17 Blood Modified by: Olga E. Vazquez.

17 Blood Modified by: Olga E. Vazquez

Cardiovascular System
Cardio = heart Vascular = blood vessels Consists of three interrelated components: Blood Heart Blood vessels

Blood is Fluid Connective Tissue Blood components
Basics of Blood Blood is Fluid Connective Tissue Blood components Plasma (matrix) - nonliving Formed elements (cells) - living Hematopoiesis – formation of blood cells

Blood Blood is unique from person to person Health care professionals routinely examine and analyze its differences through various blood tests to determine the causes of different diseases. Hematology = study of blood

Blood: An Overview 2 components: Cellular component Liquid component

Blood: An Overview Blood is a specialized type of connective tissue in which living blood cells, the formed elements (cells), are suspended in a nonliving fluid matrix called plasma.

Blood: An Overview Blood and the interstitial fluid (IF) are 2 fluids that provide O2 and nutrients and remove CO2 and other waste. How do they do it? IF bathes body cells O2 and nutrients diffuse from blood → IF → cells Waste and CO2 diffuse cell → IF → blood

Physical Characteristics and Volume
Total blood volume: 8% of body weight Average volume in healthy males: 5-6 L (~ 1.5 gallons) Average volume in healthy females: 4-5 L (1.05 to 1.32 gallons)

Physical Characteristics and Volume
Blood is more dense than water and about 5 times more viscous. Why?

Physical Characteristics
Slightly alkaline pH between 7.35 and 7.45 Temperature is slightly higher than body temperature 38ºC or 100.4ºF

Functions Blood performs a number of functions, all concerned in one way or another with: Distribution Regulation Protection

There are six functions:
1. Transportation O2 lungs → cells CO2 cells → lungs Nutrients GI → cells waste from cells → kidneys

Functions 2. Defense WBC – disease blood proteins – antibodies

4. Prevents loss – blood clots
Functions 3. Temperature regulation - absorbs and distribute heat throughout body and skin 4. Prevents loss – blood clots 5. Hormone movement – endocrine gland → cells 6. Regulates pH – through buffers

Components of Blood If a sample of blood is spun in a centrifuge, the heavier formed elements are packed down by centrifugal force and the less dense plasma remains at the top.

Bottom – erythrocytes (what are they?)
Components Bottom – erythrocytes (what are they?) Erythro = red Buffy coat – whitish layer present at the erythrocyte-plasma junction Contains platelets and leukocytes Plasma

90% water; plasma also contains :
Makes up 55% of blood 90% water; plasma also contains : Proteins such as antibodies Gases Hormones Waste

Plasma Proteins: Most proteins are produced by the liver, except for hormones and gamma globulins. 8% by weight of plasma volume Plasma proteins serve a variety of functions, but they are not taken up by cells to be used as fuels or metabolic nutrients as are most other plasma solutes, such as glucose, fatty acids, and amino acids.

Plasma Proteins Some examples are: Albumins
Accounts for some 60% of plasma protein It acts as a carrier to shuttle certain molecules through the circulation Important blood buffer Major blood protein contributing to the plasma osmotic pressure (the pressure that helps to keep water in the bloodstream).

Antibodies (Immunoglobulins)
Plasma Proteins Antibodies (Immunoglobulins) 36% of plasma proteins Release by plasma cells during an immune response Fibrinogens 4% of plasma proteins Produced by liver Forms fibrin threads of blood clot

Other components of plasma
Nutrients and hormones Electrolytes – Ca++, K+, Na+ ions Help to maintain osmotic pressure Sodium ions are the other major solute contributing to blood osmotic pressure Help maintain normal blood pH Gases - CO2 and O2 O2 mostly bound to hemoglobin and CO2 bound to hemoglobin or dissolved in plasma as bicarbonate ion

Other Components of Plasma
Waste – such as uric acid, urea and bilirubin By-product of cellular metabolism Protein metabolism

Components of Whole Blood

Formed Elements The formed elements are present in the buffy coat and the bottom red layer. In other words the formed elements are the erythrocytes, leukocytes, and platelets.

Components of Whole Blood
Figure 17.2

These cells have unusual features.
Formed Elements These cells have unusual features. Two of the three are not even true cells. Why? Erythrocytes have no nuclei or organelles, and platelets are cell fragments. Only leukocytes are true cells Most of the formed elements survive in the bloodstream for only a few days. Most blood cells do not divide.

Erythrocytes normally constitute 45% of the total volume of blood.
Formed Elements Erythrocytes normally constitute 45% of the total volume of blood. This percentage is known as hematocrit (“blood fraction”). In males and females, this percentage might differ: males: 47% ± 5% females: 42% ± 5%

RBC or erythrocytes are involved in gas transport
Formed Elements RBC or erythrocytes are involved in gas transport Carry O2 Carry CO2

Structural Characteristics of RBCs
Major function of RBC is to transport hemoglobin. Erythrocytes are over 97% hemoglobin.

Structural Characteristics
No nucleus (anucleate) or organelles In the RBC cytosol there are different proteins such as: Hemoglobin – made before loss of nucleus Not only carries oxygen but also acts as protein buffer Spectrin – promote changes in RBC shape Antioxidant enzymes

Destruction of Erythrocytes
RBCs are anucleate Limitations due to lack of nucleus: Red blood cells are unable to synthesize new proteins, to grow, or to divide. Erythrocytes become “old” & hemoglobin begins to degenerate.

Destruction of Erythrocytes
Red blood cells have a useful life span of 100 to 120 days, after which they become trapped in the spleen. In the red pulp of the spleen, RBC rupture when they try to squeeze through because of their fragile old membrane. For this reason, the spleen is sometimes called the “red blood cell graveyard”.

Formed Elements WBC (white blood cells) or leukocytes have many specialized functions. What is the purpose of WBCs ?

Formed Elements Leukocytes: Granulocytes Neutrophils Eosinophils
Basophils Agranulocytes Lymphocytes Monocytes

Formed Elements Platelets Cell fragments Encourage clot formation

Formed Elements Formation
Hematopoiesis (hemato = blood, poiesis = to make) Process in which formed elements of the blood develop Erythropoiesis Leukopoiesis Before birth it occurs Yolk sac Later in the liver, spleen, thymus and lymph nodes Last 3 months of gestation in the red bone marrow

Hematopoiesis During childhood (up to 5 years) occurs in the epiphysis of almost all long bones. In adults it occurs also in flat and irregular bones such as the skull, sternum, hip bone, ribs, and vertebra. Formed element production in adults occurs in the humerus and femur.

Checking Understanding
Explain why blood is classified as a connective tissue. (You must give two reasons) What is the average blood volume in human adult? What are the two components of the blood? Why blood is more viscous than water? What is blood’s pH? List three major functions of blood and provide an example of each. Name the formed elements. Why are they elements instead of cells?

Checking Your Understanding
What is the hematocrit? What is the normal value? Are plasma proteins used as fuel for body cells? Explain. Have scratch paper always handy At the end of the class you will write one thing that you did not understand. Do so for today. I’ll discussed those on the following lecture. Review today’s notes.

Topics: RBC and Blood Typing
Structural characteristics Hemoglobin Erythropoiesis Erythrocyte destruction Human Blood types ABO system Rh factor

Red Blood Cells Erythrocytes
The erythrocyte is an excellent example of complementarity of structure and function. Each structural characteristic contributes to its gas transport functions.

Structural Characterstics
Its small size and biconcave shape provides 30% more surface area than other spherical cells. Why is this important?

Because erythrocytes lack mitochondria and generate ATP by anaerobic mechanisms, what happens to the oxygen content inside?

RBC are strong and flexible. Major factor contributing to blood viscosity. There are about 5 million cells per microliter (5,000,000/μl). Glycoproteins – ABO and Rh

It’s the protein that makes RBC red.
Hemoglobin It’s the protein that makes RBC red. Binds easily and reversibly to oxygen Oxygen moves in the blood bound to hemoglobin Normal values of hemoglobin 14-20 g/100ml in infants 13-18 g/100ml in adult males 12-16 g/100ml in adult females

Hemoglobin It’s made of two parts: Heme Globin

Heme – non-protein (pigment)
Hemoglobin Heme – non-protein (pigment) Source of iron in body Iron – held in organic lattice Each iron holds 1 O2

A single RBC contains about 250 million hemoglobin molecules.
So, each RBC can hold about 1 billion molecules of O2.

Hemoglobin Globin - protein 4 polypeptide chains
Mother cells in bone marrow 2 , 2  Any abnormalities in these chains can alter the physical characteristics of hemoglobin.

Hemoglobin When oxygen binds to iron, the hemoglobin, now called oxyhemoglobin, assumes a new three-dimensional shape and becomes ruby red. Oxygen detaches from iron, hemoglobin resumes its former shape, and the resulting deoxyhemoglobin, or reduced hemoglobin, becomes dark red.

Hemoglobin and CO2 The hemoglobin molecule carries 20% of the carbon dioxide in amino acids of the globin part of the molecule rather than the heme group. This forms carbaminohemoglobin, which occurs when hemoglobin is dissociated from oxygen.

Hemoglobin Cooperativity
As it interacts with different molecules it changes the shape of the molecule O2 enters, affinity ↑ The binding of oxygen allows iron to be more accessible and increases the affinity for more oxygen.

Hemoglobin Cooperativity O2 leaves, affinity ↓
The loss of one oxygen molecule from the deoxyhemoglobin lowers the affinity for the remaining oxygen and more oxygen is released.

= erythrocyte production
Erythropoiesis = erythrocyte production Although the various formed elements have different functions, they all arise from the same stem cell. Pluripotent hematopoietic stem cell (or hemocytoblast) Derived from mesenchyme – once committed it follows path Myeloid stem cell - forms into granular leukocytes, monocytes, platelets and erythrocytes

Erythropoiesis Ertyhropoiesis begins when a hemocytoblast descendant called a myeloid stem cell (which develop in the bone marrow) is transformed into a proerythroblast.

Besides the myeloid stem cells, there are also lymphoid stem cells.
Erythropoiesis Besides the myeloid stem cells, there are also lymphoid stem cells. Red bone marrow then lymph tissue Lymphocytes

Erythropoiesis Erythropoiesis needs to be controlled so there is a balance between RBC production and destruction. New cells are made at a rate of more than 2 million per second in healthy people. This process is controlled hormonally and depends on adequate supplies of iron, amino acids and certain B vitamins. Vitamin B12 Intrinsic factor is needed for its absorption Lack of this vitamin causes incomplete maturation of RBC

Erythropoiesis Control
Erythropoietin – EPO (glycoprotein) There is always a small amount of this hormone in the blood keeping a basal rate of production of RBC Produced mainly by the kidneys but the liver produces some A drop in normal oxygen levels triggers EPO formation Tissue becomes oxygen deprived (hypoxia) Too many erythrocytes depresses EPO production.

Erythropoietin Hormone effects: Increases number of proerythroblast
Stimulates red bone marrow to increase rate of cells

1 IMBALANCE Homeostasis: Normal blood oxygen levels Stimulus:
Hypoxia (low blood O2- carrying ability) due to • Decreased RBC count • Decreased amount of hemoglobin • Decreased availability of O2 IMBALANCE Figure 17.6, step 1

1 2 IMBALANCE Homeostasis: Normal blood oxygen levels Stimulus:
Hypoxia (low blood O2- carrying ability) due to • Decreased RBC count • Decreased amount of hemoglobin • Decreased availability of O2 IMBALANCE Kidney (and liver to a smaller extent) releases erythropoietin. 2 Figure 17.6, step 2

1 2 3 IMBALANCE Homeostasis: Normal blood oxygen levels Stimulus:
Hypoxia (low blood O2- carrying ability) due to • Decreased RBC count • Decreased amount of hemoglobin • Decreased availability of O2 IMBALANCE Kidney (and liver to a smaller extent) releases erythropoietin. 2 3 Erythropoietin stimulates red bone marrow. Figure 17.6, step 3

1 4 2 3 IMBALANCE Homeostasis: Normal blood oxygen levels Stimulus:
Hypoxia (low blood O2- carrying ability) due to • Decreased RBC count • Decreased amount of hemoglobin • Decreased availability of O2 IMBALANCE 4 Enhanced erythropoiesis increases RBC count. Kidney (and liver to a smaller extent) releases erythropoietin. 2 3 Erythropoietin stimulates red bone marrow. Figure 17.6, step 4

1 5 4 2 3 IMBALANCE Homeostasis: Normal blood oxygen levels Stimulus:
Hypoxia (low blood O2- carrying ability) due to • Decreased RBC count • Decreased amount of hemoglobin • Decreased availability of O2 5 O2- carrying ability of blood increases. IMBALANCE Enhanced erythropoiesis increases RBC count. 4 Kidney (and liver to a smaller extent) releases erythropoietin. 2 3 Erythropoietin stimulates red bone marrow. Figure 17.6, step 5

Analyzing How might your hematocrit change if you move from a town at sea level to a high mountain village?

Erythrocyte Destruction
Macrophages in spleen, liver and red bone marrow phagocytize dying RBC. Globin – breaks into amino acids, which can be reused to produce other proteins Heme – iron and organic lattice Fe – removed and recycled in spleen Organic lattice – converted to bilirubin Yellow pigment secreted by liver into bile, which is excreted in urine and feces

Low O2 levels in blood stimulate kidneys to produce erythropoietin.
1 Low O2 levels in blood stimulate kidneys to produce erythropoietin. Figure 17.7

1 Low O2 levels in blood stimulate kidneys to produce erythropoietin. 2 Erythropoietin levels rise in blood. Figure 17.7

1 Low O2 levels in blood stimulate kidneys to produce erythropoietin. 2 Erythropoietin levels rise in blood. 3 Erythropoietin and necessary raw materials in blood promote erythropoiesis in red bone marrow. Figure 17.7

1 Low O2 levels in blood stimulate kidneys to produce erythropoietin. 2 Erythropoietin levels rise in blood. 3 Erythropoietin and necessary raw materials in blood promote erythropoiesis in red bone marrow. 4 New erythrocytes enter bloodstream; function about 120 days. Figure 17.7

1 Low O2 levels in blood stimulate kidneys to produce erythropoietin. 2 Erythropoietin levels rise in blood. 3 Erythropoietin and necessary raw materials in blood promote erythropoiesis in red bone marrow. 4 New erythrocytes enter bloodstream; function about 120 days. 5 Aged and damaged red blood cells are engulfed by macrophages of liver, spleen, and bone marrow; the hemoglobin is broken down. Hemoglobin Figure 17.7

Hemoglobin Heme Globin Figure 17.7

Hemoglobin Heme Globin Amino acids Figure 17.7

Figure 17.7 Hemoglobin Heme Globin Bilirubin Iron stored as ferritin,
hemosiderin Amino acids Figure 17.7

hemosiderin Amino acids Iron is bound to transferrin and released to blood from liver as needed for erythropoiesis Figure 17.7

hemosiderin Amino acids Iron is bound to transferrin and released to blood from liver as needed for erythropoiesis Bilirubin is picked up from blood by liver, secreted into intestine in bile, metabolized to stercobilin by bacteria and excreted in feces Figure 17.7

Figure 17.7 Circulation Hemoglobin Heme Globin Bilirubin Iron stored
as ferritin, hemosiderin Amino acids Iron is bound to transferrin and released to blood from liver as needed for erythropoiesis Bilirubin is picked up from blood by liver, secreted into intestine in bile, metabolized to stercobilin by bacteria and excreted in feces Circulation Food nutrients, including amino acids, Fe, B12, and folic acid are absorbed from intestine and enter blood Figure 17.7

Figure 17.7 Circulation Raw materials are made available in
Hemoglobin Heme Globin Bilirubin Iron stored as ferritin, hemosiderin Amino acids Iron is bound to transferrin and released to blood from liver as needed for erythropoiesis Bilirubin is picked up from blood by liver, secreted into intestine in bile, metabolized to stercobilin by bacteria and excreted in feces Circulation Food nutrients, including amino acids, Fe, B12, and folic acid are absorbed from intestine and enter blood 6 Raw materials are made available in blood for erythrocyte synthesis. Figure 17.7

Any decrease in blood’s oxygen-carrying capacity is known as anemia.
Causes: Insufficient number of RBC Low hemoglobin content Abnormal hemoglobin One of the major effects of anemia is the greatly increased work load on the heart.

RBC membranes have glycoprotein antigens on their external surfaces
Human Blood Groups RBC membranes have glycoprotein antigens on their external surfaces These antigens are: Unique to the individual Recognized as foreign if transfused into another individual Promoters of agglutination and are referred to as agglutinogens Presence or absence of these antigens is used to classify blood groups

Agglutinogens = antigens that promote agglutination
Markers on RBC Agglutinogens = antigens that promote agglutination A B O – 2 glycoprotein antigens, A and B Rh Duffy & Kell, many others – at least 30 blood groups

ABO Markers ABO – glycoproteins
Which one is most common? Least prevalent?

ABO Markers Unique to the ABO blood groups is the presence in the plasma of preformed antibodies called agglutinins. Appear within 2 months and reach peak levels between 8-10 years of age.

ABO Markers

There are 45 different types of Rh agglutinogens.
Rh Factor There are 45 different types of Rh agglutinogens. Three of which (C, D, and E) are common About 85% of Americans are Rh positive, which means they carry the D antigen. Presence of the Rh agglutinogens on RBCs is indicated as Rh+ As a rule, a person’s ABO and Rh blood groups are reported together, for example, O+, A-, and so on.

Rh Factor Hemolysis does not occur after 1st transfusion with Rh factor but it occurs in later transfusions. Why?

Rh Factor and Pregnanacy
Mom Rh (-) child Rh (+) Mom makes antibodies at birth. Why? Erythroblastocis fetalis or HDN (hemolytic disease of newborn) Occurs when Rh- mother has a second child that is Rh+ Mom’s antibodies attack and destroy baby’s RBC Baby becomes anemic and hypoxic

Rh Factor and Pregnancy
Rho GAM Injection of anti-Rh antibodies given soon after every delivery, miscarriage, abortion-binds Inactivates fetal Rh antigens so mother’s immune system doesn’t respond

What is the main function of RBC? How does the structure of RBC explains its physiology? How many molecules of oxygen can each hemoglobin molecule transport? What part of the hemoglobin binds the oxygen? What determines whether blood is bright red or a dull, dark red? When RBCs are destroyed, the body processes three components of hemoglobin. List these three components and explain what ultimately happens to each.

Patients with advanced kidney disease often have anemia. Explain this connection. Nigel is told he has type B blood. Which ABO antibodies (agglutinins) does he have in his plasma? Which agglutinogens are on his RBCs? Could he donate blood to an AB recipient? Could he receive blood from an AB donor? Explain. Any questions?

Categories of leukocytes
Characteristics Leukocytosis Categories of leukocytes Granulocytes Agranulocytes Leukopoiesis Disorders

Leukocytes Leuko = They are also known as white blood cells Only formed elements that are complete cells with a nucleus and usual organelles.

Leukocytes What do you know about these cells?

What extra stuff should you know about leukocytes?
1. Diapedesis Able to slip out of the capillary blood vessels “leaping across” The circulatory system is simply their means of transport to areas of the body (mostly loose connective tissues or lymphoid tissues) where they are needed to mount inflammatory or immune responses.

Leukocytes 2. Amoeboid motion
This is how leukocytes move through the tissue spaces. They form flowing cytoplasmic extensions that move them along (pseudopods). What is it for?

Leukocytes 3. Positive chemotaxis
the chemical trail of molecules released by damaged cells or other leukocytes How is this useful?

Leukocytes Leukocytosis
This condition appears when the white blood cell count is over 11,000 cells/µl (normally ,800). Whenever white blood cells are mobilized for action, the body speeds up their production and twice the normal number may appear in the blood within a few hours. This condition is a normal homeostatic response to an infection in the body. What is its significance?

Categories of Leukocytes
Leukocytes are grouped into two major categories: Granulocytes Neutrophils Eosinophils Basophils Agranulocytes Lymphocytes Monocytes

How to remember all the cells and in order of abundance?
List leukocytes from most abundant to least abundant: Never Let Monkeys Eat Bananas N = neutrophils L = lymphocytes M = monocytes E = eosinophils B = basophils

Granulocytes All are roughly spherical in shape Stored in bone marrow until needed They are larger than erythrocytes

They are phagocytes (some more than others)
Granulocytes They have membrane-bound cytoplasmic granules (reason for their category) They can be stain specifically with Wright’s stain The cytoplasmic granules contain enzymes involved in detoxification of foreign substances, blood clotting, and various immune responses. They are phagocytes (some more than others)

Neutrophils Most numerous (50-70% of WBC), life span less than a week
Twice as large as RBC Stain pale lilac with very fine granules that are difficult to see Why are their granules lilac? Neutro= neutral, phils = loving Their granules take up both basic (blue) and acidic (red) dyes Explains: Neutral name and lilac color Some contain hydrolytic enzymes; others have antimicrobial proteins (defensins)

Neutrophils Respond most quickly to tissue destruction by bacteria or fungus Active in phagocytosis

Neutrophils Neutrophils are our body’s bacteria slayers First one at “war zone”. Can phagocytize 5-20 bacteria before it dies.

Eosinophils Eos = dawn 2-4% of all leukocytes (~450 cells)
Usually found in other tissues besides blood or bone marrow The place with most eosinophils is the GI About the same size as neutrophils but weaker phagocytes Life span is less than 2 weeks in CT Deep red nucleus with 2 lobes

Eosinophils Parasitic worms (most important role)
Release enzymes onto the parasite’s surface, digesting it away

Basophils Rarest WBC (0.5 - 1% of WBC)
Large histamine-containing granules Affinity for basic dyes so they stain purplish black (baso = basic) Deep purple nucleus with U or S shape and 2 or three lobes. Life span is long (1-1.5 years)

Similar in function to mast cells
Basophils Similar in function to mast cells Bind to IgE, which causes cells to release histamine Release of histamine intensifies inflammatory reactions

Granulocytes All granulocytes are phagocytic but neutrophils are the most phagocytic of them all.

Include lymphocytes and monocytes
Agranulocytes Include lymphocytes and monocytes Both produced in red bone marrow but lymphocytes can also be produced in lymphatic organs such as lymph nodes and spleen. Major soldiers with a life span of days

B Lymphocytes B cells Attack bacteria, viruses and toxins
Plasma cells → antibodies (Ig = immunoglobulin) Memory cells Keep a “record” of pathogens

T Lymphocytes T cells Acting directly against virus-infected cells and tumor cells CD 4 T helper cells CD 8 T cytotoxic cells

NKC Natural Killer Cells
Wide variety of microbes and tumor/cancer cells

Movement of Lymphocytes
Recirculate (another difference from granulocytes) blood → interstitial space → lymphatic fluid → blood Show ability to deformate

Monocytes They have abundant pale-blue cytoplasm and a darkly staining purple nucleus, which is distinctively U or kidney shaped Life span is less than 3 days in bloodstream

Take longer to get there but arrive in larger numbers
Monocytes Take longer to get there but arrive in larger numbers Migrate from blood into tissues where they enlarge and become macrophages (which are phagocytic) Destroy more microbes 100 bacteria because they extrude toxins

Macrophages Most powerful phagocyte Engulf larger and 5 times as many particles as neutrophils They can phagocytize whole RBC, malarial parasites and dead neutrophils They are very important in starting immune responses They can be called different names when they stay in different tissues.

Macrophages and MHC MHC – major histocompatibility complex (self antigen) Glycoproteins that protrudes from plasma membrane into ECF Cell identity markers unique for each person, what about identical twins?

Leukocytes - review Figure 17.10

Leukopoiesis Production of white blood cells
It’s stimulated by chemical messengers Messengers Glycoproteins that fall into two families of hematopoietic factors Interleukins Numbered (e.g., IL-3, IL-5) Colony-stimulating factors, or CSFs. Named for the leukocyte population they stimulate Thus granulocyte-CSF (G-CSF) stimulates production of granulocytes.

Myeloid Stem cell Lymphiod stem cell
Granulocytes and monocytes (agranulocyte) Lymphiod stem cell Lymphocytes (agranulocyte)

Imbalances (Leukocyte disorders)
Leukopenia – abnormally low numbers of WBC due to drugs such as glucocorticoids and anticancer agents. Leukemia – cancerous conditions involving WBC, named based on cell type affected. Lymphocytic leukemia – involves lymphocytes Affects formation of other formed elements Infectious mononucleosis – highly contagious viral disease (Epstein-Barr virus), it causes an excessive number of atypical agranulocytes

Checking your understanding on Leukocytes
What is the importance of leukocytes? Which stem cell gives rise to WBC? How is their production stimulated? Besides the ability to move by amoeboid motion, what other physiological attributes contribute to the function of WBC? Which granulocytes would be higher in numbers for a bacterial infection? Parasitic infection? Allergy?

Checking your understanding on Leukocytes
Which WBC turns into macrophages in tissues? Which other WBC is a voracious phagocyte? If you have a severe infection, would you expect your WBC count to be closest to 5,000, 10,000, or 15,000 μl? What is this condition called? Amos has leukemia. Even though his WBC count is abnormally high, Amos is prone to infections, bleeding, and anemia. Explain. Any questions?

Platelets Topics Characteristics Platelet formation Hemostasis
Vascular spasm Platelet plug formation Coagulation Requirements for clotting Clot retraction Fibrinolysis and anticoagulants

Thrombocytes Megakaryocyte Plateletes Throm = clot
Huge cells, splinter into cytoplasmic fragments ¼ diameter of a lymphocyte

Platelet = cytoplasmic fragments
Platelets Platelet = cytoplasmic fragments Granules contain array of chemicals that act in clotting process, include: Serotonin, Ca2+, a variety of enzymes, ADP, and platelet-derived growth factor (PDGF)

Platelets Platelets are essential for the clotting process that occurs in plasma when blood vessels are ruptured or their lining is injured. By sticking to the damaged site, platelets form a temporary plug that helps seal the break.

Platelets are anucleate
Consequently, they age quickly and degenerate in about ten days if they are not involved in clotting In the meantime, they circulate freely, kept mobile but inactive by molecules (nitric oxide, prostacyclin) secreted by endothelial cells lining the blood vessels.

Platelet Formation The stem cell for platelets is the hemocytoblast (myeloid stem cell) The sequential developmental pathway is as shown. Endomitosis – mitosis without cytokinesis

150,000-400,000 platelets/mm3 of blood
Platelet Formation 150, ,000 platelets/mm3 of blood Life span of 10 days Thrombopoietin Hormone that regulates platelet formation Produced by liver Stimulates stem cells to develop into precursor cells - megakaryoblast

Sequence of responses that stop bleeding
Hemostasis Hemo = blood Stasis = halting Sequence of responses that stop bleeding 3 Steps to stop bleeding: (1) vascular spasms (2) platelet plug formation (3) coagulation, or blood clotting

Initial stimulus or triggered by
Vascular spasms Initial stimulus or triggered by Mechanical damage to vessel (direct injury to vascular smooth muscle) Chemicals released by endothelial cells and/or platelets Reflexes initiated by local pain receptors

Leads to blood vessel constriction
Vascular spasm Leads to blood vessel constriction Serotonin – hormone that is a major vasoconstrictor For which platelets are the major storage Reduces blood loss for about minutes Which allows blood clotting to occur Most effective in smaller blood vessels

Platelet Plug Formation
Platelets do NOT stick to endothelial cells or to each other. They bind to collagen fibers that are exposed when damage is done to the vessel. Platelet plug formation: Platelet adhesion Platelet release reaction Platelet aggregation

Platelet Adhesion Exposed collagen fibers make a rough surface to which platelets are attracted Stick to parts of damaged blood vessel Temporarily seals the break

Platelet Release Reaction Release contents of vesicles which causes decrease of blood flow through vessel Serotonin – enhance vascular spasms ADP – aggregating agent – attracts more platelets Thromboxane A2 – stimulates both

Platelet Aggregation A positive feedback cycle that activates and attracts greater and greater numbers of platelets to the area begins and, within one minute, a platelet plug is built up, which further reduces blood loss

Coagulation or Blood Clotting
Blood is transformed from a liquid to a gel It is a multistep process that leads to its critically important last three phases: A complex substance called prothrombin activator is formed. Prothrombin activator converts a plasma protein called prothrombin into thrombin, an enzyme. Thrombin catalyzes the joining of fibrinogen molecules present in plasma to a fibrin mesh, which traps blood cells and effectively seals the hole until the blood vessel can be permanently repaired.

Coagulation or Blood Clotting
Serum = plasma without clotting factors (contains antibodies) Any factor that enhances clot formation is called a clotting factor. Factors I to XIII Named by discovery not steps Anticoagulant will be those that inhibit coagulation Normally these dominate unless there is injury to blood vessels.

Coagulation Clotting may be initiated by either intrinsic or extrinsic pathways. Each pathway involves a cascade of activation steps yielding factor X (common intermediate). PF3 (platelet factor 3) and calcium (clotting factor IV) are needed for both pathways.

Extrinsic Pathway Fast (clot form b/w sec) Occurs when blood is exposed to tissue factor (TF), which is found on the surface of cells. When Ca++ and PF3 are present, TF stimulates the formation of prothrombin activator Prothrombin → Thrombin Thrombin + Ca causes fibrinogen to change to fibrin

All factors needed for clotting are present in the blood.
Intrinsic Pathway All factors needed for clotting are present in the blood. Slow (3-6 min) due to many intermediate steps Triggered by negatively charged surfaces (collagen, platelets and glass) Platelets detect collagen in blood vessel CT and release PF3 → prothrombin activator → prothrombin → thrombin → fibrinogen → fibrin

Why does blood clotting ends with fibrin formation?
Fibrin strands glue platelets together Makes a web that forms the structural basis of the clot. Makes plasma become gel-like Traps formed elements that try to pass through it

Requirements for Clotting
Calcium Needed as a cofactor in many of the enzyme conversions Vitamin K Not directly involved in coagulation Required for synthesis of 4 clotting factors by hepatocytes Factors II (prothrombin), VII, IX and X Produced by bacteria in large intestine

As clot retraction is occurring, vessel healing is taking place.
Coagulation Within 30 to 60 minutes, the clot is stabilized further by a platelet-induced process called clot retraction. Platelets contract, they pull on the surrounding fibrin strands, squeezing liquid (serum), compacting the clot and drawing the ruptured edges of the blood vessel more closely together. As clot retraction is occurring, vessel healing is taking place.

Fibrinolysis Removes unneeded clots when healing has occurred
If it doesn’t happen, vessels get blocked. Plasminogen – inactive plasma enzyme incorporated into clot Plasmin (activated plasminogen) Breaks down fibrin Body tissues and blood contain substances that activate plasminogen to plasmin

Fibrinolysis Fibrinolysis begins within two days and continues slowly over several days until the clot is finally dissolved

Anticoagulant Heparin Natural anticoagulant in basophil and mast cells
Also produced by endothelial cells Used in medicine to to prevent blood clotting during open-heart surgery, bypass surgery, and dialysis Inactivates thrombin

Imbalances (Disorders of Hemostasis)
Thrombus – clot that develops and persists in an unbroken vessel which can lead to thrombosis where tissue/organ die because of obstruction (coronary thrombosis) Embolism – when small vessel is obstructed from embolus (piece of thrombus that broke away) Thrombocytopenia – number of platelet is deficient in blood

Imbalances (Disorders of Hemostasis)
Hemophilia – group of hereditary bleeding disorders that have similar signs and symptoms. Hemophilia A – deficiency of clotting factor VIII Most common type of hemophilia (X-linked) Hemophilia B Deficiency in factor IX (X-linked) Hemophilia C Less severe and found in both sexes and due to clotting factor XI deficiency

Checking your understanding: Platelets
Which stem cell gives rise to platelets? Which cell fragments to form platelets? What regulates platelets formation? What are the three steps of hemostasis? Explain each briefly. What is the difference between fibrinogen and fibrin? What factors (2) are needed for intrinsic and extrinsic pathway? Compare and contrast intrinsic and extrinsic pathways. How can liver dysfunction cause bleeding disorder? What is the importance of fibrinolysis? Which bleeding disorder results from not having enough platelets? From absence of clotting factor VIII?

THE END

17 Blood Modified by: Olga E. Vazquez.

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