BMD 252 - Exam 2

List four production requirements for continual blood cell replacement.

1. Adequate iron (Fe) supply. 2. Adequate amino acids for hemoglobin (Hb) production. 3. B vitamins for DNA synthesis. 4. Release of kidney erythropoetin (EPO), as required.

Recall three classes of anti-clotting agents, related agents, chemical makeup, and mechanisms of action.

1. Anticoagulants: Substances used to suppress and/or prevent blood clotting after a heart attack, stroke, deep vein thrombosis (DVT), or pulmonary embolism (PE). • Antithrombin III: A plasma protein that quickly inactivates any thrombin not bound to fibrin. • Protein C: Inhibits that activity of other intrinsic pathway clotting factors. • Heparin (iv) or Warfarin/Coumarin (oral): Inhibits thrombin by enhancing the activity of antithrombin III; inhibits the intrinsic pathway. 2. Anti-Thrombotic Agents (Drugs): Low-dose aspirin (40-100mg) that blocks platelet enzyme synthesis and lowers platelet aggression. • Plavix/Clopidogrel: An ADP receptor inhibitor. 3. Antithrombolytic Agents (Clot Busters): Injected substances that dissolve formed clots by activating plasminogen. • Streptokinase and Tissue Plasminogen Activator (tPA).

For the pituitary gland: Name/explain synonyms, functions, feedback mechanisms and imbalances for growth hormone, thyroid stimulating hormone, adrenocorticotropic hormone, gonadotropins (LH & FSH, prolactin, oxytocin and antidiuretic hormone.

1. Growth Hormone (GH): • GH, and/or somatotropin, is prduced by somatotropic cells. • GH is an anabolic (tissue building) hormone that has both metabolic and growth promoting actions. • Direct Actions on Metabolism: - Increase blood levels of fatty acids. - Decreases the rate of glucose uptake, conserving glucose. - Increases blood-glucose levels (glucose sparing action) opposing the effects of insulin (anti-insulin effect). - Increases amino acids in cells. • Indirect Actions on Growth: ~ Insulin-like growth factors (IGF's): Mediate the growth-enhancing effects of GH (produced by liver, skeletal muscle, & bone). - Increase body cell size/cell division. - Promotes bone growth. - Increases muscle mass of skeletal muscles. ~ Secretion of GH is regulated by growth hormone-releasing (GHRH) and inhibiting (GHIH) hormones. 2. Thyroid-Stimulating Hormone (TSH): • TSH, and/or thyrotropin, stimulates normal development and secretory activity of the thyroid gland. • The thyrotropin-releasing hormone (TRH) triggers the release of TSH from thyrotopic cells. 3. Adrenocorticotropic Hormone (ACTH): • ACTH, and/or corticotropin, is secreted by corticotropic cells. • ACTH stimulates the adrenal cortex to release corticosteroid hormones and glucocorticoids that help the body resist stress. • ACTH release, elicited by corticotropin-releasing hormones (CRH), has a daily rhythm, with levels peaking in the morning shortly after awakening. • Rising levels of glucocorticoids block secretion of CRH and ACTH release. • ACTH rhythm can be altered by external factors such as fever, hypoglycemia, and stressors of all types. 4&5. Follicle-Stimulating Hormone (FSH) & Luteinizing Hormone: • FSH and LH are collectively referred to as gonadotropins, which regulate the function of the gonads (ovaries & testes). •In both sexes, FSH stimulates production of gametes (sperm or eggs) and LH promotes production of gonadal hormones. - In females, LH causes an egg-containing ovarian follicle to mature, triggers ovulation, and promotes synthesis/release of ovarian hormones. - In males, LH stimulates the cells of the testes to produce the male testosterone hormone. • Gonadotropins are absent in prepubertal boys and girls until gonadotropic cells are activated during puberty, causing the gonads to mature. • Gonadotropin-Releasing Hormone (GnRH): Prompt gonadotropin release. 6. Prolactin (PRL): • PRL is a protein hormone produced by prolactin cells that stimulates milk production by the breasts. • PRL release is controlled by the prolactin-inhibiting hormone (PIH) now known to be dopamine, which prevents prolactin secretion. • Estrogen stimulates prolactin release directly and indirectly. - In females, prolactin levels rise and fall in rhythm with estrogen blood levels. - In pregnant women, PRL levels rise dramatically at the end of pregnancy. 7. Oxytocin: • Strong stimulant of uterine contractions and initiates labor. It also initiates milk ejection from breasts. • Released in higher amounts during childbirth and in nursing women. • Oxytocin acts via the PIP2-Ca2+ second-messenger systemn to mobilize Ca2+, which allows for stronger contractions. • Childbirth and milk ejection result from positive feedback mechanisms. • Oxytocin is also a neurotransmitter in the brain referred to as the "cuddle" hormone. It is involved in sexual/affectionate behavior and promotes nurturing, couple bonding, and trust. 8. Antidiuretic Hormone (ADH): • Prevents wide swings in water balance, helping the body avoid dehydration and water overload. • Osmoreceptors: Hypothalamic neurons that continually monitor the solute/water concentration of the blood. When solutes become too concentrated, osmoreceptors transmit impulses releasing ADH, which produces less urine and the solute concentration declines. As solute levels fall, osmoreceptors stop, ending ADH release. • Other stimuli triggering ADH release include pain, low blood pressure, and such drugs as nicotine, morphine, & barbiturates. • Severe blood loss triggers exceptionally large amounts of ADH, which causes vasoconstriction and raises blood pressure. This response gives ADH its nickname/second name "vasopressin." • Drinking lots of alcohol or water inhibits ADH release.

List 2 characteristics of blood hormone levels.

1. Hormones Circulate in Blood in 2 Forms: • Free (Unbound): Water-soluble (peptide) hormones that lack carrier proteins. • Bound: Lipid-soluble (steroid) hormones that attach to carrier proteins in the blood plasma. 2. The Concentration of Circulating Hormones in the Blood Reflects: • Its rate of release. • Its speed of inactivation/body removal. • Some hormones are degraded by enzymes in their target cells, though most are removed from the blood by the kidneys/liver. • Half-Life: The length of time for a hormone's blood level to decrease by half (50%). - Varies from a fraction of a minute to a week. - Water-soluble hormones have the shortest half lives because they are rapidly removed from the blood by the kidneys.

List 3 general characteristic of all hormones.

1. Hormones regulate the metabolic activity of other cells. 2. Most hormones exhibit lag/delay times. 3. Most hormones have prolonged/lasting effects.

Differentiate between a thrombus, embolus, and thromboembolus by location and structure.

• A clot that develops and persists in an unbroken vessel is called a thrombus. - A stationary blood clot that does not obstruct blood flow and remains attached to the vessel wall. - Nonocclusive (adequate oxygen). • If the thrombus breaks away from the vessel wall and floats freely in the bloodstream, it becomes an embolus. - Solid, liquid, or gas moving in the blood that causes blood vessel obstruction (embolism). ~ Air bubble, marrow fat, bacterial mass, foreign body, etc. - Occlusive (inadequate oxygen). • An embolus or "wedge" is usually no problem until it encounters a blood vessel too narrow for it to pass through, then it becomes an embolism, obstructing the vessel. • Thrombosis is a stationary blood clot that obstructs blood flow, and may break free from the vessel wall. - Occlusive (inadequate oxygen). • Thromboembolism: A blood clot causing blood vessel obstruction. - Occlusive (inadequate oxygen).

Given the antibodies (anti-A, anti-B) present in the plasma, interpret the ABO blood type (AB, A, B, O).

• ABO Blood Groups: Based on the Presence of 2 Agglutinogens: Type A or B: - A: Presence of the A agglutinogen, and anti-B antibodies. - B: Presence of the B agglutinogen, and anti-A antibodies. - AB: Has both antigens A and B, and is the least common; neither antibody. - O: Has neither agglutinogen A or B, and is the most common ABO group in North America; possesses both A and B antibodies.

Given the red blood cell ABO antigens (type A, type B), interpret the ABO blood type (AB, A, B, O).

• ABO Blood Groups: Based on the Presence of 2 Agglutinogens: Type A or B: - A: Presence of the A agglutinogen, and anti-B antibodies. - B: Presence of the B agglutinogen, and anti-A antibodies. - AB: Has both antigens A and B, and is the least common; neither antibody. - O: Has neither agglutinogen A or B, and is the most common ABO group in North America; possesses both A and B antibodies.

For the adrenal cortex: List its 3 layers and correctly order them from either outside to inside or inside to outside.

• Adrenal Cortex: Synthesizes over two dozen steroid hormone, collectively called corticosteroids. These steroid hormones are not stored in cells and therefore their rate of release depends on their rate of synthesis. - Three Layers: Outer to Inner: 1. Zona Glomerulosa: Cells of this layer produce mineralocorticoids (such as aldosterone) that help control the balance of minerals and water in the blood. 2. Zona Fasiciculata: Cells of this layer produce metabolic hormones called flucocoticoids (such as corisol). 3. Zona Reticularis: Cells of this layer produce adrenal sex hormones, or gonadocorticoids.

For the adrenal glands: Describe the relative location of its 2 regions.

• Adrenal Glands: Also called the suprarenal glands are pyramid-shaped organs perched atop the kidneys, where they are enclosed in a fibrous capsule and a cushion of fat. - Each adrenal gland is structurally and functionally two endocrine glands. - The inner adrenal medulla, more like a knot of nervous tissue than a gland, is part of the sympathetic nervous system. - The outer adrenal cortex, encapsulating the medulla and forming the bulk of the gland, is glandular tissue derived from embryonic mesoderm.

Describe the different membrane passage mechanisms used by amino acid and steroid-based hormones.

• Amino-Acid Based: These hormones are water soluble and cannot cross the plasma membrane (except for the thyroid hormone). - Cyclic AMP (cAMP) second-messenger mechanism of water-soluble hormones: 1. Hormone (1st messenger) binds to receptor. 2. Receptor activates G-protein. 3. G-protein activates adenylate cyclase. 4. Adenylate cyclase converts ATP to cAMP (2nd messenger). 5. cAMP activates protein kinases. • Steroids: Hormones synthesized from cholesterol that are lipid soluble and can cross the plasma membrane. - Direct gene activation mechanism of lipid-soluble hormones: 1. The steroid hormone diffuses through the plasma membrane and binds to an intracellular receptor. 2. The receptor-hormone complex enters the nucleus. 3. The receptor-hormone complex binds to a specific DNA region. 4. Binding initiates transcription of the gene to mRNA. 5. The mRNA directs protein synthesis.

Differentiate between anemia and polycythemia.

• Anemia: A condition in which the blood's oxygen-carrying capacity is too low to support normal metabolism. - It is a sign of some disorder rather than a disease itself. - Anemic individuals are fatigued, often pale, short of breath, and chilled. - The causes of anemia are divided into 3 groups: blood loss, not enough RBC's produced, or too many RBC's destroyed. • Polycythemia: An abnormal excess of erythrocytes that increases blood veolcity, causing it to flow sluggishly. - Polycythemia Vera: A bone marrow cancer characterized by dizziness and exceptionally high RBC count. - Polycythemia (Secondary): When less oxygen is available or EPO production increases. - Blood Doping: Artificially induced polycythemia.

For the pituitary gland: Discuss adenohypophysis tissue composition, embryonic origin, portal system & its 6 hormones.

• Anterior Pituitary/Adenopophysis: - Composed of glandular tissue not originating in the hypothalamus. - Manufactures and releases a number of hormones. • Anterior Pituitary-Hypothalamic Relationship: - Originates from epithelial tissue of the oral mucosa. - Has no direct neural connection to the hypothalamus, but a vascular connection. - Hypophyseal Portal System: Composed of the primary capillary plexus, hypophyseal portal veins, and the secondary capillary plexus, the portal is a local blood capillary system that links the hypothalamus and anterior pituitary. The portal system ensures that the minute quantities of hormones released by the hypothalamus arrive rapidly at the anterior pituitary without being diluted. - 6 cell types synthesize and release 6 peptide hormones. - Releasing Hormones: Stimulate hormone synthesis/release. - Inhibiting Hormones: Shut off hormone synthesis/release. • Anterior Pituitary Hypothalamic Hormones: - The anterior pituitary is also called the "master endocrine gland" because many of its hormones regulate the activity of other endocrine glands. - The anterior pituitary releases 6 hormones, all peptides or proteins (growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone, follicle-stimulating hormone, luteinizing hormones, and prolactin). - Four of the six anterior pituitary hormones (thyroid-stimulating, adrenocorticotropic, follicle-stimulating, & leutinizing) are tropic hormones/tropins, which regulate the secretory action of the other endocrine glands. - Anterior pituitary hormones affect their target cells via a cyclic AMP second-messenger system. 1. Growth Hormone (GH): • GH, and/or somatotropin, is prduced by somatotropic cells. • GH is an anabolic (tissue building) hormone that has both metabolic and growth promoting actions. • Direct Actions on Metabolism: - Increase blood levels of fatty acids. - Decreases the rate of glucose uptake, conserving glucose. - Increases blood-glucose levels (glucose sparing action) opposing the effects of insulin (anti-insulin effect). - Increases amino acids in cells. • Indirect Actions on Growth: ~ Insulin-like growth factors (IGF's): Mediate the growth-enhancing effects of GH (produced by liver, skeletal muscle, & bone). - Increase body cell size/cell division. - Promotes bone growth. - Increases muscle mass of skeletal muscles. ~ Secretion of GH is regulated by growth hormone-releasing (GHRH) and inhibiting (GHIH) hormones. 2. Thyroid-Stimulating Hormone (TSH): • TSH, and/or thyrotropin, stimulates normal development and secretory activity of the thyroid gland. • The thyrotropin-releasing hormone (TRH) triggers the release of TSH from thyrotopic cells. 3. Adrenocorticotropic Hormone (ACTH): • ACTH, and/or corticotropin, is secreted by corticotropic cells. • ACTH stimulates the adrenal cortex to release corticosteroid hormones and glucocorticoids that help the body resist stress. • ACTH release, elicited by corticotropin-releasing hormones (CRH), has a daily rhythm, with levels peaking in the morning shortly after awakening. • Rising levels of glucocorticoids block secretion of CRH and ACTH release. • ACTH rhythm can be altered by external factors such as fever, hypoglycemia, and stressors of all types. 4&5. Follicle-Stimulating Hormone (FSH) & Luteinizing Hormone: • FSH and LH are collectively referred to as gonadotropins, which regulate the function of the gonads (ovaries & testes). •In both sexes, FSH stimulates production of gametes (sperm or eggs) and LH promotes production of gonadal hormones. - In females, LH causes an egg-containing ovarian follicle to mature, triggers ovulation, and promotes synthesis/release of ovarian hormones. - In males, LH stimulates the cells of the testes to produce the male testosterone hormone. • Gonadotropins are absent in prepubertal boys and girls until gonadotropic cells are activated during puberty, causing the gonads to mature. • Gonadotropin-Releasing Hormone (GnRH): Prompt gonadotropin release. 6. Prolactin (PRL): • PRL is a protein hormone produced by prolactin cells that stimulates milk production by the breasts. • PRL release is controlled by the prolactin-inhibiting hormone (PIH) now known to be dopamine, which prevents prolactin secretion. • Estrogen stimulates prolactin release directly and indirectly. - In females, prolactin levels rise and fall in rhythm with estrogen blood levels. - In pregnant women, PRL levels rise dramatically at the end of pregnancy.

Define the term anticoagulant.

• Anticoagulant: Substances that inhibit clotting.

Distinguish between local acting hormones - autocrines and paracrines.

• Autocrines: Short distance chemical signals that act on the same cells that secrete them. - Example: Prostaglandin released by smooth muscle cells causes them to contract. • Paracrines: Short distance chemical signals that act locally (within the same tissue) on nearby cells, but affect cell types other than those releasing the paracrine chemicals. - Example: Pancreatic somatostatin inhibits the release of both insulin and glucagon.

Describe the heart events indicated by the lup-dup-pause heart sounds.

• Basic pattern is "lub-dup-pause." - 1st "lub" = Closing of AV valves. ~ Signifies the point when ventricular pressure rises above atrial pressure (the beginning of ventricular systole). ~ The first sound tends to be louder, longer, and more resonant than the second. - 2nd "dup" = Closing of semilunar valves. ~ Indicate the beginning of ventricular relaxation (diastole), resulting in a short, sharp sound. - Pause = Quiescent (relaxation) period.

Describe two basic mechanisms of blood loss.

• Bleeding Disorders: 1. Thrombocytopenia: Insufficient/low number of circulating platelets to control physiological bleeding. - Petechiae: Widespread hemorrhage indicated by small purplish spots. 2. Impaired Liver Function: When the liver is unable to synthesize its usual supply of clotting coagulation factors and regulatory enzymes, abnormal and often severe bleeding occurs. - Liver cells require vitamin K to produce clotting factors. 3. Hemophilia: Hereditary bleeding disorders resulting from an insufficient amount of pro-coagulation factors. - Hemophilia A: Deficiency in factor VIII (anti-hemophilic factor). ~ Accounts for 77% of cases. ~ Occurs primarily in males. - Hemophilia B: Deficiency of factor IX. ~ Occurs primarily in males. - Hemophilia C: A less severe form seen in both sexes; lack of factor XI.

Recall three bleeding disorders and their associated causes.

• Bleeding Disorders: 1. Thrombocytopenia: Insufficient/low number of circulating platelets to control physiological bleeding. - Petechiae: Widespread hemorrhage indicated by small purplish spots. 2. Impaired Liver Function: When the liver is unable to synthesize its usual supply of clotting coagulation factors and regulatory enzymes, abnormal and often severe bleeding occurs. - Liver cells require vitamin K to produce clotting factors. 3. Hemophilia: Hereditary bleeding disorders resulting from an insufficient amount of pro-coagulation factors. - Hemophilia A: Deficiency in factor VIII (anti-hemophilic factor). ~ Accounts for 77% of cases. ~ Occurs primarily in males. - Hemophilia B: Deficiency of factor IX. ~ Occurs primarily in males. - Hemophilia C: A less severe form seen in both sexes; lack of factor XI.

Recall three sources of bleeding disorders and their related defects.

• Bleeding Disorders: 1. Thrombocytopenia: Insufficient/low number of circulating platelets to control physiological bleeding. - Petechiae: Widespread hemorrhage indicated by small purplish spots. 2. Impaired Liver Function: When the liver is unable to synthesize its usual supply of clotting coagulation factors and regulatory enzymes, abnormal and often severe bleeding occurs. - Liver cells require vitamin K to produce clotting factors. 3. Hemophilia: Hereditary bleeding disorders resulting from an insufficient amount of pro-coagulation factors. - Hemophilia A: Deficiency in factor VIII (anti-hemophilic factor). ~ Accounts for 77% of cases. ~ Occurs primarily in males. - Hemophilia B: Deficiency of factor IX. ~ Occurs primarily in males. - Hemophilia C: A less severe form seen in both sexes; lack of factor XI.

Recall the characteristics of blood (e.g., pH, volume, etc.).

• Blood Characteristics: - Physical: Blood is a sticky, opaque fluid with a characteristic metallic taste (Na+). - Color: Depending on the amount of oxygen its carrying, the color of blood varies from scarlet red (oxygen-rich) to dark red (oxygen-poor). - pH: Slightly alkaline, with a pH between 7.35 and 7.45. - Viscosity: Blood is more dense than water and about five times more viscous, largely because of its formed elements. Erythrocytes are the major factor contributing to blood viscosity. - Volume: Women typically have a lower RBC count than men (4.2-5.4 million cells vs. 4.7-6.1 million cells). ~ When the number of RBC's increases beyond the normal range, blood becomes more viscous and flows more slowly. ~ As the number of RBC's drops below the lower end of the range, the blood thins and flows more rapidly. - Percentage of Body Weight: 8%. ~ Its average volume in healthy adult males is 5-6 liters. ~ Its average volume in healthy adult females is 4-5 liters. - Temperature: 38 degrees Celsius; slightly higher than resting body temperature.

Describe blood circulation starting and ending at heart.

• Blood Circulation: Blood serves as a transport "vehicle" for the organs of the cardiovascular system. - Continuous and uninterrupted blood circulation is initiated by the pumping action of the heart. - Blood exits the heart via arteries, which branch repeatedly until they become tiny capillaries that service all of the tissue in the body. - Oxygen and nutrients leave the blood, crossing capillary walls into the body's tissues; carbon dioxide and wastes move from the tissues to the capillaries. Oxygen-deficient blood flows from the capillaries into larger veins that carry blood back to the heart. - The returning blood then flows from the heart to the lungs, where it picks up oxygen and then returns to the heart to be pumped throughout the body once again.

Define the terms blood plasma, formed elements.

• Blood Plasma: A straw-colored. sticky fluid composed of 90% water and the remaining 10% being over 100 different dissolved solutes. - Dissolved Solutes: ~ Electrolytes: The most abundant solutes by number, and help to maintain plasma osmotic pressure and normal blood pH. ~ Plasma Proteins: Make up 8% (by weight) of plasma and include: albumin, globulins (alpha, beta, & gamma), and fibrinogen. ~ Albumin accounts for 60% of plasma protein. ~ Nonprotein Nitrogenous Substances: urea, uric acid, creatine, and ammonium salts. ~ Organic Nutrients: Glucose and other simple carbohydrates, amino acids, fatty acids, glycerol and triglycerides, cholesterol, and vitamins. ~ Respiratory Gases: O2 and CO2. ~ Hormones: Steroid/Thyroid hormones carried by plasma proteins. • The formed elements of blood (erythrocytes, leukocytes, and platelets) have some unusual features. - Two of the Three are not even true cells: ~ Erythrocytes (RBC's) have no nuclei or organelles. ~ Platelets are cell fragments. ~ Only leukocytes are complete cells. - Most Types of Formed Elements Survive in the Bloodstream for only a few days. ~ RBC's = 110-120 days. ~ Platelets = 10 days. ~ WBC's = days to years. - Most Blood Cells do not Divide, and therefore have Limited Life Spans. ~ For this reason, stem cells divide continuously in red bone marrow to replace them.

Discuss the paradoxical nature of blood and its relationship to disease.

• Blood is examined more often than any other tissue when trying to determine the cause of disease.

Define the terms hematocrit, buffy coat, whole blood volume, RBC fraction.

• Blood is the only fluid tissue in the body. Blood is a specialized connective tissue in which living blood cells, called the formed elements, are suspended in a nonliving fluid matrix called plasma. - If a sample of blood is centrifuged, centrifugal force packs down the heavier formed elements and the less dense plasma remains at the top. ~ Most of the reddish mass at the bottom of the tube is erythrocytes, the res blood cells that transport oxygen. ~ A thin, whitish layer called the buffy coat is present at the erythrocyte-plasma junction. This layer contains leukocytes, the white blood cells that act in various ways to protect the body, and platelets, cell fragments that help stop bleeding. - Erythrocytes normally constitute about 45% of the total volume of a blood sample (whole blood volume), a percentage known as the hematocrit or RBC fraction. ~ Normal hematocrit values in healthy males is 47% +/- 5%, and in females is 42% +/- 5%. - Leukocytes and platelets contribute less than 1% of blood volume. - Plasma makes up most of the remaining 55% of whole blood.

Discuss what is meant by the phrase "blood travels in a closed circuit".

• Blood must travel in its closed circuit, or it will be lost to surrounding tissue spaces. Hence, continuous, uninterrupted blood flow. • Blood loss only stops when pressure is equalized on both sides of the vessel wall.

Recall what happens at the blood-interstitial fluid interface.

• Blood plasma makeup constantly changes as substance exchange takes place.

For the thyroid gland: Describe calcitonin functions, feedback mechanisms, and effects.

• Calcitonin: A polypeptide hormone released by the parafollicular, or C, cells of the thyroid gland in response to a rise in blood Ca2+ levels. - Does not have a known physiological role in humans; however, at pharmacological doses (doses higher than normally found in the body), calcitonin has a bone-sparing effect where it (1) inhibits osteoclast activity, inhibiting bone resorption and release of Ca2+ from the bony matrix, and (2) stimulates Ca2+ uptake and icorporation into bone matrix. - Calcitonin does not need to be replaced in patients whose thyroid gland has been removed. - Can be used therapeutically to treat patients with Paget's disease and osteoporosis.

Define the terms cardiac output, heart rate (HR), stroke volume (SV), and cardiac reserve.

• Cardiac Output: The amount of blood (mL) pumped out by each ventricle in 1 minute. It is the product of heart rate (HR) and stroke volume (SV). • Heart Rate (HR): Number of heartbeats per unit of time (beats/minute). - Normal resting HR is between 60-100 beats per minute. • Stroke Volume (SV): The amount of blood that one ventricle pumps out during a single beat (mL/beat). - Resting SV is approximately 70 ml/beat. • Cardiac Reserve: The difference between resting and maximum cardiac output. - In nonathletic people, cardiac reserve is typically 4-5 times higher than resting cardiac output. - In trained athletes, cardiac reserve may reach 7 times the resting cardiac output.

Explain how cardiac output is maintained when stroke volume is reduced.

• Cardiac output varies directly with HR and SV. This means that CO increases when the stroke volume increases or the heart beats faster or both, and it decreases when either or both of these factors decrease.

Differentiate between three hormones chemical classes.

• Chemical Classifications of Hormones: 1. Amino-Acid Based: These hormones are water soluble and cannot cross the plasma membrane (except for the thyroid hormone). - Most hormones are based on amino acids. - Molecular size varies from amines, to short peptide chains, to long polymer proteins. 2. Steroids: Hormones synthesized from cholesterol that are lipid soluble and can cross the plasma membrane. - Only gonadal and adrenocortical hormones are steroids. 3. Eicosanoids: Biologically active lipids whose effects are highly localized, affecting only nearby cells. Because hormones influence distant targets, eicosanoids are considered to be "hormone-like." - Include leukotrienes & prostaglandins.

Describe what happens during the coagulation cascade and list its requirements.

• Coagulation Cascade: Sequential activation of circulating coagulation proteins (factors) to first form prothrombin activator, which then generates thrombin. - This is usually the slowest step of the blood clotting process, but once prothrombin activator is present, the clot forms in 10-15 seconds. - Thrombin converts fibrinogen to fibrin. - This then forms a stabilized platelet plug and traps RBC's. - The cascade is controlled by regulatory enzymes that either accelerate (+) or decelerate (-) thrombin formation. - Coagulation cascade requires ionized Ca2+.

For the adrenal cortex: List the 3 types of major corticosteroids and explain each one's function.

• Corticosteroids: 1. Mineralocorticoids: Regulate the electrolyte (mineral salt) concentrations in extracellular fluids, particularly Na+ and K+. - Extracellular concentration of Na+ largely determines the volume of the extracellular fluid; where Na+ goes, water follows. Changes in Na+ lead to changes in blood volume/pressure and is coupled to changes in K+, H+, HCO3-, and Cl-. - Extracellular concentration of K+ sets the resting membrane potential of all cells and determines how easily action potentials are generated in nerve and muscle. - The primary job of aldosterone is to maintain homeostasis by regulating Na+ and K+. Accounting for 95% of mineralocorticoids, aldosterone is the most potent and is essential for life. ~ Aldosterone reduces excretion of Na+ from the body. Its primary target is the kidney tubules, where it (1) stimulates Na+ reabsorption and (2) causes K+ secretion into the tubules for elimination from the body. ~ Aldosterone also enhances Na+ reabsorption from perspiration, saliva, and gastric juice. ~ Decreasing blood volume and blood pressure, and rising blood levels of K+, stimulate aldosterone secretion. The revere conditions inhibit its secretion. - 4 Mechanisms that Regulate aldosterone Secretion: 1. The Renin-Angiotension-Aldosterone Mechanism: Influence blood volume and blood pressure by regulating the release of aldosterone and therefore Na+ and water reabsorption by the kidneys. All of these effects ultimately raise blood pressure. 2. Plasma Concentration of Potassium: Fluctuating K+ levels influence zona glomerulosa (aldosterone producing) cells. Increased K+ stimulates aldosterone release, whereas decreased K+ inhibits aldosterone release. 3. ACTH: In a severely stressed person, the hypothalamus releases more corticotropin-releasing hormone (CRH), and the resulting rise in ACTH blood levels steps up the rate of aldosterone secretion to a small extent. 4. Atrial Natuiuretic Peptide (ANP): A hormone secreted by the heart when blood pressure rises that fine tunes blood pressure and sodium-water balance of the body. ANP's main function is to decrease blood pressure by allowing Na+ (and water) to flow out of the body in urine. 2. Glucocorticoids: Influence the energy metabolism of most body cells and helps us resist stressors. They keep blood-glucose levels fairly constant, and help maintain blood pressure. - Glucocorticoids include: Cortisol (hydrocortisone), cortisone, and corticosterone. ~ Only cortisol is secreted in significant amounts in humans. - Negative feedback regulates glucocorticoid secretion. - Cortisol release is promoted by ACTH. - ACTH release is triggered in turn by the hypothalamic releasing hormone CRH. - Rising cortisol levels feed back to act on both the hypothalamus and the anterior pituitary, preventing CRH release and shutting of ACTH and cortisol secretion. ~ Various stressors (hemmorrhage, infection, or physical or emotional trauma) interrupt the normal cortisol rhythm. - Cortisol provokes a rise in blood levels of glucose, fatty acids, and amino acids. - Cortisol's prime metabolic effect is to provoke glusoneogenesis, that is, the formation pf glucose from fats and proteins. - Excessive Levels of Glucocorticoids: 1. Depress cartilage and bone formation. 2. inhibit inflammation by decreasing the release of inflammatory chemicals. 3. Depress the immune system. 4. Disrupt normal cardiovascular, neural and gastrointestinal function. 3. Gonadocorticoids (Adrenal Sex Hormone): Most gonadocorticoids are weak androgens, or male sex hormones, such as androstenedione and dehydroepiadrosterone (DHEA). Most are converted in tissue cells to more potent ,ale hormone, such as testosterone, and some are converted to estrogens. - The adrenal sex hormones contribute to axillary pubic hair development. - In adult women, adrenal androgens are thought to contribute to the sex drive, and they largely account for the estrogens produced after menopause when ovarian estrogens are no longer produced.

For the adrenal cortex: Describe the causes and symptoms of Cushing's syndrome and Addison's disease.

• Cushing's Syndrome: May be caused by an ACTH-releasing pituitary tumor (in which case it is called Cushing's disease): by an ACTH-releasing malignancy of the lungs, pancreas, or kidneys,; or by a tumor of the adrenal cortex. However, it most often results from the clinical administration of glucocorticoid drugs. The syndrome is characterized by persistent elevated blood glucose levels (steroid diabetes), dramatic losses in muscle and bone protein, and water and salt retention, leading to hypertension and edema. • Addison's Disease: The major hyposecretory disorder of the adrenal cortex, usually involves deficits of both glucocorticoids and mineralcorticoids. Affected individuals tend to lose weight; plasma glucose and sodium levels drop, and potassium levels rise. Severe dehydration and hypotension are common. A common early sign of Addison's disease is a characteristic bronzing of the skin. This occurs because the lack of negative feedback by corticosteroids increases ACTH release by the anterior pituitary.

Differentiate between O2-depleted blood and O2-rich blood based upon O2/CO2 gas contents.

• Depending on the amount of oxygen it's carrying, the color of blood varies from scarlet (oxygen-rich) to dark red (oxygen-poor).

Describe why circulating red blood cells do not last as long as leukocytes, why they are removed from circulation, and what happens to them after they are removed.

• Destruction of Erythrocytes: - Red blood cells have a useful life span of 100-120 days. - Red blood cells are unable to synthesize new proteins, grow, or divide. Due to these limitations, erythrocytes become "old" as they lose their flexibility, become increasingly rigid and fragile, and their hemoglobin begins to degenerate. • Recycling of Erythrocytes: - Macrophages engulf and destroy dying erythrocytes. - The heme of their hemoglobin is split off from globin. ~ Its core of iron is salvaged, bound to protein (as ferritin or hemosiderin), and stored for reuse. ~ The balance of the heme group is degraded to bilirubin, a yellow pigment that is released to the blood and binds to albumin for transport. Liver cells pick up bilirubin and in turn secrete it (in bile) to the intestine, where it is metabolized to urobilinogen. Most of this degraded pigment leaves the body in feces, as a brown pigment called stercobilin. - The protein (globin) part of hemoglobin is metabolized or broken down to amino acids, which are release into circulation.

Define diabetes mellitus (DM) and recall the cardinal signs.

• Diabetes Mellitus: A chronic, metabolic disorder caused by an absolute or relative deficiency of insulin. - When insulin is absent, the result is Type 1 diabetes mellitus. If insulin is present, but its effects are deficient, the result is Type 2 diabetes mellitus. In either case, blood glucose levels remain high after a meal because glucose is unable to enter most tissue cells.

Describe events creating an aortic dicrotic notch.

• Dicrotic Notch: A small dip in aortic pressure as some blood moves (rebounds) back towards the left ventricle as the aorta recoils. - Closes aortic semilunar valve superiorly.

Order the steps in direct gene activation (lipid-soluble hormones).

• Direct gene activation mechanism of lipid-soluble hormones: 1. The steroid hormone diffuses through the plasma membrane and binds to an intracellular receptor. 2. The receptor-hormone complex enters the nucleus. 3. The receptor-hormone complex binds to a specific DNA region. 4. Binding initiates transcription of the gene to mRNA. 5. The mRNA directs protein synthesis.

Explain 3 types of endocrine gland stimuli causing hormone release.

• Endocrine Gland Stimuli: 1. Humoral Stimuli: Hormones are secreted in direct response to changing blood levels of certain critical ions and nutrients. - The simplest of endocrine controls. 2. Neural Stimuli: Direct neural input/nerve fiber innervation that stimulates hormone release. - Example: Responses to stress in which the sympathetic nervous system stimulates the adrenal medulla to release NE and EPI. 3. Hormonal Stimuli: Glands release hormones in response to hormones produced by other endocrine organs.

Recognize the major feedback mechanism controlling hormone release.

• Endocrine Gland Stimuli: 1. Humoral Stimuli: Hormones are secreted in direct response to changing blood levels of certain critical ions and nutrients. - The simplest of endocrine controls. 2. Neural Stimuli: Direct neural input/nerve fiber innervation that stimulates hormone release. - Example: Responses to stress in which the sympathetic nervous system stimulates the adrenal medulla to release NE and EPI. 3. Hormonal Stimuli: Glands release hormones in response to hormones produced by other endocrine organs. • Synthesis and release is controlled by a negative feedback system.

Define the terms endocrine system and hormone.

• Endocrine System: Interacts with the nervous system to coordinate/integrate the activity of body cells, and influences metabolic activity by means of hormones; an integrated system of small organs exerting large effects on cell metabolic activity. - Initiates responses slowly. - Long-duration responses. - Acts via hormones released into the blood. - Acts at diffuse locations: Targets can be anywhere blood reaches. - Hormones act over long distances. • Hormones: Long distance chemical messengers secreted by cells into the extracellular fluids that travel through the blood and regulate the metabolic function of other cells in the body. - Initiating responses takes a lag period of seconds or even days, but once initiated, normal responses tend to last much longer than others. - Produce widespread and diverse effects. - Can stimulate or inhibit the growth/function of a target tissue. • Hormones Control/Integrate: - Reproduction. - Growth & Development. - Maintenance of electrolyte, water, and nutrient balance of the blood. - Regulation of cellular metabolism and energy balance. - Mobilization of body defenses.

Discuss why circulating red blood cells and platelets are not considered complete cells.

• Erythrocytes (RBC's) have no nuclei or organelles because they lose these components before leaving bone marrow. • Platelets are cell fragments of bone marrow-bound cells. • Only leukocytes are complete cells since they retain their nucleus.

Differentiate between an exocrine, endocrine, and mixed glands.

• Exocrine Glands: Produce nonhormonal substances and have ducts. They are moved through the excretory ducts directly into adjoining areas where they exert their action. - Sweat - Salivary Glands - Digestive Juices • Endocrine Glands: Produce hormones and lack ducts. They release their hormones into the surrounding tissue fluid. The hormones are then transported through the bloodstream and finally bind to target organ receptors. - Pituitary - Thyroid - Parathyroid - Adrenal - Pineal • Mixed (Endocrine/Exocrine) Glands: - Pancreas - Gonads - Placenta

Differentiate between the four forms of hemoglobin-gas associations (e.g., carbaminohemoglobin).

• Forms of Hemoglobin: 1. Oxyhemoglobin: Oxygen loading occurs in the lungs, and is transported from lungs to tissue cells. Oxygen diffuses from the lungs to the blood an then into erythrocytes where it binds to the iron in hemoglobin. As a result, the oxyhemoglobin protein forms, assumes a new three-dimensional shape, and becomes ruby red. 2. Deoxyhemoglobin: The process is reversed in body tissues. Oxygen detached from iron, hemoglobin resumes its former shape, and reduced hemoglobin (dark red) results. 3. Carbaminohemoglobin: When carbon dioxide bind to globin's amino acids rather to the heme group. Carbon dioxide loading occurs in the tissues, and the direction of transport is from tissues to lungs, where CO2 is eliminated from the body. 4. Carboxyhemoglobin: Hemoglobin is bound to available CO2, preventing O2 release to tissues.

Recall relative percentages, structural differences, and their associated functions of each WBC type.

• Granulocytes Include: - Neutrohpils: The most numerous white blood cells accounting for 50-70% of the WBC population. ~ Are twice as large as erythrocytes. ~ Neutrophils get their name ("neutral-loving") because their granules take up both basic (blue) and acidic (red) dyes. Together, the two types of granules give the cytoplasm a lilac color. ~ Some granules contain a potent "brew" of antimicrobial proteins, called defensins. ~ Neutophil nuclei typically have 3-6 lobes and are called polymorphonuclear leukocytes (PMN's) or polys. ~ Neutrophils are our body's bacteria slayers. One way neutrophils kills bacteria is a process called a respiratory burst. During the burst, the cells metabolize oxygen to produce potent germ-killer oxidizing substances such as bleach and hydrogen peroxide. ~ Defensins pierce holes in the membrane of the "foe" and the bacteria lyses. - Eosinophils: Account for 2-4% of all leukocytes and are the size of neutrophils. ~ Nucleus usually has 2 lobes. ~ The most important role or eosinophils is to lead the counter attack against parasitic worms. ~ Eosinophils reside in the loose connective tissues at the same body sites, and when they encounter a parasitic worm "prey," they gather around and release the enzymes from their cytoplasmic granules onto the parasite's surface, digesting it away. - Basophils: The rarest white blood cells, accounting for only 0.5-1% of the leukocyte population. ~ Their cytoplasm contains granules with an affinity for the basic dyes (basophil = base loving) and stain purplish-black. • Agranulocytes Include: - Lymphocytes: Account for 25% or more of WBC population, and are the second most numerous leukocytes in the blood. ~ Large, dark-purple nucleus that occupies most of the cell volume. ~ A thin rim of pale-blue cytoplasm surrounds the usually spherical, but sometimes slightly indented nucleus. ~ Classified as small (5-8 micrometers) and large (14-17 micrometers). ~ T Lymphocytes or T Cells: Function in the immune response by acting directly against virus-infected cells and tumor cells. ~ B Lymphocytes or B Cells: Give rise to plasma cells, which produce antibodies that are released to the blood. - Monocytes: Account for 3-8% of WBC's, and are the largest leukocytes. ~ When circulating monocytes leave the bloodstream and enter the tissues, they differentiate into highly mobile macrophages with prodigious appetites. • Mnemonic Device: Leukocytes - most abundant to least abundant: - Never: Neutrophils - Let: Lymphocytes - Monkeys: Monocytes - Eat: Eosinophils - Bananas: Basophils

Define hormone half-life, permissiveness, synergism and antagonism.

• Half-Life: The length of time for a hormone's blood level to decrease by half (50%). - Varies from a fraction of a minute to a week. - Water-soluble hormones have the shortest half lives because they are rapidly removed from the blood by the kidneys. • Permissiveness: Situation in which one hormone cannot exert ts full effects without another hormone being present. • Synergism: When one or more hormones produces the same effects at the target cell and their combined effects are amplified. • Antagonism: When one hormone opposes the action of another.

Discuss the relationship between heart sounds and chamber contraction.

• Heart sounds, often described as lub-dup, are associated with the heart valves closing.

Define the terms hematopoiesis, pluripotent stem cells, myeloid stem cells, & lymphoid stem cells.

• Hematopoiesis: Blood cell formation occurring in red bone marrow, which is composed of connective tissue called blood sinusoids that border blood capillaries; self-renewing cells that are "signaled" by cytokines to produce each cell line. • Myeloid Stem Cells: Produce RBC's, platelets, and all other leukocytes/formed elements. • Lymphoid Stem Cells: Produce only lymphocytes.

Define the terms hemostasis, hemorrhage, coagulation factors, coagulation cascade, and fibrinolysis.

• Hemostasis: A fast, localized, and carefully controlled process that quickly stops bleeding when blood vessel endothelium are lost/disrupted and prevents further blood loss. - Involves many clotting factors. - During hemostasis, 3 steps occur in rapid sequence: 1. Vascular Spasm 2. Platelet Plug Formation 3. Coagulation (Blood Clotting) • Hemorrhage: Escape of blood through either ruptured or unruptured vessel walls (leaky vessels). - Types of Skin Hemorrhages: 1. Petechiae: Subcutaneous capillary bleeding that causes small (pinpoint) blood spots near the skin surface; widespread hemorrhage indicated by small purplish spots. 2. Pupura: Larger petechiae that also result from the loss of blood from smaller blood vessels. 3. Contusion: Hemorrhage due to mechanical injury (traumatic blow) to muscle that results in a bruise. • Coagulation Factors or Procoagulants: Factors that assist in blood clotting and the reinforcement of the platelet plug. - Most clotting factors are plasma proteins synthesized by the liver. - Numbered I-XIII. • Coagulation Cascade: Sequential activation of circulating coagulation proteins (factors) to first form prothrombin activator, which then generates thrombin (factor XI ---> factor I). - This usually is the slowest step of the blood clotting process, but once prothrombin activator is present, the clot forms in 10-15 seconds. • Fibrinolysis: Enzymatic breakdown of fibrin-stabilized blood clots to restore normal blood flow when blood vessel repair has been completed (new endothelium); the removal of unneeded clots when healing has occurred. - Without fibrinolysis, blood vessels would gradually become completely blocked. - The critical natural "clot buster" is a fibrin-digesting enzyme called plasmin, which is produced when the plasma protein plasminogen is activated. Like a built-in self-destruction mechanism, plasminogen is incorporated into a forming clot, where it remains inactive until appropriate signals reach it. - Tissue Plasminogen Activator (tPA): Substance released by endothelial cells to activate plasminogen to plasmin. ~ As a result, plasmin is confined to the clot, and plasmin that strays into the plasma is destroyed by enzymes. - Fibrinolysis continues slowly over several days until the plasmin enzymatically "cuts" fibrin, and the clot dissolves.

List 5 hormone effects on target cells.

• Hormonal Effects on Target Cells: 1. Alters plasma membrane permeability or membrane potential, or both, by opening or closing ion channels. 2. Stimulates synthesis of enzymes and other proteins within the cell. 3. Activates or deactivates enzymes. 4. Induces secretory activity. 5. Stimulates mitosis.

Distinguish between peptide and steroid hormone activation mechanisms.

• Hormone Signaling: Steroid vs. Peptide 1. Steroid Hormone: Direct mechanism that changes cell activity by stimulating transcription. - Enters cell. - Binds to a chaperone protein. - Complex migrates to the nucleus. - Binds to internal receptor. 2. Peptide Hormone: Indirect mechanism that changes cell activity via triggered response. - Binds to an extracellular receptor. - Signal transduction occurs. - Generates cAMP. - Activates enzymes.

Differentiate between bound and free hormones.

• Hormones Circulate in Blood in 2 Forms: 1. Free (Unbound): Water-soluble (peptide) hormones that lack carrier proteins. 2. Bound: Lipid-soluble (steroid) hormones that attach to carrier proteins in the blood plasma.

Determine the effects of changing the SV or HR on cardiac output.

• Increased HR causes CO to increase. • Increased CO = HR x Increased SV • Decreased CO = HR x Decreased SV

For the pancreas: Explain dynamic antagonism of glucagon and insulin action in regulating blood glucose levels.

• Insulin and glucagon's effects are antagonistic: - Glucagon is s hyperglysemic hormone (increases blood glucose), whereas insulin is a hypoglycemic hormone (decreases blood glucose). - Insulin enhances glucose transport into tissue cells and stimulates glucose conversion to its storage form = glycogen. - Glucagon's major target is stored liver glycogen. Cortisol also stimulates glucose formation from stored lipids (fats).

Describe how intact endothelium inhibits platelet action and what happens when these cells are disturbed/disrupted.

• Intact endothelial cells secrete prostacyclin, which inhibits circulating platelets from attaching to its surface. • Damaged or disturbed endothelium exposes collagen fibers in underlying basement membrane, which promotes platelet action. - Platelets attach to basement membrane collagen and activate. - The activated platelets then release cytoplasmic granules that contain platelet aggregation factors like ADP. - Platelets aggregate (stick/clump) together and change shape.

Differentiate between WBC disorders lekopenia/leukocytosis and leukemia/lymphoma.

• Leukocyte Disorders: 1. Leukopenia: Abnormally low white blood cell count commonly induced by drugs, particularly glucocorticoids and anticancer agents. - Neutropenia: A decrease in only the neutrophil component. - Lymphocytopenia: A decrease in only the lymphocyte component. 2. Leukocytosis: Unusually large numbers of leukocytes. - Reactive: An increase in normal WBC's associated with inflammation. - Leukemia: Over production of abnormal WBC's (myeloid cells). ~ Acute Leukemia: Is quickly advancing because it derives from stem cells. ~ Chronic Leukemia: Is slowly advancing because it involves proliferation of later cell stages. ~ Myeloid Leukemia: Involves myeloblast descendants. ~ Lymphocytic Leukemia or Lymphoma: Involves lymphocytes. 3. Infectious Monounucleosis or "Kissing Disease": A highly contagious viral disease caused by the Epstein-Barr virus (excessive numbers of lymphocytes).

Classify leukocytes as either granulocytes or agranulocytes.

• Leukocytes are Grouped into 2 Major Categories: 1. Granulocytes: Contain obvious membrane-bound cytoplasmic granules. - Roughly spherical in shape. - Are larger and much shorter lived. - Have lobed nuclei. - Cytoplasmic granules stain with Wright's stain. • Granulocytes Include: - Neutrohpils: The most numerous white blood cells accounting for 50-70% of the WBC population. ~ Are twice as large as erythrocytes. ~ Neutrophils get their name ("neutral-loving") because their granules take up both basic (blue) and acidic (red) dyes. Together, the two types of granules give the cytoplasm a lilac color. ~ Some granules contain a potent "brew" of antimicrobial proteins, called defensins. ~ Neutrophil nuclei typically have 3-6 lobes and are called polymorphonuclear leukocytes (PMN's) or polys. ~ Neutrophils are our body's bacteria slayers. One way that neutrophils kill bacteria is a process called a respiratory burst. During the burst, the cells metabolize oxygen to produce potent germ-killer oxidizing substances such as bleach and hydrogen peroxide. ~ Defensins pierce holes in the membrane of the "foe" and the bacterium lyses. - Eosinophils: Account for 2-4% of all leukocytes and are the size of neutrophils. ~ Nucleus usually has 2 lobes. ~ The most important role of eosinophils is to lead the counter attack against parasitic worms. ~ Eosinophils reside in the loose connective tissues at the same body sites, and when they encounter a parasitic worm "prey," they gather around and release the enzymes from their cytoplasmic granules onto the parasite's surface, digesting it away. - Basophils: The rarest white blood cells, accounting for only 0.5-1% of the leukocyte population. ~ Their cytoplasm contain granules with an affinity for the basic dyes (basophil = base loving) and stain purplish black. 2. Agranulocytes: Lack obvious membrane-bound granules. - Nuclei are spherical or kidney shaped. • Agranulocytes Include: - Lymphocytes: Account for 25% or more of WBC population, and are the second most numerous leukocytes in the blood. ~ Large, dark-purple nucleus that occupies most of the cell volume. ~ A thin rim of pale-blue cytoplasm surrounds the usually spherical, but sometimes slightly indented nucleus. ~ Classified as small (5-8 micrometers) and large (14-17 micrometers). ~ T Lymphocytes or T Cells: Function in the immune response by acting directly against virus-infected cells and tumor cells. ~ B Lymphocytes or B Cells: Give rise to plasma cells, which produce antibodies that are released to the blood. - Monocytes: Account for 3-8% of WBC's, and are the largest leukocytes. ~ When circulating monocytes leave the bloodstream and enter the tissues, they differentiate into highly mobile macrophages with prodigious appetites.

Describe general characteristics of WBCs and their related tissue locations (circulating or tissues).

• Leukocytes: Structural & Functional Characteristics: - Leukocytes. or white blood cells, are the only formed elements that are complete cells, with nuclei and the usual organelles. - WBC's account for less than 1% of total blood volume. They are far less numerous then red blood cells. - Leukocytes are crucial to our defense against disease. - Red blood cells are confined to the the bloodstream, but WBC's are able to slip out of the capillary blood vessels by a process called diapedesis. - Once out of the blood stream, leukocytes move through tissue spaces by amoeboid motion (they form flowing cytoplasmic extensions that move them along). - Positive Chemotaxis: When leukocytes pinpoint areas of tissue damage and infection and gather there in large numbers to destroy foreign substances and dead cells. - Leukocytosis: When white blood cells are mobilized for action, the body speeds up their production and their numbers double within a few hours; a WBC count of over 11,000 cells.

Describe blood tissue's "dual" composition.

• Liquid Plasma: fluid portion. - Water - Soluble proteins - Electrolytes - Chemicals • Formed Elements: - Erythrocytes = Red Blood Cells (RBC's) - Leukocytes = White Blood Cells (WBC's) - Thrombocytes = Platelets

Describe blood constituents, including relative percentages of each, if given.

• Liquid Plasma: fluid portion. - Water (90%) - Soluble proteins (remaining 10%) - Electrolytes (remaining 10%) - Chemicals (remaining 10%) • Formed Elements: - Erythrocytes = Red Blood Cells (RBC's) - Leukocytes = White Blood Cells (WBC's) - Thrombocytes = Platelets • Erythrocytes normally constitute about 45% of the total volume of a blood sample (whole blood volume), a percentage known as the hematocrit or RBC fraction. - Normal hematocrit values in healthy males is 47% +/- 5%, and in females is 42% +/- 5%. • Leukocytes and platelets contribute less than 1% of blood volume. • Plasma makes up most of the remaining 55% of whole blood.

Recall expected hematocrit values for males, females, and infants.

• Males: 47% +/- 5% • Females: 42% +/- 5% • Infants: 55% +/- 6%

List the 3 ways hormones can be removed from the body.

• Most Hormones are Removed By Target Cell: 1. Enzyme degradation. 2. Kidney action. 3. Liver action.

Recall the average life expectancies of each formed element.

• Most types of formed elements survive in the blood for only a few days. - RBC's = 110-120 days. - WBC's = days to years. - Platelets = 10 days.

For the pancreas: Recall normal, hyperglycemic, and hypoglycemic blood glucose values.

• Normal Range: 70-140 • Hyperglycemia: >200 • Hypoglycemia: <60

Discuss why leukocytes (WBCs) are considered the only true (complete) circulating blood cell.

• Only leukocytes are complete cells since they retain their nucleus.

For the parathyroid glands: Describe its macroscopic & microscopic anatomy; functions, feedback mechanisms, target organs and imbalances.

• Parathyroid Glands: Tiny, yellow-brown glands usually located on the posterior thyroid; there are usually 4 of these glands. - The parathyroid's glandular cells are arranged in thick, branching cords containing scattered oxyphil cells and large number of smaller parathyroid cells. - Parathyroid cells secrete parathyroid hormone, while the function of oxyphil cells in unclear. - Parathyroid Hormone (PTH) or Parathormone: Protein hormone of the parathyroid glands that is the single most important hormone controlling calcium balance in the blood. - Ca2+ homeostasis is essential for transmission of nerve impulses. muscle contraction, and blood clotting. - Falling blood Ca2+ levels trigger PTH release, and rising blood Ca2+ levels inhibit its release. - PTH increases Ca2+ levels in blood by stimulating three target organs: the skeleton, the kidneys, and the intestine. • PTH Release: - Bone: Stimulates osteoclasts (bone-resorbing cells) to digest some of the calcium-rich bony matrix and release ionic calcium phosphates to the blood. - Kidney: Enhances the kidney's resorption of Ca2+ from the forming urine into the blood (and excretion of phosphate, PO4 3-). - Intestine: Promotes activation of vitamin D, thereby increasing absorption of Ca2+ by intestinal mucosal cells. Vitamin D is required for absorption of Ca2+ from food, but first the kidneys must convert it to its active vitamin D3 form, calcitriol. PTH stimulates the transformation.

Describe how pressure changes in heart chambers and their associated vessels regulate blood movement.

• Phases of the Cardiac Cycle: 1. Ventricular Filling: Mid-to-Late Diastole - Pressure in the heart is low, blood returning from the circulation is flowing passively through the atria and the open AV valves into the ventricles, and the aortic and pulmonary valves are closed. - Following depolarization (P wave of ECG), the atria contract, compressing the blood in their chambers. This causes a sudden slight rise in atrial pressure, which propels residual blood out of the atria into the ventricles. At this point the ventricles have the maximum volume of blood they will contain in the cycle, an amount called end diastolic volume (EDV). - Then the atria relax and the ventricles depolarize. 2. Isovolumetric Contraction: - As the atria relax, the ventricles begin contracting. Their walls close in on the blood in their chambers, and ventricular pressure rises rapidly and sharply, closing the AV valves. - As ventricular pressure continues to rise, it finally exceeds the pressure in the large arteries issuing from the ventricles. - This stage ends as the SL valves are forced open. 3. Ventricular Ejection: - Blood rushes from the ventricles into the aorta and pulmonary trunk. - The pressure in the aorta normally reaches about 120 mm Hg. 4. Isovolumetric Relaxation: Early Diastole - Following the peak of the T wave, the ventricles relax. - Because the blood remaining in their chambers, referred to as the end systolic volume (ESV), is no longer compressed, ventricular pressure drops rapidly and blood in the aorta and pulmonary trunk flows back toward the heart, closing the SL valves.

Associate thymus, pineal, heart, GI tract, placenta, kidneys, skin, adipose tissue & hormones with their source and list their mode of action.

• Pineal Gland: Tiny, pinecone-shaped gland that hangs from the root of the third ventricle in the diencephalon. Its secretory cells, called pinealocytes, are arranged in compact cords and clusters. This gland's major secretory product is melatonin, an amine hormone derived from serotonin. - Peak levels of melatonin occur during the night and make us drowsy, and lowest levels occur around noon. - The pineal gland indirectly receives input from visual pathways (retina --> suprachiasmatic nucleus of hypothalamus --> superior cervical ganglion --> pineal gland) concerning the intensity and duration of daylight. • The Placenta is a temporary endocrine gland. Besides sustaining the fetus during pregnancy, it secrets several steroid and protein hormones that influence the course of pregnancy. - Placental hormones include: Estrogen, progesterone, and human chorionic gonadotropin (hCG). • Adipose Tissue: Adipose cells release leptin, which serves to tell your body how much stored energy (as fat) you have. Leptin binds to CNS neurons concerned with appetite control, producing a sensation of satiety. It also appears to stimulate increases energy expenditure. • Gastrointestinal (GI) Tract: Enteroendocrine cells (paraneurons) are scattered in the mucosa of the gastrointestinal tract and regulate digestive functions. • Heart: Chambers of the heart called atria contain specialized cardiac muscles that secrete atrial natriuretic peptide (ANP). ANP decreases the amount of sodium in the extracellular fluid, thereby reducing blood volume and blood pressure. • Kidneys: Cells in the kidneys secret erythropoietin, a glycoprotein hormone that signals the bone marrow to increase production of red blood cells. The kidneys also release renin, which acts as an enzyme to initiate the renin-angiotensin-aldosterone mechanism of aldosterone release. • Skin: The skin produces cholecalciferol, an inactive form of vitamin D, when modified cholesterol molecules are exposed to ultraviolet radiation. The active form of vitamin D3, calcitriol, is an essential regulator of the carrier system that intestinal cells use to absorb Ca2+ from food. Without calcitriol, bones become soft and weak. • Thymus: Thymic epithelial cells secrete several peptide hormones such as thymosins, thymulin, and thymopoietins. These hormones are thought to be involved in the normal development of T lymphocytes and the immune response. Although called hormone, they mainly act as paracrines.

For the pituitary gland: Describe its gross anatomy (lobes and infundibulum).

• Pituitary Gland/Hypophysis: Two-lobed gland that secretes 8 peptide hormones. It is connected to the hypothalamus via the infundibulum stalk.

For the pituitary gland: Discuss neurohypophysis tissue composition, embryonic origin, neural connections & its 2 hormones.

• Posterior Pituitary/Neurohypophys: - Composed of neural tissue and nerve fibers originating in the hypothalamus. - Releases neurohormones received from the hypothalamus. - Hormone storage area. • Posterior Pituitary-Hypothalamic Relationship: - The pituitary lobe is a part of the brain deriving from hypothalamic tissue growing downward. - Hypothalamic-Hypophyseal Tract: A bundle of axons maintaining neural connection between the posterior pituitary and hypothalamus. This tract arises from neurons in the paraventricular and supraoptic nuclei of the hypothalamus, which together act as a transport pathway for delivery of oxytocin/ADH to the posterior pituitary. • Posterior Pituitary Hypothalamic Hormones: - Paraventricular Neurons primarily make oxytocin. - Supraoptic neurons produce antidiuretic hormone (ADH). ~ Oxytocin and ADH, each composed of 9 amino acids, are nearly identical and differ in only two amino acids, and they have dramatically different physiological effects. 1. Oxytocin: • Strong stimulant of uterine contractions and initiates labor. It also initiates milk ejection from breasts. • Released in higher amounts during childbirth and in nursing women. • Oxytocin acts via the PIP2-Ca2+ second-messenger systemn to mobilize Ca2+, which allows for stronger contractions. • Childbirth and milk ejection result from positive feedback mechanisms. • Oxytocin is also a neurotransmitter in the brain referred to as the "cuddle" hormone. It is involved in sexual/affectionate behavior and promotes nurturing, couple bonding, and trust. 2. Antidiuretic Hormone (ADH): • Prevents wide swings in water balance, helping the body avoid dehydration and water overload. • Osmoreceptors: Hypothalamic neurons that continually monitor the solute/water concentration of the blood. When solutes become too concentrated, osmoreceptors transmit impulses releasing ADH, which produces less urine and the solute concentration declines. As solute levels fall, osmoreceptors stop, ending ADH release. • Other stimuli triggering ADH release include pain, low blood pressure, and such drugs as nicotine, morphine, & barbiturates. • Severe blood loss triggers exceptionally large amounts of ADH, which causes vasoconstriction and raises blood pressure. This response gives ADH its nickname/second name "vasopressin." • Drinking lots of alcohol or water inhibits ADH release.

For the pituitary gland: Explain how the hypothalamus controls activity of both pituitary lobes.

• Posterior Pituitary/Neurohypophys: - Hypothalamic-Hypophyseal Tract: A bundle of axons maintaining neural connection between the posterior pituitary and hypothalamus. This tract arises from neurons in the paraventricular and supraoptic nuclei of the hypothalamus, which together act as a transport pathway for delivery of oxytocin/ADH to the posterior pituitary. - Hypothalamic nuclei fibers extend downward through the infundibulum stalk and into the posterior pituitary. - Hypothalamic nuclei cause direct release of ADH and oxytocin hormones. • Anterior Pituitary/Adenohypophysis: - Hypophyseal Portal System: Composed of the primary capillary plexus, hypophyseal portal veins, and the secondary capillary plexus, the portal is a local blood capillary system that links the hypothalamus and anterior pituitary. The portal system ensures that the minute quantities of hormones released by the hypothalamus arrive rapidly at the anterior pituitary without being diluted. - Hypothalamic hormones use capillaries to reach/stimulate anterior pituitary cells. - Hypothalamic hormones indirectly cause release of anterior pituitary hormones.

Define the terms preload, contractility, and afterload and their effects on SV.

• Preload: The degree to which cardiac muscle cells are stretched just before they contract. - Controls stroke volume. - This relationship between preload and stroke volume is called the Frank-Starling law of the heart. - During vigorous exercise, SV may double as a result of increased venous return. - Low venous return decreases EDV, causing the heart to beat less forcefully and lowering SV. • Contractility: The contractile strength achieved at a given muscle length. - Enhanced contractility means more blood is ejected from the heart (greater SV), and so ESV is lower. • Afterload: The pressure that the ventricles must overcome to eject blood. - In healthy individuals, afterload is not a major determinant of stroke volume because it is relatively constant. - However, in people with hypertension (high blood pressure), afterload is important because it reduces the ability of the ventricles to eject blood. Consequently, more blood remains in the heart after systole, increasing ESV and reducing stroke volume.

Differentiate between primary hemostasis and secondary hemostasis based upon final product and typically involved blood vessels.

• Primary Hemostasis: Forms a platelet plug, and occurs in all vessel types (arteries, veins, capillaries). • Secondary Hemostasis: Forms a stabilized platelet plug (thrombus), and occurs in higher pressure arteries/arterioles.

Recognize the blood group responsible for the Rh factor and its major antigen.

• Rh Blood Groups: - Named this because one Rh antigen (agglutinogen D) was originally identified as Rhesus Macaques. - There are 52 Rh agglutinogens, each called an Rh factor. ~ The 5 most common include: C, D, E, c, and e antigens. - Rh+ (Rh positive): Individuals that carry the D antigen; 85%. - Rh- (Rh negative): Individuals that do not carry the D antigen; 15%.

Order the sequence of systole/diastole events of cardiac cycle.

• Sequence of Events: - Atrial Systole - Atrial Diastole - Ventricular Systole - Ventricular Diastole

Describe cell replacement numbers in terms of production/destruction for growth, maintenance, and/or repair conditions.

• Stages of Erythrocyte Production/Erythropoiesis: 1. Hematopoietic Stem Cell descendant/Myeloid Stem Cell. 2. Proerythroblast. 3. Basophilic Erythroblasts: Produce large numbers of ribosomes. 4. Polychromatic Erythroblast. 5. Orthochromatic Erythroblast: Accumulates hemoglobin (pink) and ejects organelles/nucleus. 6. Reticulocyte: A young erythrocyte. 7. Erythrocyte. - During the first two phases, the cell divides many times. - Hemoglobin is synthesized and iron accumulates as the basophilic erythroblast transforms into a polychromatic erythroblast and then an orthochromatic erythroblast. - The color of the cell cytoplasm changes as the blue-staining ribosomes become masked by the pink color of hemoglobin. - From hematopoietic stem cell to reticulocyte = 15 days. - Reticulocytes mature within 2 days of entering the bloodstream. - Reticulocytes account for 1-2% of all erythrocytes in the blood. - Reticulocytes counts provide a rough index of the rate of RBC formation. • Erythropoiesis: Regulation & Requirements: - Hormonal Controls: ~ Erythropoietin (EPO): A glycoprotein hormone that stimulates the formation of erythrocytes. ~ The kidneys play the major role in EPO production, although the liver also produces some. ~ When certain kidney cells become hypoxic (oxygen deficient), oxygen-sensitive enzymes are unable to carry out their normal functions of degrading an intracellular signaling molecule called hypoxia-inducible factor (HIF). As HIF accumulates, it accelerates the synthesis and release of EPO. ~ The drop in normal blood oxygen levels that triggers EPO formation can result from: 1. Reduced numbers of red blood cells dut to hemorrhage (bleeding) or excessive RBC destruction. 2. Insufficient hemoglobin per RBC (iron deficiency). 3. Reduced availability of oxygen, as might occur at high altitudes or during pneumonia. ~ Conversely, too many erythrocytes, or excessive oxygen in the bloodstream, dpresses EPO production. - In males, testosterone also enhances the kidney's production of EPO. - Dietary Requirements: The raw materials reqwuired for erythropoiesis include: ~ Nutrients: Amino acids, lipids, and carbohydrates are essential for the synthesis of all cells. ~ Two B-Comples Vitamins: Vitamin B12 and folic acid are necessary for normal DNA synthesis. ~ Iron: Iron is essential for hemoglobin synthesis. ~ 65% of the body's iron supply is in hemoglobin. The remainder is stores in the liver, spleen, and bone marrow. ~ Free iron ions (Fe2+, Fe3+) are toxic and are therefore stored inside cells as protein-iron complexes: ferritin and hemosiderin. ~ In blood, iron is transported loosely bound to a transport protein called transferrin. • Destruction of Erythrocytes: - Red blood cells have a useful life span of 100-120 days. - Red blood cells are unable to synthesize new proteins, grow, or divide. Due to these limitations, erythrocytes become :old: as they lose their flexibility, become increasingly rigid and fragile, and their hemoglobin begins to degenerate. • Recycling of Erythrocytes: - Macrphages engulf and destroy dying erythrocytes. - The heme of their hemoglobin is split off from globin. ~ Its core of iron is salvaged, bound to protein (as ferritin or hemosiderin), and stored for reuse. ~ The balance of the heme group is degraded to bilirubin, a yellow pigment that is released to the blood and binds to albumin for transport. Liver cells pick up bilirubin and in turn secrete it (in bile) to the intestine, where it is metabolized to urobilinogen. Most of this degraded pigment leaves the body in feces, as a brown pigment called stercobilin. - The protein (globin) part of hemoglobin is metabolized or broken down to amino acids, which are release into circulation.

Recall the major components and stages of hemostasis.

• Step 1: Vascular Spasm - In the first step, the damaged blood vessels respond to injury by constricting (vasoconstriction). - Factors that trigger this vascular spasm include direct injury to vascular smooth muscle, chemicals released by damaged endothelial cells and activated platelets, and reflexes initiated by local pain receptors. - This spasm response is valuable because a strongly constricted artery can significantly reduce blood loss for 20-30 minutes, allowing time for the next two steps to occur. • Step 2: Platelet Plug Formation - In the second step, platelets play a key role in hemostasis by aggregating (sticking together), forming a plug that temporarily seals the break in the vessel wall. - Intact endothelial cells release nitric oxide and a prostaglandin called prostacyclin or PGI2. Both chemicals prevent platelet aggregation (clumping) in undamaged tissue and restrict aggregation to the site of injury. - After a large plasma protein, the platelet becomes activated: They swell, form spiked processes, and become stickier. They also release chemical messengers including the following: ~ Adenosine Diphosphate (ADP): A potent aggregating agent that causes more platelets to stick to the area and release their contents. ~ Serotonin and Thromboxane A2: Messengers that enhance vascular spasm and platelet aggregation. - As more platelets aggregate, they release more chemicals, aggregating more platelets (positive feedback loop). • Step 3: Coagulation - The third step, coagulation or blood clotting, reinforces the platelet plug with fibrin threads that act as a "molecular glue" for the aggregated platelets. - Effective in sealing larger breaks in a blood vessel. - This multistep process involves a series of substances called clotting factors or procoagulants. ~ Most clotting factors are plasma proteins synthesized by the liver. ~ Numbered I-XIII. - The coagulation sequence shows how clotting factors work together to form a clot. Once one clotting factor is activated, it activates the next in sequence, and so on, in a cascade (exceptions: fibrinogen & Ca2+). - Coagulation occurs in 3 phases. • Coagulation - Phase 1: Two Pathways to Prothrombin Activator - Coagulation may be inhibited by either the intrinsic or extrinsic pathway. - Coagulation Cascade: Sequential activation of circulating coagulation proteins (factors) to first form prothrombin activator, which then generates thrombin. ~ This is usually the slowest step of the blood clotting process, but once prothrombin activator is present, the clot forms in 10-15 seconds. - The Intrinsic Pathway is: ~ Called intrinsic because the factors needed for clotting are present within (intrinsic to) the blood. ~ Triggered by negatively charger surfaces such as activated platelets, collagen, or glass. ~ Slower because it has many intermediate steps. - The Extrinsic Pathway is: ~ Called extrinsic because the tissue factor it requires is outside of the blood. ~ Triggered by exposing blood to a factor found on cells in tissues surrounding the blood vessel. This factor is called tissue factor (TF) or factor III. ~ Faster because it bypasses several steps of the intrinsic pathway; can form a clot in 15 seconds. - Phase 1 ends with the formation of a complex substance called prothrombin activator. • Coagulation - Phase 2: Common Pathway to Thrombin - Prothrombin activator catalyzes the conversion of a plasma protein called prothrombin into the active enzyme thrombin. • Coagulation - Phase 3: Common Pathway to the Fibrin Mesh - The endpoint of phase 3 is a fibrin mesh that traps blood cells and effectively seals the hole until the blood vessel can be permanently repaired. - Thrombin transforms fibrinogen into fibren. - The fibrin molecules then polymerize (join together) to form long, hairlike, insoluble fibrin strands. The fibrin strands glue the platelets together and make a web that forms the structural basis of the clot. - Fibrin makes the liquid plasma become gel-like and traps formed elements that try to pass through it. - Thrombin also activates factor XIII (fibrin stabilizing factor), a cross-linking enzyme that binds the fibrin strands tightly together, forming a fibrin mesh. ~ Requires the presence of calcium ions (Ca2+). • Clot Retraction: A platelet-induce process that further stabilizes the clot. - Platelets contain contractile proteins (actin & myosin), and as the platelets contract, they pull on the surrounding fibrin strands, squeezing serum (plasma minus the clotting proteins) from the mass, compacting the clot and drawing the ruptured edges of the blood vessel more closely together. - Platelet-Derived Growth Factor (PDGF): Released by platelets to stimulate smooth muscle cells and fibroblasts to divide and rebuild the vessel wall. ~ Fibroblasts form connective tissue, while endothelial cells multiply and restore the endothelial lining. • Fibrinolysis: Enzymatic breakdown of fibrin-stabilized blood clots to restore normal blood flow when blood vessel repair has been completed (new endothelium); the removal of unneeded clots when healing has occurred. - Without fibrinolysis, blood vessels would gradually become completely blocked. - The critical natural "clot buster" is a fibrin-digesting enzyme called plasmin, which is produced when the plasma protein plasminogen is activated. Like a built-in self-destruction mechanism, plasminogen is incorporated into a forming clot, where it remains inactive until appropriate signals reach it. - Tissue Plasminogen Activator (tPA): Substance released by endothelial cells to activate plasminogen to plasmin. ~ As a result, plasmin is confined to the clot, and plasmin that strays into the plasma is destroyed by enzymes. - Fibrinolysis continues slowly over several days until the plasmin enzymatically "cuts" fibrin, and the clot dissolves.

Define the terms end diastolic volume (EDV) and end systolic volume (ESV) and relate them both to SV.

• Stroke Volume is the amount of blood forcibly ejected during a single contraction event, determined by two volumes: 1. End Diastolic Volume (EDV): The amount of blood volume that collects in the ventricles during end ventricular loading (diastole). 2. End Systolic Volume (ESV): The amount of blood volume that remains in the ventricles after ventricular contraction (systole).

Recall structural/functional aspects of red blood cells (RBCs) including hemoglobin composition, oxygen carrying capacity, normal RBC size/shape, cytoskeleton.

• Structural Characteristics of Erythrocytes: - Erythrocytes or red blood cells (RBC's) are small cells, about 7.5 micrometers in diameter. - They are shaped like biconcave discs; flattened discs with depressed centers. ~ Under a microscope, they appear lighter in color at their thin centers than at their edges. - Mature RBC's are essentially "bags" of hemoglobin (Hb) bound by a plasma membrane. They lack a nucleus (are annucleate) and have no organelles. - Spectrin is a protein network that maintains the boconcave shape of a erythrocyte while still allowing them the flexibility to change shape if necessary and then to resume their biconcave shape. - Three structural characteristics contribute to erythrocyte gas transport functions: 1. Its small size and shape provide a huge surface area relative to volume. The disc shape is ideally suite for gas exchange because no point within the cytoplasm is far from the surface. 2. Discounting water content, an erythrocyte is over 97% hemoglobin, the molecule that binds to and transports respiratory gases. 3. Because erythrocytes lack mitochondria and generate ATP by anaerobic mechanisms, they do not consume any of the oxygen they carry, making them very efficient oxygen transporters. • Functions of Erythrocytes: - The job of erythrocytes is to transport respiratory gases (O2 and CO2). ~ Hemoglobin is the protein that helps get the job done.

For the thyroid gland: Explain the importance of iodine in the synthesis of thyroid hormone.

• Synthesis of the Thyroid Hormone - In Steps: 1. Thyroglobulin is synthesized and discharged into the follicle lumen. - After being synthesized on the ribosomes of the follicular cell's rough endoplasmic reticulum, thyroglobulin is transported to the Golgi apparatus, where sugar molecules are attached and the thyroglobulin is packed into transport vesicles. These vesicles move to the apex of the follicular cell, where they discharge their contents into the follicular lumen to become part of the stpred colloid. 2. Iodide is Trapped: - To produce the functional iodinated hormones, the follicular cells must accumulate iodides (anions of iodine, I-) from the blood. Iodide trapping depends on active transport (the concentration of I- is over 30 times higher inside the cell than in blood). Once trapped inside the follicular cell, iodide then moves into the follicle lumen by facilitated diffusion. 3. Iodide is Oxidized to Iodine: - At the border of the follicular cell and colloid, iodides are oxidized (by removal of electrons) and converted to iodine (I2). 4. Iodine is Attached to Tyrosine: - Iodine is attached to tyrosine amino acids that are part of the thyroglobulin molecule. This iodination reaction, mediated by peroxidase ensymes, occurs at the junction of the follicular cell and the colloid. Attachment of one iodine to a tyrosine produces monoiodotyrosine (MIT), and attachment of two iodines produces diiodotyrosine (DIT). 5. Iodinated Tyrosnes are Linked Together to form T3 and T4: - Enzymes in the colloid link MIT and DIT together. Two linked DITs result in T4, and coupling of MIT and DIT produces T3. At this point, the hormones are still part of the thyroglobulin colloid. 6. Thyroglobulin Colloid is Endocytosed: - To secret the hormones, the follicular cells must reclaim iodinated thyroglobulin by endocytosis and combine the vesicles with lysosomes. 7. Lysosomal Enzymes Split T4 and T3 from Thyroglobulin and the Hormones Diffues from the Follicular Cell into the Bloodstream: - The main hormonal product secreted is T4. Some T4 is converted to T3 before secretion, but most T3 is generated in the peripheral tissues.

Define the terms systole, diastole, and cardiac cycle.

• Systole: Periods of contraction. • Diastole: Periods of relaxation. • Cardiac Cycle: All events associated with the blood flow through the heart during one complete heartbeat.

Describe the principles of peptide hormone receptor up-regulation and down-regulation.

• Target Cell Activation - Regulation: The control of target cell peptide receptors. - Up-Regulation: Persistently low hormone levels cause an increase in membrane receptors. - Down-Regulation: Continuously high hormone levels cause a decrease in receptors.

List 3 controlling factors of target cell activation.

• Target Cell Activation: Controlling Factors: 1. Hormone blood levels (concentration). 2. Relative number of target cell receptors (how many). 3. Hormone-receptor affinity (attractive force/binding strength).

Describe the relationship between a target cell receptor and its recognized hormone.

• Target Cells: Tissue cells that have specific receptors for a particular hormone. - Exact cellular hormonal responses depend on target cell type. - A single cell can express several different hormone receptor types. - Receptor-binding of a hormone turns on a "pre-programmed" function. • In order for a target cell to respond to a hormone, the cell must have specific receptor proteins on its plasma membrane or in its interior to which a hormone can bind.

For the adrenal medulla: List 3 catecholamines, production, and their effects.

• The Adrenal Medulla: Medullary chromaffin cells are modified postganglionic sympathetic neurons that crowd aorunf porous bloos-filled capillaries. These cells synthesize epinephrine and norepinephrine from tyrosine to dopamine to NE to epinephrine. - Approximately 80% is epinephrine stored and 20% norepinephrine. - Epinephrine: The more potent stimulator of metabolic activities and dilator of small airways (bronchioles). It is used clinically as a heart stimulant and to dilate the brinchioles during acute asthmatic attacks and severe allergic reactions. - Norepinephrine: Has greater influence on peripheral vasoconstriction and blood pressure. - Dopamine: A precursor of both epinephrine and norepinephrine. - Catecholamines (EPI and NE) cause fairly breif, short-term stress responses.

Recall 2 factors that determine the concentration of a hormone in the blood.

• The Concentration of Circulating Hormones in the Blood Reflects: 1. Its rate of release. 2. Its speed of inactivation/body removal. • Some hormones are degraded by enzymes in their target cells, though most are removed from the blood by the kidneys/liver. • Half-Life: The length of time for a hormone's blood level to decrease by half (50%). - Varies from a fraction of a minute to a week. - Water-soluble hormones have the shortest half lives because they are rapidly removed from the blood by the kidneys.

For the pancreas: Differentiate between endocrine & exocrine functions, including hormone producing cells.

• The Pancreas: Tadpole-shaped gland composed of both endocrine and exocrine gland cells that is located partially behind the stomach in the abdomen. - Acinar cells, forming the bulk of the gland, produce an enzyme-rich juice that is carried by ducts to the small intestine during digestion. - Scattered among the acinar cells are approximately a million pancreatic islets (islets of Langerhans), tiny cell clusters that produce pancreatic hormones. ~ These islets contain 2 major hormone-producing cells: 1. Alpha Cells: Release glucagon and are fewer in number. 2. Beta Cells: Release insulin and are more numerous.

For the pancreas: Describe its macroscopic and microscopic anatomy.

• The Pancreas: Tadpole-shaped gland composed of both endocrine and exocrine gland cells that is located partially behind the stomach in the abdomen. - Acinar cells, forming the bulk of the gland, produce an enzyme-rich juice that is carried by ducts to the small intestine during digestion. - Scattered among the acinar cells are approximately a million pancreatic islets (islets of Langerhans), tiny cell clusters that produce pancreatic hormones. ~ These islets contain 2 major hormone-producing cells: 1. Alpha Cells: Release glucagon and are fewer in number. 2. Beta Cells: Release insulin and are more numerous. - Insulin and glucagon's effects are antagonistic: Glucagon is s hyperglysemic hormone (increases blood glucose), whereas insulin is a hypoglycemic hormone (decreases blood glucose).

Define the roles of plasminogen, plasmin & tissue plasminogen activator (tPA) in fibrinolysis.

• The critical natural "clot buster" is a fibrin-digesting enzyme called plasmin, which is produced when the plasma protein plasminogen is activated. Like a built-in self-destruction mechanism, plasminogen is incorporated into a forming clot, where it remains inactive until appropriate signals reach it. • Tissue Plasminogen Activator (tPA): Substance released by endothelial cells to activate plasminogen to plasmin. • As a result, plasmin is confined to the clot, and plasmin that strays into the plasma is destroyed by enzymes.

Describe the hypothalamus's endocrine system role.

• The hypothalamus is the "boss" or major endocrine controller. It produces and releases hormones and is classified as a neuroendocrine gland.

Define the roles of thrombin & fibrin in coagulation.

• Thrombin transforms fibrinogen to fibrin. • The fibrin molecules then polymerize (join together) to form long, hairlike, insoluble fibrin strands. The fibrin strands glue the platelets together and make a web that forms the structural basis of the clot. • Fibrin makes the liquid plasma become gel-like and traps formed elements (RBC's) that try to pass through it. • Thrombin also activates factor XIII (fibrin stabilizing factor), a cross-linking enzyme that binds the fibrin strands tightly together, forming a fibrin mesh. - Requires the presence of calcium ions (Ca2+).

For the thyroid gland: Describe macroscopic and microscopic anatomy (including cell types found).

• Thyroid Gland: Being the largest pure endocrine gland in the body, this butterfly-shaped gland is located in the anterior neck, on the trachea just inferior to the larynx. - Isthmus: A median tissue mass connecting the 2 lateral lobes of the thyroid gland. - Internally, the gland is composed of hollow, spherical follicles. ~ Each follicle is formed by cuboidal/squamous epithelial cells called follicular cells. ~ Follicular cells produce the glycoprotein thyroglobulin. ~ The central cavity of each follicle stores colloid, an amber-colored, sticky material consisting of thyroglobulin and attached iodine atoms. ~ Thyroid hormone = iodinated thyroglobulin. - Parafollicular cells produce calcitonin to regulate blood Ca2+ levels.

For the thyroid gland: Recall 2 thyroid hormone types, production, functions, feedback mechanisms, and imbalances.

• Thyroid Hormone (TH): The body's major metabolic hormone, which is further composed of two iodine-containing amine hormones: thyroxine (T4) and triiodiothyronine (T3). - Thyroxine (T4) is the major hormone secreted by the thyroid follicles. ~ Most triiodothyronine is formed by conversion of T4 to T3. ~ T4 = 4 bound iodine atoms. ~ T3 = 3 bound iodine atoms. - Functions of the TH: 1. Calorigenic Effect: Increase metabolic rate and body heat production. 2. Regulates tissue growth. 3. Regulates skeletal and nervous system development. 4. Maturation and reproductive capabilities. 5. Maintains blood pressure. - The thyroid gland is unique from other endocrine glands because it has the ability to store its hormone extracellularly and in large quantities.

Distinguish between the terms Total WBC Count and WBC differential.

• Total WBC Count: Determines the total number of leukocytes in a volume of blood regardless of type. - How many of ALL types. • WBC Differential: Detects relative numbers (%) of each leukocyte type by counting 100 cells. - Percentage of each type.

Describe what happens during a transfusion reaction.

• Transfusion Reactions: When mismatched blood is infused and the recipient's plasma antibodies attack the donor's RBC's. - In these reactions the donor's RBC antigens are attacked by pre-existing recipient antibodies. The recipient's RBC antigens are attacked by the donor's antibodies. - These reactions can cause problems: (1) The transfused blood cells cannot transport oxygen, and (2) The clumped red blood cells in small vessels hinder blood flow to tissues beyond those points. - Treatment focuses on preventing kidney damage, because this can cause the recipient to die. - Group O is the universal donor. - Group AB are the universal recipients.

Differentiate between blood distribution, regulatory, and protective functions.

• Transport Functions: - Delivering oxygen from the lungs and nutrients from the digestive tract to all body cells. - Transporting metabolic waste products from cells to elimination sites (to the lungs to eliminate carbon dioxide and to the kidneys to dispose of nitrogenous wastes in urine). - Transporting hormones from the endocrine glands to their target organs. • Regulatory Functions: - Maintaining appropriate body temperature by absorbing and distributing heat throughout the body and to the skin surface to encourage heat loss. - Maintaining normal pH in body tissues. Many blood proteins and other blood borne solutes act as buffer to prevent excessive abrupt changes in blood pH that could jeopardize normal cell activities. Blood also acts as a reservoir for the body's "alkaline reserve" for bicarbonate ions (HCO3-). - Maintaining adequate fluid volume in the circulatory system. Blood proteins prevent excessive fluid loss from the bloodstream into the tissue spaces. as a result, the fluid volume in the blood vessels remains ample to support efficient blood circulation to all parts of the body. • Protective Functions: - Preventing Blood Loss: When a blood vessel is damaged platelets and plasma proteins initiate clot formation, halting blood loss. - Preventing Infection: Drifting along in blood are antibodies, complement proteins, and leukocytes (white blood cells), all of which help defend the body against foreign invaders such as bacteria and viruses.

Differentiate between type 1, type 2, & gestational DM

• Type 1 DM: Absolute insulin deficiency (hyposecretion) due to beta-islet cell absence; insulin is required. • Type 2 DM: Relative insulin deficiency (hypoactivity) due to increased insulin resistance; insulin is not required. • Gestational Diabetes Mellitus (GDM): High blood glucose levels in pregnant women with no history of diabetes that may lead to Type 2 DM.

Classify skin hemorrhages given their associated characteristics (petechiae, purpura contusion).

• Types of Skin Hemorrhages: 1. Petechiae: Subcutaneous capillary bleeding that causes small (pinpoint) blood spots near the skin surface; widespread hemorrhage indicated by small purplish spots. 2. Pupura: Larger petechiae that also result from the loss of blood from smaller blood vessels. 3. Contusion: Hemorrhage due to mechanical injury (traumatic blow) to muscle that results in a bruise.

Describe the role of cAMP in peptide hormone signaling.

• cAMP acts as the 2nd messenger in the Cyclic AMP (cAMP) second-messenger mechanism of water-soluble hormones. • cAMP activates protein kinases.

Differentiate between causes of RBC reduction or overage (over production).

•Erythrocyte Disorders: Most are classified as anmeia or polycythemia. 1. Anemia: A condition in which the blood's oxygen-carrying capacity id too low to support normal metabolism. - It is a sign of some disorder rather than a disease itself. - Anemic individuals are fatigued, often pale, short of breath, and chilled. - The causes of anemia are divided into 3 groups: blood loss, not enough red blood cells produced, or too many erythrocytes destroyed. 2. Hemorrhagic Anemia: Causes by excessive blood loss. 3. Iron-Deficiency Anemia: Results form inadequate intake of iron-containing foods or impaired iron absorption. - The erythrocytes produced under these conditions, microcytes, are small and pale because they cannot synthesize their normal complement of hemoglobin. - Not enough RBCs produced. 4. Pernicious Anemia: An autoimmune disease that most often affects the elderly when the immune system of theses individuals destroys cells of their own stomach mucosa. - These destroyed cells normally produce a substance called intrinsic factor that must be present for vitamin B12 to be absorbed by intestinal cells. - Without vitamin B12, the developing erythrocytes grow but cannot divide, and large, pale cells called macrocytes result. - Often found in strict vegetarians because meats, poultry, and fish provide ample vitamin B12. - Not enough RBC's produced. 5. Renal Anemia: Caused by lack of EPO hormone that controls rec blood cell production. - Not enough RBCs produced. 6. Aplastic Anemia: May result from destruction of inhibition of red bone marrow by certain drugs and chemicals, ionizing radiation, or viruses. - Not enough RBC's produced. 7. Hemolytic Anemia: When erythrocytes rupture, or lyse, prematurely. - Hemoglobin abnormalities, transfusion of mismatched blood, and certain bacterial and parasitic infections are possible causes. - Too many RBC's destroyed. 8. Thalassemia: One of the globin chains is absent or faulty, and the erythrocytes are thin, delicate, and deficient in hemoglobin. - Inadequate production of either alpha or beta chains. - Too many RBC's destroyed. 9. Sickle-Cell Anemia: Effects caused nu abnormal hemoglobin S (Hb-S) result from a change in just one of the 146 amino acids in a beta chain of the globin molecule. - Causes red blood cells to beomce crecent shaped. - The stiff, deformed erythrocytes rupture easily and tend to jam up in small blood vessels. These events interfere with oxygen delivery, leaving the victims gasping for air and in extreme pain. - Too many RBC's destroyed. 10. Polycythemia: an abnormal excess of erythrocytes that increases blood velocity, causing it to flow sluggishly. - Polycythemis Vera: A bone marrow cancer characterized by dizziness and exceptionally high RBC count. - Polycythemia (Secondary): When less oxygen is available or EPO production increases. - Blood Doping: Artificially induced polycythemia.