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1. Functions of Muscles: • Movement: Muscles contract to produce movement in the body, such as walking, running, or even facial expressions. • Posture and Stability: Muscles help maintain posture and stabilize joints, preventing falls or loss of balance. • Heat Production: Muscle contractions generate heat, which is vital for maintaining body temperature. • Protection of Internal Organs: Muscles, particularly in the abdominal region, protect internal organs from injury. • Circulation of Blood and Lymph: Cardiac and smooth muscles play roles in circulating blood and lymph throughout the body. 2. Characteristics of Muscles: • Excitability (Responsiveness): Muscles can respond to stimuli (like nerve signals). • Contractility: Muscles can contract or shorten when stimulated. • Extensibility: Muscles can be stretched without damage. • Elasticity: Muscles can return to their original shape after being stretched or contracted. 3. Locations of Smooth, Cardiac, and Skeletal Muscle: • Smooth Muscle: Found in walls of internal organs (e.g., stomach, intestines, blood vessels). • Cardiac Muscle: Found only in the heart. • Skeletal Muscle: Attached to bones and responsible for voluntary movements. 4. Events of Skeletal Muscle Contraction: 1. Nerve Impulse: A signal is sent from a motor neuron to the muscle. 2. Release of Acetylcholine: The neurotransmitter acetylcholine is released into the neuromuscular junction. 3. Muscle Fiber Activation: Acetylcholine stimulates muscle fibers, causing an action potential. 4. Calcium Release: The action potential triggers the release of calcium ions from the sarcoplasmic reticulum. 5. Cross-Bridge Formation: Calcium binds to troponin, moving tropomyosin, which allows myosin heads to attach to actin. 6. Power Stroke: Myosin heads pull actin filaments inward, causing the muscle to contract. 7. Relaxation: ATP breaks the cross-bridge, and the muscle relaxes when calcium is pumped back into the sarcoplasmic reticulum. 5. Isometric vs. Isotonic Contractions: • Isometric Contraction: The muscle generates tension without changing its length (e.g., holding a weight in a fixed position). • Isotonic Contraction: The muscle changes length while generating tension (e.g., lifting a weight). 6. Primary Functions of the Skeletal System: • Support: Provides structural support for the body. • Protection: Shields vital organs (e.g., brain, heart, lungs). • Movement: Works with muscles to allow movement. • Mineral Storage: Stores minerals like calcium and phosphorus. • Blood Cell Production: Bone marrow produces blood cells. • Energy Storage: Fat is stored in bone cavities. 7. Parts of a Long Bone: • Diaphysis: The shaft of the bone. • Epiphysis: The ends of the bone. • Metaphysis: Region between the diaphysis and epiphysis. • Medullary Cavity: Hollow cavity inside the diaphysis, containing bone marrow. • Periosteum: Outer membrane covering the bone. • Endosteum: Inner lining of the medullary cavity. 8. Inner and Outer Connective Tissue Linings of a Bone: • Outer: Periosteum. • Inner: Endosteum. 9. Structure of a Flat Bone: • Compact Bone: Dense bone found on the outside. • Spongy Bone: Lighter, less dense bone found inside, filled with red or yellow marrow. • No medullary cavity (unlike long bones). 10. Parts of the Osteon: • Central Canal (Haversian Canal): Contains blood vessels and nerves. • Lamellae: Concentric layers of bone matrix surrounding the central canal. • Lacunae: Small spaces containing osteocytes (bone cells). • Canaliculi: Small channels that connect lacunae and allow for nutrient exchange. 11. How Calcitonin, Calcitriol, and PTH Affect Blood Calcium: • Calcitonin: Lowers blood calcium levels by inhibiting osteoclast activity (bone resorption). • Calcitriol: Increases blood calcium by promoting calcium absorption in the intestines and bone resorption. • PTH (Parathyroid Hormone): Raises blood calcium by stimulating osteoclasts to break down bone and release calcium. 12. Two Forms of Ossification: • Intramembranous Ossification: Bone develops directly from mesenchymal tissue (e.g., flat bones of the skull). • Endochondral Ossification: Bone replaces a cartilage model (e.g., long bones). 13. Difference Between Appositional and Interstitial Growth: • Appositional Growth: Increase in bone diameter (growth at the surface). • Interstitial Growth: Increase in bone length (growth from within). 14. Different Joint Types: • Fibrous Joints: Connected by fibrous tissue (e.g., sutures of the skull). • Cartilaginous Joints: Connected by cartilage (e.g., intervertebral discs). • Synovial Joints: Have a fluid-filled joint cavity (e.g., knee, elbow). 15. Components of a Synovial Joint: • Articular Cartilage: Covers the ends of bones. • Synovial Membrane: Lines the joint capsule and produces synovial fluid. • Joint Capsule: Surrounds the joint, providing stability. • Ligaments: Connect bones to other bones. • Synovial Fluid: Lubricates the joint. 16. Hinge Joint Location: • Found in the elbow and knee. 17. Pivot Joint Location: • Found between the first and second cervical vertebrae (atlantoaxial joint). 18. Difference Between a Tendon and a Ligament: • Tendon: Connects muscle to bone. • Ligament: Connects bone to bone. 19. What is a Bursa? • A fluid-filled sac that reduces friction and cushions pressure points between the skin and bones or muscles and bones. 20. Three Types of Arthritis: • Osteoarthritis: Degeneration of joint cartilage and underlying bone, often due to wear and tear. • Rheumatoid Arthritis: Autoimmune disease causing inflammation in joints. • Gout: Caused by the accumulation of uric acid crystals in the joints. 21. Strain vs. Sprain: • A strain is damage to a muscle or tendon, whereas a sprain is damage to a ligament
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Introduction to Tissues A. Histology=the study of tissues. B. Although studying tissues can be accomplished using a light microscope, studying cell parts often requires an electron microscope and the study of atoms and molecules can only be examined through special imaging techniques and experimental procedures. Types of Tissues A. Despite the fact the body is composed of trillions of cells, there are only about 200 different cell types. These cells in turn produce only four principle tissue types: 1. Epithelial tissues=covers exposed surfaces; lines internal passageways; and produces glandular secretions. 2. Connective tissues=fills internal spaces; provides structural support, and stores energy 3. Muscle tissues=contracts to produce active movements 4. Nervous tissue=conducts electrical impulses; detects, interprets, and responds to stimuli B. Relative contribution of the four tissue types to the overall weight of the adult body. C. Embryonic origins: There are three types of embryonic tissues from which all adult tissues are derived. a. Endoderm=gives rise to the functional linings of the digestive and respiratory tracts as well as to the associated accessory glands and organs (i.e. liver, stomach, pancreas, etc.) b. Mesoderm= gives rise to the components of the skeletal, muscular, and circulatory systems c. Ectoderm= gives rise to the epidermis of skin and all of the components of the nervous system D. Tissue Membranes 1. Mucous Membranes=composed of epithelial tissues. These membranes line body cavities that open to the exterior environment such as those of the digestive tract, respiratory tract, or urogenital tract. In all cases, these are "wet" or moist membranes because of the secretion of mucous. The moisture helps reduce friction and in many cases, facilitates absorption or secretion activities. 2. Serous Membranes=consists of a mesothelium supported by areolar tissue. These are never exposed or connected to the exterior. Serous membranes secrete transudate, or serous fluid. There are three serous membranes that line the ventral body cavity: a. Pleura=lines the chest cavity and surrounds the lungs. b. Pericardium=lines the pericardial cavity and surrounds the heart c. Peritoneum=lines the peritoneal cavity and lines the surfaces of the visceral organs 3. Cutaneous Membranes=made of stratified squamous and areolar tissue reinforced by dense irregular connective tissue. In contrast to mucous and serous membranes, cutaneous membranes are dry, relatively thick, and waterproof. 4. Synovial Membranes=line mobile joint cavities but do not cover the opposing joint surfaces. Secretes synovial fluid. Although the covering of the synovial membrane is often called an epithelium, it differs from true epithelia in four respects: it develops within a connective tissue, no basal lamina is present, gaps of up to 1 mm may separate adjacent cells, and the synovial fluid and capillaries in the underlying connective tissue are continuously exchanging fluid and solutes. Epithelial Tissues A. Functions of Epithelial Tissues 1. Epithelia provide physical protection. Epithelial tissues protect exposed and internal surfaces from abrasion, dehydration, and destruction by chemical or biological agents. 2. Epithelia control permeability. Any substance that enters or leaves the body has to cross an epithelial tissue. Some epithelia are relatively impermeable, whereas others are permeable to compounds as large as proteins. Most are capable of selective absorption or secretion. The epithelial barrier can be regulated and modified in response to various stimuli. For example, a callus forms on your hands when you do rough work for an extended period of time. 3. Epithelia provide sensation. Sensory nerves extensively innervate most epithelia. Specialize epithelial cells can detect changes in the environment and convey information about such changes to the nervous system. 4. Epithelial cells that produce secretions are called glands. Individual gland cells are often scattered among other cell types in an epithelium that may have many other functions. B. Location of Epithelial Tissues 1. Epithelia=forms sheets or layers of cells that line the body tubes, cavities, or coverings of the body surfaces. 2. Glands=formed of epithelial cells with secretory functions. Two types of glands are found in the human body: a. Endocrine glands=secrete hormones (or hormonal precursors) into the interstitial fluid or bloodstream. These glands are ductless. b. Exocrine glands=secretes non-hormonal substances (milk, wax, enzymes, oil, acids, etc.) onto external surfaces or internal passageways (ducts) that connect to the exterior. C. Characteristics of Epithelial Tissues 1. Polarity=epithelial cells possess two structurally and functionally different surfaces: a. Apical surface=free edge which faces the exterior of the body or the lumen of an internal space. b. Basal surface=attached surface which anchors the cells to adjacent tissues. 2. Supported by a basal lamina=also known as the basement membrane, is a complex structure produced by the basal surface of the epithelial cells and the underlying connective tissue. The underlying connective tissue is composed of two things: 3. Cellularity=epithelial cells are extensively interconnected so that they create an effective barrier that behaves as if it were a single cell. a. Occluding junctions=form a barrier that isolates the basolateral surfaces and deeper tissues from the contents of the lumen. At an occluding junction, the attachment is so tight that it prevents the passage of water and solutes between the cells. b. Adhesion belt=locks together the terminal webs of neighboring cells, strengthening the apical region and preventing distortion and leakage at the occluding junctions. It forms a continuous band that encircles cells and binds them together. c. Gap junctions=permits chemical communication that coordinates the activities of adjacent cells. At a gap junction, two cells are held together by interlocking junctional proteins called connexons which serve as channels that form a narrow passageway to let small molecules and ions to pass from cell to cell. d. Desmosomes=provides firm attachment between neighboring cells by interlocking their cytoskeletons. At a desmosome, the opposing plasma membranes are very strong and resist stretching and twisting. Hemidesmosomes attach the basal surface to the basement membrane. e. CAM=cell adhesion molecules; present in the adhesion belt and desmosomes; transmembrane proteins that bind to each other and to extracellular materials. 4. Avascular=epithelial tissues lack blood vessels; all nutrient and waste exchange occurs as a result of diffusion and osmosis from underlying tissues. 5. Highly innervated=epithelial tissues are supplied with many nerve endings 6. Regenerate rapidly=although the exact rate varies from one type of epithelia to another, most epithelial tissues regenerate within days (rather than weeks or years). D. Naming Epithelial Tissues 1. Almost all epithelial tissues possess a two part name where the first part of their name indicates their arrangement (number of layers) while the second part of their name indicates the shape of the cells. 2. Arrangement of epithelial tissues a. Simple=only one layer thick b. Stratified=more than one layer thick c. Pseudostratified= “false layers”; it looks like more than one layer but in fact its only one layer thick 3. Shape of epithelial cells a. Squamous=thin, flat, and somewhat irregular in shape. From the surface, they look like fried eggs lay side by side. In a sectional view, they look like a pancake with a pat of butter (indicating the nucleus). b. Cuboidal=are about as wide as they are tall; resemble hexagonal boxes with the spherical nucleus located in the center of each cell. c. Columnar=are taller than they are wide; resemble rectangles with the elongated nuclei tend to crowd into a narrow band close to the basal lamina. E. Diversity of Epithelial Tissues 1. Simple squamous epithelium a. Description: single layer of flattened cells with a disc-shaped central nuclei and sparse cytoplasm. b. Function: allows passage of materials by diffusion and filtration in sites where protection is not important. Also secretes lubricant. c. Locations: Kidney glomeruli, air sacs of lungs, capillaries, linings of heart and lymphatic system. 2. Stratified squamous epithelium a. Description: thick layers of flattened cells; often keratinized layer and a mitotic layer. b. Function: protects underlying tissues in areas subject to abrasion c. Location: non-keratinized type lines the mouth and vagina; keratinized type forms the epidermis of skin. 3. Simple cuboidal epithelium a. Description: single layer of cube-like cells with large spherical centrally located nuclei. b. Function: secretion and absorption c. Locations: Kidney tubules, ducts and secretory portions of glands, ovary surface 4. Stratified cuboidal epithelium a. Relatively rare in the human body. b. Most common along the ducts of sweat glands, mammary glands, and other exocrine glands. c. DO NOT NEED TO KNOW FOR THE LAB PRACTICAL!! 5. Simple columnar epithelium a. Description: single layer of tall cells with round to oval nuclei; some cells bear cilia; may contain goblet cells that produce mucus; may contain microvilli. b. Function: absorption; secretion of mucus and enzymes; cilia propel substances. c. Location: non-ciliated type lines digestive tract, gallbladder, and ducts from glands; ciliated type lines small bronchi, uterine tubes, and uterus. 6. Stratified columnar epithelium a. Relatively rare in the human body. b. Most often found lining large ducts such as those of the salivary glands and pancreas. c. DO NOT NEED TO KNOW FOR THE LAB PRACTICAL!! 7. Pseudostratified columnar epithelium a. Description: single layer of cells of differing heights so that nuclei are a differing levels; may contain goblet cells and bear cilia. b. Function: secretion, propulsion by ciliary action. c. Location: non-ciliated type lines male reproductive ducts; ciliated type lines much of respiratory tract. 8. Transitional epithelium a. Description: resembles both stratified squamous and stratified cuboidal. Basal cells are cuboidal or columnar; surface cells are dome shaped. b. Function: stretches readily and permits distension. c. Location: Lines uterus, bladder, and urethra F. Glandular Epithelia are Specialized for Secretion 1. Endocrine glands= “ductless” glands that produce hormones. Secrete directly into interstitial fluids or bloodstream. Examples: pituitary gland, adrenal gland, thyroid gland, etc. 2. Exocrine glands=glands possessing ducts. Exocrine glands secret their substance either on the body surfaces or within ducts. They general demonstrates one of two different modes secretion: a. Merocrine=secrete products from secretory vesicles by exocytosis. Most common type. Example: salivary glands of the oral cavity b. Holocrine=accumulate products until the cell ruptures. Destroys the cell and must be replaced by cell division. Example: sebaceous glands of the skin c. Apocrine=products accumulate within the cells then the apex of the cell pinches off packets that contain the secretion. Example: mammary gland of the breast 3. Exocrine glands are unicellular or multicellular. a. Unicellular=goblet cells that produce mucin which mixes with water to form mucus. b. Multicellular=two structural classes: i. Simple=a single duct that does not branch on its way to the secretory cells (examples: gastric glands, sebaceous glands) ii. Compound= duct divides one or more times on its way to the secretory cells (examples: duodenal glands, mammary glands and salivary glands) Connective Tissues: Supports and Protects A. Location of Connective Tissues 1. Most abundant tissue in the body. 2. Never exposed to the outside environment. B. Characteristics of Connective Tissues 1. All types of connective tissue originate from mesenchyme. 2. Connective tissues vary widely in appearance and function but all forms share three basic components: a. Specialized cells=the cells present in each type of connective tissue helps to distinguish the various types from one another. A few of the cells are listed here: i. Fibroblast cells=produce connective tissue proper ii. Chondrocytes=produce cartilage iii. Osteocytes=produce bone iv. Hemocytoblast cells=produce blood b. Extracellular proteins fibers=three primary fibers are produced in connective tissues i. Elastic fibers=slender, straight, and very stretchy. They recoil to their original length after stretching or distortion. ii. Collagen fibers=thick, straight or wavy, and often forms bundles. They are very strong and resist stretching. iii. Reticular fibers=strong fibers that form a branching network or scaffolding c. Ground substance=material that fills the space between cells and surrounds the extracellular fibers. In some connective tissues the ground substance is gel-like while in others it is liquid based and in others it is rigid or calcified. Ground substance and extracellular fibers make up the matrix of connective tissues. 3. Many types of connective tissue are highly vascular and contain sensory receptors that detect pain, pressure, temperature, and other stimuli. C. Functions of Connective Tissues 1. Establish a structural framework for the body. 2. Transport fluids and dissolved materials. 3. Protect delicate organs. 4. Support, surround, and interconnect other types of tissue. 5. Store energy reserves, especially in the form of triglycerides. 6. Defend the body from invading microorganisms. D. Diversity of Connective Tissues 1. Connective Tissue Proper=includes connective tissues with many types of cells and extracellular fibers in a gel-like ground substance. a. Loose Connective Tissues – fibers created a loose, open framework i. Areolar tissue=most common form of connective tissue proper in adults. It is the general packing material in the body. Attaches skin to underlying body parts and is sometimes called the superficial fascia. All of the cell types found in other forms of connective tissue proper can be found in areolar. ii. Adipose tissue=found deep to the skin, especially at the flanks, buttocks, and breasts. It also forms a layer that provides padding within the orbit of the eyes, in the abdominopelvic cavity, and around the kidneys. The distinction between areolar tissue and adipose is the larger number of adipocytes (fat cells). iii. Reticular tissue=found in the liver, kidney, spleen, lymph nodes, and bone marrow, where it forms a tough, flexible network that provides support and resists distortion. In reticular tissue, reticular fibers create a complex supporting network known as a stroma. Fixed macrophages and fibroblasts are present but these cells are seldom visible. DO NOT NEED TO KNOW FOR THE LAB PRACTICAL!! b. Dense Connective Tissues – fibers are densely packed together i. Dense regular=all collagen fibers are oriented parallel to each other providing strength along the axis of the collagen fibers. Found in cords (such as tendons) or sheets (ligaments). Tendons connect muscle to bones. Ligaments connect bones to bones. ii. Dense irregular=collagen fibers are non-parallel forming an interwoven network. These tissues provide strength in many directions and are particularly important in areas subjected to stress from many directions such as the dermis of the skin. iii. Elastic=when elastic fibers outnumber collagen fibers, the tissue has a springy, resilient nature that allows it to tolerate cycles of extension and recoil. This elastic tissue is bound between the vertebrae of the spinal column and the erectile tissues of the penis. DO NOT NEED TO KNOW FOR THE LAB PRACTICAL!! 2. Fluid Connective Tissues=have distinctive populations of cells suspended in a watery matrix that contains dissolved proteins. NOT ON LAB PRACTICAL! a. Blood – flows within the cardiovascular system 3. Supporting Connective Tissues=differ from connective tissue proper in have a less diverse cell population and a matrix containing much more densely packed fibers. Supporting connective tissues protect soft tissues and support the weight of part or all of the body. a. Cartilage – solid, rubbery matrix containing chondrocytes. All cartilage is surrounded by a membrane of connective tissue called the perichondrium. i. Hyaline cartilage=found connecting the ribs to the sternum, covering the articular surfaces of long bones, supporting the respiratory passageways such as the trachea, and forming the tip of the nose and part of the nasal septum. Has an amorphous matrix with few visible fibers. It provides stiff but somewhat flexible support and reduces friction between bony surfaces. ii. Elastic cartilage=found in the ear and epiglottis. Has many more elastic fibers within the matrix and is therefore more flexible. iii. Fibrous cartilage=found within the intervertebral discs, the meniscus of the knee, and pubic symphysis. Has many more collagen fibers within its matrix and is therefore very strong. b. Bone – solid, crystalline matrix containing osteocytes. All bone is surrounded by a membrane of connective tissue called the periosteum. NOT ON LAB PRACTICAL! c. Comparison of cartilage and bone. Muscle Tissue in Motion (discussed in detail in Chapter 10-11) NOT ON LAB PRACTICAL! A. Highly vascularized muscular tissue is comprised of elongated cells (called fibers) containing myofilaments (actin and myosin proteins). 
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Hematology Basics & Hematopoiesis HEMATOLOGY What is it? Encompasses: Skill, Art, Instinct Relationships BM:circulation Plasma:RBC Hgb:RBC What Will I Learn? Students find Hematology difficult because it requires you to think in a new way. Begin with limited knowledge: Given Facts and you must be able to answer “WHY” Given images and you must be able to recognize and classify This Course Hematology I – MLTS 207 Intro Red Cells Hematology II – MLTS 208 White Cells Coagulation Our Tool Safety First Standard Precautions PPE Hand washing Proper disposal Proper cleaning Know what to do in case of an emergency Fire Spill Needle stick QA vs QC Quality Assurance Comprehensive Preanalytical – Analytical - Post-analytical Ensures reliable patient results = positive outcome Quality Control is Analytical only – focuses on actual measurement of the analyte Quality Control Standards / Calibrators Controls Statistical quality control system Normals AKA Reference ranges Plt 150 – 450 X 103/ul Unique to analyte, method, instrument and patient population Delta Check Critical Values Blood Basics Average blood volume 4 – 6 liters Blood pH = 7.35 – 7.45 Components of whole blood 55% plasma - 44% RBCs - 1% WBCs and platelets (buffy coat) Red Blood Cell (Erythrocyte or RBC) White Blood Cell (Leukocyte or WBC) Platelets (Thrombocyte) Plasma is 91.5% water and 8.5% solutes Reference Ranges (patient normals) RBC 4.2 – 5.4 X 1012/L (106/ul) females 4.7 – 6.1 X 1012/L (106/ul) males WBC 5 – 10 X 109/L (103/ul) Platelets 150 – 450 X 109/L (103/ul) Blood Smears (Slides) Cells evaluated in an area where red cells are almost touching but do not overlap Smears can be made by hand or mechanically Smears are stained with Wright’s stain Smear is examined on 100X using oil to evaluate RBC morphology RBC Morphology Red cells are biconcave disk that are 7 – 8 um in diameter with a volume - 90fL (femtoliters) When stained they appear as: Circular cells with distinct smooth margins Dull pinkish hue Area of central pallor Fairly uniform in size No nucleus or inclusions Platelet Morphology Platelets are 2 – 4um in diameter and discoid shaped they contain reddish-purple granules in a small amount of bluish cytoplasm and have no nucleus Leukocytes Segmented neutrophils - AKA segs or PMN Band neutrophils Eosinophils Basophils Lymphocytes Monocytes Hematopoiesis Definition? Daily Production Quotas RBCs – 3 billion WBCs – 1.5 billion Plts – 2.5 billion Your body can: Constantly supply mature blood cells for circulation Mobilize Bone Marrow to increase production of a particular type of blood cell Compensate for decreased hematopoiesis by providing hematopoietic sites outside the BM The Beginning All blood cells are the progeny of hematopoietic pluriopotential stem cell In adults these are found in the bone marrow. Why? Monophyletic Theory A common precursor cell, the pluripotential stem cell, which under the influence of certain factors gives rise to each of the principle blood cell lines Cytokines - Pretty much universally accepted today based on clinical and experimental evidence and started with mice in 1961 Based on this theory, hematopoietic cells may be divided into 3 cellular catagories dependant on maturity 1 Multipotential stem cell able to self-renew and to differentiate into all blood cell lines 2 Committed progenitor cell destined to develop into distinct cell lines 3 Mature cells with specialized functions which have lost the capability to proliferate Hematopoietic Stem Cell Most important characteristic – must self renew Ability to differentiate into commited progenitor cells of lymphoid or myloid lineages Maturation Process (p.20) Hematopoiesis From Coception to Adulthood (p.16) Yolk Sac (embryonic hemoglobin) Begins 2 -3 weeks after fertilization and ceases after 8 – 10 weeks Fetal Liver (fetal hemoglobin) Production from about 2 – 7 months Liver is main site but spleen, thymus, lymph nodes, and kidney are also involved Bone Marrow – called medullary hematopoiesis Begins to function in 3rd month of gestation Primary site by the end of 5th month of gestation and continues after birth and throughout adulthood Children distal long bones Adults axial bones Extramedullary Hematopoiesis is hematopoiesis outside bone marrow Not a normal occurrence after 5th month of gestation Happens in certain disorders Occurs in liver and spleen Erythropoiesis Definition? Mature erythrocytes carry oxygen from the lungs to tissue where it is exchanged for CO2 Erythropoietin (a cytokine) Hormone produced by the kidney Stimulates red cell production Secreted daily in small amounts Kidney will sense hypoxia and secrete more if needed What happens when more EPO is secreted by the kidneys? Development of Red Cell Reduction in cell volume Condensation of chromatin (Loss of nucleoli) Decrease in N:C ratio (less nucleus – more cytoplasm) Decrease of RNA in cytoplasm Increased hemoglobin synthesis – to a point cell turns from blue to red Developmental Stages (images p33 - 35) Rubriblast (Pronormoblast) Each produces 8 – 16 mature red cells Stage where hemoglobin synthesis begins Prorubricyte (Basophilic Normoblast) Rubricyte (Polychromatophilic Normoblast) Last stage capable of division Large amounts of hemoglobin synthesized at this stage Metarubricyte (Orthochroimatophilic Normoblast) Nucleated Red Blood Cell (NRBC) seen on peripheral smear Reticulocyte (Polychromatophilic Erythrocyte) Non-nucleated (nucleus extruded) Contains residual RNA and mitochondria which gives cell bluish tinge with Wright’s stain Last stage to synthesize hemoglobin Part of this phase occurs in the bone marrow, later part takes place in circulating blood Mature Erythrocyte Stains pink because of large amount of hemoglobin No RNA or mitochondria = no synthesizing of proteins or lipids Normal lifespan 120 days Have You Seen Your Spleen Fist shaped organ located on the left side under the rib cage Blood filled organ consisting of Red pulp – red cell filtration Cull old or abnormal RBCs (Reticuloedothelial System) Pit RBC inclusions Remove Antibodies - spherocytes White pulp – lymphocyte processing Marginal zone – WBC & Plt storage 1/3 population of each Bone Marrow not Bowel Movement One of the largest organs in the body Inside you find erythroid cells, myloid cells, and megakaryocytes in various stages of development – stem cells, fatty tissue, osteoclasts, etc. As you age marrow in long bones is replaced by fat Adult marrow in iliac crest and sternum. M:E ratio -Myeloid to erythroid ratio Normally 3-4:1 Why are there more myloid cells in the bone marrow and more RBCs in circulation?
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Negative and Positive Feedback Loops Control hormone levelsNegative feedback loopHormone release stops in response to decrease in stimulus- Stimulus (eating) raises blood glucose levels- Pancreas releases insulin in response to elevated blood   glucose- Blood glucose decreases as it is used by the body or  stored in the liver - Insulin release stops as blood glucose levels normalize Positive feedback loop As long as stimulus is present, action of hormone continues- Infant nursing at mother’s breast→stimulates  hypothalamus→stimulates posterior pituitary- Oxytocin released→stimulates milk production  and ejection from mammary glands- Milk release continues as long as infant  continues to nurse The Major Endocrine OrgansThe major endocrine organs of the body include: the pituitary, pineal, thyroid, parathyroid, thymus, and adrenal glands, pancreas, and gonads (ovaries and testes)Endocrine glands - Ductless - Release hormones - Directly into target tissues - Into bloodstream to be carried to target tissuesHormones(Greek word hormone – to set into motion)     Pituitary Gland and Hypothalamus o The pituitary gland is approximately the size of a pea. o It hangs by a stalk from the inferior surface of the hypothalamus of the brain, where it is snugly surrounded by the sella turcica of the sphenoid bone. o It has two functional lobes – the anterior pituitary (glandular tissue) and the posterior pituitary (nervous tissue). o The anterior pituitary gland controls the activity of so many other endocrine glands (“master endocrine gland”) o The release of each of its hormones is controlled by releasing hormones and inhibiting hormones produced by the hypothalamus. o The hypothalamus also makes two additional hormones, oxytocinand antidiuretic hormone, which are transported along the axons of the hypothalamic nuerosecretory cells to the posterior pituitary for storage. They are later released into the blood in response to nerve impulses from the hypothalamus. Oxytocin o Is released in significant amounts only during childbirth and nursing. o It stimulates powerful contractions of the uterine muscle during sexual relations, during labor, and during breastfeeding. o It also causes milk ejection (let-down reflex) in a nursing woman. Antidiuretic Hormone (ADH) o ADH is a chemical that inhibits or prevents urine production. o ADH causes the kidneys to reabsorb more water from the forming urine; as a result, urine volume decreases, and blood volume increases. o In larger amounts, ADH also increases blood pressure by causing constriction of the arterioles (small arteries). For this reason, it is sometimes referred to as vasopressin. Anterior Pituitary HormonesThe anterior pituitary produces several hormones that affect many body organs. Growth Hormone (GH) o Its major effects are directed to the growth of skeletal muscles and long bones of the body o At the same time, it causes fats to be broken down and used for energy while it spares glucose, helping to maintain blood sugar homeostasis. ProlactinIts only known target in humans is the breast.After childbirth, it stimulates and maintains milk production by the mother’s breasts.Gonadotropic Hormones (FSH and LH) o Regulate the hormonal activity of the gonads (ovaries and testes) o In women, the FSH stimulates follicle development in the ovaries. o In men, FSH stimulates sperm production by the testes. o LH triggers ovulation of an egg from the ovary and causes the ruptured follicle to produce progesterone and some estrogen. o LH stimulates testosterone production by the interstitial cells of the testes. Pineal Gland The pineal gland is a small, cone-shaped gland that hangs from the roof of the third ventricle of the brain. Melatonin o The only hormone secreted from pineal gland in substantial amounts o Believed to be a “sleep trigger” that plays an important role in establishing the body’s sleep-wake cycle. o The level of melatonin rises and falls during the course of the day and night. o The peak level occurs at night and makes us drowsy o The lowest level occurs during daylight around noon. Thyroid Gland • The thyroid gland is located at the base of the throat, just inferior to the Adam’s apple. • It is a fairly large gland consisting of two lobes joined by a central mass, or isthmus. • The thyroid gland makes two hormones, one called thyroid hormone, the other called calcitonin. Thyroid Hormone o Referred to as body’s major metabolic hormone o Contains two active iodine-containing hormones, thyroxine (T4)and thriiodothyronine (T3) o Most triiodothyronine is formed at the target tissues by conversion of thyronine to triiodothyronine o Thyroid hormone controls the rate at which glucose is “burned”, or oxidized, and converted to body heat and chemical energy (ATP). o Thyroid hormone is also important for normal tissue growth and development, especially in the reproductive and nervous systems. Homeostatic Imbalance ➢ Without iodine, functional thyroid hormones cannot be made. ➢ The source of iodine is our diet (seafoods) ➢ Goiter is an enlargement of the thyroid gland that results when the diet is deficient in iodine. Hyposecretion of thyroxine may indicate problems other than iodine deficiency. If it occurs in early childhood, the result is cretinism. ▪ Results in dwarfism and mental retardation (if discovered early, hormone replacement will prevent mental impairment) Hypothyroidism occurring in adults results in myxedema ▪ Characterized by both physical and mental sluggishness (no mental impairment) ▪ Other signs are puffiness of the face, fatigue, poor muscle tone, low body temperature, obesity, and dry skin (Oral thyroxine is prescribed to treat this condition)   ➢ Hyperthyroidism generally results from a tumor of the thyroid gland. ➢ Extreme overproduction of thyroxine results in a high basal metabolic rate, intolerance of heat, rapid heartbeat, weight loss, nervous and agitated behavior, and a general inability to relax. Graves’ disease o A form of hyperthyroidism o The thyroid gland enlarges, the eyes bulge (exophthalmos) Calcitonin ➢ Second important hormone product of the thyroid gland ➢ Decreases the blood calcium ion level by causing calcium to be deposited in the bones Parathyroid Glands ➢ The parathyroid glands are tiny masses of glandular tissue most often on the posterior surface of the thyroid gland. ➢ Parathyroid hormone (PTH) is the most important regulator of calcium ion homeostasis of the blood. ➢ Although the skeleton is the major PTH target, PTH also stimulates the kidneys and intestine to absorb more calcium ions. Homeostatic Imbalance o If blood calcium ion level falls too low, neurons become extremely irritable and overactive. They deliver impulses to the muscles so rapidly that the muscles go into uncontrollable spasms (tetany), which may be fatal. o Severe hyperparathyroidism causes massive bone destruction. The bones become very fragile, and spontaneous fractures begin to occur. Thymus o Is located in the upper thorax, posterior to the sternum. o Large in infants and children, it decreases in size throughout adulthood. o By old age, it is composed mostly of fibrous connective tissue and fat. o The thymus produces a hormone called thymosin and others that appear to be essential for normal development of a special group of white blood cells (T lymphocytes) and the immune response. Adrenal Glands o The two adrenal glands curve over the top of the kidneys like triangular hats. o It is structurally and functionally two endocrine organs in one.   • it has parts made of glandular (cortex) and neural tissue (medulla) • The central medulla region is enclosed by the adrenal cortex, which contains three separate layers of cells. Hormones of the Adrenal CortexThe adrenal cortex produces three major groups of steroid hormones, collectively called corticosteroids: 1. Mineralocorticoids (aldosterone) ➢ Are produced by the outermost adrenal cortex cell layer. ➢ Are important in regulating the mineral (salt) content of the blood, particularly the concentrations of sodium and potassium ions. ➢ These hormones target the kidney tubules(Distal Convulating Kidney Tubles) that selectively reabsorb the minerals or allow them to be flushed out of the body in urine. ➢ When the blood level of aldosterone rises, the kidney tubule cell reabsorb increasing amounts of sodium ions and secrete more potassium ions into the urine. ➢ When sodium is reabsorbed, water follows. Thus, the mineralocorticoids help regulate both water and electrolyte balance in body fluids. 2. Glucocorticoids (Cortisone and Cortisol)  ➢ Glucocorticoids promote normal cell metabolism and help the body to resist long-term stressors, primarily by increasing the blood glucose level. ➢ When blood levels of glucocorticoids are high, fats and even proteins are broken down by body cells and converted to glucose, which is released to the blood. ➢ For this reason, glucocorticoids are said to be hyperglycemic hormones. ➢ Glucocorticoids also seem to control the more unpleasant effects of inflammation by decreasing edema, and they reduce pain by inhibiting the pain-causing prostaglandins. ➢ Because of their anti-inflammatory properties, glucocorticoids are often prescribed as drugs to suppress inflammation for patients with rheumatoid arthritis. ➢ Glucocorticoids are released from the adrenal cortex in response to a rising blood level of ACTH (Adrenocorticotropic hormone). 3. Sex Hormones ➢ In both men and women, the adrenal cortex produces both male and female sex hormones throughout life in relatively small amounts. ➢ The bulk of the sex hormones produced by the innermost cortex layer are androgens (male sex hormones), but some estrogens (female sex hormones) are also formed. Homeostatic Imbalance1. Addisson’s disease (hyposecretion of all the adrenal cortex hormones) ✓ Bronze tone of the skin (suntan) ✓ Na (sodium) and water are lost from the body ✓ Muscles become weak and shock is a possibility ✓ Hypoglycemia (↓ glucocorticoids) ✓ Suppression of the immune system 2. Hyperaldosteronism (hyperactivity of the outermost cortical area) ✓ Excessive water and sodium ions retention ✓ High blood pressure ✓ Edema ✓ Low potassium ions level (hypokalemia) 3. Cushing’s Syndrome (Excessive glucocorticoids) ✓ Swollen “moon face” and “Buffalo hump” ✓ High blood pressure and hyperglycemia (steroid diabetes) ✓ Weakening of the bones (as protein is withdrawn to be converted to glucose) ✓ Severe depression of the immune system 4. Hypersecretion of the sex hormones leads to masculinization, regardless of sex. Hormones of the Adrenal Medulla ➢ When the medulla is stimulated by sympathetic nervous system neurons, its cells release two similar hormones, epinephrine(adrenaline) and norepinephrine (noradrenaline), into the bloodstream. ➢ Collectively, these hormones are called catecholamines. ➢ The catecholamines of the adrenal medulla prepare the body to cope with short-term stressful situations and cause the so-called alarm stage of the stress response. ➢ Glucocorticoids, by contrast, are produced by the adrenal cortex and are important when coping with prolonged or continuing stressors, such as dealing with the death of a family member or having a major operation (resistance stage). Pancreatic Islets ➢ The pancreas, located close to the stomach in the abdominal cavity, is a mixed gland. ➢ The pancreatic islets, also called the islets of Langerhans, are little masses of endocrine (hormone-producing) tissue of the pancreas. ➢ The exocrine, or acinar, part of the pancreas acts as part of the digestive system. ➢ Two important hormones produced by the islet cells are insulin and glucagon. Insulin ➢ Hormone released by the beta cells of the islets in response to a high level of blood glucose. ➢ Acts on all body cells, increasing their ability to import glucose across their plasma membranes. ➢ Insulin also speeds up these “use it” or “store it” activities. ➢ Because insulin sweeps the glucose out of the blood, its effect is said to be hypoglycemic. ➢ Without it, essentially no glucose can get into the cells to be used. Glucagon ➢ Acts as an antagonist of insulin ➢ Released by the alpha cells of the islets in response to a low blood glucose levels. ➢ Its action is basically hyperglycemic. ➢ Its primary target is the liver, which it stimulates to break down stored glycogen to glucose and to release the glucose into the blood. Gonads ➢ The female and male gonads produce sex cells. ➢ They also produce sex hormones that are identical to those produced by adrenal cortex cells. ➢ The major differences from the adrenal sex hormone production are the source and relative amounts of hormones produced. Hormones of the OvariesBesides producing female sex cells (ova, or eggs), ovaries produce two groups of steroid hormones, estrogens and progesterone. 1. Estrogen (Steroid Hormone) ➢ Responsible for the development of sex characteristics in women (primarily growth and maturation of the reproductive organs) and the appearance of secondary sex characteristics at puberty. ➢ Acting with progesterone, estrogens promote breast development and cyclic changes in the uterine lining (the menstrual cycle) 2. Progesterone (Steroid Hormone) ➢ Acts with estrogen to bring about the menstrual cycle. ➢ During pregnancy, it quiets the muscles of the uterus so that an implanted embryo will not be aborted and helps prepare breast tissue for lactation. Hormones of the TestesIn addition to male sex cells, or sperm, the testes also produce male sex hormones, or androgens, of which testosterone is the most important. 3. Testosterone ➢ Promotes the growth and maturation of the reproductive system organs to prepare the young man for reproduction. ➢ It also causes the male’s secondary sex characteristics to appear and stimulates the male sex drive. ➢ It is necessary for continuous production of sperm. ➢ Testosterone production is specifically stimulated by LH. Other Hormone-Producing Tissues and OrgansPlacenta ➢ During very early pregnancy, a hormone called human chorionic gonadotropin (hCG) is produced by the developing embryo and then by the fetal parts of the placenta. ➢ hCG stimulates the ovaries to continue producing estrogen and progesterone so that the lining of the uterus is not sloughed off in menses. ➢ In the third month, the placenta assumes the job of the ovaries of producing estrogen and progesterone, and the ovaries become inactive for the rest of the pregnancy. ➢ The high estrogen and progesterone blood levels maintain the lining of the uterus and prepare the breasts for producing milk. ➢ Human placental lactogen (hPL) works cooperatively with estrogen and progesterone in preparing the breasts for lactation. ➢ Relaxin, another placental hormone, causes the mother’s pelvic ligaments and the pubic symphysis to relax and become more flexible, which eases birth passage. Developmental Aspects of the Endocrine System ➢ In late middle age, the efficiency of the ovaries begins to decline, causing menopause. o Reproductive organs begin to atrophy o Ability to bear children ends o Problems associated with estrogen deficiency begin to occur (arteriosclerosis, osteoporosis, decreased skin elasticity, “hot flashes”) ➢ No such dramatic changes seem to happen in men. ➢ Elderly persons are less able to resist stress and infection. ➢ Exposure to pesticides, industrial chemicals, dioxin, and pother soil and water pollutants diminishes endocrine function, which may explain the higher cancer rates among older adults in certain areas of the country. ➢ All older people have some decline in insulin production, and type 2 diabetes mellitus is most common in this age group. BLOOD ➢ It is the only fluid tissue in the body. ➢ A homogenous liquid that has both solid and liquid components. ➢ Taste, Odor, 5x thicker than water ➢ Classified as a connective tissue ❖Living cells = formed elements ❖Non-living matrix = plasma (90% water) Components •Formed elements (blood cells)are suspended in plasma •The collagen and elastin fibers typical of other connective tissues are absent from blood; instead, dissolved proteins become visible as fibrin strands during blood clotting •If a sample of blood is separated, the plasma rises to the top, and the formed elements, being heavier, fall to the bottom. •Most of the erythrocytes (RBCs) settle at the bottom of the tube •There is a thin, whitish layer called the buffy coat at the junction between the erythrocytes and the plasma containing leukocytes (WBCs) and platelets   Physical Characteristics and Volume • Color range ➢ Oxygen-rich blood is scarlet red ➢ Oxygen-poor blood is dull red • pH must remain between 7.35–7.45 • Slightly alkaline • Blood temperature is slightly higher than body temperature • 5-6 Liters or about 6 quarts /body   Functions and Composition of Blood 1. Transport of gases, nutrients and waste products 2. Transport of processed molecules 3. Transport of regulatory molecules 4. Regulation of pH and osmosis 5. Maintenance of body temp 6. Protection against foreign substances 7. Clot formation   Plasma • The liquid part of the blood; 90 percent water • Over 100 different substances are dissolved in this straw-colored fluid: ➢ nutrients ➢ electrolytes ➢ respiratory gases ➢ hormones ➢ plasma proteins; and ➢ various wastes and products of cell metabolism   • Plasma proteins are the most abundant solutes in plasma (albumin and clotting proteins) • Plasma helps to distribute body heat, a by-product of cellular metabolism, evenly throughout the body. Formed Elements Erythrocytes (RBCs) • Function primarily to ferry oxygen to all cells of the body. • RBCs differ from other blood cells because they are anucleate (no nucleus) • Contain very few organelles (RBCs circulating in the blood are literally “bags” of hemoglobin molecules ) •Very efficient oxygen transporters (they lack mitochondria and make ATP by anaerobic mechanisms) • Their small size and peculiar shape provide a large surface area relative to their volume, making them suited for gas exchange • RBCs outnumber WBCs by about 1,000 to 1 and are the major factor contributing to blood viscosity. • There are normally about 5 million cells per cubic millimeter of blood. • The more hemoglobin molecules the RBCs contain, the more oxygen they will be able to carry. • A single RBC contains about 250 million hemoglobin molecules, each capable of binding 4 molecules of oxygen. • Normal hemoglobin count is 12-18 grams of hemoglobin per 100 ml of blood • Men: 13-18g/ml Women: 12-16 g/ml   Homeostatic Imbalance Anemia • a decrease in the oxygen-carrying ability of the blood, whatever the reason is. • May be the result of (1) a lower-than-normal number of RBCs or (2) abnormal or deficient hemoglobin content in the RBCs.   Polycythemia Vera • An excessive or abnormal increase in the number of erythrocytes; may result from bone marrow cancer or a normal physiologic response to living at high altitudes, where the air is thinner and less oxygen is available (secondary polycythemia)     Formed Elements Leukocytes (WBCs) • Are far less numerous than RBCs • They are crucial to body defense • On average, there are 4,800 to 10,800 WBCs/mm3 of blood • WBCs contain nuclei and the usual organelles, which makes them the only complete cells in the blood. • WBCs are able to slip into and out of the blood vessels – a process called diapedesis • WBCs can locate areas of tissue damage and infection in the body by responding to certain chemicals that diffuse from the damaged cells (positive chemostaxis) • Whenever WBCs mobilize for action, the body speeds up their production, and as many as twice the normal number of WBCs may appear in the blood within a few hours. • A total WBC count above 11,000 cells/mm3 is referred to as leukocytosis. • The opposite condition, leukopenia, is an abnormally low WBC count (commonly caused by certain drugs, such as corticosteroids and anti-cancer agents) • WBCs are classified into two major groups – granulocytes and agranulocytes – depending on whether or not they contain visible granules in their cytoplasm.   Granulocytes Neutrophils ➢ Are the most numerous WBCs. ➢ Neutrophils are avid phagocytes at sites of acute infection. Eosinophils ➢ Their number increases rapidly during infections by parasitic worms ingected in food such as raw fish or entering through the skin. Basophils ➢ The rarest of the WBCs, have large histamine-containing granules. Histamine ➢ is an inflammatory chemical that makes blood vessels leaky and attracts other WBCs to the inflamed site   Agranulocytes Lymphocytes ➢ Have a large, dark purple nucleus that occupies most of the cell volume. ➢ Lymphocytes tend to take up residence in lymphatic tissues, such as the tonsils, where they play an important role in the immune response. ➢ They are the second most numerous leukocytes in the blood Monocytes ➢ Are the largest of the WBCs. ➢ When they migrate into the tissues, they change into macrophages. ➢ Macrophages are important in fighting chronic infections, such as tuberculosis, and in activating lymphocytes Platelets   ➢ They are fragments of bizarre multinucleate cells called megakaryocytes, which pinch off thousands of anucleate platelet “pieces” that quickly seal themselves off from the surrounding fluids. ➢ Normal adult has 150,000 to 450,000 per cubic millimeter of blood ➢ Platelets are needed for the clotting process that stops blood loss from broken blood vessels. ➢ Average lifespan is 9 to 12 days   Hematopoiesis • Occurs in red bone marrow, or myeloid tissue. • In adults, this tissue is found chiefly in the axial skeleton, pectoral andpelvic girdles, and proximal epiphyses of the humerus and femur. • On average, the red marrow turns out an ounce of new bloodcontaining 100 billion new cells every day. • All the formed elements arise from a common stem cell, thehemocytoblast, which resides in red bone marrow. • Once a cell is committed to a specific blood pathway, it cannotchange. • The hemocytoblast forms two types of descendants – the lymphoidstem cell, which produces lymphocytes, and the myeloid stem cell,which can produce other classes of formed elements.   Formation of RBCs • Because they are anucleate, RBCs are unable to synthesizeproteins, grow, or divide. • As they age, RBCs become rigid and begin to fall apart in 100 to 120 days. • Their remains are eliminated by phagocytes in the spleen, liver, and other body tissues. • RBC components are salvaged. Iron is bound to protein as ferritin, and the balance of the heme group is degraded to bilirubin, which is then secreted into the intestine by liver cells where it becomes a brown pigment called stercobilin that leaves the body in feces. • Globin is broken down to amino acids which are released into the circulation.The rate of erythrocyte production is controlled by a hormone called erythropoietin (from the kidneys) • Erythropoietin targets the bone marrow prodding it into “high gear” to turn out more RBCs. • An overabundance of erythrocytes, or an excessive amount of oxygen in the bloodstream, depresses erythropoietin release and RBC production. • However, RBC production is controlled not by the relative number of RBCs in the blood, but by the ability of the available RBCs to transport enough oxygen to meet the body’s demands   Formation of WBCs and Platelets   • The formation of leukocytes and platelets is stimulated by hormones • These colony stimulating factors (CSFs) and interleukins not only prompt red bone marrow to turn out leukocytes, but also enhance the ability of mature leukocytes to protect the body. • The hormone thrombopoietin accelerates the production of platelets from megakaryocytes, but little is know about how process is regulated. • When bone marrow problems or disease condition is suspected, bone marrow biopsy is done.   Hemostasis If a blood vessel wall breaks, a series of reactions starts the process of hemostasis (stopping the bleeding). Phases of Hemostasis 1. Vascular spasms occur. 2. Platelet plug forms. 3. Coagulation events occur.       Human Blood Groups • An antigen is a substance that the body recognizes as foreign; it stimulates the immune system to mount a defense against it. • The “recognizers” are antibodies present in plasma that attach to RBCs bearing surface antigens different from those on the patient’s RBCs.   ABO and Rh Blood Types The blood group system recognizes four blood types: • Type A, B, AB, and O • They are distinguished from each other in part by their antigens and antibodies. • Specific antibodies are found in the serum based on the type of antigen on the surface of the RBC   ABO and Rh Blood Types BLOOD TYPE Can Accept From Can Donate To A A, O A, AB B B, O B, AB AB A, B, AB, O AB O O O, A, B, AB   The Rh Factor Rh-Positive Rh-Negative Contains the Rh antigen -No Rh antigen   -Will make antibodies if given Rh-positive blood   -Agglutination can occur if given Rh-positive blood     Summary • Blood is responsible for transporting oxygen, fluids, hormones, and antibodies and for eliminating waste materials. • The major components of blood include the formed elements and plasma. • RBCs transport oxygen and carbon dioxide; WBCs destroy foreign invaders. • WBCs include granulocytes and agranulocytes. • Plasma is the liquid portion of unclotted blood. Serum is the liquid portion of clotted blood • Hemostasis includes four stages: blood vessel spasm, platelet plug formation, blood clotting, and fibrinolysis. • ABO and Rh types are determined by the antigen found on the RBCs
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