Anatomy 2: Blood Vessels

Important functions of blood

- Transportation of dissolved substances (oxygen, CO2, nutrients, hormones, waste)
- Regulation of pH and ions
- Restriction of fluid losses at injury sites
- Defense against toxins and pathogens
- Stabilization of body temperature

Whole blood contents

Plasma, formed elements

Plasma

Fluid consisting of water, dissolved plasma, and other solutes

Formed elements

All cells and solids

General Characteristics of Blood

- 38C normal temperature
- High viscosity (4x water)
- Slightly alkaline pH (7.35-7.45)
- Red color from hemoglobin
- Blood volume (liters) - 7% of body weight

Adult male blood volume

5 to 6 liters

Adult female blood volume

4 to 5 liters

Composition of Plasma

- Makes up 50-60% of blood volume
- More than 90% water
- Plasma proteins
- Solutes

Extracellular fluids in Plasma

- Interstitial fluid (IF) and plasma (intravascular (IV))
- Materials plasma and IF exchange across capillary walls (water, ions, small solutes)

Plasma Proteins - Albumins (60%)

- Transport substances such as fatty acids, thyroid hormones, and steroid hormones
- Control osmotic pressure (movement inside and out of vessels)
- Blood viscosity

Plasma Proteins - Globulins (35%)

- Antibodies called immunoglobulins
- Transport globulins

Transport globulins

Hormone-binding proteins, metalloproteins, apolipoproteins (lipoproteins), and steroid-binding proteins

Plasma Proteins - Fibrinogen (4%)

Molecules that form clots and produce long, insoluble strands of fibrins

Plasma Proteins - Other (1%)

- Changing quantities of specialized plasma proteins
- Peptide hormones normally present in circulating blood (insulin, prolactin, TSH, FSH, LH)

Other solutes in Plasma - Organic nutrients

- Lipids (fatty acids, cholesterol, glycerides)
- Carbohydrates (primarily glucose)
- Amino acids

Other solutes in Plasma- Electrolytes

Na+, K+< Ca2+, Mg2+, Cl-, HCO3-, HPO4-, and SO24-

Other solutes in Plasma - Organic wastes

Urea, uric acid, etc.

Serum in Plasm

- Clotting factors
- Liquid part of blood sample in which dissolved fibrinogen has converted to solid fibrin
- Fibrinogen involved in clotting

Formed Elements of RBCs

- Make up of 99.9% of blood's formed elements
- Hemoglobin (red pigment that gives blood its color)
- Hb binds and transports oxygen and carbon dioxide

Abundance of RBCs

- Red blood cell count - number of RBCs in 1 microliter of whole blood
- Male -4.5-6.3 million (produces testosterone --\> produces RBCs)
- Female: 4.2-5.2 million (have menstrual cycles)

Erythrocytosis

More than normal RBCs (7-8 million)

Erythrocytopenia

Less than normal

Hematocrit PCV

- Packed cell volume
- Percentage volume of RBCs in centrifuged whole blood
- Male: 44-54
Female: 37-47
- Higher hematocrit, more than normal RBCs

Structure of RBCs

- Small and highly specialized discs
- Thin in middle and thicker at edge

Three Important Effects of RBC Shape on Function

- High surface area-to-volume ratio (quickly absorbs and releases O2)
- Discs form stacks called rouleaux (smooth the flow through narrow blood vessels)
- Discs bend and flex entering small capillaries )(7.8 micrometer RBC passes through 4 micrometer capillary)

Hemoglobin (Hb)

- Protein molecule that transports respiratory gasses
- Normal hemoglobin for adult male: 14-18 g/dL
- Normal hemoglobin for adult female (12-16 g/dL)

Hemoglobin Structure

- Complex quaternary structure
- Four globular protein subunits
- Each with one molecule of heme
- Each heme contains one iron ion

Iron ions in Hemoglobin

- Associate easily with oxygen (oxyhemoglobin, HbO2)
- Dissociate easily from oxygen (deoxyhemoglobin) no oxygen bound to hemoglobin

Hemoglobin Function

- Carries oxygen
- With low O2, hemoglobin releases O2 and binds CO2 to carry it to the lungs (--\> carbaminohemoglobin)
- Carboxyhemoglobin - CO attaches to heme

RBC Formation and Turnover

- RBCs formed in bone marrow, can survive for 120 days
- 1% of circulating RBCs wear out per day (about 3 million RBCs per second)

Hemoglobin Conversion and Recycling

- Macrophages of liver, spleen, and bone marrow
- RBCs can be destroyed as they pass through liver and spleen
- Monitor RBCs
- Engulf RBCs before membranes rupture (hemolyze)

Phagocytes break hemoglobin into components

- Globular proteins to amino acids
- Heme to biliverdin
- Iron

Hemoglobinuria

Hemoglobin breakdown products in urine due to excess hemolysis in blood stream

Hematuria

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

Iron has to be bound or it is toxic to tissue it is present in

- Iron transported to bone marrow or to spleen
- Iron reused to form new hemoglobin

Biliverdin metabolizes to bilirubin

- Lipid soluble, has to be bound to transport protein (albumin)
- Bilirubin excreted by liver, after being converted into soluble form

Biliverdin (green) is converted to bilirubin (yellow)

- Excreted by liver as bile
- Jaundice caused by bilirubin buildup
- Intestinal bacteria convert to urobilins and stercobilins
- Bilirubin then converted into water soluble form and released into bile

Jaundice (icterus)

- Normal bilirubin levels less than 1-1.5 mg/dL
- 2-3 mg/dL causes yellow discoloration
- Producing more bilirubin than liver can handle

Conjugated bilirubin

Bilirubin + glucuronic acid + glucuronyl transferase --\> bilirubin diglucuronide conjugated (90% of plasma bilirubin)

Unconjugated bilirubin

Albumin + bilirubin \= unconjugated

Malaria

More RBCs being destroyed, more bilirubin being built up --\> jaundice

Iron Recycling

- Iron removed from heme leaving biliverdin
- Transport proteins (transferrin)
- Storage proteins (ferritin and hemosiderin)

Erythropoiesis

- Occurs only in myeloid tissue (red bone marrow) in adults
- Stem cells mature to become RBCs

RBC Production

- Formed in red bone marrow before being released into circulation
- Starts out with pluripotent undifferentiated cell
- Turns into stem cell
- Lymphoid stem cell --\> lymphocyte
- Myeloid stem cell --\> three progenitor cells

Day 1 of RBC Formation - Proerythroblast

Before red cell is recognized

Day 2 of RBC Formation - Basophilic erythroblast

- Dense intricate net of ribosomes (to make more proteins)
- Will stain

Day 3 of RBC Formation - Polychromatophilic erythroblast

Mixture of red and blue cytoplasm (hemoglobin and ribosomes)

Day 4 of RBC Formation - Normoblast

- Nucleus is ejected
- Cells get biconcave shape

Day 5-7 of RBC Formation - Reticulocyte

Released into circulation
- To mature cell

Erythropoietin (EPO)

- Erythropoiesis-stimulating hormone
- Secreted when oxygen in peripheral tissues is low (hypoxia) due to disease or high altitude
- Stimulates maturation of RBC
- Produced by kidneys

Step 1 of RBC Production

Stimulus
- Hypoxia (low blood O2 carrying ability) due to decreased RBC count, decreased amount of hemoglobin, decreased availability of O2

Steps 2-5 of RBC Production

2. Kidney and liver to smaller extent releases erythropoietin
3. Erythropoietin stimulates red bone marrow
4. Enhanced erythropoiesis increases RBC count
5.

RBC Surface Antigens

- Agglutinogens
- Cell surface proteins that identify cells to immune system
- Normal cells are ignored and foreign cells attacked

Blood Types

- Genetically determined
- By presence of absence of RBC surface antigens A, B, Rh (or D)

4 Basic Blood Types

- Type A (surface antigen A, Type B antibodies)
- Type B (surface antigen B, Type A antibodies)
- Type AB (antigens A and B, both A and B antibodies)
- Type O (neither A nor B surface antigens or antibodies)

Rh factor

- D antigen
- Either Rh+ or Rh-
- Only sensitized Rh- blood has Rh antibodies
- May cause HDN (Hemolytic Disorder of Newborn)

Cross Reactions in Transfusions

- Transfusion reaction
- Plasma antibody meets its specific surface antigen
- Blood will agglutinate and hemolyze
- Occur if donor and recipient blood types not compatible

Testing for Transfusion Compatability

- Performed on donor and recipient blood for compatibility
- Without cross-match, type O- is universal donor

White Blood Cells

- 5000 to 10,000 per microliter
- Leukocyte s
- Do not have hemoglobin
- Have nuclei and other organelles

WBC Functions

- Defend against pathogens
- Remove toxins and wastes
- Attack abnormal cells

WBC Circulation and Movement

- Can migrate out of bloodstream (emigration via diapedesis)
- Have amoeboid movement
- Attached to chemical stimuli (positive chemotaxis
- Some are phagocytic (neutrophils, eosinophils, and monocytes)

Neutrophils

- Polymorphonuclear leukocytes
- 50-70% of circulating WBCs
- Pale cytoplasm granules with lysosomal enzymes and bactericides (hydrogen peroxide and superoxide)

Neutrophil Action

- Very active, first to attack bacteria
- Engulf and digest pathogens
- Degranulation
- Removing granules from cytoplasm
- Defensins (peptides from lysosomes) attack pathogen membranes
- Release prostaglandins and leukotrienes
- Forms pus

Eosinophils

- Acidophils
- 2-4% of circulating WBCs
- Attack large parasites
- Excrete toxic compounds (NO, 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
- Accumulate in damaged tissue
- Release histamine (dilates blood vessels)
- Release heparin (prevents blood clotting)

Monocytes

- 2-8% of circulating WBCs
- Large and spherical
- Enter peripheral tissues and become macrophages
- Engulf large particles and pathogens
- Secrete substances that attract immune system cells and fibrocytes to injured area (+ pimples)
- Increased monocytes \= chronic infection

Lymphocytes

- Larger than RBCs
- Migrate in and out of blood
- In connective tissues and lymphoid organs
- Part of body's specific cell defense system
- T cells, B cells, NK cells

T cells

Cell mediate immunity

B cells

Antibody mediated immunity

NK cells

- Natural killer cells
- Immunological surveillance

Differential Count and Changes in WBC Profiles

- Detects changes in WBC populations
- Infections, inflammations, and allergic reactions

WBC Production

- All blood cells originate from hemocytoblasts
- Produce progenitor cells called myeloid stem cells and lymphoid stem cells

Leukopenia

Abnormally low WBC count

Leukocytosis

Abnormally high WBC count

Leukemia

- Extremely high WBC count
- WBC may not be functional

Platelets

- Cell fragments involved in human clotting system
- Nonmammalian vertebrates have thrombocytes (nucleated cells)
- Circulate 9-12 days
- Removed by spleen
- 2/3 are reserved for emergencies

Platelet Production

- Megakarocytes (up to 160 microns)
- Giant cells in bone marrow
- Release cytoplasmic fragments (platelets involved in human clotting system)

Platelet Counts

150,000 to 500,000 per microliter

Thrombocytopenia

Abnormally low platelet count

Thrombocytosis

Abnormally high platelet count

Three Functions of Platelets

- Release important factors (ADP, thromboxane, serotonin, PDGF, Ca2+)
- Temporarily path damaged vessel walls
- Reduce size of a break in a vessel wall

Platelet Production - Thrombocytopoiesis

Occurs in bone marrow

Platelet Production - Megakaryocytes

- Giant cells in bone marrow
- Manufacture platelets from cytoplasm

Hemostasis

- Cessation of bleeding
- Consists of three phases: vascular, platelet, coagulation

Endothelial cells (inner lining of blood vessels)

- Antiplatelet (NO + prostacyclin as vasodilators, ADP phosphate)
- Heparin (activates antithrombin III --\> breaks down --\> thrombin, XA, and IXa)
- Thrombomodulin --\> stimulates thrombin --\> activates Protein C --\> breaks down VIIIa and V
- tPA (tissue plasminogen activator)

Components of Hemostasis

- Myogenic response (direct injury)
- Neurogenic response (pain reflex)
- Endothelial response (endothelin release)

Vascular Phase

- Lasts for 30 minutes after injury occurs
- Endothelial cells contract and release endothelins which stimulate smooth muscle contraction and endothelial division
- Endothelial cells become "sticky" and adhere to platelets and each other

Platelet Phase - Platelet adhesion

- Begins 15 seconds after injury
- Damaged endothelial cells produce Von Willebrand (VW) factor
- Sticky endothelial cells
- Basement membrane
- Expose collagen fibers

Platelet aggregation (stick together to form platelet plug)

- GPIb (glycoprotein Ib) receptors bind to VW factor causing
- Thromboxane A formation from cell membrane phospholipids using phospholipase and cyclic oxygenase enzyme
- Release from granules of serotonin (vasoconstriction), ADP (platelet adhesion), and Ca2+ (clotting)

Factors that Limit the Growth of the Platelet Plug

- Prostacyclin released by endothelial cells --\> inhibit platelet aggregation
- Inhibitory compounds released by other WBCs
- Circulating enzymes break down ADP
- Negative (inhibitory) feedback from serotonin
- Development of blood clot isolates area

Coagulation Phase

- Begins 30 seconds or more after injury
- Blood clotting (coagulation)
- Cascade reactions
- Chain reactions of enzymes and proenzymes
- Form three pathways
- Convert circulating fibrinogen into insoluble fibrin

Clotting Factors

- Procoagulants
- Proteins or ions in plasma
- Required for normal clotting

Thirteen Clotting Factors

- Fibrinogen (protein)
- Prothrombin (protein)
- Thromboplastin (lipoprotein)
- Calcium (ion)
- Labile factor (protein)
- Stable factor (protein)
- Anti hemophilic factor A (protein factor)
- Christmas factor (AHF-B) (protein factor)
- Stuart-prower factor (protein)
- Plasma thromboplastin antecedent (protein)
- Fibrin stabilizing factor (protein factor)

Three Coagulation Pathways

Extrinsic, intrinsic, common

Extrinsic Pathway

- Begins in vessel wall outside blood stream
- Damaged cells release tissue factor (TF)
- TF activated factor VII
- TF + VIIa + Ca2+ \= enzyme complex
- Activates Factor X

Intrinsic Pathway

- Begins with circulating proenzymes with blood stream
- Cascade activation of clotting factors ( X\__ --\> XI --\> IX --\> VIII)
- IXa + VIIIa + platelets + Ca2+ \= enzyme complex
- Activates Factor X

Intrinsic Pathway Initiated By

- Activated platelets which release factors e.g. PF3
- Exposure of collagen
- Damaged endothelium

Common Pathway

- Where intrinsic and extrinsic pathways converge
- Factor X is activated which activates V
- Xa +Va + Ca2+ + Platelets \= enzyme complex (prothrombinase)
- Converts prothrombin to thrombin
- Thrombin converts fibrinogen to fibrin

Clot Retraction

- Platelet contraction pulls torn edges of vessel closer together
- Reduces residual bleeding and stabilizing injury site
- Reduces size of damaged area
- Makes it easier for fibrocytes, smooth muscle cells, and endothelial cells to complete repairs

Fibrinolysis

- Slow process of dissolving clot
- Thrombin and tissue plasminogen activator (tPA) which activates plasminogen
- Plasminogen produces plasmin which digests fibrin strands