A&P II Lecture Exam 1

Homeostasis

the condition of equilibrium or balance in the body’s internal environment due to the interplay of the body’s many regulatory processes.

Negative Feedback

an increase in one physiological parameter leads to a physiological process that results in a decrease in the parameter

Direct Communication

\-This occurs between two cells of the same type where the cells are in extensive physical contact, therefore the communication is limited to these two cells only

\-The transmission of information occurs through gap

junctions.

\-This occurs with epithelial cells and cardiac cells.

Paracrine Communication

\-in the form of cellular chemicals called paracrine factors, are released from one cell into the surrounding extracellular fluid.

\-The paracrine factors then diffuse to the many neighboring cells in the same tissue

\-Prostaglandins are examples of this type of factor.

\*ENDOCRINE COMMUNICATION

\-cells release chemicals called hormones directly into the bloodstream. The hormones then travel throughout the body.

\-the hormones are specific to what cells they will affect. These cells are called target cells. The target cells have receptors that the hormones attach to, in order for the target cell to “read” the hormonal information or commands and react in a certain way.

\*HORMONES MAY AFFECT A TARGET CELL BY

\-Stimulating the synthesis of an enzyme or structural protein not already present in the cytoplasm via transcription and translation.

\-Increase or decrease the rate of synthesis

of an enzyme or protein.

\-Turn an existing enzyme or membrane

channel “on” or “off” by changing its shape or structure

Hormones

\- a single hormone can alter the metabolism of multiple tissues or entire organs simultaneously

\-The effects of a single hormone may last for

days.

\-The observable effects of hormones are at their greatest during embryological and fetal development, growth and puberty.

Synaptic Communication

\-The release of neurotransmitters in the synaptic cleft

\-limited to adjacent neurons or muscle cells

that have specific receptor for the neurotransmitter.

\-done to propagate the action potential.

\*THE ENDOCRINE SYSTEM

\-all the cells and tissues in the body that produce hormones or paracrine factors.

\-It is the fact of the release of these chemicals directly into the bloodstream that defines these cells or tissues as endocrine

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\*AMINO ACID DERIATIVES

\-small molecules that are structurally related to amino acids, the building blocks of proteins.

\-Specifically they are synthesized from the amino acids tyrosine and tryptophan.

\-Tyrosine derivatives include thyroid hormones and the catecholamines: epinephrine, norepinephrine and dopamine.

\-Tryptophan derivatives include melatonin produced by the pineal gland.

\*PEPTIDE HORMONES

\-Chains of amino acids

\-Glycoproteins: thyroid stimulating hormone (TSH), lutinizing hormone (LH), follicle-stimulating hormone (FSH)

\-Other than Glycoproteins: antidiuretic hormone (ADH), oxytocin, growth hormone (GH), prolactin (PRL).

\*LIPID DERIATIVES

\-Eicosaniods: small molecules with a five-carbon ring at one end and derived from arachidonic acid (a 20- carbon fatty acid).

\-Steroid hormones: lipids derived from cholesterol.

Eicosaniods

\-Leukotrienes: released by white blood cells (aka leukocytes). Important in coordinating tissue responses to injury or disease

\-Prostaglandins: produced in most tissues of the body and may be converted to thromboxanes and prostacyclins. Prostaglandins may be secreted by injured cells or tissues causing the increase of blood flow to the injured area causing it to become red and warm. They are the “pain” producing chemicals.

\*STEROID HORMONES

\-Androgens: secreted by the testes, e.g: testosterone

\-Estrogens and progestins: secreted by the ovaries. E.g.: estrogen, progesterone.

\-They also include corticosteroids (produced by the cortex of the adrenal glands) and calcitriol (produced by the kidneys).

Secretion of Hormones

\-Once hormones are released into the blood stream, they may either circulate freely or bind to a special carrier protein.

\-A freely circulating hormone remains functional for less than one hour and becomes inactivated in the bloodstream by either binding to the receptors of the target cells, absorbed and broken down by cells in the liver or kidneys, or broken down by enzymes in the blood plasma or interstitial fluid

\-Hormones that bind to the special carrier proteins remain in circulation much longer, up to several months (ex: thyroid and steroid hormones)

\*HORMONE RECEPTORS

\-Receptors of target cells may be on the plasma

membrane or within the cytoplasm.

\-Water-soluble hormones, such as the catecholamines or peptide hormones, cannot penetrate the plasma membrane, therefore their receptors are located on the outer surface of the plasma membrane (extracellular receptors).

\-Eicosaniods are lipid derivatives and therefore lipidsoluble. They are able to penetrate the plasma membrane to reach receptors on the inner surface of the membrane (intracellular receptors)

First and Second Messengers

\-If a hormone binds to receptors in the plasma membrane, they cannot directly affect the activities inside the cell (such as transcription and translation).

\-Therefore, the hormone, called the first messenger, needs an intracellular intermediary, called the second messenger, to exert its effects

\*SECOND MESSENGERS

\-Cyclic-AMP (cAMP): a derivative of ATP

\-Cyclic-GMP (cGMP): a derivative of GTP,

another high energy compound

\-Calcium ions

\-The link between the first and second messenger involves a G protein, which is an enzyme complex coupled to a membrane receptor. This protein when activated will bind to GTP

\*G PROTEINS AND cAMP

\-When a hormone binds to a receptor on the plasma

membrane, the G protein becomes activated

\-The activated G protein then activates the enzyme

**adenylate cyclase** which converts ATP to cyclic-AMP

\-Cyclic-AMP activates the enzyme kinase which accelerates the metabolic activity of the target cell ultimately resulting in the opening of ion channels or the activation of enzymes.

\-In order to prevent the cell from “burning out”, another enzyme called **phosphodiesterase (PDE**) found in the cytoplasm inactivates the c-AMP once the desired effect is accomplished (negative feedback).

G proteins and Calcium Ions

\-An activated G protein can trigger either the

opening of calcium ion channels in the plasma membrane or the release of calcium ions from intracellular stores.

\-The activated G protein will activate the enzyme phospholipase C (PLC) which causes the production of diacylglycerol (DAG) and inositol triphosphate (IP3) in the plasma membrane

\*G PROTEINS AND CALCIUM IONS

\-IP3 diffuses into the cytoplasm and causes the release of calcium ions from intracellular reserves (smooth endoplasmic reticulum)

\-The calcium ions and DAG activates the membrane protein **protein kinase C (PKC)** which will open up the calcium ion channels allowing extracellular calcium ions to enter the cell (positive feedback).

\-These ions bind with an intracellular protein called **calmodulin** which accelerates the metabolic activity in the cell.

Hormones and Intracellular Receptors

Steroids are lipid soluble and can penetrate the plasma membrane easily. Their receptors are found in the cytoplasm or nucleus. Therefore they can quickly alter the rate of transcription, translation and protein synthesis causing a possible change in the metabolism and structure of the target cell

\-Thyroid hormones are lipid soluble because they are very small in size.Their receptors are in the mitochondria (for increase of ATP production) or the nucleus (for transcription rate change

Endocrine Reflexes

\-Simple reflexes: endocrine cells secrete one hormone in response to changes in the composition of the extracellular fluid, causing the target cells to adjust their activity and restore homeostasis

\-Complex Reflexes: involve one or more intermediary steps and two or more hormones

Hypothalamus

\-The hypothalamus secretes regulatory hormones, special hormones that control endocrine cells in the adenohypophysis (anterior lobe) of the pituitary gland. The adenohypophysis, in turn, secretes hormones that control the endocrine cells of the thyroid, adrenal cortex and reproductive organs

\- contains autonomic centers that exert direct neural control over the endocrine cells of the adrenal medullae

\-Neuroendocrine reflex: When the sympathetic division is activated (“fight or flight”) the hypothalamus commands the adrenal medullae to secrete epinephrine and norepinephrine into the bloodstream

\*HYPOTHALAMUS

\- synthesizes hormones, transports them along axons within the infundibulum (the “stem” of the pituitary gland) to the neurohypophysis (posterior lobe of the pituitary gland) where it would be released into the bloodstream.

\-ADH and oxytocin

\*THE PITUITARY GLAND

\-AKA hypophysis

\-small, oval gland protected in the sella turcica of the sphenoid bone and secured in place by a dural sheet called the diaphragma sellae

\-It hangs inferior to the hypothalamus and is connected

by a funnel-shaped structure called the infundibulum

Adenohypophysis

\-anterior lobe of the pituitary gland that secretes 7 peptide hormones

\-Pars distalis: largest and most anterior

\-Pars tuberalis: wraps around the inferior part of the infundibulum

\-Pars intermedia: a narrow band bordering the neurohypophysis

\*HYPOPHYSEAL PORTAL SYSTEM

\-An extensive capillary network radiates through the adenohypophysis giving every endocrine cell immediate access to the circulatory system

\-These capillaries are called **fenestrated capillaries** because they are lined with endothelial cells that are unusually permeable so larger hormones can enter the bloodstream easily.

\-The **median eminence** which is a swollen area at the base of the infundibulum, is supplied by the superior hypophyseal artery which brings blood from the heart

\-The superior hypophyseal artery brings oxygenated blood to a capillary network in the median eminence which is then carried by portal vessels that deliver the blood to another capillary network in the adenohypohysis.

\-blood and hormones leave via hypophyseal veins in order to reach the target cells

\*HORMONES OF THE ADENOPYPHOSIS: Thyroid-Stimulating Hormone (TSH)

targets the thyroid gland and triggers the release of thyroid hormones (thyroxine, triiodothyronine). It is secreted in response to the production of thyrotropin-releasing hormone, which is secreted by the hypothalamus.

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\*HORMONES OF THE ADENOPYPHOSIS: Adrenocorticotropic Hormone (ACTH):

\- stimulates the release of glucocorticoids (steroids that affect glucose metobolism) by the adrenal cortex. ACTH is released in response to the production of corticotropin-releasing hormone (CRH), by the hypothalamus

\*HORMONES OF THE ADENOPYPHOSIS: Gonadotropins

\- hormones that regulate the activities of the gonads (testes and ovaries). They are released by the adenohypophysis in response to the production of gonadotropin-releasing hormone (GnRH) from the hypothalamus

\*HORMONES OF THE ADENOPYPHOSIS: Follicle-Stimulating Hormone (FSH)

promotes follicle development in females and, in combination with LH, stimulates the secretion of estrogens by ovarian cells. In males, FSH stimulates nurse cells, that promote physical maturation of sperm cells

\*HORMONES OF THE ADENOPYPHOSIS: Luteinizing Hormone (LH)

induces ovulation (production of ova in females), promotes the secretion of estrogens and progestins by the ovary that prepare the body for possible pregnancy. In males, LH stimulates the production of sex hormones called androgens (e.g. testosterone) by the interstitial cells of the testes.

\*HORMONES OF THE ADENOPYPHOSIS: prolactin

helps stimulate mammary gland development and milk production during and after pregnancy.

\*HORMONES OF THE ADENOPYPHOSIS: Growth Hormone (GH):

stimulates cell growth and replication by accelerating the rate of protein synthesis. The production of GH is regulated by growth hormone-releasing factor (GH-RH) and growth hormoneinhibiting hormone (GH-IH)

\*HORMONES OF THE ADENOPYPHOSIS: Melanocyte Stimulating Hormone (MSH):

stimulates the melanocytes of the skin increasing the production of the yellow-brown pigment called melanin. It is secreted during exposure to the sun and may be administered synthetically to obtain a “sunless tan”

\*HORMONES OF THE NEUROPOPHYSIS: Antidiuretic Hormone (ADH)

released in response to a decrease in blood volume or pressure or increase of solute concentration of the blood picked up by osmoreceptors. The function is to decrease the amount of water lost in the kidneys and vasoconstriction of peripheral blood vessels in order to increase the blood pressure. ADH release is inhibited by alcohol, which explains the “breaking the seal” phenomena.

\-Diabetes insipidus is the condition where not enough ADH is produced therefore causing excess loss of water in the urine (polyuria) resulting in constant thirst, dehydration, electrolyte imbalances and possible death. Desmopressin is a synthetic form of ADH and is used to treat diabetes insipidus

\*HORMONES OF THE NEUROPOPHYSIS: Oxytocin (OXT)

stimulates the smooth muscle contractions of the uterus promoting labor and delivery. It also promotes the ejaculation of milk from the nipples after pregnancy as the milk let-down reflex. In men, OXT stimulates smooth muscle contraction in the sperm duct and prostate gland to allow emission (ejection of sperm and gland secretions into the urethra before ejaculation).

Thyroid gland

\-Located across the anterior trachea, this gland has two lobes united by a narrow connection called the isthmus.

\-Also has an extensive blood supply in order to easily deposit its hormones into the bloodstream.

\-Contains thyroid follicles cells which are hollow spheres lined with simple cuboidal epithelium. Within these cells are follicle cavities that contain the colloid (fluid and dissolved proteins)

\-Thyroid stimulating hormone (TSH) stimulates the transport of iodide ions into the follicle cells causing the production of the thyroid hormones. It also stimulates the release of these hormones into the bloodstream.

\*THYROID GLAND

\-The follicle cells synthesize a protein called thyroglobulin which is deposited into the colloid. This protein contains the amino acid tyrosine, which is the building block of thyroid hormones.

\-Iodide ions absorbed in the bloodstream from ingested foods in the GI tract are delivered into the colloid of the follicle cells and bind to the tyrosine of the thyroglobulin protein.

\-If the molecule contains 4 iodide ions, it forms the hormone thyroxine (T4). If the molecule contain 3 iodide ions the hormone is triiodothyronine (T3)

\*FUNCTION OF THYROID HORMONES

\-Thyroid hormones binding to receptor in the target cell’s mitochondria increase ATP production, increasing energy and metabolic rate of the cell.

\-They also help control growth and development of skeletal, muscular and nervous systems in growing children

Hypothyroidism

\-(aka myxedema) results from the deficiency of T3 and T4 directly (underactive thyroid) or a deficiency of TSH (underactive pituitary gland).

\-Symptoms in children include reduction of growth velocity and arrest of pubertal development.

\-In adults the symptoms may be non-pitting edema, dryness of skin and swelling of the face, hair loss on the scalp and lateral 1/3 of the eyebrows, carpal tunnel syndrome, cold sensitivity, pericardial and pleural effusions or bradycardia. A goiter may be present if the thyroid is being destroyed and replaced by scar tissue as in the case of Hashimoto’s autoimmune thyroiditis

Hyperthyroidism

\-aka thyrotoxicosis: due to the excess secretion of T3 and T4.

* Grave’s Disease is a common cause. It is characterized by a diffuse goiter, pretibial myxedema, tachycardia, tremor, weight loss, exophthalmos and sensitivity to hot weather. Treatment are anti-thyroid drugs or thyroidectomy

\*THYROID GLAND: C CELLS

\-(clear) cells (aka parafollicular cells) are found between the follicular cells.

\-They secrete the hormone calcitonin (CT) which decreases calcium ion concentrations in the body fluids.

\-In the case that the body has too much calcium in the body fluids, the C cells will secrete calcitonin which inhibits the activity of osteoclasts in bone and stimulates calcium excretion at the kidneys

\*PARATHYROID GLANDS

\-The parathyroid cells produce parathyroid hormone (PTH) which has the opposite function of calcitonin. If calcium ion levels in body fluids fall below normal levels, PTH is secreted inhibiting osteoblastic activity and triggers the production of more osteoclasts. It also enhances the resorption of calcium ions at the kidneys and stimulates the production of calcitriol by the kidneys which increases the absorption of calcium and phosphate by the GI tract.

Adrenal Glands

\-Also known as the suprarenal glands, they are pyramid-shaped glands located on the superior surfaces of the kidneys.

\-Like every other endocrine gland, they are very vascular.

\-Each are subdivided into two parts: the adrenal cortex and adrenal medulla.

\*ADRENAL CORTEX: Zona Glomerulosa:

\-outermost region that produces the mineralocorticoids. These are hormones that affect the electrolyte composition of the body fluids. Aldosterone is the main mineralocorticoid and stimulates the conservation of sodium ions as well as the elimination of potassium ions at the kidneys, sweat glands, salivary glands, and pancreas

\*ADRENAL CORTEX: Zona Fasciculata

produces steroid hormones called glucocorticoids which regulate glucose metabolism. The main glucocortioid is cortisol and is secreted in response to ACTH. It accelerates the rates of glucose synthesis and glycogen production. It also breaks down adipose tissue and other tissues in order to release fatty acids and proteins into the blood for immediate energy for cells.

Cortisol

\-released in response to sympathetic responses, including stress. Chronic stress can lead to over-secretion of cortisol and may lead to excessive breakdown of tissue in the body that could result in exhaustion, chronic pain and Type II diabetes.

\-Cushing’s syndrome is due to the release of glucocorticoids in response to excess ACTH secreted by the pituitary gland or excess use of synthetic glucocorticoids.

\*ADRENAL CORTEX: Zona reticularis

\-deepest of the zones. Under stimulation of ACTH, this zone produces small quantities of androgens. Once released into the blood, the androgens are converted to estrogens. These androgens stimulate the development of pubic hair in prepubescent boys and girls. While not important in adult men, in adult women these androgens promote muscle mass, blood cell formation and libido support

\*ADRENAL MEDULLA

\-This is the core of the adrenal glands which contain large, round cells innervated by preganglionic sympathetic fibers.

\-Secretion is controlled by the sympathetic division of the ANS.

\-It secretes epinephrine and norepinephrine.

\-Epinephrine make up 75-80% of the secretions by the medulla. The remainder is norepinephrine.

\-Most cells of the body are the target cells. Their function is increase in cardiac activity, blood pressure, glycogen breakdown, blood glucose levels and the release of lipids by adipose tissue

\*PINEAL GLAND

\-Part of the epithalamus, it is located in the posterior roof of the third ventricle.

\-Contains secretory cells called pinealocytes that secrete the hormone melatonin. These cells are influenced by visual pathways and therefore produce more melatonin at night than in the day.

\-Functions of this hormone is inhibiting reproductive functions by slowing the maturation of the sperm, oocytes and organs, protects against free radicals (therefore is an anti-oxidant), setting circadian rhythms. Increased melatonin secretion in times of extended darkness has been suggested as the cause for seasonal affective disorder

\*PANCREAS

\-both an endocrine and exocrine gland.

\- produces digestive enzymes that is sent to the small intestine through ducts. This is the exocrine pancreas

\-The endocrine pancreas consists of cells called pancreatic islets or islets of Langerhans. Each islet contains alpha cells, which produce the hormone glucagon, and beta cell which produces the hormone insulin.

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\*PANCREAS: insulin

\- a peptide hormone released into the bloodstream when blood-glucose levels exceed normal levels (70-110 mg/dl), when high blood-amino acid levels are too high, or by parasympathetic activation.

\-Insulin facilitates the uptake of glucose by target cells (insulin-dependent cells). Some cells are insulin-independent, such as cells in the brain, kidney, lining of the GI tract and RBCs, because they can absorb and utilize glucose without insulin stimulation.

\*PANCREAS: Glucagon

\- is secreted when glucose levels fall below normal.

\-This hormone stimulates the breakdown of glycogen stored in skeletal muscle and liver cells, the breakdown of triglycerides in adipose tissue and stimulates the production of glucose in the liver (gluconeogenesis)

Diabetes Mellitus

\-Type I or insulin-dependent diabetics are born without or have their beta cells destroyed (virus, autoimmune). They are unable to produce insulin and require multiple injections daily in order to live.

\-Type II or non-insulin-dependent diabetes results when the insulin receptors on the cell membrane become desensitized. This is due to a phenomenon called down-regulation, where a presence of a hormone triggers a decrease in the number of hormone receptors. Therefore, when levels of insulin are high, such as in the case of a poor diet and constant stress, cells become less sensitive to it.

\*KIDNEYS: Calcitriol

\-a steroid that is secreted in response to the presence of PTH. A type of vitamin D, calcitriol stimulates the absorption of calcium and phosphate ions in the GI tract, the formation and activity of osteoclasts, resorption of calcium ions in the kidneys, and suppresses PTH production.

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\*KIDNEYS: Erythropoietin

a peptide hormone released in response to low oxygen levels in the kidney tissue. This hormone stimulates the production of RBCs in bone marrow, which will in turn deliver more oxygen to the kidneys

\*KIDNEYS: Renin

secreted in response to sympathetic stimulation or a decline in renal blood flow. Once secreted in the blood, a cascade occurs called the renin-angiotensin system. Renin converts angiotensinogen (protein produced by the liver) into angiotensin I. When angiotensin I travels to the lungs, it is converted to angiotensin II, which stimulates the secretion of aldosterone from the adrenal cortex and ADH at the neurohypophysis. Together both hormones restricts salt and water loss at the kidneys, increasing thirst, blood pressure and blood volume

\*HEART

The endocrine cells of the heart are those cardiac muscle cells that are found in the walls of the atria and ventricles. If blood volume is too great, these cells stretch excessively and secrete natriuretic peptides which function as the opposite of angiotensin II. They promote the loss of water and sodium ions at the kidneys and inhibit the secretion of aldosterone and ADH, causing a decrease in blood pressure and volume.

Thymus

Located in the mediastinum, it secretes a hormone called thymosin, which promotes the development and maturation of lymphocytes (WBCs responsible for immunity)

\*GONADS: males

\-interstitial cells in the testes produce androgens. Testosterone is an androgen that supports the maturation of sperm, protein synthesis in skeletal muscles, male secondary sex characteristics (facial hair, deep voice), and associated behaviors.

\-Nurse cells in the testes secrete inhibin that will target the adenohypophysis in order to inhibit the production of FSH.

\*GONADS: females

\-the steroid hormones produced by follicular cells are called estrogens. Estradiol is the main estrogen and functions to support follicle maturation, female secondary sex characteristics, and associated behavior. Inhibin is also secreted by the follicular cells and acts the same way as that in the male.

\-Progestins are hormones secreted by the corpus luteum (follicular cell after it releases the oocyte). Progesterone is the principle progestin and prepares the uterus for implantation, the mammary glands for secretory activity

Adipose Tissue

\-Leptin is a peptide hormone released from adipose tissue when we eat. As the adipose absorbs glucose and lipids and synthesizes triglycerides for storage, it releases leptin which binds to neurons in the hypothalamus resulting in a sense of satiation and the suppression of appetite

Cardiovascular System

\-Consists of all the structures responsible for delivering the necessary materials to the approximately 75 trillion cells in the body in order for them to maintain a homeostatic status, as well as removing their waste

\-heart, blood vessels, and blood

\-blood is carried away from the heart via arteries and returns via veins

\-Capillaries are microscopic vessels that interconnect the smallest arteries to the smallest veins.

\*FUNCTION OF BLOOD

\-Transportation of dissolved gasses, nutrients, hormones, and metabolic wastes.

\-Regulation of the pH, by neutralizing lactic acid produced by skeletal muscle, and ion composition (such as calcium and potassium) of interstitial fluids.

\-Restriction of fluid losses at injury sites via clotting.

\-Defense against toxins and pathogens via WBCs and antibodies.

\-Stabilization of body temperature by absorbing excess heat produced by skeletal muscle and distributing it to other tissue (sweat glands), or by providing heat to temperature-sensitive organs (brain) when the body is too cold

\*STRUCTURE OF BLOOD

\-Blood is liquid connective tissue having a matrix called plasma, which is a viscous solution filled with a unique assortment of suspended proteins.

\-Blood also consists of three types of formed elements:

1\. Red blood cells (aka erythrocytes): specialized cells that transport oxygen.

2\. White blood cells (aka leukocytes): cells involved with body defense and immunity.

3\. Platelets: small cell fragments that contain enzymes for blood clotting.

\-Hemopoiesis is the production of formed elements.

Whole Blood

\-This is the combination of plasma and the formed elements.

\-Its temperature is slightly above normal body temperature (100.4 degrees F).

\-It is 5x more viscous than water due to dissolved proteins, formed elements and water molecules.

\-Slightly alkaline with a pH around 7.4.

\-Approximately 5-6 liters of blood in an adult male and 4-5 liters in an adult female.

Venipuncture

\-This is the procedure where blood is collected for analysis from a superficial vein. A vein is preferred because:

1\. Superficial veins are easy to locate

2\. The walls of veins are thinner than those of arteries

3\. Because blood pressure is lower than that in arteries, the puncture wound seals quickly.

\-An arterial puncture or “arterial stick” is performed in order to check the oxygen or carbon dioxide levels in the blood for the efficiency of gas exchange in the lungs

Composition of Plasma

\-Plasma makes up 46-63% of whole blood volume

\-Water is the major component of plasma (92%), but it also includes proteins (7%) and other solutes such as electrolytes, organic nutrients and wastes (1%).

\-Serum is plasma without these proteins and clotting components.

Plasma Proteins

\-Three major types synthesized by the liver:

1\. Albumins: most abundant (60%) and are the major contributors to plasma’s osmotic pressure. Also transport fatty acids, thyroid and steroid hormones.

2\. Globulins: account for 35%, and includes antibodies (aka immunoglobulins) and transport globulins that bind to ions, hormones and triglycerides in order to deliver them to where they need to go (transferrin, lipoproteins).

3\. Fibrinogen: responsible in forming insoluble strands of fibrin during clotting (4%)

Erythropoiesis

\-This is the formation of RBCs in bone marrow.

\-RBCs account for 99.9% of the formed elements and are deep red in color due to hemoglobin, the protein which binds and transports oxygen and carbon dioxide.

\-Hematocrit is the percentage of whole blood volume contributed by formed elements. The normal values for adult males is 40-54% and for adult females is 37-47%. The sex difference is due to the fact that androgens stimulate erythropoiesis and estrogens do not. Hematocrit may be low due to internal bleeds or anemia or high due to dehydration.

\*RBC STRUCTURE

\-Biconcave disc with a thin central area and thick on the periphery. This unusual shape allows for three effects:

1\. A large surface area-to-volume ratio allowing a faster exchange of oxygen and carbon dioxide with surrounding plasma.

2\. Enables RBCs to “stack” so to flow through narrow vessels smoothly.

3\. Enables RBCs to bend and flex when entering capillaries

\-During differentiation, RBCs lose most of their organelles, including the nuclei, mitochondria and ribosomes.

\-Therefore, they cannot reproduce via mitosis, so their life span is relatively short (120 days).

\-And without mitochondria, they “steal” ATP from cells in the surrounding plasma

\*HEMOGLOBIN (Hb)

\-Each molecule has a complex quaternary structure: two alpha chains and two beta chains of polypeptides.

\-Each of these chains contain a single molecule of heme, a non-protein pigment complex that contains an iron ion, that is responsible for binding to oxygen.

\-When hemoglobin binds to oxygen it is called oxyhemoglobin which causes the blood to be bright red; found in arteries.

\-Deoxyhemoglobin is when the molecule loses the oxygen and the blood becomes a very dark red; found in veins.

Hemoglobin Function

\-Due to heme, each RBC can carry more that a billion molecules of oxygen at a time.

\-If the surrounding plasma oxygen levels are low, such as in the case of peripheral body tissues, the hemoglobin releases their oxygen and picks up the waste carbon dioxide forming carbaminohemoglobin. Then in the capillaries of the lungs, where plasma oxygen levels are high and carbon dioxide levels are low, the RBCs release the waste and picks up the oxygen.

\-Anemia is the condition where the hematocrit or Hb levels are low and therefore decrease the delivery of oxygen to peripheral tissues. Symptoms include weakness, lethargy, fatigue and confusion.

\*RBC FORMATION

\-The travel time for a particular RBC from the heart to the tissues and back to the heart takes less than one minute.

\-It travels about 700 miles in its 120 day life span and “dies” usually by the rupture of the plasma membrane in the bloodstream (hemolysis) or by the breakdown by macrophages found in the liver, spleen and bone marrow (autolysis).

\-If hemolysis occurs, the Hb breaks down and is eliminated in urine. When abnormally large numbers of RBCs lyse, urine may turn red or brown (hemoglobinuria) which may be a symptom of sickle cell anemia, renal cancer or infection, burns or malaria.

\-Hematuria is the presence of RBCs in the urine due to kidney damage or vessel damage along the urinary tract.

\*RBC RECYCLING

\-If the RBC breaks down by autolysis, the Hb is disassembled into amino acids, which is then used by surrounding cells. The heme is stripped of the iron and converted to biliverdin, an organic compound with a green color (seen in bruises).

\-Biliverdin is then converted to bilirubin, an orangeyellow pigment, which is delivered to the liver and excreted in bile, a digestive fluid.

\-If the bile ducts are blocked or the liver is damaged and the bilirubin cannot be absorbed, it is released in the blood and causes jaundice

\*HEMOGLOBIN RECYCLING

\-The iron extracted from the heme bind with a plasma protein called transferrin which transports the iron (which is toxic to cells in the free form) in circulation to the bone marrow.

\-It then is used immediately by developing RBCs or stored as two protein-iron complexes called ferritin and hemosiderin for future use

\*RBC PRODUCTION

\-The precursor cells of all formed elements are the hemocytoblasts (aka pluripotent stem cells) found in bone marrow.

\-They produce myeloid stem cells which differentiate into nucleated proerythroblasts and then to erythroblasts.

\-The erythroblasts start to synthesize Hb and after 4 days become normoblasts. These cells then shed their nucleus and become a reticulocyte. They then are released into the bloodstream and in 24 hours become a mature RBC

RBC production

\-Essential nutrients are needed for erythropoiesis including adequate supplies of amino acids, iron and vitamins B12, B6 and folic acid.

\-Vitamin B12 is obtained through dairy and red meat in the diet and needs intrinsic factor produced in the stomach for absorption.

\-Pernicious anemia results with a B12 or intrinsic factor deficiency and the symptomology is similar to irondeficiency anemia but with possible peripheral neuropathies. B12 injections are the treatment.

\-Erythropoiesis is also under the hormonal control of erythropoietin (EPO) formed by the kidneys.

\-When plasma is hypoxic and flows through the kidneys, the kidney cells release erythropoietin that stimulates erythropoiesis in the bone marrow.

\*BLOOD TYPES

\-Type A has surface antigen A only (40% of population).

\-Type B has surface antigen B only (10%).

\-Type AB has both A and B (4%).

\-Type O has neither (46%)

\*BLOOD TYPES: EXPLAINED

\-Rh positive indicates the presence of the Rh surface antigen (aka Rh factor).

\-Rh negative indicates the absence of this surface antigen.

\-Therefore Type A negative blood has the surface antigen A only and no Rh factor on the plasma membrane of the RBC.

\*AGGLUTINOGENS

\-surface antigens our immune system ignores

\-plasma also has antibodies called agglutinins, that will attack the antigens on foreign RBCs

\-When this happens, the foreign cells clump up or agglutinate and may lead to hemolysis.

\-Type A blood plasma contains anti-B antibodies; Type B plasma contains anti-A antibodies; Type O plasma has both anti-A and B antibodies, and Type AB plasma has neither anti-A nor B antibodies.

\-Type O is then the universal donor for blood cells, not plasma, and Type AB is the universal receiver. For plasma transfusions it is the opposite.

Hemolytic Disease in the Newborn

\-This involves anti-Rh antibodies because unlike the anti-A or anti-B antibodies, they are able to cross the placenta.

\-An Rh-positive mother (lacks anti-Rh antibodies) can carry an Rh-negative fetus without problems. However, if the opposite occurs, danger starts at the time of delivery where fetal blood cell antigens are exposed to the maternal blood when bleeding takes place at the placenta and uterus. This triggers the mother’s immune system to produce anti-Rh antibodies

\-If the mother has a subsequent pregnancy with an Rh positive fetus, the maternal antiRh antibodies will cross the placenta and destroy the fetal RBCs leading to severe anemia and death.

\-The administration of RhoGam antibodies to the mother in the last three months of pregnancy and after delivery will destroy any fetal RBCs that enter into the mother’s bloodstream.

Leukocytes (WBCs)

\-Unlike the RBCs, the WBCs have nuclei and other organelles, but lack Hb.

\-Represent less than 1% of formed elements.

\-They function to defend the body from invading pathogens and remove toxins, wastes and abnormal or damaged cells. -Two Types:

1\. Granulocytes: neutrophils, eosinophils and basophils.

2\. Agranulocytes: monocytes and lymphocytes.

\*WBC CIRCULATION

\-All WBCs can migrate out of the bloodstream by squeezing between adjacent endothelial cells and enter the surrounding tissue (emigration). Occurs when the WBC detects damage or invasion of pathogens outside of the circulatory system.

\-The WBCs are capable of amoeboid movement allowing it to move in the peripheral tissues.

\-WBCs are attracted to specific chemical stimuli which guides them to pathogens, damaged tissue or other WBCs (positive chemotaxis).

\-Neutophils, eosinophils and monocytes are capable of phagocytosis

\*NEUTROPHILS

\-Represent 50-70% of WBCs.

\-Multi-lobular nuclei (2-5 lobes), and a cytoplasm with granules containing lysosomal enzymes and bactericides.

\-Highly mobile and first at the site of injury. Engulfs bacteria via phagocytosis where it then is digested by enzymes found in the lysosomes called defensins.

\-Secrete prostaglandins, to increase capillary permeability in the affected area, and leukotrienes, to attract other WBCs. Life span of 10 hours or less. Large increase in number during bacterial infections.

\*EOSINOPHILS

\-2-4% of WBCs.

\-Contains dark red granules and a bi-lobed nucleus.

\-They attack pathogens or cells that are covered with antibodies and are too large to be destroyed by phagocytic WBCs.

\-They do this by the exocytosis of toxic compounds.

\-Large increase of eosinophils during a parasitic infection or allergic reactions.

\*BASOPHILS

\-Less than 1% of WBCs.

\-Their granules contain histamine, which causes vasodilation, and heparin, which prevents blood clotting.

\-Assists mast cells that initiate the inflammatory response.

\*MONOCYTES

\-2-8% of WBCs.

\-Very large in shape, with a single, large, kidney-shaped nucleus.

\-Attempts to engulf very large items via phagocytosis.

\-Lives for months or longer

\*LYMPHOCYTES

\-20-30% of WBCs. Increased with viral infections.

\-Contains a vary large nucleus.

\-Types:

1\. T cells: responsible for cell-mediated immunity: attack pathogens directly.

2\. B cells: responsible for humoral immunity: B cells become plasma cells that synthesize and secrete antibodies which attack antigens.

3\. Natural Killer Cells: responsible for immune surveillance: detection and destruction of abnormal tissue cells, such as cancer.

\*WBC DIFFERENTIAL COUNT

\-Neutrophils: 60, Lymphocytes:30, Monocytes: 8, Eosinophils: 2, Basophils:0

\-Leukopenia: inadequate number of

WBCs, as in anemia.

\-Leukocytosis: excess numbers of WBCs, as in infections or cancers, such as leukemia

WBC production (leukopoiesis)

\-Hemocytoblasts produce myeloid and lymphoid stem cells.

-Myeloid stem cell creates progenitor cells which give rise to all WBCs except lymphocytes. The granulocytes complete their development in the marrow, while monocytes mature in the bloodstream and tissues.

\-Lymphocytes develop from the lymphoid stem cells. If they mature in the bone marrow they become B cells. If they mature in the thymus gland they become T cells

\*PLATELETS

\-Cell fragments rather than individual cells that function in the clotting process.

\-Has a life span of 9-12 days then are removed by phagocytosis, mostly in the spleen.

\-Vast amounts are stored in the spleen as reserves, which are released during a circulatory crisis with severe bleeding.

Platelet Function

\-Platelets release chemicals and enzymes that initiate and control the clotting process.

\-They form a temporary patch in the walls of damaged vessels called a platelet plug.

\-Platelets contain actin and myosin and are able to shrink the newly formed clot and reduce the size of the break in the vessel wall.

\*PLATELET PRODUCTION

\-Termed thrombocytopoiesis, occurs in the

bone marrow.

\-Megakaryocytes are enormous cells in the marrow that begin to shed cytoplasm in small membrane-enclosed packets (platelets) which is deposited into the bloodstream.

\-Each megakaryocyte forms approximately 4000 platelets.

\*HEMOSTASIS: THE VASCULAR PHASE

\-The cutting of a vessel triggers a contraction of the smooth muscle fibers in the wall called a vascular spasm. This results in the decrease of the diameter of the vessel to slow or stop the flow of blood. This lasts for approximately 30 minutes.

\-During this time the endothelial cells:

1\. contract and expose the basal lamina to the bloodstream, 2. secrete chemicals and hormones (endothelins) to promote vascular spasm and division of endothelial cells, smooth muscle cells and fibrocytes,

3\. Become “sticky” in order for the attachment of platelets.

\*HEMOSTASIS: PLATELET PHASE

\-The platelets attach to the affected area and form a platelet plug, that may close the break in the vessel wall if small enough. This occurs 15 seconds post injury.

\-Platelets become activated and start to produce chemicals to stimulate further platelet aggregation at the injury site

\*HEMOSTASIS: COAGULATION PHASE

\-Begins 30 seconds post injury.

\-Involves a complex sequence of steps that converts circulating, soluble protein fibrinogen into the insoluble protein fibrin. The fibrin covers the platelet plug and traps passing blood cells and platelets forming a blood clots (thrombus).

\-Clotting depends on clotting factors and proenzymes in the plasma.

\-There are two pathways that coagulation can follow: extrinsic or intrinsic. Both converge at the common pathway

Extrinsic Pathway

\-Begins outside the bloodstream in the vessel

wall.

\-Starts with the release of Factor III (aka tissue factor) by damaged endothelial cells or peripheral tissues.

\-Tissue factor combines with calcium ions and Factor VII forming a complex that activates Factor X, which is the first step in the common pathway