A & P Ii - Blood

Front 1

How much blood is in the vascular compartment?

Back 1

4 - 6 liters

Front 2

Vascular Compartment

Back 2

consist of all places you normally have blood—arteries, veins, hepatic sinusoids, dural sinuses, etc.

Front 3

What 2 parts make up blood?

Back 3

The liquid component is (1) plasma and suspended in plasma are (2) the formed elements. The formed elements are comprised of erythrocytes (RBCs), leukocytes (WBCs) and platelets. Is a suspension (suspension meaning there are solid structures suspended in liquid).

Front 4

What percentage of formed elements are RBCs?

Back 4

99%

Front 5

Hematocrit

Back 5

the percentage of RBCs in whole blood. Normal = 33-45% (lower # more typical in females) (anemia = <33%).

Higher in people who live at higher elevations and smokers.

Front 6

Plasma

Back 6

Is a true solution. Most of it is H2O—90-92%. There are over 100 solutes dissolved in it.

Front 7

plasma proteins

Back 7

Most abundant solute in plasma. 3 broad groups—albumen, globulins, and fibrinogen. Is what makes plasma different than interstitial fluid.

Front 8

albumens

Back 8

60% of all plasma proteins. Synthesized in the liver. They are the smallest of the plasma proteins. Role is to maintain proper osmotic balance between blood and interstitial fluid. (think of end-stage liver disease—person with a big belly b/c blood has decreased albumen, so fluid stays out of the vascular compartment).

Front 9

Globulins

Back 9

36% of all plasma proteins.

3 groups
a. Alpha globulins
b. Beta globulins
alpha and beta have same function—lipid transport in blood. Synthesized in the liver. Form the protein portion of lipoproteins.
c. Gamma globulins—(aka antibodies, or immunoglobulins/Ig)

Front 10

Gamma globulins—(aka antibodies, or immunoglobulins/Ig)

Back 10

made in lymphoid tissues (tonsils, lymph nodes, spleen). When the body encounters a new antigen (large “non-self” molecules, usually proteins, that are part of a bacterium, virus, toxin, etc) these are made by lymphocytes. Somewhere in the body are lymphocytes that recognize the foreign protein and so start reproducing and specializing and make antibodies. So in other words, these can recognize and bind to very specific foreign (non self = not made by your body)macromolecules. e.g. foreign proteins—aka antigens.. The reason for vaccinations.

Front 11

Clotting factors, esp. Fibrinogen

Back 11

last stage of blood clotting involves turning fibrinogen into fibrin. Fibrinogen molecules are small soluble monomers, like one pearl. Fibrin is a large threadlike insoluble polymer, like a necklace of pearls. If a blood vessel gets cut, fibrinogens get together to form fibrin. (uses other clotting factors to get to this point)
**there are a vast number of other proteins in plasma, but in small amounts e.g. there are 13 proteins needed for clotting.

Front 12

Plasma nutrients

Back 12

glucose, free amino acids (FAA), free fatty acids (FFA), lipoproteins, etc.

Front 13

Nitrogenous compounds

Back 13

largely waste products—urea from protein catabolism, NH3, creatinine—from breakdown of creatine phosphate (source of quick ATP in muscles). 2 main: creatinine and urea.

Everytime you catabilize a protein, you for an ammonia. The liver detoxes the ammonia in 6 steps into urea.

Gout - build up of uric acid in joints

Front 14

Electrolytes

Back 14

Na+, Cl-, Ca++, K+, Mg+, HCO3-, etc. blood work will look closely at these levels to check kidney fx.

Front 15

Erythrocytes (RBCs)

Back 15

small cells. Smallest of the body. Biconcave disc shaped (like a jelly donut squished on both sides). They are anucleate. Fx: gas transport in blood. Carry all O2 and some CO2. Hemoglobin is the molecule. (in thinking structure and fx—why is an RBC anucleate?? no way to make new proteins (no ‘blueprints’) so have a short life span—120 days max. and are biconcave, so need to have a cytoskeleton. Biconcave vs. spherical. When go from spherical to biconcave, increase the surface area per unit volume. Cytoplasm is closer to the surface and so gas exchange is faster. And these are small cells and a nucleus would take up too much room. So, bye -bye nucleus and leaves room for Hb, 1/3 of cell is Hb. Which is a lot in the grand scheme of things where most cells are mostly H2O. Trade-off is that the body must make billions of new RBCs daily).

Front 16

Erythropoesis

Back 16

is the production of RBCs. In a fetus, this occurs mostly in the liver. After birth, it is mostly in the red bone marrow. By adulthood, it is mostly in the ribs, sternum, and ilium. In the red marrow are hemopoietic stem cells (hemocytoblasts). These are pluripotent (able to form many cell types) and so are able to give rise to all of the formed elements. Stem cells make erythroblasts, which are large, spherical and nucleated. These begin to make Hb and then go through a series of changes. These changes involve exclusion of many of the organelles (spits them out), including the nucleus and by doing so assume a disc shape. One stage of this change is when erythroblasts become reticulocytes—anucleate disc but still has some endoplasmic reticulum. At this point, they enter the blood stream and in 1-3 days, lose the rough endo retic and become erythrocytes. So reticulocytes are what leaves the red marrow.

Front 17

Hemopoietic Stem Cells (hemocytoblasts)

Back 17

Found in the red marrow. They are pluripotent (able to form many cell types) and so are able to give rise to all of the formed elements.

Front 18

erythroblasts

Back 18

Stem cells make them, which are large, spherical and nucleated. These begin to make Hb and then go through a series of changes. These changes involve exclusion of many of the organelles (spits them out), including the nucleus and by doing so assume a disc shape.

Front 19

reticulocytes

Back 19

anucleate disc but still has some endoplasmic reticulum. At this point, they enter the blood stream and in 1-3 days, lose the rough endo retic and become erythrocytes. What leaves the red marrow.

Front 20

What controls the rate of erythropoiesis?

Back 20

A negative feedback mechanism involving a hormone called erythropoietin—made in the kidneys.

Front 21

Leukocytes (WBCs)

Back 21

Fx: to defend body against microorgs. Do most of their work outside the blood compartment, in the tissue spaces. Use blood to travel to site of injury or infection. 5 types in normal blood. Broken into 2 large groups. Commute in blood.

Front 22

Grandulocytes (3 types)

Back 22

when stained, have darkly staining granules.
1. neutrophils
2. eosinophils
3. basophils

Front 23

neutrophils or PMNs (polymorphonucleocyte)

Back 23

Most abundant of the WBCs in normal blood—54-62%. Nucleus is composed of 2-5 lobes connected by thin strands. Granules will stain a light pink in a neutral pH stain (granules are lysosomes—a bag of digestive enzymes). They are very phagocytic—phagocytize bacteria—a lot of it. They are the first WBC to arrive at the site of injury or infection and are also the first to die (as they ingest so much bacteria, become filled with waste and die).

Front 24

Eosinophils

Back 24

1-3% of all WBCs. Have a bilobed nucleus. Granules will stain a deep red in eosin (an acid stain). The granules are large lysosomes. Their specialty in terms of fx is that they are your best defense against helminth infections (parasitic worms. Worms are hard to kill due to their outer waxy cuticle). The enzyme in the granule is very powerful against the waxy coat.

Front 25

Basophils

Back 25

--<1%. Rarest of WBCs. Have a bilobe nucleus. Easy to identify b/c granules will stain deep blue/purple/black, particularly in basic stains. The granules are not lysosomes. They contain some chemicals, primarily histamine. Involved in inflammation.

{mast cell in CT contain histamine and fx identically to these cells—work tog.}

Front 26

Agranulocytes (2 types)

Back 26

1. Monocytes
2. Lymphocytes

Front 27

Monocytes

Back 27

3 to 9 % of WBCs. Largest cells found in blood. They are resting blood born macrophages. Convert to macrophages in the tissue spaces. When gets to an infection, leaves blood into tissues and enlarges and converts into a macrophage. {monocytes and neutrophils are the most active/impt phagocytes}

Front 28

Lymphocytes (3 types)

Back 28

25 to 33% of WBCs. Of course there are more lymphocytes in lymph tissue. They are the smallest of the WBCs (only a bit bigger than RBCs). They have a round nucleus that can recognize specific antigens.

3 Types:
1. B cells - Synthesize and secrete antibodies. Need chemical signal to make antibodies from Helper (CDT₄⁺) T-cells.
2. Helper (CDT₄⁺) T-cells - Release paracrine chemical that helps B cells make antibodies. Best defense against extracellular infections (live between cells - most bacteria)
3. Cytotoxic (CDₔ⁺) T-cells - Identify and destroy infected "self" cells (intracelluar). All viruses are intracellular.

Front 29

WBC Ranked by percentage (“Never Let Monkeys Eat Bananas”)

Back 29

1. neutrophils (54-62%)
2. lymphocytes (25-33%)
3. monocytes (3-9%)
4. eosinophils (1-3%)
5. basophils (<1%)

2 most important phagocytes:
neutrophils (eat little things)
monocytes (eat big things)

Front 30

Action of leukocytes….phagocyte migration

Back 30

Start with an injury:

When a tissue is injured or infected, a large number of chemicals are released. Paracrine chemicals are those that affect a localized area (vs endocrine affecting entire body). Paracrine chems (or cytokines) get released near the injury and then diffuse away from it. They are not involved in stopping the bleeding, but rather are acting on intact vessels nearby. Paracrines will cause a vasodilation (esp. of the arterioles) and an increase in permeability (esp. of the capillaries and venules) (Vaso d, increase P). So blood flow will increase into the injured area. Vessel walls are more leaky so leaks out into tissue spaces (RBCs, all plasma proteins will remain in vessel). Velocity of blood will decrease. Viscosity of blood will increase.

So a PMN (neutrophil) will come along and will start to move toward the vessel wall—it gets tumbled over to the wall in a process called margination. It moves from center stream, toward the wall. The WBC will then attach itself to the inside of the wall in a process called pavementing. How pavementing works is that the paracrines will stimulate the endothelial cells to start making proteins known as CAMs. CAMs are cellular adhesion molecules. (there are many different CAMs—e.g. ELAM I—endothelial leukocyte adhesion molecule #1). The CAMS stick out into the lumen of the blood vessel. It is a “handle” for the WBCs to grab hold of. On the WBCs are ligands for the CAM (binds to it). The first CAMs for pavementing are specific to the neutrophils (PMNs). The after awhile, begin to make a different CAM (ELAM I) for the monocytes. After pavementing, a diapedesis occurs (extravasation). The WBC crawls out of the blood vessel into the tissue space and will move toward the source of paracrines in a process called positive chemotaxis.

Front 31

Paracrine chemicals

Back 31

those that affect a localized area (vs endocrine affecting entire body). Get released near the injury and then diffuse away from it. They are not involved in stopping the bleeding, but rather are acting on intact vessels nearby. Will cause a vasodilation (esp. of the arterioles) and an increase in permeability (esp. of the capillaries and venules) (Vaso d, increase P). So blood flow will increase into the injured area. Vessel walls are more leaky so leaks out into tissue spaces (RBCs, all plasma proteins will remain in vessel). Velocity of blood will decrease. Viscosity of blood will increase.

Front 32

margination

Back 32

So a PMN (neutrophil) will come along and will start to move toward the vessel wall—it gets tumbled over to the wall.

Front 33

pavementing

Back 33

PMN (neutrophil) moves from center stream, toward the wall. The WBC will then attach itself to the inside of the wall. The paracrines will stimulate the endothelial cells to start making proteins known as CAMs. CAMs are cellular adhesion molecules. (there are many different CAMs—e.g. ELAM I—endothelial leukocyte adhesion molecule #1). The CAMS stick out into the lumen of the blood vessel. It is a “handle” for the WBCs to grab hold of. On the WBCs are ligands for the CAM (binds to it). The first CAMs for it are specific to the neutrophils (PMNs). The after awhile, begin to make a different CAM (ELAM I) for the monocytes.

Front 34

diapedesis (extravasation)

Back 34

The WBC crawls out of the blood vessel into the tissue space and will move toward the source of paracrines in a process called positive chemotaxis.

Front 35

Platelets

Back 35

are not cells, they are cell fragments pinched off of giant synctial cells (synctial = multi nucleated) in the red marrow called megakaryocytes. Pieces of the upper cell membrane break off into blood stream. Stem cells give rise to the megakaryocytes. Play an important role in the early stages of stopping of bleeding.

Front 36

Hemostasis

Back 36

a stopping of bleeding

Front 37

3 Stages of hemostasis

Back 37

(recall that the inner lining of the blood cell is the endothelium—a simple squamous cell lining. When cut through the endothelium, cause blood turbulence and cause the blood to encounter collagen)

1. Vascular spasm__ a reflex vasoconstriction at the cut site. This will last ~30 min. When the platelets encounter collagen they develop sticky threads and so at the cut site, they will build up and form a …
2. Platelet plug—but this won’t stop the bleeding. As the plug is forming, the platelets release serotonin. Serotonin enhances and prolongs the vasoconstriction.
3. Clot formation takes place with fibrinogen combining to form fibrin.

Front 38

clotting
(presented in reverse order….last step first, etc)

Back 38

Fibrinogen (monomers) join together to form FIBRIN (insoluble threads). A clot is a mass of fibrin threads. Ca++ is required in this step (the conversion of fibrinogen to fibrin). The primary thing needed though is THROMBIN which is an enzyme. Don’t want active thrombin in the system (otherwise whole system clots). Thrombin is present in the blood in precursor form—
PROTHROMBIN. So prothrombin is activated by
PROTHROMBIN ACTIVATOR—which is not a single chemical, but a combination of several proteins. The most important aspect of forming prothrombin activator is the activation of Clotting Factor X (ten.)There are 2 pathways occurring at the same time to activate Factor X
1. EXTRINSIC MECHANISM—involves production of a chemical that is not part of the blood. When a vessel is cut, there is damage to the surrounding tissue. The damaged tissues around the vessel will make Tissue Thromboplastin (or Tissue Factor.)
2. INTRINSIC MECHANISM—is occurring at the same time as the extrinsic. This involves the sequential activation of various blood clotting factors that are made in the liver.

Front 39

clot retraction

Back 39

As soon as the clot forms, then it occurs. All the fibrin threads shrink a little bit. The broken edges of the vessel are drawn together and healing occurs. Serum leaves the clot, is basically what is happening. Then, fibroblasts invade the clot and start producing collagen to further strengthen the clot.

Front 40

Serum

Back 40

plasma minus the clotting factors

Front 41

fibrinolysis

Back 41

Clot removal

Front 42

Plasminogen

Back 42

Produced by plasmin, a fibrin-digesting enzyme, which is a critical natural "clot buster." Large amounts are incorporated into a forming clot, where it remains inactive until appropriate signals reach it.

Front 43

TPA—Tissue Plasminogen Activator (used in CVA, MI)

Back 43

The area heals itself and then the tissues around it forms this, which converts plasminogen to plasmin. The plasmin starts to dissolve the fibrin and therefore the clot.

Front 44

Thrombus

Back 44

an abnormal blood clot attached to a vessel wall. It forms in a vessel with a build up of fatty plaque which attracts the build up of Ca++ on it and therefore gets a roughened area. As the blood flows by, turbulence is created leading to the cascade events of the clotting factors. A clot such as this can close the vessel down.

Front 45

Heparin

Back 45

Prevents clotting and is most abundant in the lungs and liver. Don’t want clots where they are not needed. Places where don’t want clots are highly vascular structures such as the lungs and liver.

Front 46

Erythropoietin (EPO)

Back 46

A hormone that controls erythropoiesis, or red blood cell production. Regulated by negative feedback. People at high altitudes and smokers have higher levels. Used as an performance enhancement drug.

Front 47

Fate of RBCs

Back 47

Phagocytized by macrophages in liver and spleen.