Blood Physical Characteristics

Adult contains 5-6L Adult contains 4-5L T is about 100.4 F

Is this higher or lower than normal body T?

5 times as viscous as water

Is it more or less resistant to flow than water? What accounts for its viscosity?

pH ranges from 7.35 7.45 (slightly alkaline) Color ranges from scarlet (oxygenated blood) to a deep red (deoxygenated blood).

Whole Blood

Plasma

Formed Elements (37-54%)

(46-63%)

1. Water (92%) 2. Plasma Proteins (7%) 3. Other Solutes (1%)

1. Red Blood Cells (99.9%) 2. Platelets 3. White Blood Cells

(0.1%)

Functions of Blood
Transportation of dissolved gases, nutrients, hormones, and metabolic wastes Regulation of the pH and electrolyte composition of interstitial fluids throughout the body Restriction of fluid losses Defense against toxins and pathogens Stabilization of body temperature

These red blood cells function in oxygen transport

Blood and Transportation

Red blood cells are packed with the protein hemoglobin (Hb) which carries O2 CO2 is carried by Hb, and dissolved in plasma in multiple ways Nutrients absorbed at the GI tract, or released by the liver or adipocytes, are distributed by blood Hormones (blood-borne chemical messengers) are transported from the endocrine glands where theyre produced to their target organs via the bloodstream Metabolic wastes produced by tissue cells are absorbed by the blood and carried to the kidneys for excretion

Blood & Regulation

Blood absorbs heat from active skeletal muscles and distributes it to other tissues. If body T is already high, that heat will be lost across the skin surface. If body T is too low, that heat will be directed to the brain and to other T sensitive organs. The blood absorbs and neutralizes the acids generated by active tissues (e.g., lactic acid from skeletal muscles). The blood acts as both a conduit and reservoir for important electrolytes (Na+, Ca2+, etc.) Blood volume is regulated in response to the bodys water levels.

The above represents a relative distribution of blood in response to warm and cold ambient temperatures.

Blood & Protection

Blood transports white blood cells, specialized cells that migrate into peripheral tissues to fight infections and remove debris. Blood delivers antibodies, proteins that attack invading organisms and foreign compounds. Blood contains enzymes that respond to a break in a blood vessel wall by forming a clot to restrict further fluid loss.

Above, we have a SEM image of a blood clot. Notice the RBCs.

Red Blood Cells (Erythrocytes)

Most abundant blood cells (99.9% of formed elements)
In , 1L of blood contains 4.5-6.3 million RBCs In , 1L of blood contains 4.2-5.5 million RBCs

Contains the red pigment hemoglobin which binds and transports O2 and CO2 Each RBC is a biconcave disc
Diameter 8m Thickness 2.5m

Erythrocytes
Why a biconcave disc?
Provides a large surface area for O2 entry/exit Enables them to bend and flex when entering small capillaries

RBCs lack a nucleus and most organelles.

Instead they are simply membranous bags of hemoglobin What is a functional advantage of the fact that the RBC lacks mitochondria?
Here, we have an RBC bending to fit thru a small capillary

Hemoglobin
Large protein consisting of 4 polypeptides
2 chains and 2 chains

Each chain contains a single molecule of heme, an iron-containing pigment

The iron ion in heme is able to reversibly bind an oxygen molecule. Meaning, O2 can bind to Hb at the lungs and then be released at the tissues Note the 2 chains and 2 chains. Notice how each has an associated heme molecule with an iron atom.

Based on the above, how many molecules of O2 can each Hb protein bind?

RBC Formation (Erythropoiesis)

In the adult, all blood cell formation (including erythropoiesis) occurs in the red bone marrow All blood cells develop from stem cells called hemocytoblasts
Red Blood Cells Monocytes Platelets Granulocytes

Myeloid Stem Cell

Hemocytoblast

Lymphoid Stem Cell

Lymphocytes

Control of Erythrocyte Production

Figure 10.5

Lifecycle of an RBC
RBCs are subjected to incredible mechanical stress.
Why are they unable to synthesize replacements for damaged parts?

After 120d, the RBC cell membrane ruptures, or the damage is detected by phagocytic cells and the RBC is engulfed. If the RBC hemolyzes, its contained Hb will be excreted by the kidneys

Above, we have a macrophage phagocytizing multiple RBCs

Once an RBC has been engulfed & broken down by a phagocytic cell, each component of Hb has a different fate.

1. Globular proteins
Disassembled into component amino acids and metabolized by the cell or released into the circulation for use by other cells

2. Heme
Stripped of its iron and converted to bilirubin, which has an orange-yellow color. Bilirubin is released into the circulation where it binds to albumin and is transported to the liver. Liver modifies and then secretes bilirubin into the small intestine as a component of bile.
If the bile ducts are blocked, or if the liver is unable to absorb/excrete bilirubin, plasma [bilirubin] rises and diffuses into peripheral tissues where it can impart a yellow color to the skin and sclera of the eye (jaundice)

Inside the large intestine, bacteria convert the bilirubin into urobilinogens and stercobilinogens. Some urobilinogens are absorbed back into the circulation and excreted by the kidneys as urine. Urobilinogen gives urine its yellow color. The brownish color of feces is due to the presence of urobilinogens and stercobilinogens.

Complete Blood Count (CBC)

Determination of the number of red and white blood cells per mL of blood One of the most routinely performed clinical tests and a very valuable screening and diagnostic technique Can be performed manually or via an electric counter Different disorders can have a dramatic effect on the total number or relative proportion of blood cells.

Hematocrit
Percentage of whole blood occupied by packed red blood cells Average in a is 46 (range of 40-54) Average in a is 42 (range of 37-47)
Greater in b/c androgens (e.g., testosterone) stimulate RBC synthesis while estrogens do not

Determined by centrifuging a blood sample so that all formed elements come out of suspension Low Hct values may indicate anemia whereas high values may indicate polycythemia

Polycythemia
An elevated hematocrit with a normal blood volume I.e., an increase in the number of erythrocytes in the blood. May be primary (polycythemia vera) and due to cancer of the bone marrow

May be secondary when less oxygen is available or erythropoietin (kidney hormone that stimulates RBC synthesis) production increases. How does polycythemia affect blood viscosity and thus affect blood flow? Polycythemia can be treated by blood dilution removing blood and replacing it with isotonic saline. Endurance athletes often attempt to induce polycythemia as a means of increasing their athletic performance. Why?

Anemia
Condition where the blood has an abnormally low oxygen-carrying capacity Symptom rather than a disease in/of itself Why are anemic individuals often short of breath, fatigued, and chilly? Types:
Hemorrhagic Aplastic Pernicious Thalassemia Hemolytic Iron-deficiency Sickle Cell

Anemia
Hemorrhagic
Results from blood loss (i.e., RBC loss) Can be acute (stab wound perhaps) or chronic (due to hemorrhoids or an undiagnosed bleeding ulcer)

Hemolytic

Compare the 2 slides of red bone marrow. Blue dots indicates developing blood cells. Left-hand slide is during aplastic anemia; right-hand slide is almost back to normal

RBCs rupture (lyse) prematurely Can be due to hemoglobin abnormalities, mismatched blood transfusions, parasitic or bacterial infection, or autoimmune.

Aplastic
Results from destruction of red bone marrow from bacterial toxins, drugs, or radiation. Not only impacts RBCs but WBCs and platelets as well. Why?

Anemia
Iron-Deficiency
What role does iron play in oxygen transport? Iron-deficiency anemia can be secondary to hemorrhagic anemia or can occur due to inadequate iron intake or absorption

Pernicious
Due to a lack of Vitamin B12 intake or absorption. Stomach mucosa produces a substance called intrinsic factor which is necessary for Vitamin B12 absorption. Lack of intrinsic factor is often a cause of pernicious anemia

Thalassemias
Often seen in people of Mediterranean origin. One of the globin genes is absent or faulty.

Sickle-cell Anemia
A single mutation in the gene for the chain of the globin molecule results in abnormal hemoglobin (HbS) Due to the structural change, the chains link together and become stiff rods under low-O2 conditions. This causes the RBCs to become sickle-shaped and these malformed RBCs can then block and clog small blood vessels.

Erythroblastosis Fetalis
A type of hemolytic anemia Suppose we have an Rh- mom whose 1st child is Rh+. At birth, the placenta ruptures and the babys blood mixes with the mothers blood. This sensitizes the mom to the Rh antigen and she begins to produce antibodies against the Rh antigen. The 1st child is fine he/she has already been born. However if the mom has a 2nd Rh+ child, her anti-Rh antibodies will cross the placenta and begin to attack the fetal RBCs.. This condition is erythroblastosis fetalis (a.k.a. hemolytic disease of the newborn) The baby becomes anemic and hypoxic; brain damage and death may result if blood transfusions are not performed.

Blood Types
Recipient[1] Donor[1]

O O Y

O+

A+

B+

AB

AB+

O+ A

A+ B

B+

AB

AB+

Blood typing
http://nobelprize.org/educational_games/m edicine/landsteiner/

White Blood Cells

Leukocytes (leuko=white, cyte=cell) All contain nuclei and organelles unlike Help defend the body against invasion by pathogens, and they remove toxins, wastes, and abnormal/damaged cells A typical L of blood contains 6000-9000 WBCs. Compare that to RBCs Most of the WBCs in the body at a given moment are in the connective tissue proper or in organs of the lymphatic system Circulating WBCs are just a fraction of the total #

Types of WBCs
Can be classified based on the appearance of granules when viewed under the light microscope. 1. Granulocytes
Contain visible granules. Includes:
Basophils Eosinophils Neutrophils

2. Agranulocytes
Do not contain visible granules. Includes:
Lymphocytes Monocytes

WBC Circulation and Movement

Use the bloodstream mainly to travel from organ to organ or to quickly go to areas of invasion/injury. Characteristics of circulating WBCs: Capable of amoeboid movement
What role might this play in WBC function?

They can migrate out of the bloodstream by squeezing thru endothelial cells (this process is called diapedesis) They are attracted to specific chemical stimuli. This is known as positive chemotaxis and allows WBCs to converge on pathogens and damaged tissues

Granulocytes Neutrophils
50-70% of circulating WBCs Cytoplasm is packed with pale (neutral colored) granules that contain bactericidal compounds Mature neutrophils have a segmented nucleus. They are a.k.a polymorphonuclear leukocytes. About 12m in diameter. Highly mobile and generally the first WBCs to arrive at an injury site. Specialize in attacking and digesting bacteria that have been marked for destruction. Survive in the bloodstream for only about 10hrs

Granulocytes Eosinophils
2-4% of circulating WBCs Similar in size to neutrophils but have reddish-orange staining granules (Eos is the Greek goddess of dawn) and a bilobed nucleus. Move into tissues after several hours and survive from minutes to days. They will phagocytize antibody-coated bacteria, protozoa, and cellular debris, but their main method of attack is the exocytosis of toxic compounds onto the surface of their target. Important defenders against large, multicellular parasites such as flukes or parasitic worms. They in # dramatically during a parasitic infection. Also sensitive to allergens and in # during allergic reactions as well.

Granulocytes Basophils
>1% of circulating leukocytes Smaller than neutrophils and eosinophils, only about 8-10m in diameter. Contain granules that appear deep purple or blue Basophils migrate to injury sites and discharge the contents of their granules histamine (a vasodilator and increaser of capillary permeability) and heparin (an anticoagulant). This enhances the local inflammation initiated by mast cells and attracts other WBCs

Agranulocytes Monocytes
2-8% of circulating WBCs Almost twice as big as an RBC Nucleus is large and tends to be oval or kidney-shaped Individual monocytes use the bloodstream as a highway, staying in circulation for only about 24hrs before entering peripheral tissues to become a tissue macrophage, an aggressive phagocyte.

Agranulocytes Lymphocytes
20-30% of circulating leukocytes Slightly larger than RBCs. In blood smears, you typically only see a thin halo of cytoplasm around a relatively large nucleus. Continuously migrate from the bloodstream thru peripheral tissues and back into the bloodstream. Circulating lymphocytes are only a minute fraction of the total # in the body. Most are in other connective tissues and in lymphatic organs. Circulating blood contains 3 classes:
T cells: defend against foreign cells and tissues and coordinate the immune response B cells: produce and distribute antibodies that attack foreign materials

WBCs in order of abundance: Never (neutrophils Let (lymphocytes) Monkeys (monocytes) Eat (eosinophils) Bananas (basophils) How do I remember the relative percentages? 60 + 30 + 6 + 3 +1
(i.e., 60% neutrophils, 30% lymphocytes, 6% monocytes, 3% eosinophils & 1% basophils)

Platelets
Flattened disk-like cell fragments that are about 1m by 4m. Act as a participant in the vascular clotting system. Platelets are sometimes referred to as thrombocytes (thrombus=clot) Continuously being replaced. Each platelet circulates for 9-12 days before being removed by splenic phagocytes. On average there are 350,000 platelets/L of blood. Produced in the bone marrow. Large cells called megakaryocytes release fragments (platelets) into the circulation.

Platelet Functions
Transport of chemicals important to the clotting process. By releasing enzymes and other factors, platelets help initiate the clotting process Formation of a temporary patch (platelet plug) in the walls of damaged blood vessels. What do you suppose thrombocytopenia is? What process would it impact?

Hemopoiesis = Leukopoiesis + Erythropoiesis + Thrombopoiesis

Lymphoid Stem Cell Hemocytoblast Lymphocyte

Myeloid Stem Cell

Megakaryocyte

Platelet

Where does all of this take place? Erythrocyte

Hemostasis (Blood Clotting)

Prevents blood loss thru the walls of damaged blood vessels Also establishes a framework for further tissue repairs 3 main phases:
Platelet Phase Vascular Phase Coagulation Phase

Platelet Phase
Occurs within 15sec of the injury Platelets begin to attach to sticky endothelial cells, the basement membrane, and to exposed collagen fibers. As platelets stick, they become activated. Activated platelets release: The aggregation of platelets eventually results in a platelet plug, a temporary mass of platelets that stops blood loss and forms a framework for the clot.

Blood Vessel Damage

Vascular Phase
Lasts about 30 mins Endothelial cells at the injury site undergo changes:
Contract and expose their basement membrane to the bloodstream Release chemical factors and local hormones serotonin initiates spasms Endothelial cell membranes become sticky

Smooth muscle in BV wall contracts Vascular Spasm

BV diameter

Blood loss slows

Coagulation Phase
Begins 30sec or more after vessel damage occurs (unlike the first 2 phases which begin almost immediately) Involves a sequence of steps leading to the conversion of fibrinogen (a circulating plasma protein) to the insoluble protein fibrin. A network of fibrin grows and covers the surface of the platelet plug. RBCs and additional platelets are trapped in this tangle, forming a blood clot that effectively seals the damaged vessel wall.

Clot Retraction
Once the fibrin meshwork has appeared, RBCs & platelets stick to the fibrin strands. The platelets then contract and the clot undergoes clot retraction which:
Pulls the torn edges of the vessel closer together, reducing residual bleeding and stabilizing the injury site Reduces the size of the injured area, making it easier for fibroblasts, smooth muscle cells, and endothelial cells to complete repairs.

Manipulating Hemostasis
Important anticoagulant drugs include:
Heparin Inactivates thrombin Coumadin Blocks the action of Vitamin K Streptokinase Converts plasminogen to plasmin Aspirin Inhibits platelet aggregation

Thrombi & Emboli

A thrombus is formed when platelets begin to stick to the wall of an intact blood vessel
Platelets are often attracted to plaques where endothelial and smooth muscle cells contain lots of lipids. What problems could a growing thrombus pose?
Above: Normal artery Below: Same artery with a large thrombus (arrow)

If the clot (thrombus) breaks off and begins to drift in the bloodstream, it is called an embolus.
What problems could an embolus cause?

Hemophilia
Refers to several different hereditary bleeding disorders with similar signs/symptoms Hemophilia A
Results from lack of Factor VIII. Most common type (83%) X-linked

Hemophilia B
Less common. Due to deficiency of Factor IX Also X-linked
What symptoms do you suppose are characteristic of hemophiliacs?