Chapter 17

Blood

Overview of Blood Circulation

Blood leaves the heart via arteries that branch repeatedly until they become capillaries

Oxygen (O2) and nutrients diffuse across capillary walls and enter tissues

Carbon dioxide (CO2) and wastes move from tissues into the blood

Blood Circulation Review

Overview of Blood Circulation

Oxygen-deficient blood leaves the capillaries and flows in veins to the heart

This blood flows to the lungs where it releases CO2 and picks up O2

The oxygen-rich blood returns to the heart

Composition of Blood

Blood is the body’s only fluid tissue It is considered a connective tissue

Contains cells: formed elements Extracellular matrix: plasma + dissolved

fibrous proteins Formed elements include:

Erythrocytes, or red blood cells (RBCs) Leukocytes, or white blood cells (WBCs) Platelets

Components of Whole Blood

Figure 17.1

• 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 (oxygen-rish) to dark red (oxygen-poor)

The pH of blood is 7.35–7.45 Temperature is 38C Blood accounts for approximately 8%

of body weight Average volume: 5–6 L for males, and

4–5 L for females

Functions of Blood

Blood performs a number of functions dealing with: Substance distribution Regulation of blood levels of particular

substances Body protection

Distribution

Blood transports: 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

Regulation

Blood maintains: Appropriate body temperature by

absorbing and distributing heat Normal pH in body tissues using buffer

systems Adequate fluid volume in the circulatory

system

Protection Blood prevents blood loss by:

Activating plasma proteins and platelets Initiating clot formation when a vessel is

broken Blood prevents 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 (8% by weight) Metabolic wastes - Lactic acid, urea,

creatinine Organic nutrients – glucose, carbohydrates,

amino acids Electrolytes – sodium, potassium, calcium,

chloride, bicarbonate Respiratory gases – oxygen and carbon

dioxide Hormones

Formed Elements Erythrocytes, leukocytes, and

platelets make up the formed elements Only WBCs are complete cells RBCs have no nuclei or organelles, and

platelets are just cell fragments

Most blood cells do not divide but are renewed by cells in bone marrow

Components of Whole Blood

Figure 17.2

Erythrocytes (RBCs) Biconcave discs, anucleate,

essentially no organelles Filled with hemoglobin (Hb), a

protein that functions in gas transport

Contain the plasma membrane protein SPECTRIN and other proteins that: Give erythrocytes their flexibility Allow them to change shape as necessary

Erythrocytes (RBCs)

Figure 17.3

Erythrocytes (RBCs)

Structural characteristics contribute to its gas transport function Biconcave shape has a huge surface area

relative to volume Erythrocytes are more than 97%

hemoglobin ATP is generated ANAEROBICALLY, so the

erythrocytes do not consume the oxygen

they transport

Erythrocyte Function

RBCs are dedicated to respiratory gas transport

Hemoglobin (Hb) reversibly binds with oxygen and most oxygen in the blood is bound to Hb

Hb is composed of the protein globin, made up of two alpha and two beta chains, each bound to a heme group

Each heme group bears an atom of iron, which can bind to one oxygen molecule

Each Hb molecule can transport four molecules of oxygen

Structure of Hemoglobin

Figure 17.4

Hemoglobin (Hb) Oxyhemoglobin – Hb bound to oxygen

Oxygen loading takes place in the lungs Deoxyhemoglobin – Hb after oxygen

diffuses into tissues (reduced Hb) Carbaminohemoglobin – Hb bound to

carbon dioxide (globin part) ~20% of carbon dioxide Carbon dioxide loading takes place in the

tissues

Production of Erythrocytes

Hematopoiesis – blood cell formation

Hematopoiesis occurs in the red bone marrow of the: Axial skeleton and girdles Proximal epiphyses of the humerus and

femur Hematopoietic stem cells

(hemocytoblasts) give rise to all formed elements

Production of Erythrocytes: Erythropoiesis

Figure 17.5

Regulation & Requirements for Erythropoiesis

Maintain homeostasis – produces 2 million cells per second

Hormonal Controls Erythropoietin = hormone produced by

kidneys Production stimulated by;

Reduced # of RBCs Insufficient hemoglobin per RBC Reduced availability of oxygen

Dietary Requirements Amino acids, lipids, & carbohydrates. IRON

Regulation & Requirements for Erythropoiesis

Dietary Requirements Amino acids, lipids, & carbohydrates. IRON

65% is in hemoglobin Free iron ions are toxic

Inside cells: ferritin, hemosiderin Blood transportation: transferrin

Homeostasis: Normal blood oxygen levels

IncreasesO2-carryingability of blood

Erythropoietinstimulates redbone marrow

Reduces O2 levelsin blood

Kidney (and liver to a smallerextent) releases erythropoietin

Enhancederythropoiesisincreases RBC count

Stimulus: Hypoxia due todecreased RBC count,decreased amount of hemoglobin, or decreased availability of O2

Start

Imbalance

Imbalance

Erythropoietin Mechanism

Figure 17.6

Fate and Destruction of Erythrocytes

The life span of an erythrocyte is 100–120 days

Old RBCs become rigid and fragile, and their Hb begins to degenerate

Dying RBCs are engulfed by macrophages

Heme and globin are separated and the iron is salvaged for reuse

Fate and Destruction of Erythrocytes

Globin is metabolized into amino acids and is released into the circulation

Hb released into the blood is phagocytized

Fate and Destruction of Erythrocytes

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 (makes feces brown)

Hemoglobin

Aminoacids

Globin

Raw materials aremade available inblood for erythrocytesynthesis.

Iron is bound to transferrin and released to blood from liver as needed for erythropoiesis

Food nutrients,including aminoacids, Fe, B12,and folic acidare absorbedfrom intestineand enter blood

Heme

Circulation

Iron storedas ferritin,hemosiderin

Bilirubin

Bilirubin is picked up fromblood by liver, secreted intointestine in bile, metabolizedto stercobilin by bacteriaand excreted in feces

Erythropoietin levelsrise in blood.

Erythropoietin and necessaryraw materials in blood promoteerythropoiesis in red bone marrow.

New erythrocytesenter bloodstream;function about120 days.

Low O2 levels in blood stimulatekidneys to produce erythropoietin.

Aged and damaged redblood cells are engulfed bymacrophages of liver, spleen,and bone marrow; the hemoglobinis broken down.

1

2

3

4

5

6

Figure 17.7

Erythrocyte Disorders

Anemias = blood has abnormally low oxygen-carrying capacity Insufficient number of RBCs

E.g. hemorrhagic anemias Low hemoglobin content

E.g. Iron-deficiency anemia Abnormal hemoglobin

E.g. Sickle-cell anemia

Leukocytes (WBCs) Leukocytes, the only blood

components that are complete cells: Are less numerous than RBCs Make up 1% of the total blood volume Can leave capillaries via diapedesis Move through tissue spaces

Leukocytosis – WBC count over 11,000 / mm3

Normal response to bacterial or viral invasion

Percentages of Leukocytes

Figure 17.9

WBCs - Granulocytes

Granulocytes1. neutrophils, 2. eosinophils, and 3. basophils

Are larger and usually shorter-lived than RBCs

Have lobed nuclei Are all phagocytic cells

Neutrophils

Neutrophils are our body’s bacteria slayers Granules contain antimicrobial proteins

(defensins) YouTube - neutrophils in action

Eosinophils account for 1–4% of WBCs Lead the body’s

counterattack against parasitic worms

Lessen the severity of allergies

Eosinophils

Account for 0.5% of WBCs and: Have U- or S-shaped nuclei

with two or three conspicuous constrictions

Contain histamine Histamine – inflammatory

chemical that acts as a vasodilator and attracts other WBCs (antihistamines counter this effect)

Basophils

Explanation of Allergies

WBCs - Agranulocytes

Two Types; Lymphocytes Monocytes

Lack visible granules Nuclei typically spherical or kidney

shaped

Account for 25% or more of WBCs and: Have large, circular nuclei Are found mostly in lymphoid

tissue Two types: T cells and B cells

T cells function in the immune response against virus infected cells and tumor cells

B cells give rise to plasma cells, which produce antibodies (like gamma globulin)

Lymphocytes

Monocytes account for 4–8% of leukocytes Largest leukocytes Purple-staining, kidney-shaped nuclei They leave the circulation, enter tissue,

and differentiate into macrophages Body’s defense against viruses, some

intracellular bacterial parasites, and chronic infections e.g. tuberculosis

Activate lymphocytes to mount an immune response

Monocytes

Leukocytes

Figure 17.10

Production & Lifespan WBCs

Leukopoiesis – production of white blood cells Stimulated by chemical messengers

Interleukins Numbered (e.g. IL-3)

Colony-stimulating factors (CSFs) Named for leukocyte them stimulate (e.g.

granulocyte-CSF = G-CSF)

Released by supporting cells of bone marrow and mature WBCs

Formation of Leukocytes

All leukocytes originate from hemocytoblasts

Hemocytoblasts differentiate into; lymphoid stem cells myeloid stem cells

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

Hemocytoblast

Myeloid stem cell Lymphoid stem cell

Myeloblast MyeloblastMyeloblast Lymphoblast

Stem cells

Committedcells

Promyelocyte PromyelocytePromyelocyte Promonocyte Prolymphocyte

Eosinophilicmyelocyte

Neutrophilicmyelocyte

Basophilicmyelocyte

Eosinophilicband cells

Neutrophilicband cells

Basophilicband cells

Develop-mentalpathway

Eosinophils NeutrophilsBasophils

Granular leukocytes

Plasma cells

Some become

Monocytes Lymphocytes

Macrophages (tissues)

Agranular leukocytes

Some become

Figure 17.11

Leukocytes Disorders: Leukemias

Leukemia refers to cancerous conditions involving WBCs

Leukemias are named according to the abnormal WBCs involved

Pictured: Acute lymphocytic leukemia

Leukemia Immature WBCs are found in the

bloodstream in all leukemias Bone marrow becomes totally occupied

with cancerous leukocytes The WBCs produced, though numerous, are

not functional Death is caused by internal hemorrhage

and overwhelming infections Treatments include irradiation, antileukemic

drugs, and bone marrow transplants

Bone Marrow Removal for Transplant

Platelets are fragments of megakaryocytes (found in bone marrow)

Platelets function in the clotting mechanism by forming a temporary plug that helps seal breaks in blood vessels

The stem cell for platelets is the hemocytoblast

Platelets

Stem cell Developmental pathway

Hemocytoblast Megakaryoblast Promegakaryocyte Megakaryocyte Platelets

Figure 17.12

Genesis of Platelets

The sequential developmental pathway is as shown.

Same stem cell for RBCs

Figure 17.5

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

Hemocytoblast

Myeloid stem cell Lymphoid stem cell

Myeloblast MyeloblastMyeloblast Lymphoblast

Stem cells

Committedcells

Promyelocyte PromyelocytePromyelocyte Promonocyte Prolymphocyte

Eosinophilicmyelocyte

Neutrophilicmyelocyte

Basophilicmyelocyte

Eosinophilicband cells

Neutrophilicband cells

Basophilicband cells

Develop-mentalpathway

Eosinophils NeutrophilsBasophils

Granular leukocytes

Plasma cells

Some become

Monocytes Lymphocytes

Macrophages (tissues)

Agranular leukocytes

Some become

Figure 17.11

Same stem cell for WBCs

Hemostasis

A series of reactions for stoppage of bleeding

During hemostasis, three phases occur in rapid sequence Vascular spasms – immediate

vasoconstriction in response to injury Platelet plug formation Coagulation (blood clotting)

Vascular Spasm

Immediate response to injury is vasoconstriction

Factors that trigger the spasm are damaged cells, platelets and pain reflexes

As damage increases, vascular spasm increases

Platelet Plug Formation Platelets do not stick to each other or to

blood vessels when there is no damage Upon damage to blood vessel endothelium

platelets: Adhere to collagen Stick to exposed collagen fibers and form a

platelet plug Release serotonin and ADP, which attract still

more platelets The platelet plug is limited to the

immediate area of injury

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

Coagulation follows intrinsic and extrinsic pathways to thromboplastin

The final three steps of this series of reactions are: Prothrombin activator is formed Prothrombin is converted into

thrombin Thrombin starts the joining of fibrinogen

(plasma protein) into a fibrin mesh

Coagulation

Fibrin mesh forming in wound

Clot Retraction and Repair Clot retraction – stabilization of the

clot by squeezing serum from the fibrin strands

Repair Fibroblasts form a connective tissue

patch Endothelial cells multiply and restore the

endothelial lining of blood vessel

Cross section of healing wound-don’t pick at it!!!

Factors Limiting Clot Growth or Formation

Two homeostatic mechanisms prevent clots from becoming large Swift removal of clotting factors Stop formation of further clotting factors

Hemostasis Disorders:Thromboembolytic Conditions

Thrombus – a clot that develops and persists in an unbroken blood vessel Thrombi can block circulation, resulting in tissue

death Coronary thrombosis – thrombus in blood vessel

of the heart

Thrombus/Embolus

Hemostasis Disorders:Thromboembolytic Conditions

Embolus – a thrombus freely floating in the blood stream Pulmonary emboli can impair the ability

of the body to obtain oxygen Cerebral emboli can cause strokes

Substances used to prevent undesirable clots: Aspirin Heparin – an anticoagulant used clinically

for pre- and postoperative cardiac care Warfarin – used for those prone to atrial

fibrillation

Prevention of Undesirable Clots

Hemophilias – hereditary bleeding disorders caused by lack of clotting factors Hemophilia A – most common type (83%

of all cases) due to a deficiency of factor VIII

Hemophilia B – due to a deficiency of factor IX

Hemophilia C – mild type, due to a deficiency of factor XI

Hemostasis Disorders: Bleeding Disorders

Hemophilia bleeding into joint

Transfusion & Blood Replacement

Cardiovascular system minimizes blood loss by1. Vasoconstriction2. Increased RBC production

Whole blood transfusions vs. Packed red cells Blood bank collects blood and adds

anticoagulant, usually separates into components Shelf life at 4ºC about 35 days

RBC membranes have glycoprotein antigens on their external surfaces

These antigens are: Unique to the individual Recognized as foreign if transfused

into another individual RBC antigens promote

agglutination, thus referred to as agglutinogens

Presence or absence of these antigens is used to classify blood groups

Human Blood Groups

Plasma Membrane

Humans have 30 varieties of naturally occurring RBC antigens

The antigens of the ABO and Rh blood groups cause vigorous transfusion reactions when they are improperly transfused

Other blood groups (M, N, Dufy, Kell, and Lewis) are mainly used for legalities

Blood Groups

The ABO blood groups consists of: Two antigens (A and B) on the surface of

the RBCs = agglutinogens Two antibodies in the plasma (anti-A and

anti-B) = agglutinins

ABO Blood Groups

ABO Blood Groups

Table 17.4

There are 45 different types of Rh agglutinogens (only 3 common – C, D, E) Rh+ = presence of the D antigen Rh- (D)= RBCs do not carry D antigen

Anti-Rh antibodies are not spontaneously formed in Rh– individuals However, if an Rh– individual receives Rh+

blood, anti-Rh antibodies form A second exposure to Rh+ blood will result

in a typical transfusion reaction

Rh Blood Groups

The blood type of the mother and the blood type of her baby can have a significant effect on the health of the fetus or newborn baby. Usually in discussions on this topic we are concerned when a mother has Rh- blood and her husband has Rh+ blood. This combination can lead to a baby with Rh+ blood. If the mother is already sensitized to Rh+ blood cells, the Rh+ baby she is carrying will be affected to some degree by Rh hemolytic disease. If the mother becomes sensitized after delivery, every future Rh+ baby is at risk.

There is a difference between these blood antigens and the A and B antigens. We are not born with antibodies against these blood antigens. For example, an Rh- person is not born with anti-D (anti-Rh) antibodies. However, if we are exposed to blood with one of these unfamiliar antigens, we can develop antibodies against blood with those antigens. We can get exposed to these blood antigens by getting a transfusion with a foreign type of blood or carrying a child with a different blood type from our own. When a woman is pregnant, a few of the baby’s blood cells will often leak through the placenta and show up in her blood system.

We do not develop the antibodies immediately. We use the blood cells that are circulating in our system, as if they were our own. When these cells get old they are processed through our spleen to reuse all the spare parts. At this point, antibody production may be started. Pregnant women do not always develop antibodies against new foreign blood cells during pregnancy. A pregnant woman’s immune system is somewhat suppressed when it finds new antigens. If it was not, her body would be more likely to reject the pregnancy. This immune suppression does not always afford protection from Rh sensitization, however.

Hemolytic Disease of the Newborn

Hemolytic disease of the newborn – Rh+ antibodies of a sensitized Rh– mother cross the placenta and attack and destroy the RBCs of an Rh+ baby

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

Hemolytic Disease of the Newborn

The drug RhoGAM can prevent the Rh– mother from becoming sensitized

Treatment of hemolytic disease of the newborn involves pre-birth transfusions and exchange transfusions after birth

Transfusion reactions occur when mismatched blood is infused

Donor’s cells are attacked by the recipient’s plasma agglutinins causing: Diminished oxygen-carrying capacity Clumped cells that impede blood flow Ruptured RBCs that release free

hemoglobin into the bloodstream that causes kidney failure

Transfusion Reactions

Blood type being tested

RBC agglutinogens Serum Reaction

Anti-A Anti-B

AB A and B + +

B B – +

A A + –

O None – –

Blood Typing

Diagnostic Blood Tests Color (high fat – lipidemia) Hematocrit (anemia) Blood glucose (diabetes) Differential White Blood Cell Count

E.g. high eosinophil -> parasitic infection Prothrombin time & Platelet count

(hemostasis system) SMAC (chemistry profile) & Complete blood

count (CBC) are routine before hospital admissions

Developmental Aspects

Early fetal development – blood formation sites Yolk sac, liver, spleen 7th month -> red marrow becomes

primary area Hemoglobin F has a higher affinity for

oxygen than adult hemoglobin After birth, rapidly destroyed by liver

Developmental Aspects

Most common blood diseases; Chronic leukemias, Anemias, Clotting disorders

Usually disorders of the heart, blood vessels, or immune system precede blood diseases