrow cancer
2. Secondary polycythemia, low levels of oxygen or EPO
increases
3. Blood doping, results in enhanced endurance and speed.
 2) Leukocytes (WBCs)
 Leukocytes, only blood components that are complete cells:
 Make up only 1% of the total blood volume

 Can leave capillaries via diapedesis and

 move through tissue spaces

 Leukocytosis – WBC count over 11,000 / mm3

 Normal response to bacterial or viral invasion

 Two main types named for whether “granules” are visible under
microscope
 Granulocytes
 Agranulocytes
Percentages of Leukocytes

Figure 17.9
2) Leukocytes (continued): Granulocytes
 Granulocytes – neutrophils, eosinophils, and basophils
 Are larger and usually shorter-lived than RBCs

 Have lobed nuclei

 ALL are phagocytic cells

 Three types
A. Neutrophils

B. Eosinophils

C. Basophils

Neutrophils Eosinophils Basophil

2. Leukocytes (continued):
Granulocytes: A. Neutrophils
 Neutrophils are our body’s bacteria slayers
 Neutrophils have two types of granules
 account for 50% - 70% of WBC

 Contain peroxidases, hydrolytic enzymes, and defensins

(antibiotic-like proteins)

Neutrophil
 2. Leukocytes (continued):
Granulocytes: B. Eosinophils
• Eosinophils attack parasitic worms
 account for 1–4% of WBCs
 Have red-staining, bilobed nuclei connected via a broad band
of nuclear material
 Have red to crimson (acidophilic) large, coarse, lysosome-like
granules
 Reduce the severity of allergies by phagocytizing immune
complexes (antigen-antibody complexes)

Eosinophil
 2. Leukocytes (continued):
Granulocytes: C. Basophils
• Basophils are functionally similar to mast cells (detect foreign
substances)
 account for 0.5% of WBCs
 Have U- or S-shaped nuclei with two or three conspicuous
constrictions
 Have large, purplish-black (basophilic) granules that contain
histamine, which is an inflammatory chemical that acts as a
vasodilator

Basophil
2. Leukocytes (continued):
Agranulocytes
 Agranulocytes
 Lack visible cytoplasmic granules

 Are similar structurally, but are functionally distinct and

unrelated cell types

 Two types:
 A. Lymphocytes

 B. Monocytes:

Lymphocyte Monocyte
 2. Leukocytes (continued):
Agranulocytes: A. Lymphocytes
 Lymphocytes account for 25% or more of WBCs
 Have large, dark-purple, circular nuclei with a thin rim of blue
cytoplasm
 Are found mostly enmeshed in lymphoid tissue (some circulate in the
blood)
 There are two types of lymphocytes:
 T cells (mature in thymus) function in the immune response
 B cells (mature in bone) give rise to plasma cells, which produce
antibodies

Lymphocyte
2. Leukocytes (continued):
Agranulocytes: B. Monocytes
 Monocytes leave the circulation, enter tissue, and differentiate
into macrophages
 account for 4–8% of leukocytes

 the largest leukocytes

 Macrophages
 Are highly mobile and actively phagocytic

 Activate lymphocytes to mount an immune response

Monocyte
Summary of Formed Elements

Table 17.2.1
Summary of Formed Elements

Table 17.2.2
 2. Leukocytes (continued):
Production of Leukocytes
Leukopoiesis is stimulated by
Stem cells Hemocytoblast


interleukins and colony- Myeloid stem cell Lymphoid stem cell

stimulating factors (CSFs)

Committed

Macrophages and T cells are the

Myeloblast Myeloblast Myeloblast Lymphoblast
 cells

most important sources of cytokines Develop-Promyelocyte

Promyelocyte
Promyelocyte Promonocyte Prolymphocyte
mental
 Many hematopoietic hormones pathway

(EPO and several of the CSFs) are Eosinophilic Basophilic Neutrophilic

myelocyte myelocyte myelocyte

used clinically to stimulate bone

marrow Eosinophilic Basophilic Neutrophilic
band cells band cells band cells

Eosinophils Basophils Neutrophils Monocytes Lymphocytes

(a) (b) (c) (d) (e)

Some
Agranular leukocytes
Granular leukocytes become
Some become
Macrophages (tissues) Plasma cells
 2. Leukocytes (continued):
Leukopoiesis Stem cells Hemocytoblast

Hemocytoblasts give rise to all formed elements Myeloid stem cell Lymphoid stem cell

Hemocytoblasts differentiate into either

1) Myeloid stem cells or 2) Lymphoid stem cells
Committed
MyeloblastMyeloblast Myeloblast Lymphoblast
cells

1) Myeloid stem cells become either

Develop-
Promyelocyte
Promyelocyte
Promyelocyte Promonocyte Prolymphocyte

A) myeloblasts or B) monoblasts mental

pathway

1A) Myeloblasts develop into granulocytes (neutrophils, Eosinophilic

Basophilic
myelocyte myelocyte
Neutrophilic
myelocyte

eosinophils, and basophils)

1B) Monoblasts develop into one type of agranulocyte Eosinophilic Neutrophilic
Basophilic
band cells band cells
band cells

(monocyte)
2) Lymphoid stem cells become lymphoblasts EosinophilsBasophils
(a) (b)
Neutrophils
(c) (d)
Monocytes Lymphocytes
(e)

2) Lymphoblasts develop into the other agranulocyte Granular leukocytes Some become
Some
Agranular leukocytes
become

(lymphocyte) Macrophages (tissues) Plasma cells

 2. Leukocytes (continued): Disorders:
Leukemias
 Leukemia refers to cancerous conditions involving
WBCs
 Leukemias are named according to the abnormal WBCs
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
3. Platelets
 Platelets are fragments of megakaryocytes with a
blue-staining outer region and a purple granular center
 Their granules contain serotonin, Ca2+, enzymes,
ADP, and platelet-derived growth factor (PDGF)
 Platelets function in the clotting mechanism by
forming a temporary plug that helps seal breaks in
blood vessels
 Platelets not involved in clotting are kept inactive by
Nitric Oxide and Prostacyclin
 3. Platelets (continues):
Genesis of Platelets
• Hemocytoblasts give rise to platelets also
• The sequential developmental pathway is as shown.

Stem cell Developmental pathway

Hemocytoblast Megakaryoblast Promegakaryocyte Megakaryocyte Platelets

Figure 17.12
 Hemostasis
 Hemostasis is the process by which
hemorrhage is stopped and excessive
bleeding is prevented.
 It involves three different
processes:
1. Vascular spasms
 When a blood vessel is damaged
the artery constricts to restrict
blood flow
2. Platelet plug formation
3. Coagulation or blood clotting
2. Platelet Plug Formation
 2. Platelet Plug Formation: Steps
1. Platelet adhesion. Occurs when von Willebrand factor connects
collagen and platelets.

2. Platelet release reaction. The release of ADP, thromboxanes, and

other chemicals that activate other platelets.

3. Platelet aggregation. Activated platelets produce surface receptors

that bind to fibrinogen (protein found in plasma). Fibrinogen forms a
bridge between platelets: platelet plug.

4. Activated platelets. Expression of phospholipids and coagulation.

 Both are important for coagulation
 Blood Clot

 Fibrin fibers trap RBC, platelets, and fluid to form a blood

clot.
 3. Coagulation
 Deep large wounds depend on coagulation or blood clotting in
addition to vascular spasms and platelet plugs to heal.
 Coagulation is regulated by:
1. clotting factors - molecules that stimulate its formation

2. anticoagulants - molecules that inhibit their formation or disrupt

clots
3. Coagulation:
Begins Along One of Two Pathways
 First step, production of Prothrombin can occur via one of two
ways
 Intrinsic pathway starts when clotting factor XII which is in

the plasma, comes in contact with the collagen of the

damaged blood vessel.
 Extrinsic pathway starts with thromboplastin (a.k.a. tissue

factor or TF), which is released outside of the blood by the

damaged tissue.
 In both cases, factor X is activated and combines with factor V
in the presence of Ca2+ to form prothrombinase.
 3. Coagulation:
Continues Along a Common Pathway

Prothrombinase, along with vitamin K and Ca2+ catalyze

the production of thrombin enzyme.

Thrombin catalyzes the production of fibrin

 Fibrin strand produces the clot
 Coagulation has occurred.
 Clot formation takes 3-6 minutes after blood vessel damage.
 Anticoagulants

 Antithrombin produced by liver slowly inactivates thrombin.

 Heparin which is produced by basophils and endothelial cells
increases effectiveness of antithrombin.
 Prostacyclin causes vasodilation and inhibits release of
coagulating factors from platelets.
Fibrinolysis
Clot Retraction & Dissolution
 Once a damaged blood
vessel has been repaired, it is
necessary to remove the clot.
 The clot is removed by
dissolving the fibrin that
holds the clot in place.
 The endothelial cells release
plasminogen activator as  Plasmin, an enzyme, dissolves the
the damaged tissue is being clot by removing fibrin.
repaired then it is changed
into plasmin.
Factors Limiting Clot Growth or Formation

 Two homeostatic mechanisms prevent clots from

becoming large
 Swift removal of clotting factors
 Inhibition of activated clotting factors
Danger of Unwanted Clots

 Thromboembolytic disorders are those where clots form

readily even in places where they should not.
 When a clot forms in an undamaged blood vessel and
stays in place this is called a thrombus.
 When a clot is dislodged from the blood vessel and is free
moving it is called an embolus.
 These conditions tend to occur in:
 Burns, trauma, arteriosclerosis, poor circulation
 The common problem here is lack of circulation to a
specific region.
 Stroke and heart attack
Prevention of Undesirable Clots

 Substances used to prevent undesirable clots:

 Aspirin – an antiprostaglandin that inhibits thromboxane A2

 Heparin – an anticoagulant used clinically for pre-and

postoperative cardiac care

 Warfarin – used for those prone to atrial fibrillation