An Introduction to Blood and the Cardiovascular System

An Introduction to Blood and the Cardiovascular System
The Cardiovascular System consists of: A pump (the heart) A conducting system (blood vessels) A fluid medium (blood) Is specialized fluid of connective tissue Contains cells suspended in a fluid matrix We talked about specific kinds of cells found in connective tissues. Blood is also a type of connective tissue. They’re swimming around separated from each other by proteins and water.

An Introduction to Blood and the Cardiovascular System
Transports materials to and from cells Oxygen and carbon dioxide Nutrients Hormones Immune system components Waste products Blood cells have a phagocytic function deliver oxygen, and can protect us from foreign invaders. A big difference in blood and other connective tissues is that blood circulates around the body to go where they are needed. It’s the traveling connective tissue.

19-1 Physical Characteristics of Blood
Important Functions of Blood Transportation of dissolved substances Regulation of pH and ions Restriction of fluid losses at injury sites Defense against toxins and pathogens Stabilization of body temperature Cells in blood have different types of function and anatomy. Know the functions of blood.

Whole Blood Plasma Fluid consisting of: Water Dissolved plasma proteins Other solutes Formed elements All cells and solids The formed elements are going to make up about 45% of blood. The combination of plasma and formed elements make up whole blood.

Figure 19-1 The Composition of Whole Blood
7% Plasma Plasma Proteins 1% Other Solutes 46–63% Water 92% Formed Elements Platelets < .1% White Blood Cells So here we see whole blood broken down to it’s components. On average about 55% plasma of which water is the most abundant component at about 92%. Platelets, WBCs, and RBCs make up the formed elements. Most of the cells floating around in the bloodstream are RBCs also called erythrocytes. They account for about 99% of the cells of the blood. 37–54% Red Blood Cells < .1% 99.9% 5

Three Types of Formed Elements Red blood cells (RBCs) or erythrocytes Transport oxygen White blood cells (WBCs) or leukocytes Part of the immune system Platelets Cell fragments involved in clotting Would a lymphocyte be considered a formed element of blood? Yes. What about an antibody? No.

Hemopoiesis Process of producing formed elements By myeloid and lymphoid stem cells Fractionation Process of separating whole blood for clinical analysis Into plasma and formed elements Whole blood for testing in a clinical laboratory is usually collected from a superficial vein. But, if a physician wants to know the efficiency of gas exchange, it might be necessary to draw the blood from an artery.

Three General Characteristics of Blood 38C (100.4F) is normal temperature High viscosity Slightly alkaline pH (7.35–7.45) …while it’s slightly alkaline, blood does have buffers that control pH. Recognize the characteristics of blood and know what’s true and false about characteristics of blood.

Blood volume (liters) = 7% of body weight (kilograms) Adult male 5 to 6 liters Adult female 4 to 5 liters Hypovolemic = low blood volume. Hypervolemic = high blood volume. So, what would you expect the total volume of blood in a 76-kg man to be in liters? 5.3.

19-2 Plasma The Composition of Plasma Makes up 50–60% of blood volume
More than 90% of plasma is water Extracellular fluids Interstitial fluid (IF) and plasma Materials plasma and IF exchange across capillary walls Water Ions Small solutes …so, plasma is very similar in composition to: interstitial fluid. The main difference b/n plasma and IF is the concentration of proteins. Let’s look at that next.

19-2 Plasma Plasma Proteins Albumins (60%) Globulins (35%)
Fibrinogen (4%) Albumins are the most abundant proteins in blood plasma. Albumin comes from the Latin Albus meaning White and refers to plasma proteins. Albumins are water soluble proteins made by the liver that experience heat denaturation. Their presence creates an osmotic force that balances fluid volume w/in a vascular space. They are different from other blood proteins because they are not glycosylated. Globulins are proteins that include gamma globulins (antibodies) and a variety of enzymes and carrier/transport proteins. Remember that antibodies are produced by mature B-lymphocytes called plasma cells. Since antibodies make up the largest portion of globulins, antibody deficiency should come to mind when globulin levels are low. The other globulins are made in the liver. Fibrinogens are soluble plasma glycoproteins made in the liver.

19-2 Plasma Albumins (60%) Globulins (35%) Fibrinogen (4%)
Transport substances such as fatty acids, thyroid hormones, and steroid hormones Globulins (35%) Antibodies, also called immunoglobulins Transport globulins (small molecules): hormone-binding proteins, metalloproteins, apolipoproteins (lipoproteins), and steroid-binding proteins Fibrinogen (4%) Molecules that form clots and produce long, insoluble strands of fibrin The main function of Albumins is to regulate the osmotic pressure of blood (to nullify osmosis). They also serve as carriers for molecules of low water solubility. They’re molecular taxis. Low albumin is a sign of poor health and a predictor of a bad outcome. Globulin levels include plasma proteins essential in body defense and may be elevated with infections, liver disease, cancers, etc. They may be decreased with liver dysfunction or nephrosis – when the kidney doesn’t filter the protein from the blood and it leaks into the urine. Fibrinogen is a plasma protein essential for blood coagulation.

19-2 Plasma Serum Liquid part of a blood sample
In which dissolved fibrinogen has converted to solid fibrin

19-2 Plasma Other Plasma Proteins 1% of plasma
Changing quantities of specialized plasma proteins Peptide hormones normally present in circulating blood Insulin, prolactin (PRL), and the glycoproteins thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH)

19-2 Plasma Origins of Plasma Proteins More than 90% made in liver
Antibodies made by plasma cells Peptide hormones made by endocrine organs While some peptide hormones that we’ll discuss are made in the kidney, most plasma proteins are made in the liver.

19-3 Red Blood Cells Red blood cells (RBCs) Hemoglobin
Make up 99.9% of blood’s formed elements Hemoglobin The red pigment that gives whole blood its color Binds and transports oxygen and carbon dioxide RBCs have one basic function. They are packed full of hemoglobin. Hg is a protein that carries blood all around the body. RBCs first pick up oxygen from the lungs then they leave the lungs with hemoglobin filled full of oxygen and they deliver the oxygen to organs like the skin or muscle or bone. So the major function of RBCs is to be filled with the Hg to carry oxygen.

19-3 Red Blood Cells Abundance of RBCs
Red blood cell count - the number of RBCs in 1 microliter of whole blood Male: 4.5–6.3 million Female: 4.2–5.5 million As we go through the different cell types, put the cell type and these numbers together so that you can recognize what a normal or abnormal blood lab test would look like. For instance, if a RBC count comes back at 5.2 million/ul is that normal?

19-3 Red Blood Cells Abundance of RBCs
Hematocrit - (packed cell volume, PCV) percentage of RBCs in centrifuged whole blood Male: 40–54 Female: 37–47 Hematocrit is the percent fraction of formed elements relative to whole blood. So a hematocrit tells us the abundance of formed elements. Like I said to do with the blood cell lab numbers, be able to recognize a normal hematocrit level.

19-3 Red Blood Cells Structure of RBCs
Small and highly specialized discs Thin in middle and thicker at edge

19-3 Red Blood Cells Three Important Effects of RBC Shape on Function
High surface-to-volume ratio Quickly absorbs and releases oxygen Discs form stacks called rouleaux Smooth the flow through narrow blood vessels Discs bend and flex entering small capillaries 7.8-µm RBC passes through 4-µm capillary

Figure 19-2ab The Anatomy of Red Blood Cells
Blood smear LM  477 When viewed in a standard blood smear, RBCs appear as two-dimensional objects, because they are flattened against the surface of the slide. Red blood cells The three-dimensional shape of RBCs SEM  1838 The 3-D shape shows that RBCs are biconcave discs. 21

Figure 19-2c The Anatomy of Red Blood Cells
Don’t need to know the numbers, but know the characteristics of RBCs. For instance, they’re small – only about 7 um in diameter, they have biconcave discs, they carry oxygen, etc. A sectional view of a mature RBC, showing the normal ranges for its dimensions 22

Figure 19-2d The Anatomy of Red Blood Cells
cell (RBC) Rouleau (stacked RBCs) Nucleus of endothelial cell Blood vessels (viewed in longitudinal section) Sectioned capillaries LM  1430 When traveling through relatively narrow capillaries, RBCs may stack like dinner plates. 23

19-3 Red Blood Cells Life Span of RBCs
Lack nuclei, mitochondria, and ribosomes Means no repair and anaerobic metabolism Live about 120 days RBCs are unusual because each RBC has destroyed its nucleus. The cell no longer has a nucleus; it has no chromosomes, so no DNA. And, in addition to destroying the nucleus, the RBCs destroy all their other organelles in the cell. So basically, there’s nothing left in a RBC but the large amounts of hemoglobin and a cell membrane.

19-3 Red Blood Cells Hemoglobin (Hb)
Protein molecule that transports respiratory gases (oxygen to cells and carbon dioxide away from cells) Normal hemoglobin (adult male) 14–18 g/dL whole blood Normal hemoglobin (adult female) 12–16 g/dL whole blood So, we can ask a simple question. Why have RBCs at all? Why not just have hemoglobin moving around the bloodstream. To have enough hemoglobin traveling through the bloodstream to work, the blood would have the viscosity of maple syrup and the heart would not be strong enough to pump the blood. So the solution is to package the Hg into little bags called RBCs that can be carried along the blood stream by the fluid circulating around them. Know the normal ranges for everything. For example, if someone has 16 g/dL of blood. Would you say they have anemia? No, their Hg level is normal.

19-3 Red Blood Cells Hemoglobin Structure Complex quaternary structure
Four globular protein subunits Each with one molecule of heme Each heme ring in Hg encloses an atom of iron

19-3 Red Blood Cells Hemoglobin Structure Iron ions
Associate easily with oxygen (oxyhemoglobin, HbO2) Dissociate easily from oxygen (deoxyhemoglobin)

Figure 19-3 The Structure of Hemoglobin
 chain 1  chain 1  chain 2 Heme Heme  chain 2 95% of protein in a RBC is hemoglobin. So how many iron atoms can we find in a Hg? 4. Hemoglobin molecule 28

19-3 Red Blood Cells Fetal Hemoglobin
Strong form of hemoglobin found in embryos Takes oxygen from mother’s hemoglobin When a RBC is formed, they originate in bone marrow. They go through an amazing transformation. One of the 1st stages in their formation is that they start making Hg. The Hg is initially made as a fetal form of Hg, which is very abundant in babies. As one matures, the precursors to RBCs in the bone marrow switch and start making a slightly different adult form of Hg.

19-3 Red Blood Cells Hemoglobin Function Carries oxygen
With low oxygen (peripheral capillaries) Hemoglobin releases oxygen Binds carbon dioxide and carries it to lungs Forms carbaminohemoglobin

Figure 19-4 “Sickling” in Red Blood Cells
Sickle cell anemia: A gene for adult hemoglobin is abnormal. Mutation in the AA sequence of the beta chains of the Hb molecule. Thalassemia: Inadequate production of alpha or beta chains of Hb resulting in slower RBC production, fragile, and short-lived RBCs. Transfusions help keep adequate numbers of RBCs in the bloodstream. Some RBCs have an abnormal gene for Hg and make abnormal Hg creating a variety of blood diseases called anemias. One prominent anemia is called sickle cell anemia. Hg tends to crystalize in the RBC and form big solid masses. This causes the shape of the RBC to become deformed and these RBCs take on a crescent shape like a sickle. This has serious consequences. For instance, the RBCs start to stick together and clog blood vessels up, which causes lots of pain in organs that are getting poor circulation. Until recently, it wasn’t known what to do about this type of disorder. It’s an inheritable disorder and tends to be more prominent in people that have an ancestry from Africa. The reason that this disorder is prominent in African Americans and Africans in general is that the anemia gives them an advantage if you happen to be living in Africa. A prominent disease in Africa is malaria. Malaria is a disorder spread by mosquitos. The mosquitos inject into the bloodstream a tiny little organism that likes to live w/n RBCs. This organism is responsible for all the symptoms of malaria. If you happen to make RBCs that the organism doesn’t like, you can have an advantage over other people. Sickle-shaped RBCs are not hospitable to the organism that causes malaria and helps them to resist malaria. On the other hand, it causes a deformation of the RBCs that can cause pain and suffering. Until recently, there wasn’t a way to treat malaria. Now we can treat people with a chemical called hydroxyurea, which travels to the BM and tricks RBCs there to start making the fetal form of RBCs, which seems to reverse the symptoms of sickle cell by at least 50%. This treatment would not have developed without an understanding of the basis of the disorder. Another type of anemia fairly common in the U.S. is a disorder called thalassemia. In thalassemia, another abnormal type of Hg is made that tends to result in unusually fragile RBCs. These RBCs die more easily and don’t have as long of a life as a normal RBC. Because of that, people with thalassemia have a smaller amount of RBCs in their bloodstream and they tend to tire more easily, because they can’t transport oxygen as well as normal. 31

19-3 Red Blood Cells RBC Formation and Turnover
1% of circulating RBCs wear out per day About 3 million RBCs per second Hemoglobin Conversion and Recycling Macrophages of liver, spleen, and bone marrow Monitor RBCs Engulf RBCs before membranes rupture (hemolyze)

19-3 Red Blood Cells Hemoglobin Conversion and Recycling
Phagocytes break hemoglobin into components Globular proteins to amino acids Heme to biliverdin Iron Iron removed from degraded hemoglobin is going to be recycled to the red bone marrow. Why might a bruise look greenish? The heme group broke down to biliverdin.

19-3 Red Blood Cells Hemoglobin Conversion and Recycling
Hemoglobinuria Hemoglobin breakdown products in urine due to excess hemolysis in bloodstream Hematuria Whole red blood cells in urine due to kidney or tissue damage Hemoglobinuria: is a condition where hemoglobin is found in high concentrations in the urine. It’s normally associated with hemotlyic anemia where RBCs are destroyed causing an increase in the levels of hemoglobin in the plasma. It can be filtered by the kidneys, which can give urine a red color. Hema-tur-e-ah: RBCs are found in the urine. It can be an indicator of a kidney stone or a tumor in the urinary tract. If WBCs are also found, than it’s a signal of a urinary tract infection.

19-3 Red Blood Cells Breakdown of Biliverdin
Biliverdin (green) is converted to bilirubin (yellow) Bilirubin Is excreted by liver (bile) Jaundice is caused by bilirubin buildup Converted by intestinal bacteria to urobilins and stercobilins Bilirubin is a waste product made by heme molecules that don’t have iron. Euro-bilin Stir-co-bilin Who gets Jaundice? Alcoholics and others with a damaged liver. The yellow color is due to excessive bilirubin and the breakdown of RBCs and hemoglobin. What would happen to plasma levels of bilirubin if bile ducts are blocked? Increase.

19-3 Red Blood Cells Iron Recycling
Iron removed from heme leaving biliverdin To transport proteins (transferrin) To storage proteins (ferritin and hemosiderin) -ferritin and hemosiderin store excess iron in the liver and spleen. …Since transferrin is transporting iron, what kind of plasma protein would it be? Metalloprotein (not hormone- or steroid-binding). Notice ferritin, hemosiderin, and transferrin all function to store or transport iron.

Figure 19-5 Recycling of Red Blood Cell Components
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19-3 Red Blood Cells RBC Production Erythropoiesis
Occurs only in myeloid tissue (red bone marrow) in adults Stem cells mature to become RBCs Erythropoiesis is the process of RBC production. …so ALL the circulating RBCs in an adult originate in the red bone marrow, and as well see soon is regulated by the hormone erythropoietin. Where is red marrow located in adults? Long bones, iliac crest, sternum, ribs, body of vertebrae.

19-3 Red Blood Cells Hemocytoblasts
Stem cells in myeloid tissue divide to produce: Myeloid stem cells become RBCs, some WBCs Lymphoid stem cells become lymphocytes

19-3 Red Blood Cells Stages of RBC Maturation Myeloid stem cell
Proerythroblast Erythroblasts Reticulocyte Mature RBC One thing RBCs do as they develop is they start pinching into two portions. So that they cytoplasm of a RBC becomes divided in half by constriction and start to become dumbbell shaped. At one end of the dumbbell the nucleus comes to rest and the other end of the dumbbell is the rest of the cytoplasm of the RBC. As the RBC matures, eventually the portion containing the nucleus is pinched off and discarded. The discarded nucleus will be eaten by macrophages in the bone marrow. The developing RBC enters the circulation as a reticulocyte. These increase in the circulation after donating blood or bleeding out.

19-3 Red Blood Cells Regulation of Erythropoiesis
Building red blood cells requires: Amino acids Iron Vitamins B12, B6, and folic acid Pernicious anemia Low RBC production Due to unavailability of vitamin B12 What’s anemia? When the oxygen-carrying capacity of blood is reduced. Pernicious anemia might be something that someone is monitored for if they have a portion of their stomach removed. How would you treat prenicious anemia? Injections of Vit B12.

19-3 Red Blood Cells Stimulating Hormones Erythropoietin (EPO)
Also called erythropoiesis-stimulating hormone Secreted when oxygen in peripheral tissues is low (hypoxia) Due to disease or high altitude One mechanism that stimulates RBCs to develop is a hormone called erythropoietin. EPO is not produced in the BM, but in fibroblasts in the connective tissue of the kidney. So the kidney, through the production of EPO from its fibroblasts, can influence how many RBCs are made in the BM. Why should the kidney have an influence on blood cells? The kidneys are in the perfect position to monitor the composition of the blood. Kidneys are very well vascularized and carry a huge amount of blood in them. Something like 20% of your blood is passing through your kidneys at any given moment. The kidney’s job is to filter the blood, remove any waste products and make sure the composition of the blood is proper. One of the things the kidney senses is the oxygen content of the blood. The fibroblasts inside the kidney are sensitive to the amount of oxygen in the bloodstream. If the concentration of oxygen in the blood falls too low, it causes the activation of hypoxia inducible factor in fibroblasts, which initiates the production of EPO. Imagine you’re climbing a mountain. As you continue to elevate, the levels of oxygen in the air decreases and the kidneys detect smaller amounts of oxygen in the bloodstream. In response to this, the kidneys will secrete EPO that will get carried to the BM and the BM will start producing more RBCs. As the number of RBCs in the bloodstream goes up, more oxygen can get delivered. So, the kidneys can adjust the oxygen carrying capacity of the bloodstream by stimulating the production of more RBCs. Since EPO was first described it’s been observed in multiple situations. For instance in people that develop cancer in the BM, it’s necessary to destroy the cells in the BM to prevent the growth of new cancer cells. Chemotherapy damages cells in the BM, which results in cancer patients developing some sort of anemia. This is great to get rid of the cancer, but what do you do about the anemia. One way to compensate for the damaging effects of chemotherapy is to inject patients with a synthetic form of EPO to stimulate the BM to make more RBCs. So, EPO regulates RBC production.

Table 19-1 RBC Tests and Related Terminology
Polycythemia: Proportion of blood volume occupied by RBCs increases. Leukocytosis: High leukocyte count normally due to an inflammatory response. Reticulocytosis: Increase in immature RBCs. Common in anemia when the BM is trying to replace RBCs. Macrocytosis: Not a specific disease, but may indicate an underlying problem. Microcytosis: Usually due to iron deficiency, thalassemia, or autoimmune. Hyperchromic: RBC count is low, but cells are larger. Polycythemia: when the proportion of blood volume that’s occupied by RBCs increases. This could be due to an increase in the number of RBCs (erythrocytosis) or a decrease in the volume of plasma (Relative polycythemia), which can be caused by a loss of body fluids through burns, dehydration, or stress. It’s also associated with obesity, smoking, drinking, and hypertension. Leukocytosis is a high leukocyte count normally due to an inflammatory response caused by an infection, epilepsy, exercise, pregnancy, or anesthesia. Reticulocytosis: is an increase in immature RBCs and is common in anemia or haemorrhaging when the BM is trying to replace RBCs. Macrocytosis isn’t a specific disease, but might indicate an underlying problem. Common causes include Vit B12 deficiency, Folate deficiency, Liver disease, Alcoholism, and Hypothyroidism. It can also be a side effect of cancer, seizure, or autoimmune medication. Treatments = diet modification or blood transfusions. Microcytosis is usually due to iron deficiency, thalassemia, or an autoimmune disorder. Hyperchromic anemia is a condition where the RBC count is low, but the cells are larger and carry larger amounts of hemoglobin. More common in older people, but can occur in children. Due to diet, poor liver function, underactive thyroid, pregnancy, etc. What would it be called if a RBC has normal amounts of Hg? Normochromic. 43

If you were to vacation in the Alps, you would expect __.
a drop in oxygen levels. the release of erythropoietin. a rise in hematocrit. an increase in RBC production. All of the answers are correct. E. Would erthropoiesis increase or decrease if you: -had an obstruction in blood flow to the kidneys? Increase. -if you were hemorrhaging? Increase. -if you were fasting? Decrease. Why? We need amino acids and vitamins B12, B6, folic acid, and iron. -if you’re a vegan? No change as long as you’re careful. Most common = Vit B12 deficiency.

19-4 Blood Typing Surface Antigens Blood Types
Are cell surface proteins that identify cells to immune system Normal cells are ignored and foreign cells attacked Blood Types Are genetically determined By presence or absence of RBC surface antigens A, B, Rh (or D) (the ABO and Rh blood groups = blood type)

19-4 Blood Typing Four Basic Blood Types A (surface antigen A)
B (surface antigen B) AB (antigens A and B) O (neither A nor B)

19-4 Blood Typing Blood Plasma Antibodies Type A Type B Type O Type AB
Type B antibodies Type B Type A antibodies Type O Both A and B antibodies Type AB Neither A nor B antibodies Which one is the universal recipient? AB Why? They lack A or B agglutinins.

Figure 19-7a Blood Types and Cross-Reactions
A person’s blood type is determined mostly by the presence of specific glycoproteins on the cell membrane. 48

19-4 Blood Typing The Rh Factor Also called D antigen
Either Rh positive (Rh) or Rh negative (Rh) Only sensitized Rh blood has anti-Rh (-D) antibodies Blood type is identified primarily by the ABO and Rh blood groups.

Figure 19-9 Hemolytic Disease of the Newborn
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…Rh neg. people exposed to the D surface antigen, will have anti-D antibodies. Does this mean all Rh+ people have anti-D antibodies? No. 52

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19-4 Blood Typing Cross-Reactions in Transfusions
Also called transfusion reaction Plasma antibody meets its specific surface antigen Blood will agglutinate and hemolyze Occur if donor and recipient blood types not compatible …so just like we just saw, if a mother is Rh neg. and the baby is Rh+, the 2nd baby may result in hemolytic disease.

19-4 Blood Typing Testing for Transfusion Compatibility
Performed on donor and recipient blood for compatibility Without cross-match, type O is universal donor …So notice the blood cells agglutinate when mixed with anti-A sera but not with anti-B or anti-D. This means this person is blood type A+. So what kind of antibodies would you find in their plasma? B antibodies.

Table 19-2 Differences in Blood Group Distribution
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19-5 White Blood Cells White Blood Cells (WBCs) Also called leukocytes
Do not have hemoglobin Have nuclei and other organelles WBC functions: Defend against pathogens Remove toxins and wastes Attack abnormal cells RBCs make up the majority of cells in the blood, but they aren’t the only ones in the bloodstream. If you collect blood from someone and centrifuge it to spin it down. You’ll find RBCs on the bottom, fluid on the top, and a little white layer in between them. This white layer contains the other types of cells found in the blood called white blood cells. These WBCs are different that RBCs, b/c , like the other cell types in our body, they have nuclei. They only account for about 1% of the cells in the blood, but they are still very important.

19-5 White Blood Cells WBC Circulation and Movement Most WBCs in:
Connective tissue proper Lymphatic system organs Small numbers in blood 5000 to 10,000 per microliter

19-5 White Blood Cells WBC Circulation and Movement
Four Characteristics of Circulating WBCs Can migrate out of bloodstream Have amoeboid movement Attracted to chemical stimuli (positive chemotaxis) Some are phagocytic Neutrophils, eosinophils, and monocytes

19-5 White Blood Cells Types of WBCs:

19-5 White Blood Cells Neutrophils
Also called polymorphonuclear leukocytes 50–70% of circulating WBCs Pale cytoplasm granules with: Lysosomal enzymes Bactericides (hydrogen peroxide and superoxide) The most common type of WBC is the neutrophil. Neutrophils are smaller than monocytes and they have a number of very strange properties. One of the things that’s unusual is they have an odd looking cell nucleus. The nucleus constrictions and bulges so that the nucleus looks like a chain of sausages. It’s unsure why they develop like this, but one can imagine there might be a reason. The main job of neutrophils is to phagocytize/ingest bacteria. To do this, they tend to migrate out of the bloodstream past the endothelial cells of blood vessels. They reside in connective tissues where they look for bacteria to eat. In order to perform this type of function, neutrophils have to squeeze past the junctions of the endothelial cells. The skinny cell nuclei probably help as a round nucleus couldn’t squeeze past the junctions. When a neutrophil eats a bacterium, it’s metabolic rate increases causing an increase in the respiratory byproducts hydrogen peroxide and superoxide anions, which kill the bacteria. The vesicles in the cells that have the engulfed pathogens fuse with lysosomes that have digestive enzymes.

19-5 White Blood Cells Neutrophil Action
Very active, first to attack bacteria Engulf and digest pathogens Degranulation Removing granules from cytoplasm Defensins (peptides from lysosomes) attack pathogen membranes Release prostaglandins and leukotrienes Live about 10 hours (30 min when engulfing debris). Form pus The digestive enzymes in the lysosomes are celled defensins. These break down the pathogens and reduce the number of granules in the cytoplasm – degranulation. While actively attacking the bacteria, neutrophils release prostaglandins and leukotrienes. The prostaglandins increase capillary permeability to contribute to local inflammation and restrict the spread of injury and infection. Leukotrienes are hormones that attract other phagocytes to coordinate an immune response.

19-5 White Blood Cells Eosinophils (Acidophils)
2–4% of circulating WBCs Attack large parasites Excrete toxic compounds Nitric oxide Cytotoxic enzymes Increase in response to allergens Control inflammation with enzymes that counteract inflammatory effects of neutrophils and mast cells Destroy antibody-labeled antigens. Another type of WBC is the eosinophil. They get their names from granules visible in the cytoplasm of the cells. These vesicles or granules stain with a pink stain called EOSIN. The reason they stain so brightly with eosin is b/c eosinophils have little vesicles on the cytoplasm and these vesicles contain a protein called major basic protein. MBP is a highly charged protein. The basic charge on the protein attracts the acid stain eosin, b/c acids like to bind with bases. Eosinophils like all the other WBCs in the bloodstream also leave the blood to look for parasites like round worms. They aren’t terribly abundant here, but are in places of the world where the water supply isn’t as safe for drinking. Something like 200 million people in the world are infected by round worms. Eosinophils release chemicals that attach to round worms and destroy them. So, eosinophils are important for fighting off blood borne parasites that could damage our health. Interestingly, eosinophils tend to be more abundant in tissues of patients that suffer from asthma. It’s not known why, but eosinophils may be releasing these chemicals and contributing to the damage in cells that occurs with asthma. Regardless of what they’re doing, a high number of of eosinophils may be diagnostic of asthma.

19-5 White Blood Cells Basophils Are less than 1% of circulating WBCs
Accumulate in damaged tissue Release histamine Dilates blood vessels Release heparin Prevents blood clotting A 4th type of WBC is the basophil. Basophils also have funny looking nuclei. Instead of staining with eosin, which is an acid stain, these cells stain with basic stains, which tend to have a blue color. Basophils are very uncommon in the bloodstream, so it’s very hard to find them. The vesicles they contain seem to function like the vesicles of mast cells. They contain histamine and function in connective tissue like Mast cells to attract other defense cells.

19-5 White Blood Cells Monocytes 2–8% of circulating WBCs
Are large and spherical Enter peripheral tissues and become macrophages Engulf large particles and pathogens Secrete substances that attract immune system cells and fibrocytes to injured area Another common WBCs is called a monocyte. Monocytes are the LARGEST cells in the blood and they have pale-staining bean-shaped nucleus. Their main function is to LEAVE the bloodstream and enter connective tissue to turn into phagocytic macrophages. The main job of macrophages is to engulf things that invade and may harm the body. Monocytes respond to a large variety of stimuli and multiply in response to the stimuli. One stimulus that causes monocytes to rapidly multiply is a bacterium called listerium monocytogenes. This is commonly known as mononucleosis. When you have mono, you’re responding to this particular type of bacterium and you’ll have an abnormal number of cells in the bloodstream. It’s fairly benign and you can recover from it in a couple of months.

19-5 White Blood Cells Lymphocytes 20–30% of circulating WBCs
Are larger than RBCs Migrate in and out of blood Mostly in connective tissues and lymphoid organs Are part of the body’s specific immunity defense system A fairly common type of WBC found in the blood is a lymphocyte. We talked about lymphocytes when we talked about connective tissues and they’re found circulating in the blood as well. Their major job, like we said before is to produce antibodies to fight off foreign invaders in the bloodstream. …What are lymphoid organs that are going to produce lymphocytes? Spleen, lymph nodes, red bone marrow, and the thymus.

19-5 White Blood Cells Three Classes of Lymphocytes T cells
Cell-mediated immunity Attack foreign cells directly

19-5 White Blood Cells Three Classes of Lymphocytes B cells
Humoral immunity Differentiate into plasma cells Synthesize antibodies Natural killer (NK) cells Detect and destroy abnormal tissue cells (cancers)

19-5 White Blood Cells The Differential Count and Changes in WBC Profiles Detects changes in WBC populations Infections, inflammation, and allergic reactions Which WBC would you expect to see the most in a differential count of a healthy person? Neutrophils. What about in someone with an infection? Neutrophils. They’re the 1st to attack bacteria.

19-5 White Blood Cells WBC Disorders Leukopenia Leukocytosis Leukemia
Abnormally low WBC count Leukocytosis Abnormally high WBC count Leukemia Extremely high WBC count Leukopenia: is a low WBC count, which means a decrease in disease-fighting cells in your blood. Could be due to an infection disrupting BM function, congenital disorder, cancer, or autoimmunity. Leukocytosis: might indicate an infection or reaction to a drug, BM disease or immune system disorder. Leukemia: is a cancer of the blood-forming tissues including the BM or lymphatic system. Symptoms include fever, chills, fatigue, weight loss, easy bleeding or bruising, bone pain, etc.

19-5 White Blood Cells WBC Production
All blood cells originate from hemocytoblasts Which produce progenitor cells called myeloid stem cells and lymphoid stem cells

19-5 White Blood Cells WBC Production Myeloid Stem Cells
Produce all WBCs except lymphocytes Lymphoid Stem Cells Lymphopoiesis - the production of lymphocytes Lymphopoiesis occurs where? The spleen, lymph nodes, red bone marrow, and thymus.

19-5 White Blood Cells WBC Development WBCs, except monocytes
Develop in bone marrow Monocytes Develop into macrophages in peripheral tissues Where do all these cells come from? They all originate from cells within the bone marrow in bones like the femur, fibula, and sternum of the breastbone. All the precursors of the blood cells originate in the bone marrow.

19-5 White Blood Cells Regulation of WBC Production
Colony-stimulating factors (CSFs) Hormones that regulate blood cell populations M-CSF stimulates monocyte production G-CSF (Neupogen) stimulates production of granulocytes (neutrophils, eosinophils, and basophils) GM-CSF stimulates granulocyte and monocyte production Multi-CSF accelerates production of granulocytes, monocytes, platelets, and RBCs While the WBCs originate in the BM, they are stimulated by another hormone protein called colony-stimulating factor. CSF represents a family of proteins that are secreted by other types of cells in the BM. When these CSFs bind to white blood cell precursors called myelocytes in the BM, they stimulate them to become neutrophils, or eosinophils, or basophils. The precursors of WBCs have little round nuclei and round cytoplasm. They lack the peculiar characteristics seen in the mature cells. One reason they develop strange looking nuclei has to do with their response the retinoic acid. Exposure to RA stimulates the strange morphologies of the cell nuclei. Where do granulocytes form? In the red bone marrow. G-CSF is genetically engineered.

Table 19-3 Formed Elements of the Blood
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Figure 19-11 The Origins and Differentiation of Formed Elements
There are also stem cells in the BM that make up less than 0.5% of all the cells in the BM. It’s hard to identify them by looking at them, but they have specific proteins that allow them to be recognized. These cells are called Hematopoietic stem cells and they have the ability to migrate from the BM and take the place of other cells in the body. For instance, they can migrate to muscle and replace damaged muscle cells. HSCs then are what we would refer to as adult stem cells. 76

also known as polymorphonuclear leukocytes. important in coagulation.
All of the following are true of neutrophils, except that they are _____. granular leukocytes. phagocytic. also known as polymorphonuclear leukocytes. important in coagulation. active in fighting bacterial infections D Can neutrophils make hydrogen peroxide? Yes Can they exit capillaries? Yes Can they destroy bacteria? Yes Are they attracted to complement-coated bacteria? Yes Are they less abundant than lymphocytes? No

19-6 Platelets Platelets Cell fragments involved in human clotting system Nonmammalian vertebrates have thrombocytes (nucleated cells) Circulate for 9–12 days Are removed by spleen 2/3 are reserved for emergencies in the spleen Another component of the bloodstream is platelets. Platelets are not cells at all, but parts of cytoplasm that have been pinched off from precursor cells in the bone marrow. While they aren’t real cells and don’t have any nuclei, they have an important function. Platelets are the first components of the bloodstream that help initiate a clotting cascade. When a blood vessel is damaged and blood leaks out of the walls of the blood vessels, platelets are attracted to the damage and stick to the tear in the blood vessel and form a clot. They also produce growth factor molecules called platelet derived growth factors that can be used to stimulate the regrowth of cells around the blood vessels.

19-6 Platelets Platelet Counts 150,000 to 500,000 per microliter
Thrombocytopenia Abnormally low platelet count Thrombocytosis Abnormally high platelet count

19-6 Platelets Three Functions of Platelets
Release important clotting chemicals Temporarily patch damaged vessel walls Reduce size of a break in vessel wall

19-6 Platelets Platelet Production Also called thrombocytopoiesis
Occurs in bone marrow Megakaryocytes Giant cells in bone marrow Manufacture platelets from cytoplasm Lastly, platelets originate from cells in the BM called megakaryocytes. These are unusually large cells with a diameter about 5-10x bigger than the other cells in the BM. They are the Godzilla of the BM world. The nucleus is not only very large, but can contain 16x the amount of DNA of most other cells. Megakaryocytes move around the BM until they attach to the walls of a blood vessel. Then, they send out a cytoplasmic process into the interior of the blood vessel. The process then develops constrictions and looks like a string of tickets from Chuck E. Cheeses. Then, they break off and enter the blood stream. They respond to a hormone secreted by the liver called thrombopoietin. This stimulates the differentiation of megakaryocytes and production of platelets. Why the liver? The liver produces all the clotting proteins that help assemble clots in the blood stream and the hormone that stimulates platelets. Similar to the kidney, the liver has a large amount of blood flowing through it and it’s constantly monitoring the composition of the blood. The kidney monitors the amount of oxygen in the blood, while the liver keeps control of how fast the blood clots. B/n these 2 organs and the hormones they secrete, the composition of the cells and the composition of the clots in the bloodstream are highly controlled.

19-6 Platelets Platelet Production Hormonal controls
Thrombopoietin (TPO) Interleukin-6 (IL-6) Multi-CSF

19-7 Hemostasis Hemostasis Is the cessation of bleeding
Consists of three phases Vascular phase Platelet phase Coagulation phase

19-7 Hemostasis The Vascular Phase
A cut triggers vascular spasm that lasts 30 minutes Three Steps of the Vascular Phase Endothelial cells contract and expose basement membrane to bloodstream

19-7 Hemostasis Three Steps of the Vascular Phase Endothelial cells
Release chemical factors ADP, tissue factor, and prostacyclin Release local hormones, endothelins Stimulate smooth muscle contraction and cell division Endothelial plasma membranes become “sticky” Seal off blood flow

Figure The Vascular, Platelet, and Coagulation Phases of Hemostasis and Clot Retraction (Step 1) 86

19-7 Hemostasis The Platelet Phase
Begins within 15 seconds after injury Platelet adhesion (attachment) To sticky endothelial surfaces To basement membranes To exposed collagen fibers beneath endothelium Platelet aggregation (stick together) Forms platelet plug which closes small breaks

19-7 Hemostasis Platelet Phase
Activated platelets release clotting compounds Adenosine diphosphate (ADP) Thromboxane A2 and serotonin Clotting factors Platelet-derived growth factor (PDGF) Calcium ions The function of platelets is to assist in the process of hemostasis. …removing calcium ions from blood prevents coagulation.

19-7 Hemostasis Factors That Limit the Growth of the Platelet Plug
Prostacyclin, released by endothelial cells, inhibits platelet aggregation Inhibitory compounds released by other WBCs Circulating enzymes break down ADP Negative (inhibitory) feedback from serotonin Development of blood clot isolates area

19-7 Hemostasis The Coagulation Phase
Begins 30 seconds or more after the injury Blood clotting (coagulation) Cascade reactions Chain reactions of enzymes and proenzymes Form three pathways Convert circulating fibrinogen into insoluble fibrin The coagulation phase involves a cascade of reactions leading to the conversion of fibrinogen to fibrin.

19-7 Hemostasis Clotting Factors Also called procoagulants
Proteins or ions in plasma Required for normal clotting Most protein factor required for clotting are synthesized by the liver.

Table 19-4 Clotting Factors
93

19-7 Hemostasis Three Coagulation Pathways Extrinsic pathway
Intrinsic pathway Common pathway

19-7 Hemostasis The Extrinsic Pathway Begins in the vessel wall
Outside bloodstream Damaged endothelium releases tissue factor (Factor III) TF + other compounds = enzyme complex Activates Factor X The extrinsic pathway of coagulation is initiated by the release of tissue factor by damaged endothelium.

19-7 Hemostasis The Intrinsic Pathway
Begins with circulating proenzymes Within bloodstream Activation of Factor XII exposed to collagen Platelets release factors (e.g., PF-3) Series of reactions activates Factor X The intrinsic pathway of coagulation is activated by the activation of Factor XII exposed to collagen. People with hemophilia A can’t make functional Factor VIII, so they lack a functional intrinsic pathway.

19-7 Hemostasis The Common Pathway
Where intrinsic and extrinsic pathways converge Conversion of Factor X to prothrombinase Converts prothrombin to thrombin Thrombin converts fibrinogen to fibrin The common pathway of coagulation begins with the conversion of Factor X to prothrombinase.

19-7 Hemostasis Feedback Control of Blood Clotting
Stimulates formation of tissue factor Stimulates release of PF-3 Forms positive feedback loop (intrinsic and extrinsic) Accelerates clotting

19-7 Hemostasis Feedback Control of Blood Clotting
Anticoagulants (plasma proteins) Antithrombin-III Alpha-2-macroglobulin Heparin Aspirin Protein C (activated by thrombomodulin) Prostacyclin

19-7 Hemostasis Calcium Ions, Vitamin K, and Blood Clotting
Calcium ions (Ca2+) and vitamin K are both essential to the clotting process Some rat poisons have a toxin that blocks the liver’s ability to use Vit. K. If you eat this poison you would die of hemorrhage. What are some sources of Vit K? green veggies, organ meats, whole grains, intestinal bacteria.

19-7 Hemostasis Clot Retraction
Pulls torn edges of vessel closer together Reducing residual bleeding and stabilizing injury site Reduces size of damaged area Making it easier for fibrocytes, smooth muscle cells, and endothelial cells to complete repairs What’s a moving blood clot called? Embolus

19-7 Hemostasis Fibrinolysis Slow process of dissolving clot
Thrombin and tissue plasminogen activator (t-PA) Activate plasminogen Plasminogen produces plasmin Digests fibrin strands The process of fibrinolysis dissolves clots. Plasmin is the enzyme that digests fibrin to dissolve a clot. Substances that activate plasminogen is an area of research to dissolve clots faster.

low levels of prothrombin low levels of Factor X
A digestive disorder that impairs a person’s ability to absorb vitamin K will result in _____. low levels of prothrombin low levels of Factor X low levels of thromboplastin prolonged bleeding All of the above E

An Introduction to Blood and the Cardiovascular System

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