Blood is a fluid connective tissue Blood has

Blood is a fluid connective tissue

Blood has *2 parts: 1) Plasma (fluid) 2) Formed elements (cells) *When blood is spun at high speeds, it separates into the two main components as shown. Ultimately everything you need is in your Blood Glucose, Amino acids, Proteins, Hormones Fatty acids, Triglycerides, Cholesterol, Vitamins Ions/Electrolytes (Na+, K+, Cl-, Ca 2+, HPO 42 Mg 2+…SO 42 -, Zn 2+, HCO 32 -…) Urea, Uric acid, Creatinine, Bilirubin, ammonia O 2 and CO 2 (dissolved in plasma) The p. H of Blood is 7. 35 to 7. 45 Note: Arterial blood has a higher p. H (ave. ~7. 41) thus is more basic than venous blood, which has a lower p. H (ave. ~7. 15), and is more acidic. However, the range of p. H for blood is still 7. 35 to 7. 45. Blood brings Warmth Blood is slightly warmer than normal body temperature (Tb), it’s about 38°C (or 100. 4 °F), compared to 37. 1°C (or 98. 6 °F) for an average internal Tb reading. As blood flows along blood vessels, friction and resistance are experienced, producing heat.

Blood = Plasma + Formed (Cellular) Elements Facts about Plasma • ~55% blood volume • ~92% of plasma is water • Has high level of O 2 and CO 2 content dissolved in it • Many Dissolved Proteins (COP) • Nutrients and Wastes (listed) ü ü Glucose, Amino acids, Hormones, Vit. Fatty acids, Triglycerides, Cholesterol* Ions/Electrolytes Urea, Uric acid, Creatinine, Bilirubin The Cells in Blood • ~45% blood volume • RBCs (~99% of cells) • WBCs (~1% of cells) Note: *Lipids, including cholesterol are critical to good health. There are special ‘carriers’ for lipids in the blood to transport them to tissues!

Proteins in Plasma* • Albumins – 60% of plasma proteins (forms lipoproteins). – transport binding for insoluble lipids; big contributor to COP. • Globulins – 35% of plasma proteins: alpha, beta, and gamma subgroups. – alpha & beta made by liver transport iron, Vit A, D, E, and K. – gamma* = antibodies (immunoglobulins) for immunity made by leukocytes (plasma cells) *only plasma pro- not made by the liver. • Fibrinogen – 4% of plasma proteins. When activated forms fibrin for clotting reaction. Plays a role in Hemostasis (stopping blood loss). v Regulatory Proteins - Less than 1%, these are enzymes, proenzymes and hormones. *serum = plasma without clotting proteins

Lipids in Plasma is 92% Water and Lipids are hydrophobic, so they require special mechanism for transport through the blood to the tissues. Free Fatty Acids – 2 are ‘essential’ for humans: 1. alpha-linolenic acid, an omega-3 fatty acid 2. linoleic acid, an omega-6 fatty acid. These are important and you must get these from your diet! The various Lipoproteins transport lipids in the Blood 1. Very Low Density Lipoproteins (VLDL) made in liver, mostly triglycerides (~50%). These travel in the body and return triglycerides to liver. They can be converted into LDLs…

Lipids in Plasma 2. Low Density Lipoprotein (LDL) These carry mostly cholesterol (~50%). These circulate in the body and release lipids to body cells, 100% required for membranes, hormones, etc. The Liver removes LDL from circulation. 3. High Density Lipoprotein (HDL) This transports cholesterol from cells back to the liver for recycling or disposal. This is where the function of HDL in picking up ‘excess cholesterol’ has become the focus of its role and the declaration of it as the “good cholesterol”. It is neither good or bad, it is essential, just like LDL! Also, please realize that HDLs and LDLs are not cholesterol: They are Carriers of Cholesterol.

Here is a nice summary of the roles of HDLs and LDLs The liver is the great cleanser and recycler Yay, thanks I needed those lipids Here, please take what I don’t need In summary, LDLs or HDL’s are not Bad or Good. They are both carries of Cholesterol and other lipids which are 100% vital to Life!

Ancel Keys cover of Time Magazine in 1961. He claimed that saturated fats in the diet clogged arteries and caused heart disease. py e e r ac d s a s w roduce y e K p Dr. d who ! Frau Science Bad Time Magazine Cover from 1984 still blaming cholesterol and saturated fats as a cause of heart disease. gs’ n i d fin for ‘ y reep tuated c e Th perpe s! r e wer 50 yea r ove Again, Time Magazine cover story in 2014. Now Scientists have to admit they were wrong about saturated fats. They don’t cause heart disease after all, they are actually good for you!

Eating fat makes you fat & increases risk of cardiovascular disease - Right? NO! Obesity % Graph (to the Left) The Yellow arrow shows approx. time of Dr. Keys “fats are bad” study which lowered fat intake in the Standard American Diet (SAD). The Red arrow shows approx. time of the introduction of High Fructose Corn Syrup (HFCS) to American market. This is when sugar intake began to superseded fat intake. Heart Disease Graph (to the Right) The reduction of animal fat intake in diets appear to have had no beneficial effect on the incidents of heart disease, in fact, it continued to increase. The reason for the decline after 1990 is speculative and may be impacted by the increasing cancer deaths in the United States. Note: Sugar consumption radically increased (see article for Heart surgeon). Article: Dr. Dwight Lundell: Prevent. Disease - Thu, 01 Mar 2012

Cellular Components of Blood The RBCs (erythrocytes) ~99% of all cells. Hematocrit = % of blood occupied by cellular components. (packed RBC volume) • Smallest blood cell • Biconcave disc (large surface area) • Super flexible (pro- spectrin) Lacks: nuclei, ribosomes, and mitochondria. Anaerobic metabolism (glycolysis) Life span = ~120 days

a) b) c) a) Image from a Light Microscope (LM) of erythrocytes or red blood cells (RBCs) that are seen free, and some that are stacked in rouleau (plural rouleaux), circled in blue. b) Scanning Electron Micrograph (SEM) image of RBCs on the tip of a hypodermic needle. c) Showing up-close normal biconcave disc RBCs with clusters of the very small platelet cells also present. Facts about RBC’s • The red bone marrow makes all blood cells, including RBCs. There about 2. 5 million RBCs per sec produced and released into the circulation. • RBCs are small cells (7 to 8 µm) in diameter, and are very flexible (due to the protein spectrin in their membrane) thus can squeeze through the smallest blood vessels. • RBC contain enzymes in cytosol for glycolysis, so they can to make limited ATP w/out using O 2. • With limited repair capability, RBCs have a limited life span (120 days). Worn, older and damaged RBCs are removed from the circulation by macrophages in the spleen and liver (esply spleen!). • If more RBCs are needed, the kidneys release the hormone erythropoietin to stimulate RBC production in the red bone marrow.

There are millions of Hb inside each RBC • RBCs have so few organelles to make more room for hemoglobin (Hb) => 250 million Hb/cell! • Hb binds and transports Oxygen (O 2) and some Carbon Dioxide (CO 2) in the body. • The Hb molecule contains 4 globin portions (2 α and 2 β chains). • At the center of each globin is an iron (Fe) containing Heme molecule. The globin portions (α and β) CO 2 binds here. The heme portions (in center of each globin). The O 2 binds here. Each Hb molecule binds 4 O 2 molecules maximum.

Anemia Deficient O 2 carrying capacity of blood (esply lower RBCs or Hb). Results in pallor, weariness. There are 3 basic categories of Anemia: • Inadequate erythropoiesis = low hematocrit e. g. , Inadequate nutrition (iron deficiency) e. g. , Low Hormone Levels (erythropoietin) • Hemolytic anemia = abnormal breakdown of RBCs e. g. , Sickle cell anemia (see right!) Normal RBC Sickle Cell • Hemorrhagic anemia = loss of blood volume e. g. , trauma, hemophilia, ruptured aneurysm Sickle Cell Anemia (from a genetic disorder)

Normal Hematocrit and Variations from Normal Polycythemia Anemia Fetal blood Dehydration % RBC of blood 70% of Volume Hematocrit: 45% 30% 70% 60% 40%

ABO Blood Grouping (Types) A blood type (group) is a classification of blood based on the presence or absence of genetically determined cell markers on the surfaces of the RBCs called antigens (agglutinogens). It is the plasma of blood that contains antibodies (agglutinins) that are ‘complementary’ to the antigens. The Antigens determine Blood Type. The ABO blood group based on two antigens, A and B • • If RBC displays only antigen A = blood type A. If RBC displays only antigen B = blood type B. If RBC displays both A and B antigens = blood type AB. If RBC displays no antigens = blood type O. The Rh factor is another RBC marker: Two options: Rh antigen present = Rh+ No Rh antigen present = Rh- In summary: There are 8 blood types. The 4 categories bases on A and B, and these are either positive (+) or negative (-) for the Rh factor. The donut icing +/- sprinkles analogy to the right, it is a handy way to visualize it!

Remember, plasma contains antibodies that are ‘complementary’ to the antigens. This means type A blood has B antibodies in the plasma; type B blood has A antibodies in the plasma; type AB blood has no antibodies in the plasma; and type O blood has both A and B antibodies in the plasma. If a RBC is type A (antigen) and it mixes with plasma containing A antibodies, agglutination or ‘clumping’ of blood would occur. This is bad, as agglutinated cells become lodged in small capillaries and over a period of hours, cells can swell, rupture, and release hemoglobin into the blood, this is called hemolysis. Therefore, certain blood types cannot be mixed! Q: If a RBC with a B ‘flag’ or antigen is mixed with the B antibodies, what would happen? Q: What if a RBC with a no antigens is mixed with the A and B antibodies, what would happen? Q: What if a RBC with A and B antigens is mixed with plasma with no antibodies, what would happen? Q: What if a RBC with A antigens is mixed with plasma with A and B antibodies, what would happen?

In Lab, testing blood types would look like this: For the set up below, the Anti A, Anti B and Anti Rh represent the antibodies in the plasma for those antigens. Compare the clear blood from the original sample (left) to how the blood responds to the addition of the various antibodies (clump or does not clump). From the visual results below, Determine the blood types shown: Sample 1) 2) Anti A Anti B Anti Rh What is the Blood Type? _______ 3) 4) Additional Questions: Q: What does “universal donor” mean and what blood type(s) is it? _______. Q: What does “universal recipient” mean and what blood type(s) is it? _______. Q: What is the most common blood type in the USA? _______ Q: What is the least common blood type in the USA? _______ Q: What is your blood type? _____.

Blood Glucose Levels The glucose in blood is used as a fuel for the body’s cellular activities, therefore, blood glucose is homeostatically controlled by a negative feedback loop: • if blood glucose gets too high, it is decreased (by actions of insulin) • if blood glucose gets too low, it is increased (by actions of glucagon) Regulation of blood glucose involves two hormones with opposing actions, Insulin and Glucagon. Plasma Glucagon (ng/ml) Note how changes in blood glucose (center panel) trigger changes in glucagon (upper panel) and insulin (lower panel) levels. Plasma Glucose (mg/dl) The green circle is just before a meal - as glucose levels were falling, glucagon increased in order to increase blood glucose. Plasma Insulin (µg/ml) The red circle shows the peak in elevated blood glucose, and a there is a corresponding spike in insulin in order to decrease the blood glucose.

Glycemic Index (GI) indicates how quickly a certain food turns into glucose in a person’s body. Glycemic Load (GL) indicates the total amount of glucose in the food. Using these parameters, the total amount of glucose in an average serving can be calculated. Refined Processed Foods White Bread, White Rice Candy and Soda Low fat Yogurt Girl Scout Cookies Whole Foods Complex Organic Vegetables Brown Rice or Quinoa Nuts and Legumes Fresh Organic Fruits

Blood Glucose Levels – How it changes, Foods that affect it. The graph shows that as blood glucose levels go up, blood insulin levels also increase B) Blood Glucose Concentrations Blood Concentrations A) This graph shows the impact of Carbohydrates, Proteins and Lipids on Blood Glucose levels Refined Carbs (bread cereals, sugary snacks) Proteins (meats, beans, eggs) Lipids (butter, avocados, nuts) Looking at graph A): Q: How long after blood glucose is elevated does it take to return to normal resting values ? ________. Q: In terms of the blood levels, a spike in ______ is always followed by a large spike in ________. Looking at graph B): Q: Which food category causes the smallest elevation in blood glucose? _______________. Q: Which food category causes the greatest elevation in blood glucose? _______________.

Glucose Tolerance Test Measuring the response of the Body to Glucose Loads The Oral Glucose Tolerance Test (OGTT) measures the body's ability to use glucose, and can be used to diagnose diabetes mellitus. A standardized dose of glucose is given orally and blood samples are taken over time to determine rate of glucose clearance from the blood. From info in previous slides, we’ve seen that certain types of food cause large spikes in glucose (thus insulin) and lead to the ‘rollercoaster’ (levels seen in the graph to the left and at the bottom). These wild changes in blood glucose are referred to as “he sugar high”, and “the sugar blues”, as when it crashes you feel low. For many reasons, these radical swings in glucose and insulin levels are not good for your health.

The A 1 C Test for Glycated Hemoglobin The A 1 C blood test provides info regarding the average blood glucose levels over the past 3 months! Used to diagnose Type 2 diabetes and prediabetes. Also called hemoglobin A 1 C, Hb. A 1 c or *glycated hemoglobin test, because Glucose attaches nonenzymatically with hemoglobin (Hb) in RBCs. Higher the blood glucose, more glucose attached to Hb. A 1 C test measures amount of Hb with attached glucose, reported as a %. The higher the %, the higher your blood glucose levels have been over last 3 months. Scale: • Below 5. 7% is considered normal. • From 5. 7 to 6. 4% is considered pre-diabetes. • At 6. 5% or higher is considered diabetic. *Related to Advanced Glycation End-Products (AGE’s) in diabetes mellitus.

Stem cells for all Blood cells from Red Bone Marrow

Order of Abundance of WBC in Healthy person All Blood cells come from Red Bone Marrow! Never 50 -70% Let 20 -30% Monkeys Eat ? ? ? Bananas Remember: Normal healthy WBC #’s in blood are less than 1% of total cells. The %’s shown under each WBC are %’s for that 1%! 2 -8% 2 -4% < 1%

White Blood Cells (Leukocytes) There are 2 categories of Leukocytes (WBCs): Granular and Agranular Granular Leukocytes Have granules in cytoplasm containing powerful enzymes & substances for defense. • Neutrophils 70% of circulating leukocytes – Highly mobile phagocytes, multi-lobed nucleus (3 or more lobes) • Eosinophils less common – Bi-lobed nucleus, ‘orange’ staining granules. They’re attracted to foreign compounds reacted with antibodies. • Basophils relatively rare – Bi-lobed, dark staining granules, release histamine and heparin. Migrate to damaged tissue. There are toxic materials made and released by ‘degranulation’ of all of these cells, this is in order to aid in the destructions and ingestion of microorganisms. This is their function.

Agranular Leukocytes These cells do not contains granules in cytoplasm. • Lymphocytes primary cell of lymphatic system • T-cells attack foreign cells directly. • B-cells produce antibodies. • Monocytes – Large ‘dimpled’ nucleus. They migrate into tissues and differentiate into Macrophages - highly mobile phagocytes. • Platelet cells (Thrombocytes) – Fragments of cells (Megakaryocytes) for clotting. Mast cells (honorable mention): These are connective tissue cells that migrant to the site of injury. They contains granules of histamine and heparin.

Hemostasis = stopping blood loss. Prevents hemorrhage (excessive bleeding). (hemo = blood; stasis= stationary) 3 Steps of Hemostasis 1. Vascular spasm 2. Platelet plug formation 3. Coagulation (blood clotting) 1) Vascular Spasm Vascular smooth muscle (VSM) in walls of ruptured/damaged blood vessel contract! Pain receptors are signal and endothelial cells release endothelin, a vasoconstrictor! This reduces blood flow/loss. 2) Platelet Plug - this occurs as platelet cells accumulate and adhere at the site of vessel injury. A damaged (ruptured) vessel exposes collagen – this triggers platelet cells (via pseudopods) to stick to damaged vessel. Then platelets degranulate releasing: Serotonin (yes, the NT!) here it acts as a vasoconstrictor; Prostaglandins, a vasoconstrictor; ADP, this attracts and degranulates more platelets. All of this causes platelet cell aggregation (a positive feedback loop) and the cycle continues until it is broken when the small vessel is sealed. 3) Coagulation (blood clotting) - this part is complex and very effective in reducing bleeding. It involves conversion of the plasma protein fibrinogen into insoluble fibrin threads, a net-like framework necessary for blood clotting to occur. Pro-coagulants (clotting factors) activate the steps to form a reaction cascade. q Extrinsic Pathway: Factors released by damaged tissues can begin the cascade. q Intrinsic Pathway: Factors found in blood can begin cascade (platelet degranulation). q Common Pathway: Both above lead here, wherein fibrin is produced to seal off vessel.

Summary overview of the 3 Steps of Hemostasis 1. Vascular spasm => Vasoconstriction. 2. Platelet Plug Formation => more and more platelets arrive. 3. Coagulation (blood clotting) => Makes Fibrin mesh-work clot!