The Cardiovascular System:

Blood

The CV System
cardiovascular system
consists of three interrelated components:
Blood Heart Blood vessels.

Blood
Hematology
The study of blood, blood forming tissues, and the disorders associated with them

Blood contributes to homeostasis by:

Transporting respiratory gasses, nutrients, and hormones to and from your bodys cells. Helping to regulate body pH and temperature. Providing protection through its clotting mechanisms and immune defenses.

Characteristics of Blood
Blood is more dense and viscous (thicker) than water. Has a temperature of 38 deg C
1 deg C higher than oral or rectal body temp

Slightly alkaline
pH ranging from 7.35 7.45

Changes from dark to bright red depending on oxygen content Plasma volume constitutes roughly 25% of extracellular fluid (ECF)
Other 75% of ECF is interstitial fluid (ISF)

Average blood volume in:

Males = 5 to 6 liters (~1.5 gal) Females = 4 to 5 liters (~1.2 gal) Difference mainly due to body size

Blood
Blood is a type of connective tissue
Composed of:
Plasma Formed elements

Interstitial fluid (ISF)

Fluid that bathes body tissues Constantly renewed by blood
Discussed in more detail during blood vessels and hemodynamics lecture

Components of Blood
Plasma
A watery liquid extracellular matrix that contains dissolved substances. ~91.5% water and 8.5% solutes
The majority of the solutes in plasma are protiens
Specific proteins confined blood are called plasma proteins Most of the plasma proteins are produce by the liver These proteins have many functions but a very important one is a contribution to the maintenance of proper blood osmotic pressure

Other solututes include electrolytes, nutrients, gasses, regulatory substances, and waste products

Components of Blood
Formed Elements
3 principal components
Red Blood Cells (RBCs) White Blood Cells (WBCs) Platelets

Formed Elements
Hemopoiesis (hematopoiesis)
Process by which the formed elements of blood develop From late fetal development to death, red bone marrow is the primary site of hemopoiesis
All Blood cells arise from pluripotent stem cells found within the red marrow
The pluripotent stem cells give rise to 2 types of stem cells: Myeliod and lymphoid stem cells Lymphoid cells are named so due to their beginning development in the red bone marrow and ending in the lymphoid tissue Some of the myeloid stem cells give rise to progenator cells The other myeloid stem cells, lymphatic stem cells, and progenitor cells give rise to precurser cells (blasts) which then differentiate into the blood cells

Regulation of Hemopoiesis
Hemopoietic growth factors
Hormones that regulate the differentiation and proliferation of particular progenator cells
Erythropoietin (EPO) increases the # of RBC precursers
EPO is primarily produced cells in the kidneys Renal failure leads to RBC defficiency Exogenous or synthetic EPO is also a banned substance in most professional sports

Thrombopoetin (TPO) stimulates formation of platelets from megakaryocytes

TPO is produced by the liver

Cytokines small glycoproteins that regulate the development of different blood cells
Typically produced by cells such as red bone marrow cells, leukocytes, macrophages, fibroblasts, and endothelial cells

Laboratory made hemopoietic growth factors have shown great promise in helping reduce some of the side effects of chemotherapy as well as treatment of particular disieases and genetic defficiencies

Formed Elements
Red Blood Cells (RBCs)
Also called erythrocytes make up the bulk of the blood cells
Hematocrit = the % of RBCs per unit blood volume
Normal Hct is around 45%

bi-concave discs
Allows for high surface area which is optimal for gas exchange Also allows RBCs to deform without rupturing
Very important in capillary circulation

Amongst many other membrane proteins, the RBC membrane contains glycolipid surface markers that designate ABO Rh blood type

Red Blood Cells (RBCs)

Developing RBCs lose their nucleus and many other organelles as they mature
When a maturing RBC loses its nucleus, it becomes a reticulocyte

The mature form is highly specialized for oxygen transport

Due to the lack of most organelles, the majority of their internal space is available for oxygen transport Cytosol of mature RBCs contain a high amount of hemoglobin
~33% of the cells weight

Each RBC contains about 280 million hemoglobin molecules Hemoglobin (Hgb) is a protein molecule adapted to carry O2 (and CO2 as well)
A Hgb molecule consists of 4 large globin proteins (2 alpha and 2 beta chains), each embedding an iron-containing heme center The iron binds oxygen

Red Blood Cells (RBCs)

Lack mitochondria
Generate ATP anaerobically so they do not use up the oxygen being transported

As previously stated, mature RBCs lack a nucleus or any protein making machinery
This means they cannot synthesize new components to repair damaged ones
Thus they are destined to die Average RBC life is about 120 days. ~1% of RBCs must be destroyed and replaced every day 250 billion cells per day!

Old RBCs a subject to bursting when passing through the narrow channels in the spleen
Ruptured RBCs are removed from circulation and destroyed by fixed phagocytotic macrophages in the spleen and liver Some of the breakdown products are recycled and others are excreted as shown in the following slide

In a sense, mature RBCs are not really cells, but remnants of cells with a very specific purpose to carry O2 to the tissues of the body

RBC Life Cycle

Circulation for about 120 days

3
Amino acids Reused for protein synthesis Fe3+ Fe3+ Transferrin

Globin

4 2 Heme
Transferrin

6
Ferritin Fe3+ + Globin + Vitamin B12 + Erythropoietin

9 1 Red blood cell

death and phagocytosis Kidney Biliverdin Bilirubin

Bilirubin

10
Bilirubin

11

Liver

Small intestine

13
Macrophage in spleen, liver, or red bone marrow Urine Urobilin

8 Erythropoiesis in
red bone marrow

12

Urobilinogen Stercobilin Feces

Bacteria

Key:
in blood in bile

Large 14 intestine

Abnormalities of Erythropoiesis
Anemia
A condition of insufficient RBCs or hemoglobin (quality or quantity) It is most often the result of low iron intake, hemolysis, autoimmune disease, blood loss, or lack of production in the bone marrow
a condition of excess number of RBCs per unit volume It occurs in response to:
Hypoxia Blood doping - receiving a transfusion of RBCs right before a sporting event to increase the bloods oxygen carrying capacity shots of EPO (illegal doping) smoking (COPD) dehydration
Natural blood doping is training at high altitude Condition in which the body or a region of the body is deprived of an adequate oxygen supply

Polycythemia

Anemias
Iron deficiency anemia is the most common anemia in the U.S., and affects primarily menstruating women
In the United States, 20% of all women of childbearing age have iron deficiency anemia, compared with only 2% of adult men

Hemorrhagic anemia is the result of precipitous blood loss, and results in an equal decrease in Hct, Hgb content, and RBC count

Anemias
Sickle-cell disease (SCD)
also called sickle-cell anemia An autosomal recessive disorder.
A genetic defect in the primary DNA sequence leads to production of a faulty Hgb chain, and RBCs that take on a rigid, sickle-shape People who only have one sickle-cell gene may experience mild symtoms People who have two copies of the sickle-cell gene may experience severe symptoms Decreased oxygen carrying capacity Easily ruptured RBCs Increased risk of stroke life expectancy is shortened Many others

Sickling decreases the cells' flexibility and results in a variety of complications;

May confer an advantage in malaria prone envoronments

People who inherit one copy of the mutated sickle-cell gene show increased resistance to infection and effects of the plasmodium parisite
http://en.wikipedia.org/wiki/File:Sickle_cell_ 01.jpg

Next Lecture
Lecture 1 part 2: Blood