1. Hemo, hemato refers to blood
Many human rituals involve blood. Recognized as essential to life.
Hemo, hemato = blood.
Hemo, hemato refers to blood

2. Characteristics of Blood
Fluid; connective tissue
Living cells = formed elements
Non-living matrix = plasma
Transport -
Gases, nutrients, wastes, hormones, heat
Regulation
Defense
Blood cells - 45% plasma - 55% formed elements
Buffy layer = WBC, platelets
More viscous than water. Viscosity important b/c affects load on heart, ease of pumping through small blood vessels.
5 liters per adult. 8% of body weight. Important organ
FUNCTI”ONS; transport, as noted.
Blood temperature is slightly higher than body temperature
Regulation of salt, sollute concentrations, pH of body fluids. pH must remain between 7.35–7.45
Protection: clotting to stop blood loss
against pathogens. WBC phagocytize bacteria, produce antibodes, interferons, complement proteins.
Important part of inflammatory response.

3. Blood Plasma about 90 percent water Includes dissolved substances:
Nutrients
Salts (metal ions)
Respiratory gases
Hormones
Proteins
Waste products
Blood Plasma makes up 55% of blood volume.
Composed of approximately 90 percent water
Includes many dissolved substances
Nutrients - glucose, amino acids, fatty acids, vitamins
Salts (metal ions) - Na+, K+, Ca++, Mg++, Cl-, H2CO3. Blood buffering, membrane permeability.
Respiratory gases- ; Hormones
Proteins - most abundant component. Albumin: helps maintain osmotic pressure, retain water in blood.
globulins: bind to cpds, for transport. Ex. LDL, HDL. Gamma globulins for defense.
Clotting proteins: stop blood loss when vessel is broken.
Antibodies - protect from pathogens.
Proteins are NOT used as fuel source by cells. Waste products - urea.

4. Formed Elements Erythrocytes = red blood cells, RBC
Leukocytes = white blood cells, WBC
Platelets = cell fragments
RBC 45%
WBC 1%
Platelets - essential to clotting

5. Erythrocytes (Red Blood Cells)
Carry oxygen
Biconcave disks
Essentially bags of hemoglobin
Anucleate (no nucleus)
Contain very few organelles
Outnumber white blood cells 1000:1
Hematocrit - % RBC
Also carry some carbon dioxide, small amount.
Shape produces large surface/volume, so well suited for gas exchange.
Hemoglobin - Iron-containing protein
Binds strongly, but reversibly, to oxygen. Bright red when bound.
Each hemoglobin molecule has four oxygen binding sites. Dependent on iron in heme group.
Each erythrocyte has 300 million hemoglobin molecules = 1.2 billion O2 per RBC.
Few organelles - no mitochondria, so no aerobic respiration. Use glycolysis alone for energy. Do not use up any of the O2 they shuttle.
No nucleus, th4, no going back to genome for different products. Must make do with whatever RNA it has.
Density ranges of RBC million per mm3
hematocrit reflects oxygen-carrying capacity of blood. Too low = anemia. Too high = polycythemia. If viscosity is too high, can cause high BP. At high altitudes, more RBC made after 3 days. Reflects need of body for more oxygen.

6. Fate of Erythrocytes Unable to divide, grow, or synthesize proteins
Wear out in 100 to 120 days
then eliminated by phagocytes in spleen or liver
RBCs replaced by dividing stem cells
Blood stem cells = hemocytoblasts.
Worn out cell parts are recycled; iron goes to bone marrow, heme group converted to bilirubin in liver and into bile duct, out w/ food waste. Sequence of colors of a healing bruise due to conversion of hemoglobin to bilirubin.
Jaundice (yellow skin color) due to excess bilirubin in circulation. Caused by bile duct is blocked or massive breakdown of RBCs.

7. Control of Erythrocyte Production
Homeostasis triggered by blood oxygen levels
Kidneys produce erythropoietin as a response to reduced oxygen levels in the blood
RBC replaced at typical rate of 2 million per sec just to maintain base level.
Erythropoietin stimulates stem cells in red bone marrow to divide.
Blood doping - using erythropoietin or synthetic version to increase RBC content. Dangerous risk of clotting, high BP with excess RBC.

8. Hematopoiesis In red bone marrow RBCs, WBCs Blood cell formation
Occurs in red bone marrow: long bones in children, hip (iliac) in adults.
All blood cells are derived from a common stem cell (hemocytoblast). Good example of why stem cells in general are valued for medical purposes. Analogy with trip across US, no backtracking allowed.
Hemocytoblast differentiation
Lymphoid stem cell produces lymphocytes
Myeloid stem cell produces other formed elements
Classification based on appearance when stained. Granules become visible. Maturation in bone marrow, mostly.
Lifespans vary from days to years, dept on type of WBC.
WBC can leave the blood vessel, move btw tissues and enter lymph system.

9. Leukocytes (White Blood Cells)
Body’s defense against disease
Has nucleus and organelles
moves into and out of blood vessels (diapedesis)
moves by amoeboid motion
responds to chemicals from damaged tissues
Moves to site of tissue damage via circulatory system, then leaves capillaries and moves like an amoeba thru tissues. Chemotaxis - responds to chemicals.
Immune and inflammatory responses lifespan from days to years, dept on type.
Normal levels are between 4,000 and 11,000 cells per millimeter
Abnormal leukocyte levels
Leukocytosis - above 11,000 leukocytes/ml
Generally indicates an infection. When needed, body doubles production of WBCs.
Leukopenia - Abnormally low leukocyte level
Commonly caused by certain drugs
Leukemia - “white blood” cancerous bone marrow produces lots more WBCs. Immature and not able to function as defense for body. Treatment can involve bone marrow transplant.

10. Granulocytes 1. Neutrophils Multilobed nucleus with fine granules
Act as phagocytes at active sites of infection
2. Eosinophils - Large brick-red cytoplasmic granules
Found in response to allergies and parasitic worms
3. Basophils - Have histamine-containing granules
Initiate inflammation
Granulocytes - W/ granules in their cytoplasm = vesicles that contain proteins, enzymes.
1.neutrophils, - about half of WBC. phagocytosis, esp agst bact and some fungi. Can increase in number during infection. First line of defense.
2. Eosinophils - rare. Only 2-3% of WBC. Conduct chemical attack agst large pathogens, moderate response to allergens.
3. Basophils - rarest WBC only 0.5% of WBC. Release histamine when tissue is damaged. Histamine causes more blood plasma to be released. Brings nutrients for repair and swelling, redness to tissue. Inflammatory response that leads to healing. Trigger for allergies.

11. Agranulocytes Lymphocytes (B, T cells) Large nucleus
Specific immune response
Monocytes
Largest of the white blood cells
Function as macrophages
Important in fighting chronic infection
Lymphocytes - 30% of WBC. In blood stream, lymph nodes, spleen, thymus gland. Part of immune response that recognizes specific threats. Vaccines stimulate their production.
B cells give rise to antibodies.
T cells destroy specific threats of virus, bact, cancer cells.
Monocytes - leave blood vessels and become larger macrophages, eating up pathogens, esp viruses and bacteria. Can stimulate production of lymphocytes.

12. leukemia

13. Platelets Derived from ruptured multinucleate cells (megakaryocytes)
Needed for the clotting process
Normal platelet count = 300,000/mm3
Platelets are fragments of cell, pinched off from megakaryocytes by the thousands. Megakaryocytes stay in bone marrow. Carry fluids that are sealed off from blood fluids.
Platelets last only a few days, then must be replaced. Continuous. Platelet concentration can be increased by hormone thrombopoietin.

14. Hemostasis = Stoppage of blood flow
Result of a break in a blood vessel
Fast reaction minutes
3 phases
Fast reaction to prevent loss of blood. Whole process takes only 3-6 minutes.

15. 1. Vascular Spasms spasm by blood vessel muscles
blood vessel narrows, decreasing blood loss
Other factors which contribute to vascular spasm:
activation of pain receptors
direct injury to smooth muscle cells.
Serotonin causes spasms. Released by bound platelets.
Spasms can last up to 30 minutes.

16. 2. Platelet Plug Formation
Collagen fibers exposed
Platelets become “sticky” and cling to fibers
release chemicals to attract more platelets
Platelets form a plug
Platelet plug formation:
Collagen fibers are exposed by a break in a blood vessel
Platelets become “sticky” and cling to fibers
Anchored platelets release chemicals to attract more platelets
Platelets pile up to form a platelet plug.
With minor injuries, that may be all; no blood clot. If bigger injury, clot forms.

17. 3. Coagulation a clotting cascade
Injured tissues stimulate release of prothrombin activator
Which (with Ca++) converts prothrombin to thrombin (an enzyme)
Thrombin joins fibrinogen proteins into hair-like fibrin. Network that traps cells.
Process also involves vitamin K, other blood protein clotting factors, thromboplastin
Chain of activation events, some involving enzymes. At least 12 clotting factors needed.
Damaged vessels & platelets release thromboplastin, which causes release of prothrombin activator.
With Ca++ present, Prothrombin activator converts prothrombin to thrombin (an enzyme).
Fibrinogen is soluble in plasma. Fibrin is not. Network traps RBCs, platelets; plug stops blood flow. All in under an hour.

18. Coagulation Fibrin forms a meshwork (the basis for a clot)
BLOOD Clotting -
Blood usually clots within 3 to 6 minutes. First fibrin tangles in less than a minute. Platelets contract, tightening clot. Requires 12 different factors.
The clot remains as endothelium regenerates
The clot is broken down after tissue repair
Hemophilia - lack of blood clotting. Most common form is hemo a, which lacks Factor VIII.
Treatment now with addition of GE protein factors. Minor injuries can be life threatening. Puts lots of blood in interstitial spaces. Causes joint problems.
Aspirin - inhibits clotting reaction by slowing platelet plug. Avoid before surgery.

19. Undesirable Clotting Thrombus A clot in an unbroken blood vessel
Embolus
A thrombus that breaks away and floats freely in the bloodstream
Bleeding Disorders
Hemophilia, thrombocytopenia
Thrombus
A clot in an unbroken blood vessel
Can be deadly in areas like the heart
Embolus
A thrombus that breaks away and floats freely in the bloodstream
Can later clog vessels in critical areas such as the brain
BLEEDING DISORDERS
Thrombocytopenia - deficiency of platelets due to suppression of myeloid tissue in the bone marrow. Can also be caused by liver that doesn’t make adequate clotting factors. Needs enough Vit K to make clotting factors. Sick liver, as with cirrhosis, hepatitis is not easily treated.

20. Blood Groups and Transfusions
Large losses of blood: consequences
Loss of 15 to 30 percent causes weakness
Loss of over 30 percent causes shock, which can be fatal
Transfusions to replace blood quickly
must be same blood group

21. Blood contains genetically determined proteins
A foreign protein (antigen) may be attacked by the immune system
There are over 30 common red blood cell antigens
The most vigorous transfusion reactions are caused by ABO and Rh blood group antigens
Describe antigen/antibody production, prelude to immune system.

22. Blood is “typed” by using antibodies that will cause blood cells to clump (agglutination)
Based on the presence or absence of two antigens
Type A
Type B
The lack of these antigens is called type O
Blood samples are mixed with anti-A and anti-B serum
Coagulation or no coagulation leads to determining blood type
Typing for ABO and Rh factors is done in the same manner
Cross matching – testing for agglutination of donor RBCs by the recipient’s serum, and vice versa

23. Blood Typing
If transfusion with wrong type of blood, clumping occurs. Vessels clogged, foreign RBCs broken down, release hemoglobin - LOTS of hemoglobin. Clogs kidney tubules, shuts down kidneys. Fatal.
Figure 10.8

24. Rh Blood Groups Named for one of eight Rh antigens (agglutinogen D)
Most Americans are Rh+
Problems can occur in mixing Rh+ blood into a body with Rh– blood
Rxn does not occur right away, as Rh antibodies are not made unless exposure has occurred.

25. Danger is only when the mother is Rh– and the father is Rh+, and the child inherits the Rh+ factor
The mismatch of an Rh– mother carrying an Rh+ baby can cause problems for the unborn child
The first pregnancy usually proceeds without problems
The immune system is sensitized after the first pregnancy
In a second pregnancy, the mother’s immune system produces antibodies to attack the Rh+ blood (hemolytic disease of the newborn)
Same problem if several transfusions are given, Rh- to Rh+.
Prevent problem by treating Rh+ mother with antibody Rhogam to reduce concentration of inciting antigen. So mother’s immune system never sees

26. Developmental Aspects of Blood
Sites of blood cell formation
fetal liver, spleen are early sites of blood cell formation
Bone marrow takes over hematopoiesis by the seventh month
Fetal hemoglobin differs from hemoglobin produced after birth
Fetal hemoglobin w/ higher affinity for oxygen. Helps to maintain enough O2 in fetus. Switches after birth to adult
alpha, beta forms. Rapic breakdown of fetal hemglbn can lead to a form of jaundice (physiological jaundice) if the liver cannot process the fetal hemoglbn fast enough.
treatment of sickle cell involves stimulating the production of fetal hmg, as this is less subject to sickling.

27. Blood Disorders Carbon monoxide poisoning
Anemia - reduced oxygen capacity
Leukemia - excess WBC
Mononucleosis - viral infection
Blood poisoning
CO poisoning - colorless, odorless gas. From any burning of carbon. 200 times higher affinity for hemoglobin than oxygen. Displaces it in heme group and stays there for hours. Treatment - fresh air, transfusion.
Use CO detector indoors.
Anemia - several causes, common result is low oxygen capacity.
Iron deficiency. Fewer heme groups. Most common world wide.
Aplastic anemia - not enough stem cells in bone marrow.
Sickle cell anemia -
Leukemia - excess WBC. Several types, common symptom is lots of immature WBC circulating which prevents normal functioning of other BC, including RBC.
Treatments involve killing rapidly dividing cells, which kills own stem cells. Then replace with matched donor marrow.
Mononucleosis caused by Epstein Barr virus. Can be transmitted person to person. Must let body fight off infection takes weeks. No magic pill.