Anatomy and Physiology - Cardiovascular System

Blood

• Continuously regenerated connective tissue

• Moves gases, nutrients, wastes, and hormones

• Transported through cardiovascular system

Cardiovascular system

• Heart pumps blood

• Arteries transport (oxygenated) blood away from heart

• Veins transport (deoxygenated) blood toward heart

• Capillaries allow exchange between blood and body tissues; exchange with systemic cells and alveoli in the lungs; innervate all body tissue

Blood components

Consists of formed elements and plasma = whole blood

Formed elements

• Erythrocytes (red blood cells) transport respiratory gases in the blood

• Leukocytes (white blood cells) defend against pathogens

• Platelets help form clots to prevent blood loss (colorless)

Centrifuged blood

Whole blood (plasma and formed elements) separated by centrifuge

1. Withdraw blood from a vein into a syringe and place it into a glass centrifuge tube.

2. Place the tube into a centrifuge and spin for about 10 minutes.

3. Components of blood separate during centrifugation to reveal plasma, buffy coat, and erythrocytes (in order from lightest to heaviest).

Erythrocytes

Bottom, red layer ~44% of sample

• 4.2-6.2 million/mm³

Buffy coat

Very thin (~1%) middle layer with gray-white

• Consists of leukocytes and platelets

Leukocytes

Part of buffy coat

4.5-11 thousand/mm³

• Neutrophils: 50-70% of leukocytes

• Lymphocytes: 20-40%

• Monocytes: 2-8%

• Eosinophils: 1-4%

• Basophils: 0.5-1%

Platelets

Part of buffy coat

• 150-400 thousand/mm³

Plasma

Straw-colored liquid at top of tube

• ~55% of sample

• Water (92% - acts as solvent) + dispersed proteins (7%) + dissolved solutes (<1%)

• An extracellular fluid

• Similar composition to interstitial fluid, but plasma has higher protein concentration

Hematocrit

Percentage of volume of all formed elements

Clinical definition: percentage of only erythrocytes

• Adult males: 42 to 56%; females 38 to 46%

• Testosterone causes more erythropoietin secretion by kidney

Colloid

Blood is a colloid

• An opaque mixture of water and solute (usually protein)

Plasma protein levels

Most produced in liver, others produced by leukocytes or other organs

Make up 7% of plasma

• Albumin: 58% of plasma proteins

• Globulins: 37%

• Fibrinogen and other clotting proteins: 4%

• Regulatory proteins - enzymes and hormones: <1%

Colloid osmotic pressure (COP)

Exerted by plasma proteins

• Prevents loss of fluid as it moves through capillaries

• Helps maintain blood volume and blood pressure

• Can be decreased with diseases, resulting in fluid loss from blood and

tissue swelling

Diseases of which organs affect colloid osmotic pressure?

• Liver diseases that decrease production of plasma proteins

• Kidney diseases that increase elimination of plasma proteins

Albumin

58% of plasma proteins

• Exerts osmotic force to retain fluid within the blood

• Contributes to blood’s viscosity

• Transport selected molecules (ex: ions, lipids, hormones)

Globulin

37% of plasma proteins

• Alpha-globulins transport lipids and some metal ions (ex: copper)

• Beta-globulins transport lipids and iron ions

• Gamma-globulins are antibodies that immobilize pathogens

Fibrinogen

4% of plasma proteins

• Participates in blood coagulation (clotting)

Regulatory proteins

<1% of plasma proteins

• Consists of enzymes and hormones

Solutes in plasma

<1% of plasma

• Electrolytes: help establish, maintain, and change membrane potentials, maintain pH balance, and regulate osmosis

• Nutrients: energy source; precursor for synthesizing other molecules; participate in metabolic processes

• Respiratory gases: oxygen is needed for aerobic cellular respiration; carbon dioxide is a waste product produced by cells during this process

• Waste products: are only being transported to the liver and kidneys for elimination

Plasma molecules ranges

• Glucose: fasting: 70-100 mg/dL; 2 hours after a meal: <145 mg/dL

• Amino acids: varies, based on specific amino acid being measured

• Lactate: 4.5-14.4 mg/dL

• Lipids: varies; molecules that generally do not dissolve in water (cholesterol, HDL, VLDL/LDL, triglycerides, phospholipids)

Glucose (plasma molecule)

Fuel molecule for cellular respiration (primary energy source for nervous tissue)

• Tightly regulated by a number of hormones, including insulin and glucagon

Amino acids (plasma molecule)

Monomers for synthesizing protein

• Also regulated by some of the same hormones as glucose

Lactate

By-product of glycolysis

Cholesterol (lipid)

100-200 mg/dL

Plasma membrane component; synthesis of steroid hormones; bile salts

• HDL: 40-80 mg/dL; transports lipids to the liver; “good” cholesterol

• VLDL/LDL: 10-100 mg/dL; transports lipids from the liver; “bad” cholesterol

Triglycerides (lipid)

30-149 mg/dL

Fuel molecules; precursors for cholesterol synthesis

Phospholipids (lipid)

6-12 mg/dL

Molecules that form the bilayer of a plasma membrane

Functions of blood

• Transportation

• Protection

• Regulation of body conditions (body temperature, pH, and fluid balance)

Transportation (functions of blood)

Transports formed elements, dissolved molecules, and ions through pulmonary and systemic circulation

• Carries oxygen from and carbon dioxide to the lungs

• Transports nutrients, hormones, heat, and waste products

Protection (functions of blood)

• Leukocytes, plasma proteins, and other molecules (of immune system) protect against pathogens

• Platelets and certain plasma proteins protect against blood loss

Regulation of body conditions (functions of blood)

• Body temperature: blood absorbs heat from body cells (especially muscle) → released at skin blood vessels

• Body pH: blood absorbs acid and base from body cells; contains chemical buffers

• Fluid balance: water is added to blood from GI tract → lost through urine, skin, and respiration

→ fluid is exchanged between blood and interstitial fluid

→ blood contains proteins and ions helping maintain osmotic balance

Color (physical characteristics of blood)

Depends on degree of oxygenation

• Oxygen-rich blood is bright red

• Oxygen-poor blood is dark red

Volume (physical characteristics of blood)

5 L on average; ranges from 4-6 L

Viscosity (physical characteristics of blood)

4.5-5.5x relative to water

Depends on amount of dissolved and suspended substances relative to amount of fluid

• Increases if erythrocyte number increases

• Increases if amount of fluid decreases

Plasma concentration of solutes

0.9%

Solutes include proteins and ions

• Osmotic pressure is important because it keeps the shape of blood vessels

• Determines the direction of osmosis across capillary walls

• For example, during dehydration, plasma is hypertonic (more solutes) → fluid is drawn from surrounding tissues

Temperature (physical characteristics of blood)

100.4 degrees F/38 degrees C

• Blood is 1°C higher than measured body temperature

• Warms area through which it travels

Blood pH (physical characteristics of blood)

Slightly alkaline at 7.35-7.45

• Crucial for normal plasma protein shape (avoiding denaturation)

Blood smear

Thin layer of blood placed on microscope slide and stained

Formed elements differ in appearance:

• Erythrocytes are most numerous: pink, anucleate, biconcave discs

• Leukocytes: larger than erythrocytes, varied in form, noticeable nucleus

• Platelets: small fragments of cells

Hematopoiesis

The origin, differentiation, and maturation of formed elements

• Occurs in red bone marrow of certain bones

• Colony-stimulating factors (CSFs) stimulate hematopoiesis

• Always starts with hemocytoblasts (hematopoietic stem cell; pluripotent and undifferentiated)

Erythropoiesis (myeloid line)

Multi-CSF acts on myeloid stem cells to start erythropoiesis

1. Stimulation by EPO → progenitor cell

2. Proerythroblast

3. Stimulation by EPO → early erythroblast

4. Late erythroblast

5. Normoblast: nucleus ejected at this stage

6. Reticulocyte

7. ERYTHRYOCYTE

Thrombopoiesis (myeloid line)

Multi-CSF acts on myeloid stem cells to start thrombopoiesis

1. Progenitor cell

2. Megakaryoblast

3. Stimulation by thrombopoietin → promegakaryocyte

4. Stimulation by thrombopoietin → megakaryocyte

5. Stimulation by thrombopoietin → proplatelets on megakaryocytes break off into PLATELETS

Leukopoiesis - granulocyte line (MYELOID line)

Multi-CSF acts on myeloid stem cells to start leukopoiesis - granulocyte line

1. Stimulation by GM-CSF → progenitor cell

2. Stimulation by G-CSF → myeloblast

3. Promyelocytes

4. Eosinophilic myelocyte / basophilic myelocyte / neutrophilic myelocyte

5. EOSINOPHIL / BASOPHIL / NEUTROPHIL

Leukopoiesis - monocyte line (MYELOID line)

Multi-CSF acts on myeloid stem cells to start leukopoiesis - granulocyte line

1. Stimulation by GM-CSF → progenitor cell

2. Stimulation by M-CSF → monoblast

3. Stimulation by M-CSF → promonocyte

4. MONOCYTE

Leukopoiesis (LYMPHOID line)

1. Lymphoid stem cell → directly to NATURAL KILLER CELL

2. B-lymphoblast → B-LYMPHOCYTE

3. T-lymphoblast → T-LYMPHOCYTE

Characteristics of erythrocytes

• Diameter: 7.5 µm

• Function: transport oxygen and carbon dioxide

• Lifespan: ~120 days

• Density (avg number per mm³ of blood): ~4.8 mil for females, ~5.4 mil for males

Characteristics of leukocytes

• Diameter: 1.5-3x larger than erythrocytes; 11.25-22.5 µm

• Function: initiate immune response; defend against potentially harmful substances

• Lifespan: varies from 12 hrs (neutrophils) to years (lymphocytes)

• Density (avg number per mm³ of blood): 4,500-11,000

Characteristics of platelets

• Diameter: <1/4x of an erythrocyte; ~2 µm

• Function: participate in hemostasis

• Lifespan: ~8-10 days

• Density (avg number per mm³ of blood): 150,000-400,000

Platelet formation

Starts in red bone marrow with megakaryocytes (lives next to blood vessels)

1. The capillary is lined with endothelial cells thru which lie the proplatelets

2. Proplatelets are spliced from the megakaryocytes by the force of blood flow → platelets

Proplatelets

Long processes/protrusions of megakaryocytes into the capillary wall that break off into platelets

Erythrocyte structure

• Small, flexible formed elements

• Lack nucleus and cellular organelles; packed with hemoglobin

• Have biconcave disc structure and a latticework of spectrin protein providing support and flexibility

• Transport oxygen and carbon dioxide between tissues and lungs

Molecular structure of hemoglobin

The red-pigmented protein found in blood

Transports oxygen and carbon dioxide (termed oxygenated when maximally loaded with oxygen and deoxygenated when some oxygen lost)

• Each hemoglobin molecule is composed of four globins (two alpha chains and two beta chains)

• Each chain has a heme group: a porphyrin ring with an iron ion in its center

Oxygen binding to hemoglobin

Oxygen binds to the iron ion, so each hemoglobin can bind four oxygen molecules

• Binding is fairly weak; rapid attachment in lungs and rapid detachment in body tissues

Carbon dioxide binds to globin protein (not iron)

• Binding is fairly weak; attachment in body tissue and detachment in lungs

Steps of erythropoietin regulating erythrocyte production

1. Stimulus: decreased blood oxygen levels

2. Receptor: kidney detects decreased blood O2

3. Control center: kidney cells release EPO in the blood

4. Effector: EPO stimulates red bone marrow to increase the rate of erythrocyte production

5. Net effect: increased numbers of erythrocytes enter the circulation, during which time their are oxygenated and blood O2 levels increase

6. Negative feedback: increased blood O2 levels are detected by the kidney, which inhibits EPO release by negative feedback

Clinical view: blood doping

Used by some athletes to enhance performance

Method 1: self-donation of erythrocytes

• Blood removal prior to competition increases EPO production

• Erythrocytes transfused back before competition

Method 2: pharmaceutical EPO

Dangers of blood doping

• Increased blood viscosity

• Heart required to work harder

• May cause permanent cardiovascular damage

• Banned from athletic competition