anatomy and Physiology 2 - blood

Cardiovascular System Includes:

• Blood (fluid connective tissue which includes ~75 trillion cells)

• Blood vessels (series of conducting hoses)

• Heart (pump)

Functions of Blood

Transportation of dissolved gases (O2, CO2) nutrients, hormones, and metabolic wastes

• Regulation of the pH and ion composition of interstitial fluids

• Restriction of fluid loss at injury sites

• Defense against toxins and pathogens

• Regulation of body temperature

Blood is a

fluid connective tissue

• About 5 liters in body (7% of body weight)

5-6 L in males, 4-5 L in females

blood Consists of:

Plasma (liquid matrix)

Formed elements (cells and cell fragments)

properties of blood are

Normal Temperature is roughly 38°C (100.4°F)

Is 5X more viscous than water

Is slightly alkaline (average pH 7.4)

Giving Blood Saves Lives

Every 2 seconds, someone in the U.S. needs blood.

• A pint of blood can save up to 3 lives.

• More than 40,000 donations are needed each day.

• Only 5% of the population is donating blood.

Plasma

55% of blood volume

Formed Elements

45% of blood volume

Whole blood may be fractionated or separated into:

plasma and formed elements

Blood Components: Plasma

Composition resembles interstitial fluid

• Exchange of water, ions, and small solutes across capillaries

• 92% water, 7% plasma proteins, 1% other solutes

• Primary differences

• Levels of respiratory gases (oxygen and carbon dioxide)

• Concentrations of dissolved proteins (plasma proteins cannot cross capillary walls)

Blood Components: Plasma Proteins

In solution rather than as fibers like other connective tissues

• Large size and globular shapes prevent leaving bloodstream

• Liver synthesizes >90% of all plasma proteins

Blood Components: Plasma Proteins

albumins, globulins, and fibrinogen

Albumins

(60%)

Maintain osmotic pressure by pulling H2O into blood Transport substances

such as fatty acids, thyroid hormones, and steroid hormones

Globulins

(35%)

• Antibodies, also called immunoglobulins

• Transport globulins (small molecules): hormone-binding proteins

Fibrinogen

4%)

• Molecules that form clots and produce long, insoluble strands of fibrin

Blood Components: Plasma Solutes

electroyles, organic nutrients, and organic waste

Electrolytes

Essential for vital cellular activities

Major ions are Na+, K+, Ca2+, Mg2+, Cl-, HCO3

-, HPO4

-, SO4

2-

Organic Nutrients

Used for cell ATP production, growth, and maintenance

Includes lipids, carbohydrates, and amino acids

• Organic Wastes

Carried to sites of breakdown or excretion

Examples: urea, uric acid, creatinine, bilirubin, NH4

+

Blood Components: Formed Elements

red blood cells, white blood cells, and platelets

Red Blood Cells (RBCs)

or erythrocytes

Essential for oxygen transport in blood

White Blood Cells (WBCs)

or leukocytes

Participate in body's defense mechanisms

Platelets

Small membrane-bound cell fragments involved in clotting

RBCs in Blood

Most numerous cell type in blood

Roughly 1/3 of all cells in the body

Abundance of RBCs

Red blood cell count (standard blood test) results

Adult males: 4.5-6.3 million RBCs/1 μL

Adult females: 4.2-5.5 million RBCs/1 μL

One drop = 260 million RBCs

RBC Characteristics

• Biconcave disc

• Average diameter ~8 μm

• High surface area-to-volume ratio

Quickly absorbs and releases oxygen

• Discs form stacks called rouleaux

Smooth the flow through narrow blood vessels

• Discs bend and flex entering small capillaries:

7.8 μm RBC can pass through 4 μm capillary

rbc lose most

organelles, including nucleus during development

Cannot repair themselves and die in ~120 days

• Contain hemoglobin (Hb): primary function is carrying respiratory gases

Normal whole blood Hb content (grams per deciliter)

14-18 dL (males), 12-16 dL (females)

• ~98.5% of blood oxygen attached to Hb in RBCs

Hemoglobin (Hb)

Protein with complex quaternary structure

• Each molecule has 4 globular protein subunits

2 alpha (α) chains

2 beta (β) chains

• Each chain contains a single heme pigment molecule

Each heme (with iron) can reversibly bind one molecule of oxygen

• oxyhemoglobin (HbO2): bright red

• Deoxyhemoglobin (not binding O2 ): dark red

Carbon monoxide poisoning prevents

Carbon monoxide (CO) is a colorless, odorless gas present in auto exhaust fumes and smoke from wood, coal, charcoal, and tobacco.

• CO binds to hemoglobin 200 times more tightly than oxygen, thus blocking oxygen transport to tissues.

• Without enough oxygen, cells cannot fully complete cellular respiration and die due to lack of ATP.

RBC Formation and Turnover

1% of circulating RBCs are replaced per day

About 3 million RBCs per second!!

• Macrophages of liver, spleen, and bone marrow

• Monitor RBCs

• Engulf RBCs before membranes rupture

(RBC hemolysis)

Hemoglobin Conversion and Recycling

Phagocytes break hemoglobin into components

• Globular proteins to amino acids

• Heme to biliverdin

• Iron

Hemoglobinuria:

Hemoglobin breakdown products found in urine due to excess hemolysis in bloodstream. Urine may turn red or brown.

Hematuria:

Whole red blood cells in urine due to kidney or tissue damage

Iron Recycling

Iron removed from heme, leaving biliverdin

• Iron is picked up by transport proteins (transferrin). Some goes to bone marrow to make new Hb and RBCs

• Also goes to storage proteins (ferritin and hemosiderin) in liver

Breakdown of Biliverdin

Biliverdin (green) is converted to bilirubin (yellow)

Bilirubin:

• excreted in bile by liver

• jaundice is caused by bilirubin buildup in bloodstream, causing skin and sclera of eyes to turn yellow

• converted by intestinal bacteria to urobilins and stercobilins, which are found in urine and feces, giving them there characteristic colors.

RBC Production

Erythropoiesis

Occurs only in myeloid tissue (red bone marrow)

Located in vertebrae, ribs, sternum, skull, scapulae, pelvis, and proximal limb bones

• Fatty yellow bone marrow can convert to red bone marrow in cases of severe, sustained blood loss

• Developing RBCs absorb amino acids and iron from bloodstream and synthesize Hb

Red Blood Cell Production and Recycling stages

Proerythroblasts

• Erythroblasts

• Reticulocyte

Erythroblasts

Actively producing Hb

• After four days becomes normoblast

Reticulocyte

(80% Hb of mature RBC)

• Ejects organelles including nucleus

• Enters bloodstream after two days

• After 24 hours in circulation, is mature RBC

Stimulating Hormones: Erythropoietin (EPO)

Released into plasma when peripheral tissues (especially kidneys) have low oxygen (hypoxia)

• During anemia

• When kidney blood flow declines

• When oxygen content of air in lungs declines due to disease or high altitude

• When respiratory surfaces are damaged

• Transported to red bone marrow and stimulates stem cells and developing RBCs

Blood Doping

Illegal practice occurring among competitive athletes involved in endurance sports.

• Whole blood is removed from athlete weeks before the sporting event. Packed RBCs are separated from plasma and stored.

• The competitor's bone marrow replaces the lost blood.

• Immediately before the event, packed RBCs are reinfused, increasing O2 carrying capacity of blood and increasing endurance.

• Risky practice, leading to strokes, kidney damage and heart attacks.

Blood Types

Determined by presence or absence of cell surface markers (antigens)

• Are genetically determined glycoproteins or glycolipids

• Can trigger a protective defense mechanism (immune response)

• Identify blood cells as "self" or "foreign" to immune system

• More than 50 blood cell surface antigens exist

Three particularly important

A, B, Rh (or D)

• Anti-A or Anti-B antibodies circulate in the plasma

Type A

A antigens

Anti-B antibodies

Type B

B antigens

Anti-A antibodies

Type AB

Both A and B antigens

No anti-A or anti-B antibodies

Type O

No A or B surface antigens

Both anti-A and anti-B antibodies

Blood Types

Rh surface antigens

• Separate antigen from A or B

• Presence or absence on RBC determines positive or negative blood type, respectively

• Examples: AB+, O-

Antigen-antibody Interactions

Antibodies "protect our bodies" from "foreign" blood cells.

• Anti-A and anti-B antibodies remain constant through life while anti-Rh antibodies develop for Rh- people after an exposure

• If one blood type is exposed to corresponding antibodies, clumping (agglutination) occurs

• Hemolysis may occur

• Cross-reactions (transfusion reactions) can block blood vessels to vital organs with agglutinated RBCs or cell fragments

Important to make sure donor and recipient blood types are compatible (will not cross-react)

Antibodies "protect our bodies" from "foreign" blood cells.

• Anti-A and anti-B antibodies remain constant through life while anti-Rh antibodies develop for Rh- people after an exposure

• If one blood type is exposed to corresponding antibodies, clumping (agglutination) occurs

• Hemolysis may occur

• Cross-reactions (transfusion reactions) can block blood vessels to vital organs with agglutinated RBCs or cell fragments

Important to make sure donor and recipient blood types are compatible (will not cross-react)

receive from A or O

Type B can donate to B or AB;

receive from B or O

Type AB can donate to AB only;

receive from all others: Universal Recipient

receive from all others: Universal Recipient

Universal Donor; receive from O only

Hemolytic Disease of the Newborn

Genetically determined antigens mean that a child can have a blood type different from either parent

• During pregnancy, the placenta restricts direct transport between maternal and infant blood

Anti-A and anti-B antibodies are too large to cross

Anti-Rh antibodies can cross

• Can lead to mother's antibodies attacking fetal RBCs

First pregnancy

with Rh- mother and Rh+ infant

• During pregnancy, few issues occur because no anti-Rh antibodies exist in maternal circulation

• During birth, hemorrhaging may expose maternal blood to fetal Rh+ cells

• Leads to sensitization or activation of mother's immune system to produce anti-Rh antibodies

Second pregnancy

with Rh- mother and Rh+ infant

• Subsequent pregnancy with Rh+ infant can allow maternal anti-Rh antibodies to cross placental barrier

• Attack fetal RBCs and cause hemolysis and anemia

= Erythroblastosis fetalis

• Full transfusion of fetal blood may be necessary to remove maternal anti-Rh antibodies

Prevention

RhoGAM antibodies can be administered to maternal circulation at 26-28 weeks and before/after birth

• Destroys any fetal RBCs that cross placenta

• Prevents maternal sensitization

white blood cells

eukocytes

White Blood Cells

Also called leukocytes

• Do not have hemoglobin

• Have nuclei and other organelles

• WBC functions

• Defend against pathogens

• Remove toxins and wastes

• Attack abnormal cells

• Small numbers found in blood; most are in extracellular fluid or lymphatic system; 5000 to 10,000 per microliter

• Spend only a short time in circulation

WBC Circulation and Movement

Characteristics of circulating WBCs

• Can migrate out of bloodstream

• Have amoeboid movement

• Attracted to chemical stimuli (positive chemotaxis)

• Some are phagocytic:

neutrophils, eosinophils, and monocytes

White blood cell types

Granular leukocytes (have cytoplasmic granules)

• Neutrophil

• Eosinophil

• Basophil

• Agranular leukocytes (lacking cytoplasmic granules)

• Monocyte

• Lymphocyte

Granular leukocytes

Neutrophil

• Eosinophil

• Basophil

Agranular leukocytes

(lacking cytoplasmic granules)

• Monocyte

• Lymphocyte

Neutrophils

Multilobed nucleus

Phagocytic cells that engulf pathogens and debris

Eosinophils

Granules generally stain bright red; nucleus two-lobed

Phagocytic cells that engulf antibody-labeled materials

• Increase abundance with allergies and parasitic infections

Basophils

Granules generally stain blue; nucleus generally not seen

• Release histamine and other chemicals promoting inflammation

Neutrophils

• Also called polymorphonuclear leukocytes

• 50-70% of circulating WBCs - most numerous

• Pale cytoplasm granules with lysosomal enzymes

• Very active, first to attack bacterial infection

• Engulf and digest pathogens

• Release prostaglandins and leukotrienes

• Form pus, which is dead neutrophils

Eosinophils

• Also called acidophils because they stain with acid dye

• 2-4% of circulating WBCs

• Attack large parasites

• Excrete toxic compounds

• Nitric oxide

• Cytotoxic enzymes

• Are sensitive to allergens

• Control inflammation with enzymes that counteract inflammatory effects of neutrophils and mast cells

Basophils

Are less than 1% of circulating WBCs

• Are small, stain blue with basic dye

• Accumulate in damaged tissue

• Release histamine which dilates blood vessels

• Release heparin which prevents blood clotting

Agranular Leukocytes

Monocytes

Large cells with bean-shaped nucleus

Enter tissues and become macrophages (phagocytes)

• Lymphocytes

Slightly larger than RBC with large round nucleus

Provide defense against specific pathogens or toxins

Monocytes

Large cells with bean-shaped nucleus

Enter tissues and become macrophages (phagocytes)

Large cells with bean-shaped nucleus

Enter tissues and become macrophages (phagocytes)

Slightly larger than RBC with large round nucleus

Provide defense against specific pathogens or toxins

Monocytes - Monster cells (large!)

• 2-8% of circulating WBCs

• Are large and spherical

• Enter peripheral tissues and become macrophages, aggressive phagocytic cells

• Engulf large particles and pathogens

• Secrete substances that attract immune system cells and fibrocytes to injured area

Lymphocytes

20-30% of circulating WBCs

• Are larger than RBCs

• Migrate in and out of blood

• Mostly in connective tissues and lymphoid organs

• Are part of the body's specific defense system

Three Classes of Lymphocytes

t cells, b cells, natural killer

T cells

Cell-mediated immunity

• Attack foreign cells directly

B cells

Humoral immunity

• Differentiate into plasma cells

• Synthesize antibodies

Natural killer (NK) cells

Detect and destroy abnormal tissue cells (cancers)

The Differential Count

Detects changes in WBC populations

• Infections, inflammation, and allergic reactions

WBC Disorders

Leukopenia, Leukocytosis, and Leukemia

Leukopenia

Abnormally low WBC count

Leukocytosis

Abnormally high WBC count - moderate increase is normal during active infection

Leukemia

Extremely high WBC count

Platelets

Cell fragments; flattened discs that appear round when viewed from top but spindle-shaped in blood smear

• Clump together and stick to damaged vessel walls where they release clotting chemicals

• Form from megakaryocytes (Giant cells in bone marrow)

• Circulate for 9-12 days

• Are removed by the spleen

Thrombocytopenia

Abnormally low platelet count

• Often results in abnormal bleeding

Thrombocytosis

Abnormally high platelet count

• Usually related to inflammation or cancer

Platelet Counts

150,000 to 500,000 per microliter

Thrombocytopenia

• Abnormally low platelet count

• Often results in abnormal bleeding

Thrombocytosis

• Abnormally high platelet count

• Usually related to inflammation or cancer

Formed Element Production

All formed elements are produced in adult red bone marrow

All cells arise from multipotent stem cells

= Hemocytoblasts (hemo-, blood + cyto, + blastos, precursor)

Give rise to two other stem cell lines

• Lymphoid stem cells (produce lymphocytes)

• Occur in red marrow and lymphoid tissues

• Myeloid stem cells (produce other formed elements)

Lymphoid stem cells

(produce lymphocytes)

• Occur in red marrow and lymphoid tissues

Myeloid stem cells

(produce other formed elements)

Hemostasis

Stops blood loss from damaged blood vessel walls

• Establishes framework for tissue repairs

• Usually divided into three phases, but continuous process

• Vascular phase

• Platelet phase

• Coagulation phase

Events of the Vascular Phase

Endothelial cells contract exposing underlying basal lamina to bloodstream

• Endothelial cells release chemical factors, local hormones, and endothelins

Endothelin functions

• Stimulate smooth muscle and vascular spasms

• Stimulate division of endothelial cells, smooth muscle cells, and fibroblasts

• Endothelial cells become sticky

In capillaries, cells can reduce flow in vessel

Can cause platelets to attach

Events of the Platelet Phase

Begins with platelet attachment to endothelial cells, basal lamina, exposed collagen fibers, and each other

• Platelets release chemicals

• ADP (stimulates platelet aggregation and secretion)

• Chemicals that stimulate vascular spasm

• Platelet factors (proteins play role in clotting)

• Platelet-derived growth factor (PDGF) (promotes vessel repair)

• Calcium ions (required for platelet aggregation and clotting process)

Events of Coagulation Phase

Starts 30 seconds or more after damage

• Involves complex sequence of steps leading to conversion of circulating fibrinogen to insoluble fibrin

• Blood cells and platelets are trapped in fibrin network

• Procoagulants (clotting factors) play a key role

• Many are enzymes essential to clotting response

• Activated enzymes lead to chain reaction (cascade)

Two pathways that both lead to common pathway

Extrinsic and Intrinsic

Extrinsic pathway

Begins with release of tissue factor (Factor III) from endothelial cells or peripheral tissues

• Tissue factor combines with Ca2+ and another clotting factor to activate Factor X (first step in common pathway)

Intrinsic pathway

Begins with proenzymes exposed to collagen fibers at injury site

• Pathway proceeds with assistance of PF-3 (factor released by aggregating platelets)

• Sequence of enzyme activations leads to Factor X

Common Pathway

Activated Factor X forms prothrombinase,

an enzyme that converts the proenzyme prothrombin to the enzyme thrombin

• Thrombin converts fibrinogen to fibrin to complete the clotting process

Clot retraction

RBCs and platelets stick to clot of fibrin

• Platelets contract to form tighter clot