A & P Chapter 19

1. Blood is a vital connective tissue composed of plasma, extracellular matrix, and formed elements. Its functions include:

• Transporting gases, nutrients, and waste products

• Moving processed molecules (e.g., vitamin D precursors) from skin to liver to kidneys

• Regulating pH and osmosis

• Maintaining body temperature

• Protecting against foreign substances

• Facilitating clot formation for tissue repair

• immune

Composition of blood:

• Plasma: 55% of blood volume (liquid matrix)

• Formed elements: 45% of blood volume (cells and cell fragments)

• Average total blood volume is 4 to 5 L in females and 5 to 6 L in males.

Blood: connective tissue with liquid matrix containing cells and
cell fragments.

2. Plasma is the liquid matrix of blood.

Plasma is a colloid: liquid containing suspended substances that
don’t settle out of solution (mostly plasma proteins). The function of plasma is to transport nutrients, hormones, and waste, regulate body temperature, maintain blood pressure, and support immune function.
• 91% water. Remainder proteins, ions, nutrients, waste products,
gases, regulatory substances.
• Composition remains relatively constant through various
homeostatic mechanisms even though materials are constantly
moving into and out of the blood.

Plasma Protein

• Albumins: viscosity, osmotic pressure, buffer, transports fatty acids, bilirubin,
  thyroid hormones. (58% of proteins), carrier

• Globulins: transports many substances, involved in immunity; α, β, γ types.(38%
  of proteins), carrier, antibodies

• Fibrinogen: blood clotting; serum is plasma without clotting factors. (4% of
  proteins)

Plasma proteins have several functions:

1. Albumin – Maintains osmotic pressure and transports substances.

2. Globulins – Support immune function by acting as antibodies.

3. Fibrinogen – Helps in blood clotting.

Components of Blood Plasma

• Ions: Essential for osmosis, membrane potentials, and maintaining acid-base balance.

• Nutrients: Include glucose, amino acids, triacylglycerol, cholesterol, and vitamins, which are vital for cellular function and energy.

• Waste Products:

  • Urea, uric acid, creatinine, ammonia salts: Byproducts of protein metabolism.

  • Bilirubin: Breakdown product of red blood cells.

  • Lactic Acid: End product of anaerobic respiration.

• Gases: Oxygen and carbon dioxide are crucial for respiration, with inert nitrogen present in minor amounts.

• Regulatory Substances: Include hormones and enzymes that help control various physiological processes.

Formed element

Red blood cells (erythrocytes). 95% of the volume of formed
elements.
• White blood cells (leukocytes).
• Granulocytes: cytoplasm contains large granules; have multi-
lobed nuclei. Three distinctive types: neutrophils, eosinophils,
basophils.
• Agranulocytes: cytoplasm contains small granules and nuclei
that are not lobed. Two distinctive types: lymphocytes and
monocytes.
• Platelets (thrombocytes). Cell fragment. Form platelet plugs,
release chemicals necessary for blood clotting.

Hematopoiesis: Process of blood cell production.
• Infant occurs in yolk sac of embryo, liver, thymus, spleen, lymph
nodes, red bone marrow.
• After birth occurs in red bone marrow and lymphatic tissue;
red bone marrow in adults is in ribs, sternum, vertebrae, pelvis,
proximal femur, proximal humerus.

Stem cells: All formed elements derived from single population of
hemocytoblasts.
• When a hemocytoblast divides, one daughter cell remains a
hemocytoblast, while the other differentiates into either a myeloid
stem cell or a lymphoid stem cell.
• Myeloid stem cells become:
• Proerythroblasts: Develop into red blood cells.
• Myeloblasts: Develop into basophils, neutrophils, eosinophils.
• Monoblasts: Develop into monocytes.
• Megakaryoblasts: Develop into platelets.
Lymphoid stem cells become Lymphoblasts: Develop into
lymphocytes.
Chemical signals such as colony-stimulating factors (CS
Fs) help regulate development.
• Erythropoietin (EPO) is a hormone released by the
kidneys that stimulates red blood cell development.

Red blood cells ( Erythrocytes ) :

Biconcave disc shape, 7.5 um in diameter.
• No nucleus in circulating RBCs.
• Flexible and capable of bending/folding, allowing them to pass
through small vessels; move with the blood flow.
• Contain hemoglobin, lipids, ATP, carbonic anhydrase.

RBS FUNCTIONS
• Transport oxygen from lungs to tissues: 98.5% attached to
hemoglobin; 1.5% dissolved in plasma.
• Carbon dioxide transported from tissues to lungs.
• 7% dissolved in plasma.
• 23% in combination with hemoglobin.
• 70% transported as bicarbonate ions produced as a result of
combination of H2O and CO2 because of enzyme carbonic
anhydrase found within RBCs

Hemoglobin - oxygen carry substance

Protein consisting of four subunits.
• Each subunit composed of a single polypeptide called globin.
• Globin bound to heme group; heme = red pigment containing one iron atom.
• Three types of hemoglobin.
• Embryonic and fetal: have greater attraction for oxygen than adult. Fetal
production stops after birth.
• Adult.
• Oxyhemoglobin: iron in hemoglobin bound to oxygen; 4 per molecule of
hemoglobin; bright red in color.
• Deoxyhemoglobin: hemoglobin not bound to oxygen; dark red.
• Carbaminohemoglobin: globin of hemoglobin bound to carbon dioxide
• Hemoglobin also transports nitric oxide (NO) that is produced
by endothelial cells lining blood vessels; causes the relaxation of
smooth muscle in blood vessels to decrease blood pressure.
• Poisons can affect hemoglobin, including carbon monoxide (CO);
CO binds very strongly to the iron of hemoglobin to form
carboxyhemoglobin which means less oxygen is being
transported.

Hemoglobin break down

Macrophages take up hemoglobin released from hemolysis.
• Globin is broken down into amino acids.
• Heme broken down, iron released.
• Non-iron part of heme converted to biliverdin, then free
bilirubin; free bilirubin is joined to glucuronic acid to form
conjugated bilirubin (more water-soluble) which is added to
the bile and passes in feces.

White blood cells

Have a nucleus and attract stain in slide preparations.
• Grouped into granulocytes and agranulocytes based on their
appearance under microscope.
• Granulocytes have large granules and lobed nuclei; include
neutrophils, eosinophils, basophils.
• Agranulocytes have granules not easily seen under scope;
include lymphocytes, monocytes.

Homeostasis

Hemostasis: arrest of bleeding.
• Events preventing excessive blood loss.
1. Vascular spasm: Vasoconstriction of damaged blood vessels.
Can occlude small vessels. Caused by thromboxanes from
platelets and endothelin from damaged endothelial cells.
2. Platelet plug formation.
3. Coagulation or blood clotting.

PLATELET PLUG FORMATION
• Accumulation of platelets that can seal small breaks in vessels.
• Activated platelets also release platelet factor III and coagulation factor V needed for clot
formation.
1. Platelet adhesion: Platelets bind to collagen that is exposed when a blood vessel is damaged.
Most platelet adhesion is mediated through von Willebrand factor (vWF), a protein
produced and secreted by blood vessel endothelial cells. Platelets have surface receptors on their membrane. These surface receptors bind to von Willebrand factor released from damaged blood vessels. Von Willebrand factor also binds to the exposed collagen of the damaged vessel, thereby forming a bridge between exposed collagen and platelets. In addition, other platelet surface receptors can bind directly to collagen.
2. Platelet release reaction: After platelets adhere to collagen, they become activated. These
activated platelets then release adenosine diphosphate (ADP), thromboxanes, and other
chemicals by exocytosis. The ADP and thromboxane bind to their respective receptors on the
surfaces of other platelets, activating them. These activated platelets release additional
chemicals, thereby producing a cascade of chemical release by the platelets. Thus, more and
more platelets become activated. This is an example of positive feedback.
3. Platelet aggregation: As platelets become activated, they change shape
and express fibrinogen receptors that can bind to fibrinogen, a plasma
protein. Fibrinogen forms a bridge between the fibrinogen receptors of
different platelets, resulting in a platelet plug.

COAGULATION
• Eye of Science/Science Source
• Stages.
• Activation of prothrombinase.
• Conversion of prothrombin to thrombin.
• Conversion of fibrinogen to fibrin.
• Clotting factors:
• Proteins found in plasma.
• Circulate in inactive state until tissues are
injured.
• Damaged tissues and platelets produce
chemicals that begin activation of the
factors.
• Pathways.
• Extrinsic.
• Intrinsic.
• Result: blood clot. A network of threadlike
fibrin fibers, trapped blood cells, platelets and
fluid.

CLOT FORMATION

1. Extrinsic pathway: Damaged
tissues release a mixture of
lipoproteins and phospholipids
called thromboplastin, also
known as tissue factor (TF) or
factor III. Thromboplastin, in the
presence of calcium, forms a
complex with factor VII that
activates factor X, which is the
clotting factor that initiates the
common pathway.
2. Intrinsic pathway: Damage to blood vessels can
expose collagen in he connective tissue beneath
the endothelium of the blood vessel. When plasma
factor XII comes into contact with collagen, factor
XII is activated. Subsequently, activated factor XII
stimulates factor XI, which n turn activates factor
IX. Activated factor IX joins with factor VIII, platelet
phospholipids, and
calcium to activate factor X, which, as stated n the
extrinsic pathway description, initiates the common
pathway. Although the extrinsic and intrinsic
pathways were once considered distinct, we now
know that the extrinsic pathway can activate tor VII
complex from the extrinsic pathway can stimulate
the formation of activated factor IX in the intrinsic
pathway.
3. Common pathway initiated: Activation of
the extrinsic and/or intrinsic pathways
results in the activation factor X.
4. Prothrombinase formed: On the surface of
platelets, activated factor X, factor V,
platelet phospholipids, and calcium
combine to form prothrombinase, or
prothrombin activator.
5. Thrombin produced: Prothrombinase
converts the soluble plasma protein
prothrombin to the enzyme thrombin.
6. Fibrin produced: A major function of thrombin is to
convert the soluble plasma protein fibrinogen to
the insoluble protein fibrin. Fibrin is the protein
that forms the fibrous network of the blood clot.
7. Positive-feedback effects of thrombin: In addition,
thrombin also stimulates factor XIII activation,
which is necessary to stabilize the clot. Thrombin
can also activate many of the clotting proteins, such
as factor XI and prothrombinase. Thus, a positive-
feedback system operates whereby thrombin
production stimulates the production of additional
thrombin. Thrombin also has a positive-feedback
effect on platelet aggregation by stimulating platelet
activation.

CLOTTING PATHWAYS

Extrinsic pathway:
• Begins with chemicals outside of blood.
• Damaged tissues release tissue factor (TF; factor III).
• When calcium is present, forms complex with factor VII,
activating factor X.
• Intrinsic pathway:
• Begins with chemicals that are part of the blood.
• In damaged blood vessels, factor XII comes in contact with
exposed collagen, activating factor XII.
• Stimulates factor XI, activates factor IX.
• Activated factor IX joins with factor VIII, platelet phospholipids and
calcium to activate factor X

COMMON PATHWAY

• Prothrombinase is formed from extrinsic and/or intrinsic
pathway(s).
• Prothrombinase converts prothrombin into thrombin.
• Thrombin converts fibrinogen to fibrin.
• Thrombin activates factor XIII, which stabilizes clot.
• Vitamin K is required for the formation of many of the blood
clotting factors.

CONTROL OF CLOT FORMATION
• Anticoagulants: prevent coagulation factors from initiating clot
formation.
• Coagulation occurs when coagulation factor concentration exceeds a
given threshold. At site of injury, threshold is exceeded.
• Anticoagulants.
• Antithrombin: produced by liver, slowly inactivates thrombin.
• Prostacyclin: prostaglandin derivate from endothelial cells. Causes
vasodilation and inhibits release of coagulating factors from platelets.
• Outside the body (for example, for transfusions): heparin, EDTA,
sodium citrate.

CLOT RETRACTION AND DISSOLUTION
• Clot retraction: clot condenses into compact structure.
• Platelets contain actin and myosin to aid in contraction.
• Serum is released as the clot contracts.
• Edges of the damaged blood vessel are pulled together, allowing
fibroblasts and epithelial cells to begin the repair process
• Clot dissolves over time through process called fibrinolysis.
• Plasmin hydrolyzes fibrin; can be activated by t-PA, urokinase,
or streptokinase.

BLOOD GROUPING
• Transfusion: transfer of blood or blood components from one
individual to another.
• Infusion: introduction of fluid other than blood.
• Transfusion success determined by antigens (agglutinogens) on
surface of RBCs.
• Antibodies (agglutinins) can bind to RBC antigens, resulting in
agglutination (clumping) or hemolysis (rupture) of RBCs.
• Groups: ABO, Rh, Lewis, Duffy, MNSs, Kidd, Kell, and Lutheran.

TRANSFUSIONS AND MATCHING BLOOD TYPES
• Type A has A antigen; blood has anti-B antibodies
• Type B has B antigen; blood has anti-A antibodies.
• Type AB has both A & B antigens; blood has no antibodies.
Universal recipient.
• Type O has no antigens; blood has both A & B antibodies;
Universal donor but can still cause a transfusion reaction.

RH BLOOD GROUP
• Types.
• Rh-positive: Have these antigens present on surface of RBCs. (most
common)
• Rh-negative: Do not have these antigens present.
• Hemolytic disease of the newborn (HDN).
• R- positive fetus, Rh-negative mother.
• Late in pregnancy, Rh antigens of fetus cross placenta (through a tear in
placenta or during delivery); mother creates anti-Rh antibodies (primary
response).
• Second Rh-positive pregnancy might initiate secondary response and HDN
(potentially fatal to fetus since antibodies to its R BCs would cross the
placenta from the mother to the fetus, destroying fetal RBCs).
• Injection of RhoGAM. Contains antibodies against Rh antigens. Antibodies
attach to any fetal RBCs and they are destroyed.

HEMOLYTIC DISEASE OF THE NEWBORN (H D N)
1. In the mother’s first pregnancy with an Rh-positive fetus, there is
often no problem. The leakage of fetal blood is usually the result
of a tear in the placenta that takes place either late in the
pregnancy or during delivery. Thus, there is not sufficient time for
the mother to produce enough anti-Rh antibodies to harm the
fetus.
2. At this point, however, sensitization occurs, and this can cause
problems in a subsequent pregnancy. Once a person is sensitized
and produces anti-Rh antibodies, they may continue to produce
the antibodies throughout their life.
3. In a subsequent pregnancy with an Rh-positive fetus, because the
mother is sensitized and produced anti-Rh antibodies, they may
be present in the maternal blood. In addition, and especially
dangerous if any fetal blood leaks into the mother’s blood, the
mother rapidly produces large amounts of anti-Rh antibodies.
4. These anti-Rh antibodies can cross the placenta and cause
agglutination and hemolysis of fetal red blood cells, resulting in
HDN or erythroblastosis fetalis.

DIAGNOSTIC BLOOD TESTS
• Blood typing determines ABO and Rh blood types. Red cells tested against
antibodies.
• Crossmatch: donor blood cells mixed with recipient’s serum and vice versa;
look for agglutination.

HEMATOCRIT
• Complete blood count.
• Red blood count: number of RBCs/
microliter of blood.
• Hemoglobin measurement: grams
of hemoglobin/100 mL of blood. For a
male, 14 to 17 g/100 mL, female 12 to
15 g/100 mL.
• Hematocrit measurement: percent
of blood that is RBCs; look for
normocytes, microcytes, and
macrocytes.
• White blood cell count: 4,500 to
11,000 /microliter of blood.

OTHER TESTS
• Differential white blood count: determines percentage of each of the five
types of W BC. Normal values:
• Neutrophils: 55 to 70%.
• Lymphocytes: 20 to 40%.
• Monocytes: 2 to 8%.
• Eosinophils: 1 to 4%.
• Basophils: 0.5 to 1%.
• Clotting assessment.
• Platelet count: 150,000 to 400,000/microliter; reduced =
thrombocytopenia.
• Prothrombin time measurement: measures how long it takes for blood
to start clotting. 9 to 12 seconds. To test, thromboplastin is added to whole
plasma.
• Blood chemistry: composition of materials dissolved or suspended in the
plasma. Used to assess functioning of many body systems.