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Body Systems Semester 1 - Contents
Lecture Page
2 – Body Fluids & Membrane Transport 1 - 5
3 – Homeostasis & ControlSystem...
Cell membranes and transport of substances 1
Body Systems Semester 1
Cell membranes and transportofsubstances
Cells are su...
Cell membranes and transport of substances 2
Membranes are neither rigid, nor uniform. Some embedded proteins are always c...
Cell membranes and transport of substances 3
Epithelia are layers of cells covering internal and external surfaces of orga...
Cell membranes and transport of substances 4
Many essential nutrients such as glucose and amino acids are lipid insoluble ...
Cell membranes and transport of substances 5
cytoplasm may involve active transport, simple or facilitated diffusion, or t...
Homeostasis 6
Homeostasis
Homeostasis is the maintenance of a constant internal environment within a narrow range. If chan...
Anatomical Terminology 7
to define “normal” homeostatic conditions. Conventionally average values are obtained by sampling...
Autonomic Nervous System (ANS) 8
autonomic ganglia. Ganglionic neurons innervate visceral effectors such as cardiac muscle...
Autonomic Nervous System (ANS) 9
hormones adrenaline and noradrenaline, where adrenaline accounts for 75-80% secretary out...
Basic Tissues 10
nerves innervating the limbs. The sacral preganglionic fibres form distinct pelvic nerves which innervate...
Basic Tissues 11
muscular walls of hollow organs; and neural tissue, which carries information from on part of the body to...
Basic Tissues 12
Portions of the respiratory tract contain a pseudostratified columnar epithelium, including several cell ...
Types of Muscle 13
Loose ConnectiveTissue
Loose connective tissue fills the space between organs, providing support, and a...
Types of Muscle 14
CardiacMuscle
Cardiac muscle cells can also be called cardiocytes or cardiac myocytes and like skeletal...
The Anatomy of Blood Vessels 15
Smooth muscle cells are relatively long and slender, they are spindle shaped with a single...
The Anatomy of Blood Vessels 16
Elastic (conducting) arteries are large vessels, such as the aorta and brachiocephalic and...
Gross Anatomy of the Circulations 17
Gross Anatomy ofthe Circulations
The cardiovascular system transports fluid throughou...
Gross Anatomy of the Circulations 18
empties into the ductus venosus, connecting a capillary network in the liver. The duc...
Anatomy of the Heart 19
efficient transport. In the process it maintains blood volume and eliminates local variations in t...
Haematology 20
The coronary circulation supplies blood to the muscle tissue of the heart and includes an extensive network...
Haematology 21
A standard blood test reveals the number of erythrocytes per micro-litre as the red blood cell count, typic...
Haematology 22
Red Blood Cell Destructionand Recycling
In a foetus, stressed and damaged red blood cells are broken down i...
Haematology 23
Blood Types
Blood type is a classification determined by the presence or absence of specific surface antige...
Haematology 24
Each platelet circulates for about 9-12 days before being removed by phagocytes, generally in the spleen.
R...
The Circulation of Blood 25
leucocytes” Their cytoplasm is packed with pale granules containing lysosomal enzymes and bact...
The Circulation of Blood 26
The capillaries, although very small, make up the greatest combined cross sectional area of al...
Body Systems: Homeostasis, blood, cardio and respiratory
Body Systems: Homeostasis, blood, cardio and respiratory
Body Systems: Homeostasis, blood, cardio and respiratory
Body Systems: Homeostasis, blood, cardio and respiratory
Body Systems: Homeostasis, blood, cardio and respiratory
Body Systems: Homeostasis, blood, cardio and respiratory
Body Systems: Homeostasis, blood, cardio and respiratory
Body Systems: Homeostasis, blood, cardio and respiratory
Body Systems: Homeostasis, blood, cardio and respiratory
Body Systems: Homeostasis, blood, cardio and respiratory
Body Systems: Homeostasis, blood, cardio and respiratory
Body Systems: Homeostasis, blood, cardio and respiratory
Body Systems: Homeostasis, blood, cardio and respiratory
Body Systems: Homeostasis, blood, cardio and respiratory
Body Systems: Homeostasis, blood, cardio and respiratory
Body Systems: Homeostasis, blood, cardio and respiratory
Body Systems: Homeostasis, blood, cardio and respiratory
Body Systems: Homeostasis, blood, cardio and respiratory
Body Systems: Homeostasis, blood, cardio and respiratory
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Body Systems: Homeostasis, blood, cardio and respiratory

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Body Systems: Homeostasis, blood, cardio and respiratory

  1. 1. Body Systems Semester 1 - Contents Lecture Page 2 – Body Fluids & Membrane Transport 1 - 5 3 – Homeostasis & ControlSystems 6 - 10 4 – Basic Tissues 10 - 15 5 – Structure & Function of Blood Vessels 15 - 17 6 – GrossAnatomy of the Circulations 17 - 19 7 – Anatomy of the Heart 19 - 20 8 – Haematology I 9 – Haematology II 20 - 25 10 – The Circulation of Blood 25 - 26 11 – Controlof Cardiac Output 27 - 28 12 – Controlof Blood Pressure 28 - 30 13 – LocalControlof the Circulation & SpecialCirculations 30 - 31 14 – When the Cardiovascular System GoesWrong 32 - 34 15 – Anatomy of the Respiratory Tract 34 - 36 16 – GrossAnatomy of the Lungsand Thorax 36 - 37 17 – Ventilation 37 18 – Gas Exchange in the Lungs 38 19 – Mechanismsof Breathing 39 - 40 20 – Blood Gas transport 40 - 41 21 – Controlof Breathing 41 – 43 22 –Types of Respiratory Disease 43 - 45
  2. 2. Cell membranes and transport of substances 1 Body Systems Semester 1 Cell membranes and transportofsubstances Cells are surrounded by a watery medium known as the extracellular fluid. The term “interstitial Fluid” encompasses extracellular fluid, transcellular fluid and plasma. The cytoplasm inside the cell can be subdivided into organelles and the liquid cytosol. The interstitial fluid bathes cells outside of blood vessels, it is mostly the same composition as plasma, but plasma contains more proteins. Transcellular fluid is separated from the interstitial fluid by an epithelial layer and plasma is separated by an endothelium. 60% of the body is made up of water (about 42 litres), and of this water, about two litres is contained within bone. There are many types of transcellular fluid including cerebrospinal fluid in the brain, urine, gastrointestinal secretions, bile, aqueous and vitreous humour in the eye, and synovial fluid in the joints. The plasma membrane is a phospholipid bilayer which separates intracellular and extracellular fluid. Conditions within and outside the cell are very different and these differences must be maintained in order to preserve homeostasis. The hydrophobic tails of the phospholipids do not associate with water molecules, this stops water and from crossing the membrane. Water moves down its concentration gradient, created by Na+ ions. Through this the cell membrane is able to control entry of ions and nutrients such as glucose, the elimination of wastes and the release of secretions. The cell membrane is the first part of the cell to be affected by changes in the composition, concentration of pH of the extracellular fluid and contains a variety of receptors that enable the cell to respond to specific molecules in its environment. The cell membrane measures from about 6-10nm in thickness and contains lipids, proteins, carbohydrates and cholesterol. The plasma protein has a highly selective permeability and lots of transport proteins for the uptake and removal of specific solutes. It is vital for regulation of the intracellular environment. Protoplasm is the living material within the cell and is divided into nucleoplasm and cytoplasm. Membraneproteins & carbohydrates There are two man classes of membrane proteins: integral and anchoring. Integral proteins are part of the membrane structure and cannot be removed without damaging the membrane. Most integral proteins span the width of the cell membrane at least once and are therefore called transmembrane proteins. Peripheral proteins are bound to the inner or outer membrane surfaces and can easily be separated. There are many more integral than peripheral proteins. Anchoring proteins attach the cell membrane to other structures and stabilise its position. Inside the cell, membrane proteins are bound to the cytoskeleton; a network of supporting filaments in the cytoplasm. Outside the cell, other membrane proteins may attach the cell to extracellular protein fibres or to another cell. Recognition proteins recognise other cells as self or non-self, many of these important proteins are glycoproteins Enzymes in cell membranes may be integral or peripheral proteins. The catalyse reactions either side of the cell membrane; dipeptides are broken down into amino acids by the enzymes on the exposed surfaces that line the intestinal tract. Receptor proteins in the cell membrane are sensitive to the presence of small extracellular ligands (which can be anything from a Ca2+ ion to a large hormone). A ligand binding to a receptor trigger changes in the activity of the cell, binding of the hormone insulin to a specific membrane protein results in the increase of glucose absorption by that cell. Carrier proteins bind to solutes and transport them across the cell membrane. The transport process involves a change in the shape of the protein and energy in the form of ATP. After transport their shape returns to normal. Virtually all cells have carrier proteins that can bring glucose into the cytoplasm without using ATP, but they must use ATP to transport ions such as Na+ and Ca2+ across the cell membrane and into the cytoplasm.
  3. 3. Cell membranes and transport of substances 2 Membranes are neither rigid, nor uniform. Some embedded proteins are always confined to the same areas of the membrane. These “rafts” mark the location of anchoring proteins and some receptor proteins. The membrane is fluid (like ice cubes in a punch bowl, integral proteins constantly drift.) The composition of the entire cell membrane can change over time, as large areas are continually being removed and recycled in the process of membrane turnover. The carbohydrates on cell membranes are components of complex molecules such as proteoglycans, glycoproteins and glycolipids. The carbohydrate portions of these large molecules extend beyond the outer surface of the membrane forming a layer called the glycocalyx. This forms a viscous layer that lubricates and protects the cell membrane. Because the components are sticky, the glycocalyx can help anchor the cell in place and aid the locomotion of specialised cells. Glycoproteins and glycolipids can also function as receptors, binding specific extracellular compounds which can alter the properties of cell surface and indirectly affect the cell’s behaviour. Finally, they can act as recognition sites by cells involved with the immune response. The characteristics of the glycocalyx are genetically determined and allow the immune system to recognise self from non-self and to destroy invading pathogens. If a cell is to survive, dissolved substances and larger compounds must be able to move across the barrier. Metabolic wastes must be able to leave the cytosol and nutrients must be able to enter the cell. Transport proteins uptake such nutrients/ substrates/ cofactors as glucose, amino acids and Na+, and excretion of such waste products as lactate, H+ and urea. The asymmetric distribution of K+ generates a membrane potential of about -70mV. There is a higher concentration of K+ inside the cell, and a higher Na+ concentration outside the cell which results in a more positive charge outside the cell. Osmosis Water distribution is determined by osmosis and moves from a region of low solute concentration to a region of high solute concentration across a partially permeable membrane until the osmotic pressures ∏i (inside the cell) and ∏o (outside the cell) are equal. Proteins are too big to move out of the plasma and into the interstitial fluid, causing water to move into the plasma by osmosis and producing a colloid osmotic pressure. Hydrostatic pressure opposes this force, and is due to the blood pressure from heart contraction. Water distribution is decided by hydrostatic and osmotic forces, and fluid collection in the tissues (oedema) can be due to a low plasma protein composition. The osmotic pressure of a solution is an indication of the force with which pure water moves into that solution as a result of its solute concentration. We can measure a solution’s osmotic pressure in several ways, for example an opposing pressure can prevent the osmotic flow of water into the solution. Pushing against a fluid generates hydrostatic pressure which generates osmotic pressure. Osmosis eliminates solute concentration differences much quicker than solute diffusion, partly because water molecules cross the membrane in groups held by hydrogen bonding, where other solutes usually diffuse through the membrane channels one at a time. Osmolarity is a measure of how much a solute attracts water, and is vital to the principal of water movement between different areas. A solution that doesn’t cause an osmotic flow of water in or out of a cell is called isotonic (same tension). Osmolarity refers to the solute concentration of the solution, while tonicity is a measure of how the solution affects a cell. If a cell is in a hypotonic solution, water will flow into the cell, causing it to swell, or eventually burst; lysis of red blood cells is called haemolysis. A cell in a hypertonic solution will lose water by osmosis, causing the cell to shrivel and dehydrate; the shrinking of red blood cells is called crenation. In patients suffering from dehydration it is often necessary to administer large volumes of fluid. 0.9% NaCl is frequently administered because it is essentially isotonic with respect to body cells. Alternatively an isotonic saline solution containing dextran, a carbohydrate that cannot cross cell membranes is used. The dextran molecules elevate the osmolarity of the blood vessels from the extracellular fluid, and blood volume increases.
  4. 4. Cell membranes and transport of substances 3 Epithelia are layers of cells covering internal and external surfaces of organ and tissues and are important for absorption and secretion of substances whilst providing a protective barrier to such problems as infection. Villi in the intestines greatly increase the surface area for absorption. Nutrients are actively taken up and water follows by osmosis down the solute concentration gradient. This is why energy drinks with salt or sugars, like lucozade, are so effective. Types oftransport Transport proteins are characterised into three main mechanisms: Diffusion, a passive process resulting from the random motion and collision of ions and molecules; carrier-mediated transport, which can be passive or active and vesicular transport, an active process involving the movement of materials within small sacs or vesicles. Diffusion Molecules and ions are constantly in motion, and will tend to become evenly distributed through the net movement of molecules from a high to a low concentration. After the concentration gradient has been eliminated, no net movement occurs in any particular direction. Carbon dioxide moves out of the cells and into the blood down its concentration gradient because cell membranes are freely permeable to CO2. Important factors influencing diffusion rates include distance, temperature, gradient size, molecule size (smaller molecules and ions diffuse more quickly) and electrical forces. The interior of the cell membrane has a net negative charge relative to that of the surface, partly due to the high concentration of proteins in the cell. This charge tends to pull positively charged ions into the cell from the extracellular fluid, while opposing the entry of negative ions. The interstitial fluid contains higher concentrations of Na+ and Cl- than the cytosol. Diffusion of Na+ into the cell is favoured by the concentration and electrical gradients; diffusion Cl- into the cell is favoured by the chemical gradient but opposed by the electrical gradient. The net result of the chemical and electrical forces acting on an ion is called the electrochemical gradient. Alcohol, fatty acids and steroids can enter cells because they can diffuse through the lipid portions of the membrane. Dissolved gases such as CO2 and O2 leave and enter by diffusion through the phospholipid bilayer. Ions and water-soluble compounds, however, are not lipid soluble and so must pass through a membrane channel. ChannelProteins On average, channel proteins have a channel about 0.8nm in diameter, water molecules can enter and exit freely, but even a small molecule such as glucose is too small to fit through. The ability of an ion to transit a membrane channel depends on many factors including the size and charge of the ion, the size of the hydration sphere, and interactions between the ion and channel walls. The rate at which an ion diffuses across the membrane can be limited by the availability of suitable channels, but for many ions including Na+, K+ and Cl-, movement across the cell membrane occurs at rates comparable to those one would expect if relying on simple diffusion. Intracellular and extracellular fluids contain a variety of dissolved materials; each solute diffuses as though it were the only one in solution. The diffusion rate of Na+ will only depend on the existence of a Na+ concentration. CarrierProteins In carrier-mediated transport, integral proteins bind specific ions or organic substrates and carry them across the membrane. All forms of carrier-mediated transport are specific and have saturation limit, just like enzymes. When all the available carrier proteins are operating at maximum speed, the carriers are said to be saturated. The binding of other molecules, like hormones, to the protein can affect the activity of carrier proteins, this is regulation and hormones thus provide an important means of regulating and co-ordinating carrier protein activity across the membrane.
  5. 5. Cell membranes and transport of substances 4 Many essential nutrients such as glucose and amino acids are lipid insoluble and too large to fit through membrane channels. These substances can be passively transported across the membrane by carrier proteins through facilitated diffusion. The molecule to be transported must first bind to a receptor site on the protein, whose shape changes transporting the molecule across the membrane. As with simple channel-mediated proteins, no ATP is required for facilitated diffusion. All cells move glucose across their membranes through facilitated diffusion. However, several different carrier proteins are involved. In muscle cells, fat cells etc. the glucose transporter only functions when stimulated by insulin. There are three types of carrier proteins: facilitators are uniport and transport one type of ion, a cotransporter is a symport and can transport two ions in the same direction, and an exchanger is an antiport, transporting two ions in opposite directions. A cotransporter can move oppositely charged ions to maintain neutrality. Some integral proteins contain a central pore, or channel, that forms a complete pathway across the cell membrane, permitting the movement of water and small solutes across the cell membrane. Since ions do not dissolve in lipids, they cannot cross the cell membrane without this channel. Many channels are highly specific, permitting the transport of only one particular ion. Activetransport A high energy bond (in ATP or another high-energy compound provides the energy needed to move ions or molecules across the membrane. Despite the energy cost, active transport is not dependent on concentration gradient, allowing the cell to import or export specific substances regardless of their concentrations. All cells contain carrier proteins called ion pumps which actively transport the cations Na+, K+, Ca2+ and Mg2+ across their cell membranes. Specialised cells can transport additional ions such as I-, Cl- and Fe2+. If counter transport occurs, the carrier is called an exchange pump. Sodium and Potassium are the principal ions in body fluids. Na+ concentrations are higher in the extracellular fluid the in the cytoplasm. The distribution of K+ is just the opposite. As a result, Na+ ions slowly diffuse into the cell and K+ ions diffuse out through leak channels. Homeostasis in the cell depends on the ejection of Na+ and recapture of lost K+. This involves the Sodium-Potassium ATPase pump. On average, for every molecule of ATP consumed, three Na+ ions are ejected and two K+ ions are re-claimed by the cell. If ATP is readily available, the rate depends on the Na+ concentration in the cytoplasm. Sodium-Potassium ATPase may use up to 40% of the ATP produced by a resting cell. Secondary ActiveTransport The transport itself does not require energy, but ATP is often required to preserve homeostasis at a later time. As with facilitated diffusion, this method of transport moves a specific substrate down its concentration gradient. These proteins can also move another substrate at the same time regardless of the concentration gradient. In effect the concentration gradient for one substance provides the driving force needed by the carrier protein and the second substance gets a “free ride”. The concentration gradient for Na+ ions most often provides the driving force for cotransport mechanisms that move substances into the cells such as glucose and amino acids along the intestinal tract. Although the initial transport actively proceeds without direct energy expenditure, the cells must expend ATP to pump the Na+ ions out of the cell using the Sodium-Potassium ATPase pump. Sodium-Calcium countertransport is required to keep the intracellular Ca2+ concentrations very low. VesicularTransport This is a bulk transport mechanism since large volumes of fluids and solutes are transported in this way. In endocytosis, materials are packaged in vesicles at the cell surface and imported into the cell; this requires energy in the form of ATP. The three major types of endocytosis are receptor-mediated, pinocytosis and phagocytosis. Vesicles produced by receptor-mediated endocytosis and pinocytosis are called endosomes and those produced by phagocytes are phagosomes. The movement of materials from the vesicles into the
  6. 6. Cell membranes and transport of substances 5 cytoplasm may involve active transport, simple or facilitated diffusion, or the destruction of the vesicle membrane. Receptor-Mediated Endocytosis A selective process involving the formation of small vesicles at the surface of the membrane, this process produces vesicles containing a specific target molecule in high concentrations. Receptor-mediated endocytosis begins when materials in the extracellular fluid bind to receptors on the membrane surface. Most receptors are glycoproteins and each binds to a specific ligand or target. Receptors bound to ligands cluster and the membrane forms packets that move to one area of the cell and pinch off to form an endosome. The endosomes produced in this way are called coated vesicles as they are surrounded by a protein-fibre network that originally covered the inner membrane surface. This coating is essential to endosome formation and movement. Inside the cell the coated vesicles fuse with primary lysosomes containing many digestive enzymes, creating secondary lysosomes. The enzymes free the ligands from the receptors, which then enter the cytosol by diffusion or active transport. The vesicle membrane detaches from the secondary lysosome and returns to the cell surface. Many important substances including cholesterol and Fe2+ ions are distributed through the body attached to special transport proteins. These are too large to pass through the membrane pores, but enter cells by receptor-mediated endocytosis. Pinocytosis The formation of endosomes filled with fluid. This is not as selective as receptor-mediated endocytosis. The target seems to be the fluid contents in general rather than specific bound ligands. The steps here are similar to the above process, but ligand binding is not the trigger in this case. Phagocytosis Phagocytosis produces phagosomes containing solid objects that may even be bigger than the cell itself. In this process, cytoplasmic extensions, or pseudophobia,surround the object and their membranes fuse to form a phagosome. This vesicle then fuses with many lysosomes where its contents are digested by lysosomal enzymes. Although most cells display pinocytosis, only such cells as macrophages perform this. Exocytosis The reverse of endocytosis, the ejected material may be secreting products, such as mucus or hormones, or waste products, such as those accumulating in endocytic vesicles. In a few specialised cells, endocytosis produces vesicles on one side of the cell that are discharged through exocytosis on the other side. This method of bulk transport is common in cells lining capillaries, which use a combination of pinocytosis and exocytosis to transfer fluid and solutes from the surrounding tissues. TransmembranePotential In relation to the unequal charge distribution across a cell membrane, positive and negative charges are held apart by the cell membrane, thus a potential difference is said to exist, known as a transmembrane potential. The transmembrane potential of a cell is about 0.07V or 70mV. The transmembrane potential of a resting cell is called the resting potential. Each type of cell has a characteristic resting potential from -10mV to -100mV. The minus sign shows that the inside of the cell membrane contains an excess of negative charges compared with the outside. The cell membrane is what retains the potential difference, if this were removed; the positive and negative charges would rush together, eliminating the potential difference. It is the transmembrane potential that makes possible the transmission of information in the nervous system and thus our perceptions and thoughts.
  7. 7. Homeostasis 6 Homeostasis Homeostasis is the maintenance of a constant internal environment within a narrow range. If changes occur then measures occur to restore the norm. Failure to maintain homeostasis can lead to illness or even death. Homeostatic regulation is the adjustment of physiological systems to preserve homeostasis. Physiological systems have evolved to maintain homeostasis in an often unpredictable and potentially dangerous environment. An understanding of homeostasis is critical to making accurate predictions aboutthe body’s responses in both normal and abnormal conditions. Our external environment causes large fluctuations in temperature, diet, water availability etc. and our internal environment experiences small fluctuations in such factors as pH, O2 or CO2 concentration, glucose concentration and blood pressure. Autoregulation, or intrinsic regulation, occurs when a tissue, organ or organ system adjusts its activities automatically in response to some environmental change. When O2 levels are low in the tissues, the cells release chemicals that dilate blood vessels, increasing the blood flow and providing more oxygen for the tissues. Extrinsic regulation results from the activities of the nervous or endocrine system; two organ systems that control or adjust the activities of many other systems simultaneously, such as the increase of heart rate or the control of blood flow to specific parts of the body. In general the nervous system directs short-term, rapid and specific responses, such as muscle contraction when your hand comes into contact with a hot surface. These contractions only last as long as the neural activity continues (usually seconds). The endocrine system releases hormones; chemical messengers which affect tissues and organs throughout the body. The responses may not be immediately apparent, but may persist for days or even weeks. Examples include long term regulation of blood volume and composition, and the adjustment of organ system function during starvation. The endocrine system also plays a massive role in growth and development. The function of homeostasis is to keep the characteristics of the human body within certain limits, there are three parts to homeostasis: a receptor that is sensitive to a particular stimulus, a control centre and an effector, which responds to the control centre and wither opposes or enhances the stimulus. NegativeFeedback Most homeostatic regulatory systems involve negative feedback, such as in thermoregulation. Here the control centre is in the hypothalamus of the brain, this receives information from temperature receptors in the skin and the hypothalamus. At the normal set point the boy temperature is about 37°C. If body temperature rises above about 37.2°, activity in the control centre targets muscle tissue in the walls of blood vessels supplying the skin and also the sweat glands. The muscle relaxes and blood vessels dilate allowing blood to flow through the vessels near the body surface while the sweat glands accelerate their secretion. The skin then radiates heat to the environment, and the evaporation of sweat requires a lot of heat energy due to the high specific heat capacity of water (second, only to ammonia) and so greatly speeds up the cooling process. As the temperature falls back to normal, temperature at the hypothalamus declines and the thermoregulatory centre becomes less active. Superficial blood flow and sweat gland activity then decrease to previous levels, although body temperature declines past the set point as the secreted sweat evaporates. Negative feedback is the primary mechanism of homeostatic regulation and provides long-term control over the body’s internal conditions and systems. Negative feedback systems usually ignore minor variations and maintain a normal range rather than a fixed value. The regulatory process itself is dynamic; the set point may vary with changing environments or differing activity levels. When you are asleep, your thermoregulatory set point is much lower than when you are working on a hot day, or when you have a temperature. The body temperature can vary due to small oscillations about the set point or changes i the set point. Comparable variations exist in all other aspects of physiology. Due to massive variability among individuals it is impractical
  8. 8. Anatomical Terminology 7 to define “normal” homeostatic conditions. Conventionally average values are obtained by sampling a large number of individuals, or as a range that includes 95% or more of the population. PositiveFeedback In Positive feedback an initial stimulus produces a response that exaggerates of enhances the change in the original conditions, rather than opposing it. This is rare because it tends to produce extreme responses and lacks control. The escalating cycle is often called a positive feedback loop. In the body, they are typically found when a particularly dangerous or stressful process must be completed quickly before homeostasis can be restored. For example, the immediate danger from a severe cut is blood loss, leading to a lower blood pressure and heart efficiency. Damage to cells in the blood vessel wall causes the release of chemicals that accelerate the process in a positive feedback loop that ends with the formation of a blood clot that patches the blood vessel and stops it bleeding. Despite the body’s amazing effectiveness, an infection, injury, or genetic abnormality can sometimes have such adverse effects that homeostasis cannot compensate. In this case, one or more of the characteristics of the internal environment may then be pushed outside normal limits and the organ systems may malfunction, causing a state of illness or disease. Systems Integration& Equilibrium A state of equilibrium exists when opposing processes are in balance, such as when heat gain and heat loss occur at the same rates. Each physiological system functions to maintain equilibrium that keeps vital conditions within the normal limits and is known as dynamic equilibrium as the systems are constantly adjusting to changing conditions. Some systems may also affect others. Excessive sweating increases the loss of both water and salts, for which other systems must compensate and re-establish a state of equilibrium for water and salts AnatomicalTerminology Transverse planes divide the body into superior and inferior regions Frontal (coronal) planes divide the body into anterior and posterior regions Sagittal planes divide the body into left and right Term Region Opposite Region Anterior The front, before Posterior The back, behind Ventral The belly side Dorsal The back side Cranial or Cephalic The head Caudal The tail (or coccyx) Superior Above Inferior Below Medial Towards midsagittal Lateral Away from midsagittal Proximal Towards attached base Distal Away from attached base Superficial Near the body surface Deep Further from the body surface AutonomicNervous System(ANS) It is the ANS that co-ordinates cardiovascular, respiratory, digestive, urinary and reproductive fitness through homeostasis. In doing so, the ANS adjusts internal water, electrolyte, nutrient and dissolved gas concentrations in body fluids without conscious thought. The somatic nervous system (SNS) controls skeletal muscles and the ANS controls visceral effectors. The integrative centres for autonomic activity are located in the hypothalamus. The neurons in these centres are comparable to the upper motor neurons in the SNS. Visceral motor neurons in the brain stem and spinal cord are known as preganglionic neurons and most of their activities reflect direct reflex responses, rather than responses to the commands of the hypothalamus. The axons of preganglionic neurons are called preganglionic fibres and leave the CNS, synapsing on ganglionic neurons (visceral motor neurons in peripheral ganglia), called
  9. 9. Autonomic Nervous System (ANS) 8 autonomic ganglia. Ganglionic neurons innervate visceral effectors such as cardiac muscle, smooth muscle, glands and adipose tissues. The axonsof ganglionic neurons are called postganglionic fibres as they begin at the ganglia and stretch to the peripheral target organs. Somatic or visceral sensory information can trigger visceral reflexes, and the motor commands of these reflexes are distributed by the ANS. Sometimes these motor commands control the activities of target organs, in cold weather the ANS stimulates the arrector pili muscles, it also increases heart rate and stops all digestive gland secretion when the body is startled. These changes in visceral activity occur in response to neurotransmitter release by postganglionic fibres. Sympathetic,Parasympathetic& EntericDivisions The ANS is divided into the sympathetic and parasympathetic divisions. Most often the two have opposing effects, but this is not always the case as they work independently. In general the sympathetic division kicks in during periods of exertion, stress or emergency, and the parasympathetic division predominates under resting conditions. In the sympathetic (thoracolumbar) division, preganglionic fibres from the thoracic and superior lumbar segments of the spinal cord (T1 – L2) have short preganglionic fibres and long postganglionic fibres (synapsing in ganglia near the spinal cord). The sympathetic division prepares the body for heightened levels of somatic activity, and when fully activated, produces the “fight or flight” response. Sympathetic responses basically include a heightened mental alertness, increased metabolic rate, reduced digestive and urinary functions, activation of energy reserves, an increased respiratory rate and dilation of respiratory passageways, increased heart rate and blood pressure and activation of sweat glands. In the parasympathetic (craniosacral) division, fibres originate in the brain stem and sacral segments of the spinal cord (S2-S4) and synapse very close to (or within) the target organs, and so have long preganglionic fibres and sort postganglionic fibres. The parasympathetic division stimulates visceral activity and is responsible for the state of “rest and repose” that follows a big dinner. Overall it produces a decreased metabolic rate, heart rate and blood pressure, an increased secretion by salivary and digestive glands and blood flow in the digestive tract, and stimulation of urination and defecation. The ANS also involves a third “enteric nervous system”, an extensive network of neuron and nerve networks in the walls of the digestive tract. Although influenced by the sympathetic and parasympathetic divisions, many complex visceral reflexes are initiated and co-ordinated by locally and without the help of the CNS. SympatheticDivision The cell bodies of the pre-ganglionic neurons are located in the lateral grey horns of the spinal cords, and the axons enter the ventral roots of these segments. The ganglionic neurons occur i three locations: The sympathetic chain ganglia, collateral ganglia and adrenal medullae. The sympathetic chain and collateral ganglia innervate the target organs by post-ganglionic fibres, whilst the adrenal medullae innervate the target organs through hormone release into the circulation, allowing the neurotransmitters to have an effect throughout the entire body. The ventral roots of spinal segments T1 – L2 contain sympathetic preganglionic fibres. After passing through the intervetebral foramen, each ventral root gives rise to a myelinated white ramus, which carries white myelinated postganglionic fibres into a nearby sympathetic chain ganglion,which may synapse here, in one of the collateral ganglia,or in the adrenal medullae. Preganglionic fibres running between the sympathetic chain ganglia interconnect them, making the chain resemble a set of pearls. Each ganglion innervates a particular body segment. The adrenal medulla is a modified sympathetic ganglion where preganglionic fibres synapse onto neuroendochrine cells; specialised neurons that secrete hormones into the bloodstream. They secrete the
  10. 10. Autonomic Nervous System (ANS) 9 hormones adrenaline and noradrenaline, where adrenaline accounts for 75-80% secretary output. Hormones are distributed in the bloodstream and cause changes in the activities of many cells. Cells not affected by sympathetic cells are affected by the hormone and the effects last much longer than those by direct sympathetic innervations as the hormones continue to diffuse out of the bloodstream for an extended period. In a crisis, the entire sympathetic division responds and this is called sympathetic activation, during which an individual can feel an increased alertness, with a higher blood pressure, heart rate and respiration rate. They may also undergo a feeling of high energy and a temporary disregard for painful stimuli, a general elevation of muscle tone, which may cause the person to look tense and possibly shiver, finally it may also trigger the mobilisation of energy reserves. Neurotransmitters and SympatheticFunction Stimulation of sympathetic preganglionic neurons leads to acetylcholine release at synapses with ganglionic neurons. These are called cholinergic synapses. The effect on the ganglionic neurons is always excitatory and leads to the release of neurotransmitters at specific target organs. The synaptic terminals are typically different from synaptic knobs in the SNS, consisting of chains of varicocities packed with neurotransmitter vesicles, which pass along or near the surfaces of effector cells. Most sympathetic ganglionic neurons release noradrenaline at their varicocities and are called adrenergic. Some also release acetylcholine and are located in the skin, body wall, brain and skeletal muscles. The noradrenaline released affects its target cells until reabsorbed or inactivated by enzymes. In general, the effects of noradrenaline on the postsynaptic membrane last a few seconds (where acetylcholine hasa 20msec duration). The effects of adrenaline or noradrenaline also last longer because the bloodstream doesn’t contain the enzymes to break the hormone down, and most tissues contain relatively low enzyme concentrations. There are two types of sympathetic receptors: α and β. Generally noradrenaline has a greater stimulatory effect on α receptors, where adrenaline stimulates both. α stimulation activates enzymes within the cell, the more common α1 receptor releases Ca2+ from reserves in the endoplasmic reticulum, which generally has an excitatory effect on a target cell. Stimulation of α2 receptors results in the lowering of cyclic-AMP levels in the cytoplasm which is an important messenger that can activate or inactivate key enzymes. This generally has an inhibitory effect and helps co-ordinate sympathetic and parasympathetic activities. Β receptors are located on the membranes of cells in many organs, including skeletal muscles and the heart, lungs and liver. The stimulation of β receptors triggers changes in the metabolic activity of the target cell. Β1 stimulation leads to an increase of metabolic activity, β2 stimulation causes inhibition, triggering a relaxation of smooth muscles along the respiratory tract and β3 stimulation leads to lipolysis. Most sympathetic postganglionic neurons are adrenergic, but a few are cholinergic and innervate sweat glands in the skin and blood vessels to skeletal muscles and the brain. In other regions of the body,acetylcholine is released by the parasympathetic division, but this does not innervate the body wall and skeletal muscles. The sympathetic division also includes nitroxidergic synapses which release nitric oxide as a neurotransmitter. Here, the activity of such synapses produces vasodilation and increased blood flow through these regions. ParasympatheticDivision Preganglionic fibres of the parasympathetic division do not diverge as extensively as hose of the sympathetic division. Terminal ganglia are located near target organs intramural ganglions are embedded in the tissues of the target organ. Intramural ganglia typically consist of interconnected masses and clusters of ganglion cells. Because all the ganglionic neurons are located in the same ganglion, influencing the same target organ, parasympathetic stimulation is often more specific and localised than sympathetic division. The vagus nerve provides roughly 75% of all parasympathetic outflow, from innervation of structures in the neck to the distal portion of the large intestine. The numerous branches of the vagus nerve intermingle with preganglionic and postganglionic fibres of the sympathetic division, forming plexuses comparable to those formed by spinal
  11. 11. Basic Tissues 10 nerves innervating the limbs. The sacral preganglionic fibres form distinct pelvic nerves which innervate intramural ganglia in the walls of the kidneys, urinary bladder, terminal portions of the large intestine and sex organs. Neurotransmitters and ParasympatheticFunction The major effects of parasympathetic activation include constriction of the pupils and focusing of the lenses of the eyes on nearby objects, secretion by digestive glands, secretion of hormones promoting absorption and uptake of nutrients by peripheral cells, changes in blood flow and glandular activity associated with sexual arousal, an increase in smooth muscle activity along the digestive tract, the stimulation and co-ordination of defecation, contraction of the urinary bladder during urination, constriction of the respiratory pathways and reduction in heart rate and contraction force. The parasympathetic has been called the anabolic system as its stimulation leads to a general increase in the nutrient content of the blood. Cells respond to this increase by absorbing nutrients and using them to support growth, cell division, and the creation of energy reserves in the form of lipids or glycogen. All parasympathetic neurons release acetylcholine, but the effects can vary widely depending on the type of receptor or secondary messenger involved. Te effects of stimulation are often short-lived because most of the neurotransmitter is inactivated by acetylcholinesterase at the synapse. Two types of receptor exist on postsynaptic membranes: nicotinic, causing the opening of chemically gated Na+ channels in the postsynaptic membrane and muscarinic, which activate or inactivate specific enzymes causing changes in membrane permeability to K+ and whose effects generally last longer. AutonomicTone The background level of activation determines a person’s autonomic tone, which is an important aspect of ANS function. If a nerve is inactive under normal conditions, all it can do is increase its activity on demand, but if the nerve maintains a background level of activity, it can increase of decrease its level of activity providing a greater range of control options. His, for example, allows precise control of heart rate and constriction of blood vessels affecting flow rate. The ANS is also organised into a series of interacting levels. At the bottom are visceral motor neurons in the brain stem and spinal cord that re involved in cranial and spinal visceral reflexes. Visceral reflexes provide autonomic motor responses that can be modified, facilitated or inhibited by higher centres, especially those of the hypothalamus. Pupil constriction and dilation is not only affected by light intensity, but also by emotional stress. When you are queasy, your pupils constrict, when sexually aroused your pupils dilate. Each visceral reflex arc consists of a receptor, sensory neuron, processing centre and two visceral motor neurons. All visceral reflexes are polysynaptic; they are either long or short reflexes. Long reflexes involve interneurons within the CNS, while short reflexes bypass the CNS entirely, controlling very simple reflex actions with localised effects. The short reflexes may only control small patterns of activity in one small part of a target organ, whereas long reflexes co-ordinate the activities of an entire organ. BasicTissues The cell is the smallest unit that carries out all the basic functions of life, tissues are masses of smaller cells and cell products that carry out a specific function, an organ is comprised of two or more tissues that work together to carry out a particular function and an organ system is a group of organs with a collective function. There are four basic tissue types: Epithelial tissue, which covers exposed surfaces, lines internal passageways and chambers and forms glands; connective tissue, which fills internal spaces provides structural support for other tissues, transports materials within the body and stores energy reserves; muscle tissue, which is specialised for contraction and includes the skeletal muscles of the body, the muscle of the heart, and the
  12. 12. Basic Tissues 11 muscular walls of hollow organs; and neural tissue, which carries information from on part of the body to another in the form of electrical impulses. EpithelialTissue Epithelia are composed almost entirely of cells bound closely together by cell junctions. In other tissue types, the cells are often widely separated by extracellular materials. In an epithelium consisting of a single layer of cells, exposed (apical) and attached (basal) surfaces differ in terms of membrane structure and function, and between the two surfaces the organelles are unevenly distributed. The base of an epithelium is bound to a thin basal lamina (basement membrane), the underlying connective tissue. Epithelial cells are also avascular (they lack blood vessels) and must obtain their nutrition by diffusion or absorption across either epithelial surface. Finally, epithelial cells that are damaged or lost at the apical membrane are constantly replaced through the divisions of stem cells in the epithelium. Epithelia provide physical protection from abrasion, dehydration and destruction; control permeability; provide sensation, they are often very sensitive as they have a large sensory nerve supply (a neuroepithelium is specialised to perform a particular sensory function and contain cells that provide the sensations of smell, taste, sight, equilibrium and hearing). Finally epithelial gland cells produce specialised secretions which are discharged onto the epithelial surface or released to the surroundings to act as chemical messengers. ClassificationofEpithelia Three cell shapes are identified: squamous, thin and flat where the nucleus occupies the thickest part of the cell; cuboidal, like small boxes and columnar, tall and slender rectangles. Once the shape of cells has been determined, one can look at the number cell layers: simple or stratified. Squamous Epithelia A simple squamous epithelium is the body’s most delicate epithelial type, located in protected regions where absorption of diffusion takes place, or where a slick, slippery surface reduces friction. Such examples include the lining of alveoli, ventral body cavities, blood vessels and the heart. Smooth linings are particularly important because irregularities may lead to the formation of a blood clot. A stratified squamous epithelium is generally located where mechanical stresses are severe. The cells form a series of layers on such areas as the skin surface, oral cavity, oesophagus and anus. On exposed surfaces prone to mechanical stress and dehydration, such as the skin, apical cells are packed with keratin filaments, toughening and waterproofing the layers. CuboidalEpithelia In 3-D these cells represent hexagonal boxes; the nuclei are near the centre of the cell. It provides limited protection and occurs where secretion or absorption occurs. Such an epithelium lines portions of the kidney tubules. Stratified cuboidal epithelia are relatively rare and are located along the ducts of sweat glands and in the larger ducts of the mammary glands. TransitionalEpithelia These types are quite rare and tolerate repeated cycles of stretching and recoil without damage. It is called transitional because the appearance changes as stretching occurs. When the urinary bladder is empty, the epithelium seems to have many layers, and the superficial cells are typically plump and cuboidal. When the bladder has stretched to its limits, the epithelium appears flattened. ColumnarEpithelia These cells typically appear rectangular in reality they are hexagonal,like the cuboidal epithelia, but taller and more slender. They are typically found where absorption or secretion occurs, like in the small intestine. In the large intestine and stomach, the secretions of simple columnar epithelia protect against chemical stresses.
  13. 13. Basic Tissues 12 Portions of the respiratory tract contain a pseudostratified columnar epithelium, including several cell types of varying shape and function. It appears to be stratified, but every cell contacts the basal lamina so it is not. Pseudostratified cells typically possess cilia. Epithelia of this type line most of the nasal cavity, the trachea, bronchi and portions of the male reproductive tract. Stratified columnar epithelia are relatively rare, providing protections along portions of the pharynx, epiglottis, anus and urethra. If the epithelium has more than two layers, only the superficial cells are columnar. GlandularEpithelia The cells range from scattered cells to complex glandular organs. Endocrine glands release secretions directly into the surrounding interstitial fluid and Exocrine glands discharge secretions onto an epithelial surface. MaintainingtheIntegrity ofEpithelia Cells in an epithelium are firmly attached to one another and the epithelium as a unit is attached to extracellular fibres of the basal lamina. Large areas of opposing cell membranes are interconnected by transmembrane proteins called cell adhesion molecules (CAMs) which bind to each other and to extracellular materials. Cell junctions are specialised areas that attach a cell to another cell or to extracellular materials. Hemidemosomes attach the cells to the basement membrane, thereby stabilising the position of the cell and anchoring the cell to the underlying tissue. The three most common types of cell junctions are tight junctions, desmosomes and gap junctions. At a tight junction the lipid portions of two cell membranes are bound together by interlocking membrane proteins. A continuous adhesion belt forms a band that encircles cells and binds them to their neighbours. This type of attachment is so tight that they prevent the passage of water and solutes between the cells. In the digestive tract, this prevents enzymes, acids and wastes from destroying the basement membrane and underlying tissues and organs. Because most epithelial cells are subject to mechanical stresses like bending, twisting, stretching or compression, they must have durable connections called desmosomes. It is the connection to the cytoskeleton that gives the desmosome, and the epithelium, its strength. They are abundant between cells in the superficial skin layers and this is why skin peels in sheets rather than cells. Some epithelial functions require rapid intercellular communication. At a gap junction, two cells are held together by interlocking membrane proteins called connexions. These care channel proteins and form a narrow passageway that lets small molecules and ions pass between cells. Gap junctions are common among epithelial cells where ion transport helps co-ordinate such functions as the beating of cilia. Gap junctions in cardiac and muscle tissue and smooth muscle are essential to the co-ordination of muscle cell contractions. ConnectiveTissue In essence, the connective tissue connects the epithelium to the rest of the body.Connective tissue includes connective tissue proper, fluid connective tissue and supporting connective tissue. Some specialised connective tissues include bone, cartilage and blood.All connective tissues share three basic components: specialised cells, extracellular cells and a fluid known as ground substance. The ground substance and extracellular fibres make up the matrix which surrounds the cells. Connective tissue plays an important role in establishing support and a structural framework, transporting fluids and dissolved minerals, protecting delicate organs, storing energy reserves (especially as lipids) and defence from microorganisms. Fibroblasts are always present in connective tissue proper; they secrete hyaluronan which makes collagen and elastic fibres. Connective tissue may also contain lymphocytes, microphages, macrophages, adipocytes, mesenchymal cells (stem cells that respond to injury), melanocytes and mast cells which release histamine on infection.
  14. 14. Types of Muscle 13 Loose ConnectiveTissue Loose connective tissue fills the space between organs, providing support, and also supports blood vessels and nerves, provides a route for the diffusion of materials and storage of lipids. Loose connective tissues include areolar, adipose and reticular tissue in adults. Areolar tissue is the least specialised and contains few fibres with a viscous ground substance accounting for the most of its volume and allowing the absorbance of shocks. Areolar tissue forms a layer that separates the skin from deeper structures and the presence of elastic fibres allows the tissue to restore its original shape, enabling a considerable amount of independent movement. Because this areolar layer under the skin hasan extensive blood supply, it is a common injection site for drugs. Dense ConnectiveTissue Collagen is the dominant fibre in these tissues and they contain little ground substance. Dense regular connective tissue contains densely packed collagen fibre bundles arranged in parallel rows and aligned with the forces applied to the tissue. Tendons are bundles of dense regular connective tissue that attach muscles to bones, this structure is also found in aponeuroses and tendons. In contrast, dense irregular connective tissue contains collagen fibres arranged with no specific pattern and strengthen tissues subject to stresses from many directions, such as the skin. Except at joints, dense irregular connective tissue forms a sheath around cartilages and bones, and also makes up the tough capsule found to surround internal organs such as the liver, kidneys and spleen. Types ofMuscle There are three types of muscle tissue: skeletal, smooth and cardiac muscles and without these tissues nothing in the body could move. Skeletal muscles move by pulling on the bones of the skeleton, cardiac muscle pushes blood through the circulatory system and smooth muscle pushes fluids and solids along the digestive tract and regulates the diameters of small arteries among other things. Skeletal muscle Skeletal muscles are organs, composed of skeletal muscle tissue, connective tissues, nerves and blood vessels. Each cell in skeletal muscle tissue is a single fibre. Skeletal muscles are made up of multinucleated, striated tissue that is innervated by the somatic nervous system. They produce skeletal movement, maintain posture, support soft tissues, guard entrances and exits as sphincters, maintain body temperature through shivering and store nutrient reserves as contractile proteins. The entire muscle is surrounded by a dense layer of collagen fibres called epimysium; the perimysium divides the skeletal muscle into a series of compartments, each containing a bundle of muscle fibres called a fascicle. The perimysium contains blood vessels and nerves which innervate the muscle fibres within the fascicles. Within a fascicle, the delicate connective endomysium tissue surrounds the individual fibres (or cells). This tissue contains capillary networks, satellite cells (embryonic stem cells that repair damaged muscle tissue) and nerve fibres that control the muscle. At each end of the muscle, the collagen fibres of the epimysium, perimysium and endomysium come together to form a tendon, or a broad sheet called an aponeurosis, which firmly attaches the skeletal muscles to the bone matrix within the bones. In a muscle fibre, there exist many bundles of protein filaments (or myofilaments) called myofibrils. There are two types of myofilament; thick, composed mainly of myosin and thin, composed mainly of actin. A myofibril consists of approximately 10,000 sarcomeres end to end. Each sarcomere has dArk bands (A) of myosin and lIght bands(I) of actin.
  15. 15. Types of Muscle 14 CardiacMuscle Cardiac muscle cells can also be called cardiocytes or cardiac myocytes and like skeletal muscle fibres, cardiac cells contain organised myofibrils and the presence of many aligned sarcomeres gives the cells a striated appearance. However, significant functional and structural differences exist between the two. Cardiac muscle cells are very small, a typical cardiac muscle cell has a single, central nucleus, although a few may have two or more. They consist of intercalated discs containing gap junctions and are innervated by the autonomic nervous system. They are almost totally dependent on aerobic metabolism to obtain the energy they need to continue contracting. Energy reserves are maintained in the form of glycogen and lipid inclusions. The sarcoplasm of cardiac muscle cells contain large numbers of mitochondria and abundantmyoglobin reserves which store the oxygen needed to break down the energy reserves in emergencies. At an intercalated disc, the cell membranes of two adjacent cardiac muscle cells are extensively intertwined and bound together by gap junctions and desmosomes, helping to stabilise the relative positions of adjacent cells and maintain the 3D structure of the tissue. Gap junctions allow ions and small molecules to move from one cell to the other, creating a direct electrical connection and allowing an action potential to quickly travel along an intercalated disc. Myofibrils in the interlocking muscle cells are firmly attached to the membrane at the intercalated disc. Because their myofibrils are essentially locked together they can pull together with maximum efficiency. Because the muscle cells are mechanically, chemically and electrically connected, the entire issue resembles a single, enormous muscle cell. Cardiac muscle contracts without neural stimulation (automaticity) and the timing is usually determined by pacemaker cells but innervation by the nervous system can alter the pace established by them. Cardiac muscle contractions last roughly ten times as long as those of skeletal muscle fibres, they also have longer refractory periods and do not readily fatigue. The properties of cardiac muscle membranes differ from those of skeletal muscle membranes. As a result, individual twitches cannot produce tetanic contractions (where a motor unit has been maximally stimulated by its motor neurons). This is important as a heart in sustained tetanic contraction could not pump blood. Smooth Muscle Smooth muscle tissue forms sheets, bundles or sheathes around other tissues in almost every organ. Smooth muscles around blood vessels regulate blood flow through vital organs. In the digestive system, rings of smooth muscle called sphincters regulate the movement of materials along internal passageways. Smooth muscle plays roles in the integumentary system, regulating the blood flow to the superficial dermis and the contraction of arrector pili muscles; in the cardiovascular system, helping to distribute blood and regulate blood pressure; in the respiratory system, allowing the diameters of respiratory passageways to change the resistance to airflow; in the digestive system; the urinary system and reproductive system, where oocytes and sperm are helped along the reproductive tracts.
  16. 16. The Anatomy of Blood Vessels 15 Smooth muscle cells are relatively long and slender, they are spindle shaped with a single, centrally located nucleus The sarcoplasmic reticulum forms a loose network throughout the sarcoplasm and smooth muscles lack myofibrils and sarcomeres, as a result they are non-striated. Thick filaments are scattered throughout the sarcoplasm and the myosin filaments are organised in a different manner than the other two muscle types, and smooth muscle cells have more myosin heads per thick filament. The thin filaments are arranged in dense bodies that are not arranged in straight lines, so when contraction occurs, the muscle twists like a corkscrew. Adjacent smooth muscle cells are bound together at dense bodies, transmitting the contractile forces from cell to cell throughout the tissue. In smooth muscle cells the trigger for contraction is the appearance of Ca2+ ions, but instead of binding to troponin, they interact with calmodulin, activating the enzyme myosin light chain kinase, which enables the attachment of the myosin heads to the actin. Because the thick and thin filaments are scattered, the cell can contract over a wide range of lengths, this is called plasticity and is especially important in digestive organs such as the stomach that undergo great changes in volume. Like skeletal muscle fibres, smooth muscle can also undergo sustained contractions. Smooth muscle cells are categorised as multiunit, which are innervated in motor units comparable to those of skeletal muscles, and visceral, which lack direct contact with any motor neuron. Both multiunit and visceral tissues have a normal background activity, or smooth muscle tone. The regulatory mechanisms simply stimulate contraction and increase or decrease muscle tone through neural, chemical or hormonal factors. The Anatomy ofBlood Vessels Arteries carry oxygenated blood away from the heart, as they enter peripheral tissues they branch and decrease in diameter, the smallest of which are called arterioles. From here, blood moves into capillaries, where diffusion occurs between the blood and interstitial fluid, and then into venules, which unite to form larger veins that return blood to the heart. Blood vessels must be able to endure pressure changes, move with surrounding structures and remain open under all conditions. The tunica intima is the innermost layer of a blood vessel, containing the endothelial lining and an underlying layer of connective tissue containing many elastic fibres. In arteries, a thicker internal elastic membrane is present. The tunica media, the middle layer, contains concentric sheets of smooth muscle in a framework of loose connective tissue. The three layers are bound by collagen fibres and in arteries a thin external elastic membrane separates the tunica media from the tunica externa. The tunica externa is a connective tissue sheath. In arteries this contains collagen fibres and scattered elastic fibres. In veins it is generally thicker than the tunica media and contains a network of elastic fibres and bundles of smooth muscle cells. The connective tissues of the tunica externa typically blend into adjacent tissues, anchoring the vessel. Because the walls are so thick, diffusion cannot occur across them, so they have their own blood supply to supply the smooth muscle cells, known as the vaso vasorum (vessels of vessels). Differences betweenArteries and Veins Arteries and veins servicing the same region usually lie side by side. In general arteries have thicker walls as the tunica media contains more smooth muscle and elastic fibres, arteries recoil and have a much smaller lumen than the veins, which tend to collapse and therefore look distorted in section. The endothelium of an artery cannot contract and so looks heavily folded when the artery is contracted, this does not happen in the case of veins. When comparing in gross dissection, arteries can be stretched, returning to their original shape when released and veins typically contain valves.
  17. 17. The Anatomy of Blood Vessels 16 Elastic (conducting) arteries are large vessels, such as the aorta and brachiocephalic and common carotid arteries, with a diameter of up to 2.5cm, which transport large volumes of blood away from the heart. The walls have a thick tunica media with a high density of elastic fibres, allowing them to withstand pressure and maintain continuous blood flow (eliminating large oscillations in pressure forces) through elastic rebound. Muscular (distributing) arteries distribute blood to the body’s skeletal muscles and internal organs. Most arteries are of this type, characterised by a thick, muscular tunica media. The diameter of these arteries can vary between 0.5mm and 0.4cm. Superficial muscular arteries are important as pressure points, allowing control of severe bleeding by forcing the vessel against deeper bones. Arterioles have a diameter of less than 30µm, a poorly defined tunica externa and the tunica media of the smallest arterioles contains scattered smooth muscle cells that do not form a complete layer. Arterioles control blood flow to organs and the diameter changes in response to local conditions or sympathetic stimulation, and so they are often called resistance vessels. Arterioles carry the blood under high pressure, occasionally; arterial pressure exceeds the capacity of the elastic components of the tunica, forming an aneurism, which could eventually suffer a catastrophic blowout. The most dangerous aneurisms occur in the brain. Capillaries are thin walled and are the site of gaseous, nutrient and waste exchange, permitting a two-way exchange of substances between the blood and interstitial fluid. They also have a diameter of 8µm, very close to the diameter of a single red blood cell. There are two types of capillaries: Continuous, where the endothelium is a complete lining, and fenestrated, where pores penetrate he epithelial lining. Continuous capillaries are most common and permit the diffusion of water, small solutes and lipid-soluble materials into the surrounding interstitial fluid, but prevent the loss of blood cells and plasma proteins. Fenestrated capillaries permit the rapid exchange of water and solutes as large as small peptides between plasma and interstitial fluid. Sinusoids resemble flattened and irregularly shaped capillaries but have gaps between endothelial cells and the basal lamina is either thinner or absent. In capillary beds (or plexuses), the entrance to each capillary is guarded by a precapillary sphincter, allowing control of the rate of blood flow and metarterioles, which connect different thoroughfare channels. A capillary bed may receive blood from more than one artery. These multiple arteries called collaterals fuse before giving rise to arterioles. The fusion of two collateral arteries is an example of an arterial anastomoses. This allows capillary circulation to continue if one artery is compressed or blocked. Atriovenous anastomoses are direct connections between arterioles and venules Venules collect blood from the capillary beds; an average venule has an internal diameter of roughly 20µm. Venules smaller than 50µm lack a tunica media. Small venules have an endothelium of the basement membrane and as they get larger they have increasing numbers of smooth muscle cells. Medium-sized veins rage from 2 to 9 mm in internal diameter, comparable in size to muscular arteries. These veins contain a thin tunica media, with relatively few smooth muscle cells. The tunica externa is the thickest layer, containing longitudinal dandles of elastic and collagen fibres. Large veins include the superior and inferior vena cavae. All the tunica layers are present in all large veins. The tunica media is surrounded by a thick tunica externa composed of a mixture of collagen and elastic fibres. Veins are often referred to as capacitance vessels and contain valves to assist blood flow. Total blood volume is distributed unevenly throughout the vessels. The systemic venous circulation contains more than half the total blood at 64%, the systemic arterial system contains 13%, the pulmonary circulation 9%, and the heart and capillaries contain 7%.
  18. 18. Gross Anatomy of the Circulations 17 Gross Anatomy ofthe Circulations The cardiovascular system transports fluid throughout the body to deliver oxygen, nutrients and hormones, and remove waste products such as carbon dioxide. The cardiovascular system consists of the pulmonary and systemic circuits. Tissues and organs are usually serviced by several vessels, often anastomoses between adjacent arteries and veins reduce the impact of a temporary or permanent occlusion of a single blood vessel. The arterial pulse can be counted at any site where a superficial artery can be pressed against a bone. Sites include the carotid, radial and ulnar arteries (easiest to find), and the facial (on the mandible), temporal, dorsalis pedis (top of the foot) and posterior tibial (back of the ankle) arteries. The Pulmonary Circuit At the lungs, oxygen is replenished and CO2 released. In the pulmonary circuit the arteries are the ones which carry the deoxygenated blood. As the pulmonary trunk curves over the superior border of the heart, it gives rise to a left and right pulmonary artery, which enter the lungs before branching repeatedly giving rise to smaller and smaller arteries and finally arterioles which provide blood to capillary networks that surround the alveoli, where gas exchange takes place. The SystemicCircuit The aortic arch branches into the brachiocephalic trunk, the left subclavian, the left vertebral artery and the thoracic aorta. The brachiocephalic trunk branches into the right common carotid and right vertebral artery, which supply the cranial region, and the right subclavian, supplying the arm. The thoracic aorta penetrates the diaphragm, where it becomes the abdominal aorta. The terminal segment of the abdominal aorta divides into the left and right common ileac arteries, which eventually become the femoral arteries. Name of Artery Region Supplying Name of Artery Region Supplying Celiac Trunk Liver, Stomach, Spleen Suprarenal Adrenal glands Superior Mesenteric Pancreas, Duodenum Renal Kidneys Inferior Mesenteric Terminal colon portions Gonodal Testes/ Ovaries Inferior Phrenic Diaphragm surface Lumbar Spinal cord, Abdominal wall The branching pattern of peripheral veins (of the limbs) is more variable than that of arteries. The Inferior vena cava pierces the diaphragm, the names being mostly similar to that of the arterial system. Blood returning from the intestines passes into the hepatic portal vein and through the liver before draining into the vena cava, ensuring the composition of the blood in the systemic circulation is relatively stable despite changes in diet and digestive activity. In the portal system, blood passes through two consecutive capillary networks before returning to the heart. Name of Vein Region Supplying Name of Vein Region Supplying Hepatic Liver Suprarenal Adrenal glands Superior Mesenteric Stomach, Intestine Renal Kidneys Inferior Mesenteric Colon Gonodal Testes/ Ovaries Phrenic Diaphragm Lumbar Spinal cord, Abdominal wall Splenic Spleen, Pancreas Foetal Circulation The nutritional and respiratory needs of the foetus are provided by diffusion across the placenta. There are three circulatory shortcuts in foetal circulation: the ductus venosus, ductus arteriosus and foramen ovale. Blood flow to the placenta is provided by a pair of umbilical arteries, arising from the internal iliac arteries. Blood returns from the placenta in the umbilical vein, bringing O2 and nutrients to the foetus. The umbilical vein
  19. 19. Gross Anatomy of the Circulations 18 empties into the ductus venosus, connecting a capillary network in the liver. The ductus venosus collects blood from the veins of the liver and empties into the vena cava. Blood passes through an opening in the heart, known as the foramen ovale, allowing blood to bypass the lungs, as they are collapsed; the foetus does not breathe in the womb. A second short-circuit known as the ductus arteriosus allows blood flow between the pulmonary artery and aorta. At birth, when an infant takes the first breath (first cry), the lungs expand, as do the pulmonary vessels. The resistance in the pulmonary circuit lessens and blood rushes into the pulmonary vessels. Rising O2 levels stimulate the closure of the ductus arteriosus through smooth muscle constriction. As pressures in the left atrium rise, the valvar flap closes the foramen ovale. Problems may develop later if these changes do not occur at birth. LymphaticSystem The lymphatic system includes the cells, tissues and organs responsible for defending the body against environmental threats, such as various pathogens, and internal threats, such as cancer. Lymphocytes are the primary cells of the lymphatic system and act to render threats harmless through a combination of physical and chemical attacks. Nonspecific defences do not distinguish one threat from the other and specific defences, such as pathogens, organise a defence against one particular type of pathogen, the ability to resist infection and disease through specific defences constitutes immunity. The immune system not only consists of the lymphatic system, but also systems it may have to interact with in order to mobilise specific defences. The lymphatic system consists of lymph fluid, lymphatic vessels, beginning in peripheral tissues and ending at connections with veins, an array of lymphoid tissues and lymphocytes, phagocytes and various other cells. Most of the body’s lymphocytes are produced and stored within lymphoid tissues, such as the tonsils, and lymphoid organs, such as the spleen and thymus. Lymphocytes are also produced in areas of red bone marrow, along with other cells such as monocytes and macrophages. Lymphocytes, monocytes and macrophages circulate within the blood and are able to enter or leave the capillaries that supply most tissues within the body. The excess fluid returns to the bloodstream through lymphatic vessels, the continuous circulation allowing
  20. 20. Anatomy of the Heart 19 efficient transport. In the process it maintains blood volume and eliminates local variations in the composition of the interstitial fluid by distributing hormones, nutrients and waste products in the general circulation. The lymphatic network begins with lymphatic capillaries which branch through peripheral tissues. Lymphatic tissues originate as pockets, rather than forming continuous tubes, have larger diameters, thinner walls and typically have a flattened or irregular outline in section. Endothelial cells of a lymphatic capillary overlap allowing the one-way diffusion of fluids, solutes, viruses, bacteria and cell debris into the lymphatic system. Prominent ‘lacteals’ in the digestive system are important, allowing the transport of absorbed lipids. The bone marrow and CNS, as well as areas lacking a blood supply, lack lymphatic vessels. The role of the lymphatic circulatory system is to absorb the excess fluid that enters the lymphatic system when filtered in capillary networks. Hydrostatic pressure, as a result of the pressure exerted in the blood as the heart contracts, forces tissue fluid into the interstitial space at the arterial end of the capillary, while at the venous end, because of colloid osmotic pressure, fluid moves back into the capillary. But, approximately 15% of interstitial fluid is left behind and this enters the lymphatic system to be returned to the blood. Oedema is swelling caused by the accumulation of tissue fluid in any organ. Lymph capillaries drain into lymph vessels, which have visible bulges, containing valves. Superficial and deep lymphatics drain into lymphatic trunks, in turn emptying into two large collecting vessels: the right lymphatic duct, draining the right side of the thorax and head, and the thoracic duct, draining the remainder of the body. The ducts empty into the subclavian veins, allowing the lymph to enter the bloodstream. Lymph nodes mostly protect the vital organs in the thoracic and abdominal cavities and are collections of lymphatic tissue, mainly located in regions around the neck, armpit and groin. They purify lymph before it reaches the venous circulation. Fixed macrophages in the walls engulf debris or pathogens. Antigens removed in this process are presented to nearby lymphocytes allowing specific antibodies to be made. Lymph nodes allow an early warning system to infection. Anatomy ofthe Heart The heart sits between the lungs within the mediastinum surrounded by the pericardial sac. The heart lies between the 2nd and 5th ribs, 2/3 lie to the left of the sternum and the great vessels arise from the base. The pericardium is lined by a delicate serous membrane, which can be subdivided into the visceral pericardium (closely covering the outer heart surface) and the parietal pericardium (lining the inner surface of the pericardial sac). The fibrous pericardium (pericardial sac) consists of a dense network of collagen fibres, stabilising the position of the heart and preventing overfilling. The space between the membranes is called the pericardial cavity and normally contains 15-50 ml of pericardial fluid, preventing friction between the surfaces as the heart beats. A section of the heart wall clearly reveals three layers: an outer epicardium, the visceral pericardium, a middle myocardium, concentric layers of cardiac muscle tissue, and an inner endocardium, a simple squamous epithelium, continuous with the epithelium of attached vessels. The fibrous skeleton of the heart consists of four dense bands of tough elastic tissue that separate, and offer electric insulation between, the atria and ventricles. It encircles the pulmonary trunk, aorta and heart valves. Heart valves are composed of flaps (cusps) which are attached to the fibrous skeleton. Atrioventricular valves prevent backflow (regurgitation) of blood from the ventricles to the aorta when the ventricles contract. Contraction of the ventricle contracts the papillary muscles, which tenses the chordate tendenae, stopping reversion of the valves. The semilunar valves are opened by the blood being forced out the ventricles as they contract. During ventricular relaxation the blood pools in the cusps and pushes them shut so there is no need for muscular braces.
  21. 21. Haematology 20 The coronary circulation supplies blood to the muscle tissue of the heart and includes an extensive network of coronary blood vessels. The left and right coronary arteries originate at the base of the aorta. As the ventricle contracts blood is pushed into the systemic circulation, as it relaxes the walls of the aorta recoil pushing blood both forwards and backwards, therefore blood is delivered to the heart during ventricular relaxation. Myocardial blood flow peaks when the heart muscle is relaxed and almost ceases while it contracts. The right coronary artery supplies the right atrium, portions of both ventricles and portions of the conducting system of the heart. It gives rise to one or more marginal arteries and the posterior interventricular artery. The left coronary artery supplies blood to the left ventricle, left atrium and the interventricular septum. It branches into the circumflex artery and the larger anterior interventricular artery. Most cardiac veins drain into the cardiac sinus, which empties into the right atrium. Coronary angiograms are performed to determine whether there is a blockage in the coronary arteries. Blockage can lead to angina or myocardial infarction. Scar tissue may mean that the cardiac muscle cannot conduct impulses, leading them to be conducted by other tissues and leading to chest pains Haematology Blood has many functions including the transportation of dissolved gases, nutrients, hormones and metabolic wastes to each of the 75 trillion cells in the body and the regulation of the pH and ion composition of interstitial fluids. Diffusion between interstitial fluids and blood eliminates excesses of ions such as Ca2+ or K+. Blood also absorbs and neutralises acids (such as lactic acid) generated by active tissues. Blood also restricts the loss of fluid at injury sites through clotting, defends against toxins and pathogens with leucocytes and the stabilisation of body temperature by absorbing heat generated by skeletal muscles and distributing it to other organs. If body temperature is too low the blood is redirected to the brain and other temperature-sensitive organs. Blood is roughly 38°C, slightly above normal body temperature, five times as viscous as water, and slightly alkaline with a pH between 7.35 and 7.45. The cardiovascular system of an adult male contains 5-6 litres of whole blood. Blood is a fluid connective tissue with a matrix called plasma, which has a high protein concentration and is therefore denser than water. It makes up 46-63%of the blood and water accounts for about92% of the plasma volume. Formed elements make up 37-54% of the blood and are the blood cells and cell fragments that are suspended in plasma. It contains erythrocytes, leucocytes and platelets.
  22. 22. Haematology 21 A standard blood test reveals the number of erythrocytes per micro-litre as the red blood cell count, typically about 5 million/µl in an adult human. An average adult has around 25 trillion red blood cells, making them count for roughly a third of all cells in the human body. The haematocrit is determined by centrifuging a blood sample and is the percentage of whole blood volume contributed by formed elements, averaging at about 46% in males and 42% in females. This reflects that androgens, male hormones, stimulate red blood cell production, whereas oestrogens, female hormones, do not. The haematocrit is commonly reported as PCV, or packed cell volume. Many conditions can affect this value; it can increase as the result of dehydration, or decrease as a result of internal bleeding or problems with red blood cell formation. Mean cell volume, or MCV is calculated as the PCV/RBC count and isusually about 90 fl (femto-litre = 10-15 litres) Red Blood Cells (Erythrocytes) The structure of red blood cells allows them to have a larger surface area-to-volume ratio and this maximises the exchange rate of O2 and CO2 in the lungs and peripheral tissues. The total surface area of all erythrocytes in the body is aboutthe size of a football pitch. Their structure also allows them to form stacks and to be flexible when passing through capillaries as narrow as 4µm. Because the mature red blood cells have no nuclei, their lifespan is limited to a lifespan of less than 120 days. Haemoglobin (Hb) molecules have complex quaternary structures, containing two α chains and two β chains of polypeptides. There are four haem units per haemoglobin molecule and each haem unit holds an Fe2+ ion in such a way that allows an oxygen molecule to bind, forming the HbO2, oxyhaemoglobin, a bright red substance. The iron-oxygen interaction is very weak and the two can easily dissociate without damaging the molecule structure. This reaction is therefore completely reversible, and a molecule whose iron is not bound to oxygen is called deoxyhaemoglobin, a dark red substance. Foetal haemoglobin (HbF) binds oxygen more readily than that of adults, allowing the foetus to “steal” oxygen from the mother’s circulation. The production of foetal haemoglobin can be stimulated in adults and this can be a treatment for conditions such as sickle cell anaemia (HbS) or thalassemia; the deficient production of one of the globulin chains. When plasma oxygen levels are low, haemoglobin releases oxygen and carbon dioxidebinds with an NH2 group of globulin chains forming carbaminohaemoglobin. Only 5% of the CO2 is transported in this way, the rest is carried as bicarbonate, soluble in plasma. The ability of Hb to carry O2 is decreased by CO2 and pH concentrations. This is known as the Bohr Effect. Carbon Monoxide binds to the same site as O2 forming carboxyhaemoglobin and has a much higher affinity for haemoglobin, about 250 times that of oxygen! H+ binds to histidine residues on globulin chains, but haemoglobin acts as a buffer which, prevents pH changes as a low pH decreases the affinity of haemoglobin for oxygen.
  23. 23. Haematology 22 Red Blood Cell Destructionand Recycling In a foetus, stressed and damaged red blood cells are broken down in the liver, spleen and muscle; infants use all bone marrow to break them down; and adults only use red bone marrow, found in the ribs, vertebrae, skull and upper ends of long bones. Macrophages of the liver, spleen and bone marrow monitor the condition of circulating red blood cells, generally recognising and engulfing them before they haemolyse. If the Hb released by haemolysis is not phagocytised, the components will not be recycled. When haemolysis occurs, the Hb breaks down and the chains are filtered by the kidneys and eliminated in urine. If large numbers are broken down the urine may turn red or brown; haemoglobinuria. If intact red blood cells are found in the urine, haematuria, it shows kidney damage or damage to the vessels along the urinary tract. Once a red blood cell has been engulfed and broken down by a phagocyte, the globular proteins are broken down to amino acids and metabolised by the cell or released into the bloodstream, the haem units are stripped of their iron and converted to biliverdin, then bilirubin and released into the bloodstream, where it binds to albumin and is transported to the liver for excretion in bile. If the bile ducts are blocked, or the liver cannot absorb or excrete bilirubin, circulating concentrations of the compound increase rapidly and diffuse into peripheral tissues giving them a yellow colour. This is called jaundice. In the large intestine, bacteria break down biirubin to related pigments which are excreted in the urine and faeces, giving them their characteristic colours. Since large quantities of free iron are toxic to cells, it is generally bound to transport or storage proteins. From breakdown in the phagocytic cell, iron binds to transferrin. Red blood cells developing in the bone marrow absorb the amino acids and transferrins from the bloodstream and use them to synthesise new Hb molecules. Excess transferrins are removed in the livr and spleen. Red Blood Cell Formation(Erythropoiesis) Red blood cell formation in adults only occurs in red bonemarrow (myeloid tissue), located in portions of the vertebrae, sternum, ribs, skull, scaplulae, pelvis and proximal limb bones. Other marrow areas contain a fatty tissue known as yellow bone marrow. Under extreme stimulation, such as in times of severe blood loss, areas of yellow marrow can covert to areas of red marrow, increasing red blood cell production. Divisions of haemocytoblasts in bone marrow produce either myeliod stem cells or lymphoid stem cells. Cells determined to become red blood cells first differentiate from myeliod stem cells into proerthroblasts and proceed through varios erythroblast stages. After four days the nucleus is ejected and the cell becomes a reticulocyte, containing 80% total Hb. The final 20% Hb is synthesised in the last two days of production, the cell is released in the circulation and after a further 24 hours, the maturation is complete.
  24. 24. Haematology 23 Blood Types Blood type is a classification determined by the presence or absence of specific surface antigens in red blood cell membranes. The surface antigens are integral glycoproteins, whose characteristics are genetically determined. The three main surface antigens of importance are A, B and Rh (D). Rh+ indicates the presence of the Rh surface antigen and Rh- indicates its absence. Type AB has both surface antigens and is therefore a universal recipient, and type O has neither antigens and is therefore a universal donor. The immune system ignores its own agglutinogens (surface antigens); however your plasma contains antibodies that will attack the antigens on “foreign” red blood cells and thus causing the cells agglutinate, and possibly even resulting in haemolysis. The plasma of an Rh negative individual only contains anti-Rh antibodies if the individual has been sensitised by previous exposure. This can happen during transfusion, or in haemolytic disease of the newborn. Blood type compatibility testing is very important when considering blood donors. A test is carried out where drops of blood are taken and mixed with different antibodies, any cross-reactions causing agglutination are recorded HaemolyticDiseaseofthe Newborn Genes controlling the antigen type are provided by both parents and as such a child may have a different blood type to either parent. During pregnancy, when the circulatory systems of the mother and foetus are intertwined, the mother’s antibodies may cross the placenta, attacking and destroying the foetal red blood cells. Forms of the disease involving Rh surface antigens are quite dangerous because, unlike anti-A and anti-B antibodies, anti-Rh antibodies can cross the placenta and enter the foetal bloodstream, so problems may occur if an Rh-negative woman carries an Rh-positive foetus. If mixing of the blood takes place at delivery, the mother becomes sensitised and starts to produce anti-Rh antibodies. Because the Rh antibodies are not produced in significant amounts until after delivery, the first child is unaffected, but if a second pregnancy of an Rh-positive child follows, the maternal anti-Rh antibodies may cross the placenta and enter the foetal bloodstream. These antibodies destroy foetal red blood cells causing the foetus to be in a constant demand for more red blood cells and the fast production of immature red blood cells. The foetus may die shortly after delivery if not treated with a full blood transfusion. In severe cases the newborn may be anaemic, and high circulating levels of bilirubin may cause jaundice. Anaemia Anaemia reduces O2 delivery to tissues and can cause weakness, lethargy and confusion. It can have numerous causes mainly including iron deficiency or small continued blood loss, such as through menstruation in females. It can also result from the massive destruction of haemoglobin due to abnormal haemoglobin or membranes. Vitamin B-12 deficiency can cause macrocytic anaemia (detected from a large MCV) or Crohn’s disease (a type of inflammatory bowel disease). Stomach acid enables vitamin B-12 absorption from food sources. Folic acid deficiency causes similar problems to vitamin-B12 deficiency. Sickle cell anaemia is hereditary, mainly found in regions such as Africa and Wet India, and produces an abnormal Hb structure so red blood cells get stuck in blood vessels. There is no cure. Thalassaemia is also hereditary, mainly in Mediterranean or Far Eastern regions and leads to the production of fewer red blood cells containing HbF, foetal-like haemoglobin, due to the deficiency in the production of the globulin chains. Platelets (Thrombocytes) Platelets, or “thrombocytes” in non-vertebrates, are a major participant in a vascular clotting system. They are small, membrane bound cell fragments which contain numerous granules and release important enzymes and chemicals. In the clotting process they clump together to form a temporary patch in the walls of damaged blood vessels and actively contract after cot formation has occurred, shrinking the size of the break in the wall.
  25. 25. Haematology 24 Each platelet circulates for about 9-12 days before being removed by phagocytes, generally in the spleen. Reserves of platelets are held in the spleen and other vascular organs, rather than the bloodstream, and are mobilised in times of crisis, such as severe bleeding. They are formed from megakaryocytes in bone marrow. Haemostasis The process of haemostasis is the cessation of bleeding, halting the loss of blood and establishing a framework for tissue repair. It consists of three stages: the vascular, platelet and coagulation phases, but in reality the boundaries of these phases are somewhat arbitrary. In the vascular phase, cutting the wall of a blood vessel triggers a vascular spasm, the local contraction of the wall of a blood vessel, lasting about 30 minutes and reducing the flow of blood at the site of injury. During this the endothelial cells contract and expose the underlying basal lamina to the bloodstream, the endothelial cells begin releasing chemical factors and local hormones, stimulating vascular spasms and the division of endothelial and smooth muscle cells for repair. The endothelial cell membranes also become sticky to facilitate re-attachment of the vessel and the attachment of platelets to the site of injury. The platelet phase involves the attachment of platelets to the sticky endothelial surfaces, as more platelets arrive they form a platelet plug through platelet aggregation. As they arrive at the site of injury they become activated, firstly they become more spherical and develop cytoplasmic processes that extend towards adjacent platelets. At this time the platelets begin to release compounds including ADP, stimulating platelet aggregation and secretion; serotonin, stimulating vascular spasms; clotting factors; PDGF, promoting vessel repair and calcium ions, required for platelet aggregation. The process undergoes a positive feedback loop that continues until various inhibiting factors are produced. The coagulation phase does not start until 30 seconds or more after the vessel has been damaged. Blood clotting involves a complex sequence of steps leading to the conversion of circulating fibrinogen into the insoluble protein fibrin. As the fibrin network grows it covers the surface of the platelet plug and traps passing blood cells and additional platelets that seal off the damaged portion of the vessel. Three pathways merge to form the blood clot; the intrinsic, extrinsic and common pathways. WhiteBlood Cells (Leucocytes) White blood cells have nuclei and other organelles; they defend the body against pathogens and remove toxins, wastes and other damaged cells. White blood cells migrate through the loose and dense connective tissues, using the blood-stream primarily to travel from one organ to another and for rapid transportation to areas of infection or injury. When problems are detected they leave the bloodstream and enter the damaged area. Leucocytes are classified into granulocytes and agranulocytes with Wright’s stain. All leucocytes can migrate out of the bloodstream, they stick to the vessel walls following activation “margination” and then squeeze between the endothelial cell and into the tissues “emigration”; are capable of amoeboid movement, a gliding motion accomplished by the movement of cytoplasm into slender processes at the front of the cell; are all attracted to positive chemical stimuli, positive chemotaxis, and neutrophils, eosinophils are capable of phagocytosis. Neutrophils and eosinophils are sometimes called macrophages. Lymphocytes are responsible for specific defences, where the other four types are nonspecific. Neutrophils contain chemically neutral granules and are diffuicult to stain with either acidic or basic dyes. A mature neutrophil hasa segmented nucleus with 2-5 lobes, and are sometimes called “polymorphonuclear Granulocytes Agranulocytes
  26. 26. The Circulation of Blood 25 leucocytes” Their cytoplasm is packed with pale granules containing lysosomal enzymes and bacteriocidal compounds. They are highly mobile and usually the first line of defence in the case of an injury. These very active cells specialise in engulfing and destroying bacteria tat have been marked with antibodies or complement proteins. On engulfing a bacterium he cell experiences a dramatic increase in metabolic activity, accompanying the prosuction of highly reactive destructive chemical elements like hydrogen peroxide. Eosinophils stain darkly with eosin, a red dye. They are also called “acidophils” as they stain with other acidic dyes. They are similar sises to neutrophils, but as well as the dar red granules they also have a bilobed nucleus. Eosinophils atack objects coated with antibodies, although they will engulf antibody-marked bacteria, protozoa, or cellular debris. Their primary mode of attack is through exocytosis of compounds like nitric oxide and cytotoxic enzymes, they are also sensitive to allergens and increase in number in allergic reactions. Basophils have numerus granules that stain darkly with basic dyes, they are smaller than neutrophils and relatively rare. Basophils migrate to injury sites and accumuate at injury sites, discharging their granules containing histimine, which dilates blood vessels and heparin, which prevents clotting. They are important in the inflammatory response. Lymphocytes are slightly larger than red blood cells and lack abundent granules. Typically they have a large nucleus surrounded by cytoplasm. They continually migrate from the bloodstream, through peripheral tissues and back. T-Cells are responsible for cell-mediated immunity, they attack foreign cells directly or control the activities of other lymphocytes. B-Cells are responsible for humoral immunity, involving the production and distribution of antibodies which, in turn attack foreign antigens throughout the body. NK (Natural Killer) Cells are responsible for immune surveillance and detect and destroy abnormal tissue cells. They are important in preventing cancer. Monocytes are he largest white blood cell with a kidney bean-shaped nucleus. They migrate out of circulation to become tissue macrophages. Macrophages are aggressive and often attempt to engulf items as large as or larger than themselves. They engulf debris, foreign material and bacteria, they also secrete substances that draw fibroblasts into the region, which form scar tissue and wall off the injured area. The CirculationofBlood To review, elastic arteries are pressure reservoirs, arterioles are resistance vessels that control arterial pressure and blood flow through organs and tissues, capillaries are exchange vessels and veins are capacitance vessels. The cardiovascular system requires the blood to remain in motion, maintaining concentration gradients and for this a pump is required. Different organs require different blood volumes as they have diverse metabolic rates and functions; this is controllable within an organ or tissue by arterioles which can act as “taps”. Blood flow is determined by two factors: pressure difference and vascular resistance (impediment). The flow of blood is calculated by the change in pressure over the change in resistance, just like Ohms law for measuring the current in electrical wires. 𝐹 = ∆𝑃 ∆𝑅 𝐶𝑢𝑟𝑟𝑒𝑛𝑡 = 𝑃𝑜𝑡𝑒𝑛𝑡𝑖𝑎𝑙 𝐷𝑖𝑓𝑓𝑒𝑟𝑒𝑛𝑐𝑒 𝑅𝑒𝑠𝑖𝑠𝑡𝑎𝑛𝑐𝑒 Small changes in arteriole diameter drastically alter tissue blood flow. Doubling the radius of a blood vessel gives rise to a 16 fold increase in blood flow, and 24 = 16. We are therefore in need of a new equation to calculate the resistance of the vessels; therefore we use the Poisseulle-Hagen equation 𝐹 = ∆𝑃 ∙ 𝜋𝑟2 8𝐿𝜂 Where: η = field viscosity L = length of tube r = Radius of tube
  27. 27. The Circulation of Blood 26 The capillaries, although very small, make up the greatest combined cross sectional area of all vessels. As the cross sectional area increases, the pressure of the blood rapidly falls, and is not restored so as the capillaries drain into veins, the average pressure still continues to decline. Blood flow velocity decrease as the blood enters the capillaries, but then increases again as the cross sectional area drops from the capillaries towards the vena cavae. Systemic blood pressures are highest in the aorta, peaking at about 120 mm Hg and reach a minimum of 2 mm Hg at the entrance to the right atrium. Control of Heartbeat Differences between systolic and diastolic blood pressures dramatically decrease as the blood enters the arterioles and capillaries. During diastole the large and medium elastic arteries act as a pressure reservoir and maintain blood flow throughout the cardiac cycle. This ensures that the pressure of the blood never reaches zero. During systole the arterial walls are stretched and during diastole elastic recoil forces blood along maintaining blood pressure but arteries harden with age and therefore systolic pressure increases as arteries cannot absorb the force from the heart and diastolic pressure decreases as elastic recoil becomes ineffective. Average blood pressure for a typical healthy adult is 120/80.Abnormally high blood pressure is called hypertension and abnormally low blood pressure is called hypotension. Two types of specialised cells are involved in a normal heartbeat: specialised muscle cells of the conducting system, which control and co-ordinate the heartbeat, and contractile cells which produce the powerful contractions that propel blood.Each heartbeat begins with an action potential generated at the sinoatrial node (SA node), sending a wave of depolarisation across the atria of the heart in the form of cell-to-cell conduction via intercalated discs, driving the blood into the ventricles. The stimulus only affects the atria because the fibrous skeleton isolates the atrial myocardium from the ventricular myocardium. The impulse passes to the atrioventricular (AV) node and down the bundle of His in the septum of the heart. Here the connections between nodal cells are less efficient so it takes longer for the impulse to travel, allowing the ventricles time to fill with blood. The impulse passes to the purkinje fibres, which radiate from the apex toward the base of the heart, and stimulate the papillary muscles in the ventricles to contract, forcing blood out of the heart. A typical heartbeat lasts only about 370 msec. Purkinje cells are larger in diameter than the contractile cells and as a result they conduct an impulse much more quickly. Spontaneous depolarisation of the sinoatrial node results in a basal rate of 80-100 bpm, but this is normally slowed down by the parasympathetic system to about 60-70 bpm. If the nerves to the heart were severed, the heart would continue to beat at a steady pace, but could not be altered. This is why people who have had a heart transplant generally have a higher heart rate. Brachycardia is a condition where the heartbeat is slower, tachycardia indicates a heart rate that is faster than normal and heart rate can be diagnosed by use of an electrocardiogram (ECG).
  • JaveriaUsmani

    Sep. 2, 2019
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