Blood A&P II Lecture

A fluid connective tissue composed of:

• 1. plasma
• 2. Formed elements
• -Erythrocytes (RBCs)
• -Leukocytes (WBCs)
• -Platelets (cell fragments)

Blood is a sticky, paque fluid tasting metallic and salty with the color scarlet (O₂ rich) to dark red (O₂ deficient)

pH--> 7.35-7.45 slightly alkaline

38 degrees C or 100.4 degrees F

About 8% of a person's body weight

• Males: 5-6L
• Females: 4-5L

• When spun in a centrifuge:
• -plasma is the least dese at 55% of the blood
• -Buffy coat in the middle makes up less than 1% (made of platelets and WBCs)
• -Hematocrit is the most dense at 45%

Hematocrit (RBCs) is 47% (plus or minus 5%) in males and 42% (plus or minus 5% in females)

Blood: Distributes, protects, and regulates

Distributes: O₂ and nutrients to body cells, metabolic wastes to the lungs (CO₂) and kidneys (nitrogenous waste) for elimination

Protects Against: Blood loss (plasma protiens and platelets initiate clot formation), and Infection (antibodies, complement protiens, and WBCs defend against foreign invaders)

Regulates: body temperature by absorbing and distributing heat, normal pH using buffers (also the alkaline reserve in bicarbonate atoms), and adequate fluid volume in the circulatory system

is 90% water, light yellow, and sticky

• 8% of the plasma is proteins and proteins are mostly produced by the liver
• *6-% albumin- major contributer to maintaing plasma osmotic pressure that helps keep water in the blood stream
• *36% globulins- gamma globulins are actually antibodies released by plasma cells
• *4% fibrinogen (threads to make fibrin for blood clot)

1. Nitrogenous by-products of metabolism- lactic acid, urea, and creatine

2. Nutrients- glucose, carbohydrates, amino acids

3. Electrolytes (help to maintain pH and plasma osmotic pressure)- Na⁺, K⁺, Ca², Cl^-, HCO₃^-


4. Respiratory Gases- O₂ and CO₂


5. Hormones

erythrocytes, leukocytes, and platelets

Only WBCs are complete cells

RBCs have no nuclei or organelles

Platelets are cell fragments

Most formed elements only survive in the blood stream for a few days

Most blood cells originate from red bone marrow and do not divide

• Their structural characteristics contribute to gas transport
• -biconcave shape makes a huge surface area relative to volume
• -Over 97% Hb (not counting water)
• -No mitochondria; ATP production is anaerobic so none of the O₂ it is carrying gets used up!

Perfect example of how function mirrors structure!

RBCs are dedicated to respiratory gas transport

Hb binds reversibly with O₂

• Hb structure: Protein globin- two alpha and two beta chains
• Heme pigmennt bonde to each globin chain contains iron

Iron atom in each heme can bind to one O₂ molecule

• Each Hb molecule can transport 4 O₂
• 

O₂ loading in the lungs produces oxyhemoglobin (ruby red)

O₂ unloading in the tissues produces deoxyhemoglobin or reduced hemoglobin (dark red)

CO₂ loading in the tissues procuces carbaminohemoglobin (carries 20% CO₂ in the blood)

Blood cell formation

Occurs in the red bone marrow of axial skeleton, gircles and proximal epiphyses of hermus and femur

• Hemocytoblasts (hemopoietic stem cells)-
• *give rise to all formed elements
• *hormones and frowth factos push the cell toward a specific pathway of blood cell development

New blood cells enter sinusoids

Red blood cell production

A hemocytoblast (myeloid stem cell) is transformed into a proerythroblast

proertythroblasts develop into early erythroblasts

15 day process

• 1.Ribosome sythesis (Early to late erythroblast)
• 2. Hemoglobin accumulation (late to normoblast)
• 3. Ejection of the nucleus and formation of reticulocytes (normoblast to reticulocytes)

• Reticulocytes become mature erythrocytes (reticulocytes help determine the rate of RBC production)
• 

too few RBCs leads to hypoxia (O₂ deprivation)

too many RBCs increases blood viscosity

• balance between RBC production and desctruction depends on:
• 1. hormone controls
• 2. adequate supplies of iron, amino acids, annd B vitamins

• Erythropoietin (EPO)
• -direct stimulus for erythropoiesis
• -released by the kidneys (and a small amount in the liver) in response to hypoxia
•        *hypoxia causes HIF (hypoxia-inducible factor) and as it accumulates it signals the release of EPO

• Effects of EPO
• - more rapid maturation of committed bone marrow cells
• -Increased curculatin reticulocyte count in 1-2 days

Testosterone also enhances Epo production, resulting in higher RBC counts in males

Hemorrhage or increased RBC destruction

Insufficient Hb (iron deficiency)

Reduced availability of O₂ (such as high altitudes)

Nutrients: - amino acids, lipids, and carbohydrates

• Iron
• *stored in Hb (65%), the liver, spleen, and bone marrow
• *stored in cells as ferritin and hemosiderin because free iron is toxic
• *transported loosely bound to the protein transferrin

Vitamin B₁₂ and folic acid- necessary for DNA synthesis for cell division

Life span: 100-120 days

Old RBCs become fragile and Hb begins to degenerate

Macrophages engulf dying RBCs in the spleen (called the RBC graveyard)

• How it happens:
• 1. Heme and globin are separated
• 2. Iron is salvaged for reuse
• 3. Heme is degraded to yellow pigment bilirubin (binds to albumin for transport)
• 4. Liver secretes bilirubin (in bile) to intestines
• 5. Degraded pigment leaves body in the feces as tercobilin
• 6. Globin is metabolized into amino acids

1. Insufficient erythrocytes

2. Low Hb content

3. Abnormal Hb

Hemorrhage anemia: acute or chronic loss of blood

Hemolytic anemia: RBCs rupture prematurely (due to mismatched transfusion, Hb abnonormalities, certain bacterial and parasitic infections)

Aplastic anemia: destruction or inhibition of red bone marrow (the cause is unknown in most cases

• 1. Iron deficiency anemia
• - secondary result of hemorrhagic anemia or
• -inadequate intake of iron-containing foods or
• - impaired iron absorption (erythrocytes produced are microcytes, small and pale)

• 2. Pernicious Anemia
• -Deficiency of vitamin B₁₂
• -Lack of intrinsic factor in stomache mucosa needed for absoption of B₁₂
• -treated by intramuscular injection of B₁₂ or application of nascobal (to the nasal lining once a week)
• *autoimmune and mostly effects the elderly

• 1. Thalassemias (Sea blood)
• -absent or faulty globin chain
• -RBCs are thin, delicate, and Hb deficient

• 2. Sickle cell Anemia
• -defective gene codes for abnormal hemoglobin (HbS)
• -causes RBCs to become sickle shaped in low O2 situations
• *they then rupture easilty and block small blood vessels
• *strikes mostly african americans from the malaria belt b/c if someone only have one gene of SSA they have a better change against malaria

Polycythemia: excess of RBCs that increase blood viscosity making it thick and sludgy

• Results from:
• -Polycythemia vera: bone marrow cancer
• -Secondary polycythemia- when less O₂ is available (high altitudes) or when EPO production increases

Treated by removing some blood and replacing it with saline

Blood doping: athletes remove some blood a few days before an event so that new RBCs are created, then the blood is put back in the day of the race.  More RBCs means a high VO₂ max

make up less than 1% of total blood volume

can leave capillaries via diapededsis

move through tissue spaces by ameboid motion and positive chemotoxis (following a train of molecules released by damaged cells)

• Leukocytosis: when WBC count is over 11,000/mm³
• -normal response to bacterial or viral invasion
• -WBC count can double in just a few hours

• Two main types:
• granulocytes and agranulocytes

Neutrophils, eosinophils, and basophils

Cytoplasmic granules stain specifically with wright's stain

larger and shorter-lived than RBCs

Lobed nuclei

• Phagocytic- engulf foreign cells
• 

most numerous WBCs

polymorphonuclear leukocytes (PMNs)

Fine granules take up bot acidic and basic dyes-gives the cytoplasm a lilac color

granules contain hydrolytic enzymes and defensins

Very Phagolytic-"bacteria slayers"-promoted by the respiratory burst where they stab bacteria

redstaining, bilobed nuclei

red to crimson (acidophilic) coarse, lysosome-like granules

digest parasitic worms that are too large to be phagocytized (they gather around a parasite and release enzymes to digest it)

modulators of the immmune response

rarest WBCs

• large, purplish-black (basophilic) granules contain histamine
• -histamine: an inflammatory checmical that acts as a vasodialiator (makes blood vessels dialate) and attracts other WBCs to the inflamed site

Are functionally similar to mast cells

Never Let Monkeys Eat Bananas

• Neutrophils
• Lymphocytes
• Monocytes
• Eosinophils
• Basophils

Lymphocytes and Monocytes

Lack visible cytoplasmic granules (they simply don't stain)

• have spherical or kidney shaped nuclei
• 

Large, dark purple, circular nuclei with a thin rim of blue cytoplasm

mostly in lymphoid tissue, few circulate in the blood

crucial to immunity

• Two types:
• T Cells- act against virus-infected cells and tumor cells
• B Cells- give rise to plasma cells, whic produce antibodies (immunoglobulins)

The largest leukocytes

Abundant pale blue cytoplasm

Dark purple staining, U or kidney shaped nucleus, crushed glass looking cytoplasm

• They can leave circulation and enter tissues where they turn ameboid and differentiate into macrophages
• -actively phagocytic cells; crucial against viruses, intracellular bacterial parasites, and chronic infections such as TB

Activate lymphocytes to mount an immune response

Production of WBCs

• Stimulated by chemical messengers from bone marroe to mature WBCs
• -Interleukins (eg. IL-1, IL-2)
• -Colony-stimulation factors (CSFs)- named for the WBC type that they stimulate (ex. CSF granulocytes)

• All leukicytes originate from hemocytoblasts
• 

1.Leukopenia: abnormally low WBC count- drug induced (esp by anti-cancer agents)

• 2. Leukemias: cancerous conditions involving WBCs
• -Named according to the abnormal WBC clone involved
• -Myolocytic leukemia involved myeloblasts while lymphocytic leukemia involved lymphocytes

Acute leukemia involved blast-type cells and primarily affects children (quickly advancing)

Chronic leukemia is more prevalent in the elderly and is slow advancing

bone marrow totally occupied with cancerous leukocytes

immature nonfunctional WBCs in the bloodstream

Death caused by internal hemorrhage and overwhelming infections

treatments include irradiation, antileukemic drugs, and stem cell transplants

Small fragments of Megakaryocytes (anucleate, degenerate quickly)

formation is regulated by thrombopoietin

blue staining outer region, purple granules

Granules contain serotonin, Ca²⁺, enzyme ADP, and platelet derived growth factor (PDGF)

They form a termporary platelet plug that helps seal breaks in blood vessels

Circulating platelets are kept inactive and mobile by Nitric Oxide (NO) and prostacyclin from endothelial cells of blood vessels

The fast series of reactions for stoppage of bleeding

• 1. Vascular Spasm
• 2. Platelet Plug Formation
• 3. Coagulation (blood clotting)
• 

Vasoconstriction of a damaged blood vessel

• Triggered by:
• -a direct injury
• -chemicals that are released by endothelial cells and platelets
• -pain reflexes

POSITIVE FEEDBACK MECHANISM

• at the site of blood vessel injury, platelets:
• -stick (aggregate) to exposed collagen fibers with the help of von Willebrand factor, a plasma protein
• -Swell, become spiked and sticky, and release chemical messengers
•      *ADP causes more platelets to stick and release their contents
•       *Serotonin and thromboxane A₂ enhance vascular spasm and more platelet aggregation

A set of reaction in which lood is transformed from a liquid to a gel using clotting factors and procoagulants

Reinforces the platelet plug with fibrin threads

• Three Phases of coagulation
• 1. Prothrombin activator is formed (both intrinsic and extrinsic pathways)
• 2. Prothrombin in converted into thrombin
• 3. Thrombin catalyzes the joing fibrinogen to form fibrin mesh