Module 1: Intro to Physiology Define physiology Physiology: the study of function in living organisms, explores the mechanisms by which the organisms control their internal environments regardless of what happens in the outside (external) environment, also attempts to explain the physical and chemical factors responsible for both normal function and disease Define homeostasis Homeostasis: the maintenance of relatively stable conditions within the internal environment regardless of what is happening in the external environment - Our body is capable of maintaining our internal environment so that our cells can function at all times - Homeostasis is maintained using negative and positive feedback control mechanisms Describe negative feedback control systems Negative Feedback Control Systems: are found throughout the body and perform different functions – maintaining body temperature, maintaining body fluid volumes – all operate the same way to maintain homeostasis - Integrator – a set point or control center - Effector – controlled variable - Receptor – sensor o Example: heating system in your house Set point: temperature at which the room is set Sensor/Control Center: represent the thermostat Effector: the furnace Controlled Variable: the heat This is a negative feedback system because the controlled variable, which is detected by the sensor, eventually shuts off its own production by the effector List the levels of organization in the human body STRUCTUAL HIERARCHY - Atoms make up molecules, which make macromolecules, which can form cellular organelles - Almost all cells of the body contain similar organelles like the nucleus, the cell membrane, proteins and so on - When groups of cells that all have the same specialization are grouped together, they are called a tissue o When two or more types of tissues are combined to form a complex, functional unit, they are called organs The heart is composed of connective tissue, muscle tissue and specialized conducting tissue Module 3: Cells Discuss the permeability of the lipid bilayer. PHOSPHOLIPIDS - Made of a phosphate head and a fatty acid, or tail o The tails are hydrophobic, meaning they do not like water o While the heads are hydrophilic, liking water - When many phospholipids are put into water, they will align themselves into a lipid bilayer so the heads face towards and the tails face away from the water List five functions of the membrane proteins. Functions Include: 1. Receptors for attachment of chemical hormones and neurotransmitters 2. Enzymes that help with chemical reactions or breakdown molecules 3. Ion channels or pores that allow water-soluble substances (ions) into the cell 4. Membrane-transport carries that transport molecules across the membrane 5. Cell-identity markers (antigens or glycoproteins); antigens are foreign particles that can stimulate the immune system List five major ways substances cross membranes. Membrane-transport mechanisms include the following: 1. Endocytosis/exocytosis (pinocytosis for small molecules) 2. Diffusion through the lipid bilayer (in the case of fat-soluble molecules) 3. Diffusion through protein channels (in the case of water and water-soluble molecules) 4. Facilitated diffusion 5. Active transport Describe the mechanism of diffusion. Diffusion: the movement of molecules from an area of high concentration to low concentration due to the molecules’ random thermal motion - - - Electrically charged molecules including ions like sodium, tend to move towards areas of opposite charge, down their electrical gradient o Positive towards negative and vice versa Charged ions can move down both their chemical concentration gradient and electrical gradient If the chemical and electrical gradients are in opposite directions, the movement of the ion will depend on the balance of the two gradients and will stop moving when the molecules reach electrochemical equilibrium – electrical force is equal to and in opposite direction of the chemical force Substances that are lipid soluble can pass right through the cell membrane while those that are water soluble have a harder time o Lipid/fat-soluble substances include oxygen, carbon dioxide, fatty acids, and some steroid hormones o These diffuse right through the membrane’s lipid bilayer and are not stopped by hydrophobic fatty chains Substances that are water soluble cannot diffuse directly through the fatty acid region of the cell membrane but may still cross the membrane o Sodium and potassium ions appear to cross the cell membranes through special protein channels or pores ***List four factors that affect the rate of movement of substances through protein channels. Describe facilitated diffusion. How does it differ from simple diffusion? Facilitated Diffusion – other water-soluble substances that cannot diffuse through the lipid bilayer and are too large to pass through protein channels still cross the membrane at a relatively fast rate, attach to a specific protein carrier and cause a change in protein shape … results: an opening of the protein channel through where the molecule passes, or the protein rotates the molecule to the inner surface, where it is released 1. Particular molecules can bind to special protein channels in the plasma membrane 2. The protein channel facilitates the diffusion process and does not require energy 3. The molecule is released on the far side of the membrane o Shows chemical specificity and may be completely inhibited by molecules that are similar in shape Describe active transport. How does it differ from facilitated diffusion? Active Transport - Require protein carriers that span the cell membrane - The transport mechanism can be saturated and shows chemical specificity as well we competitive inhibition - Involved the use of energy (ATP) o Active transport moves molecules up their concentration gradients from low to high concentration Define osmosis and describe the factors that affect the movement of water across membranes. Define osmotic pressure. OSMOSIS The movement of water down its concentration gradient Solute: is the substance that is being dissolved in a liquid Solvent: the liquid that is doing the dissolving, most cases it will be water Solution: what you get when you dissolve a solute in a solvent Steps: 1. Diffusion causes water molecules to distribute themselves equally on both sides of a permeable membrane 2. Addition of solute molecules that cannot cross the membrane reduces the number of free water molecules on that side, as they bind to the solute 3. Diffusion then causes free water molecules to move from the side where their concentration is higher to the solute side where their concentration is lower Osmosis is affected by the following: a. The permeability of the membrane to the solutes in the intracellular and interstitial fluids b. The concentration gradients of the solutes in the intracellular and interstitial fluids c. The pressure gradient across the cell membrane There are two units to describe the concentration of a solution: 1. Osmolality is equal to the number of osmoles per kg of water 2. Osmolarity is equal to the number of osmoles per liter of solution a. We assume these two units are the same Define isotonic, hypotonic, and hypertonic. Describe the effect of such solutions on biological cells. Isotonic: the same concentration as body fluids, no osmosis occurs Hypotonic: has a lower concentration compared to cellular fluids, would cause osmosis into the cell Hypertonic: higher concentration compares to the cell and would cause osmosis out of the cell – and cell would shrink Describe how chemical and electrical gradients affect the movement of molecules across membranes. CONCENTRATION GRADIENTS AND MEMBRANE PERMEABILITIES - Sodium and calcium have a higher concentration outside the cell compared to the inside o Their concentration gradients will try to move them into the cell - Potassium has a higher concentration outside of the cell o Its concentration gradient will try to move this ion out of the cell Just because they have a concentration gradient does not mean that they will diffuse in those directions The cell membrane will determine how many ions are allowed to move Therefore, the membrane is permeable to a particular ion and that permeability will vary depending on the ion and type of cell - Most cells are not very permeable to sodium – few channels for them in the membrane Define a resting membrane potential and state its normal polarity and strength (voltage). The Resting Membrane Potential: the fluids inside and outside of cells are not electrolytic (solutions that contain ions), a very minute excess of negative ions – anions – accumulates inside the cell along inner surface and an equal number of positive ions – cations – accumulates outside - This establishes an electrical potential difference across the membrane with the inside negative with respect to the outside - Each diffusible ion will have an influence on the resting membrane potential depending on its degree of permeability and its concentration gradient Describe the forces acting on ions and define equilibrium potential. Equilibrium Potentials: when the chemical concentration gradient is equal in magnitude to the electrical gradient BUT in opposite directions, there will be no net movement and the ion is in electrochemical equilibrium - The equilibrium potential for an ion is the electoral potential that must be applied to the inside of the cell in order to stop the movement of that ion down its concentration gradient State the equilibrium potentials for K+, Na+, and Cl– in a nerve membrane. E(K+) = -90 mV E(Na+) = +60 mV E(Cl-) = -70 mV o These are the voltages that would have to be applied to the cell in order to keep each ion from moving down its concentration gradient Describe two functions of the Sodium/Potassium Pump. The Sodium/Potassium Pump Pumps 3 sodium ions( Na+) out and 2 potassium ions (K+) in o Contributes to the resting potential making the inside of the cell more negative – removes more positive Na+ from the cell than it replaces with K+ Electrogenic Pump Pumps both of these ions against their concentration gradients, and requires ATP for energy, therefore, is active transport Functions - Without the sodium/potassium pump, most cells would swell until they burst - Cells contain large numbers of protein and other organic compounds to which the cell membrane is impermeable, many carrying negative charges and attracting large numbers of positive ions around, increasing the number of particles inside the cell, leading to substantial osmosis of water into the cell - Since three sodium ions for two potassium ions are pumped out, there is a reduction in particles inside the cell, causes osmosis of water out of the cell and offsets the osmosis into the cell - Module 8: Circulatory System – Cardiac Cycle State the four main functions of the cardiovascular system. The 4 principle functions of the cardiovascular system: 1. Transports oxygen and nutrients to all cells of the body 2. Transports carbon dioxide and waste products from the cells 3. Helps regulate body temperature and pH 4. Transports and distributes hormones and other substances within the body Describe the different types of myocardial cells and explain their functions. Myocardial Cells – these ions are also responsible for the action potential in the heart; however, this action potential begins by itself, the important ions will be sodium, potassium, and calcium Myocardial Cells - Myo = muscle - Cardio = heart o Contractile cells: similar features to skeletal muscle cells that have features similar to nerve cells Considered to be the real muscle cells of the heart and form most of the walls of the atria and ventricles Contain contractile proteins action and myosin arranged in bundles of myofibrils surrounded by a sarcoplasmic reticulum Differ from skeletal muscles by having only one nucleus but far more mitochondria 1/3 of their volume is taken up by mitochondria Extremely effective at extracting oxygen – extract roughly 80% of the oxygen from the passing the blood – twice the amount of other cells The cells are much shorter, branched, joined together by special structures, called intercalated discs These structures contain tight junctions that bind the cells together while gap junctions allow for the movement of ions and ion currents between myocardial cells. Because of the gap junctions, the myocardial cells of the heart can conduct action potentials from cell to cell without the need for nerves Myocardial Cells – Nodal/Conducting Cells - Second type of cells found in the heart - Contract very few contractile elements (myofibrils) - These special cells are able to spontaneously generate action potentials without the help of nervous input like regular neurons - Along with this special property of self-excitability they can also rapidly conduct the action potentials to atrial and ventricular muscle - Specialized cells provide a self-excitatory system for the heart to generate impulses and a transmission system for rapid conduction of the impulses throughout the heart Explain the origin of self-excitability and give two characteristics of the sinoatrial node which lead to selfexcitability. Origin of Self-Excitability Sinoatrial Node – generally the site of origin, located in the upper posterior wall of the right atrium, first area to spontaneously depolarize producing an action potential – this is why it’s called the pacemaker of the heart From here the action potential travels through the atria to the atrial-ventricular node (AV node) and then to the Bundle of His From the Bundle of His the action potential travels through the Purkinje Fibers, and to the ventricular muscle Describe the sequence of events leading to an action potential in the sinoatrial node. SA Node Action Potential Na+ are moving into the cell, down the concentration gradient The Na+ permeability is slightly higher here than in other cells This will make the inside of the cell more positive (depolarized) over time Ca++ are similar to Na+ - they are also trying to move into the cell and will also depolarize the cell The main cause of the spontaneous action potential is the movement of K+ o Recall: K+ are trying to leave the inside of the cell down their concentration gradient, making the inside of the cell more negative The potassium permeability of the SA node cells decreases over time (as less K+ leak out) since the Na+/K+ is always pumping K+ into the cell both of these factors cause these calls to depolarize Because Na+ and Ca+ are flowing into the cell and K+ build up inside the membrane potential of the SA nodal cells depolarizes from -60mV to -40mV o Consequently, the SA nodal cells do not have a stable “resting” membrane potential like neurons or muscle cells – this slow depolarization is completely spontaneous and is called the pacemaker potential Responsible for setting the pace of the heartbeat, and any alternation to it will affect the heart rate Once the membrane potential depolarizes to threshold (-40mV) special voltage-gated Ca++ channels will open The Ca++ will rapidly flow in producing the depolarization phase of the SA node action potential These Ca++ channels will begin closing at roughly the same as voltage-gated K+ channels to begin to open, allowing K+ out to repolarize the cell Once the cell has returned to its lowest value of roughly -60mV the pacemaker potential will begin depolarizing the cell and the sequence will repeat itself o This influx of Ca++ is important during the contraction of the heart This sequence of events is similar to the generation of a neuronal action potential, yet there are some important differences in terms of ions and their movements Explain what an electrocardiogram (ECG) is and what each peak represents. Explain what an ECG can tell you about the health of the heart. Electrocardiogram (ECG) - Since body fluids are good conductors of electricity and the heart sits in the middle of this conducting fluid, when the action potential passes through various parts of the heart the electrical current can spread to the surface of the body - If electrodes are placed on the skin around the heart, electrical potentials generated by the heart can be recorded o Such recording during the cardiac cycle is called the electrocardiogram (ECG) P Wave – represents the electrical activity in the heart associated with the depolarization of the atrial muscle leading to their contraction QRS Complex – is produced by the depolarization of the ventricular muscle just prior to its contraction T Wave – is a result of the repolarization of the ventricular muscle as it relaxes *There is no wave associated with the repolarization of the atrial muscle, this is obscured by the much larger QRS Explain how to calculate cardiac output and all of the factors that control it. Cardiac Output = Heart Rate X Stroke Volume (ml) At Rest: HR = 70 bpm SV = 70 ml/beat Therefore: C.O. = 70 bmp x 70 ml/beat = 4900 ml/min 4.9 l/min Heart Rate (HR) is the number of times the heart beats in one minute Stroke Volume (SV) is the amount of blood pumped by one ventricle during one contraction/heartbeat Describe in detail all of the factors that control heart rate. The Control of Heart Rate The autonomic nervous system (ANS) exerts powerful control over heart rate and force contraction. This is because the heart is innervated by both the parasympathetic nervous system (PSYN) and the sympathetic nervous system (SYN). - The parasympathetic nerves are distributed to mainly SA and AV nodes and to a lesser extent to atrial and ventricular muscles - Sympathetic nerves are distributed to the same areas but with a stronger innervation to the ventricular muscle - The PSYN will decrease heart rate by affecting both SA node and AV node and will (to a lesser extent) decrease the force of contraction of the heart - The SNS, will have the opposite effect, increasing heart rate and force of contraction If all of these influences from the ANS were removed, the heart would beat at its own natural rhythm of roughly 100 bpm. Yet, the resting heart rate is roughly 70 bpm. WHY? – in an individual at rest, there is constant activity from the PSYN keeping the heart rate slowed to roughly 70 bpm. This phenomenon is called VAGAL TONE Since the vagnus nerve transmits the signals from the PSYN to the heart When there is no activity from either the PSYN or the SYN the heart will beat at its intrinsic rate of 100 bpm Describe in detail all of the factors that control stroke volume. Stroke Volume = EDV – ESV At Rest: EDV = 120 ml ESV = 50 ml Therefore: SV = 120 ml – 50 ml = 70 ml At rest, your heart pumps roughly 70 ml of blood during each contraction. End Diastolic Volume (EDV) is the amount of blood in the ventricle at the end of diastole – or just before it contracts, usually 120 ml when at rest. End Systolic Volume (ESV) is the amount of blood in the ventricle at the end of systole – or just after it contracts, usually 50 ml at rest The difference of these two valves gives you the amount of blood ejected or the stroke volume. - Any change in EDV or ESV will change SV Any change to SV will change CO Since the force of contraction of the heart determines stoke volume, whatever factors can change the force of contraction will change the stroke volume (and consequently the cardiac output) Three things can alter the stroke volume (SV): 1. Input from the autonomic nervous system – either the PSYN or the SYN 2. EDV or preload 3. ESV Describe the Frank-Starling Law of the heart and explain how it works to return cardiac output to normal. FRANK-STARLING LAW OF THE HEART This law states that an increase in EDV will cause an increase in SV and vice versa, due to the mechanisms outlined prior. Changing EDV Increasing the EDV means filling the heart with more blood before it contracts. Since blood returns to the heart by the veins, one way to increase EDV is the “squeeze” the veins much like you would a tube of toothpaste. Veins contain 70% of the total blood volume of the body, since the veins have valves, which ensure blood flows in one direction, squeezing the veins will increase the venous return of the blood to the heart, which will increase EDV One way to squeeze the veins to increase venous return, is by activating the SYN: - The SYN innervates smooth muscle located in the walls of the veins - This muscle forms a ring around the inside of the vessel wall - When this muscle contracts it causes the veins to constrict and with the help of valves, squeezes the blood back to the heart - This will increase venous return, causing an increasing EDV and leading to an increase in SV, which will then increase CO Module 9: Circulatory System – vasculature Describe and explain the general organization and anatomy of the cardiovascular system, including the heart and blood vessels. Anatomy – General Organization - The circulatory system is a closed system of tubes (vessels) filled with fluid (blood) that is moved around by a central pump (the heart) - Blood vessels consist of arteries and arterioles that transport the blood away from the heart, capillaries where gas exchange takes place and venules and veins that return blood back to the heart - The large arteries branch into smaller arteries that turn smaller - The arterioles also branch into smaller vessels that lead to the capillaries – these are the smallest of all blood vessels and are the functional units of the circulatory system; where substances enter and leave - The capillaries converge into smaller venules and get larger to from veins - Two principal loops that the blood takes through the body o One loop begins on the right side of the heart and sends blood through arteries to the lungs o Gas exchange takes place in the pulmonary arteries Oxygen diffuses into the blood and carbon dioxide out The blood enters the venules and progressively larger veins to eventually return to the left side of the heart This is called – Pulmonary Circulation o The second loop begins on the left side of the heart o Freshly oxygenated blood is pumped to the rest of the body – travels from the left ventricle to the aorta and into arteries o Oxygen, nutrients, hormones, etc. are delivered to the cells and carbon dioxide and waste products are picked up This deoxygenated blood returns to the right side of the heart through venules and larger veins The circulatory loop is called the systematic circulation There are two smaller circulatory loops within the larger systematic circulation: o The hepatic portal loop o Hypothalamic-hypophyseal portal system found in the brain Describe the blood volume distribution within the different blood vessels and explain the significance of the different volumes. Blood Volume Distribution - The total blood volume (TBV) of an average human being is roughly 5 litres – 1.3 gallons - The largest portion (70%) is contained in the veins o Since they contain the most ‘capacity’ the veins are often referred to as the capacitance vessels or blood “reservoir” - Combined, the arteries contain 10% of the TBV while the heart and lungs contain about 15% - The capillaries – gas exchange vessels – contain the last 5% of the TBV Describe and explain the relationship between pressure, flow, and resistance. Pressure, Flow and Resistance - The force that moves through the entire circulatory system is a pressure gradient o A large drop in pressure from high (in aorta) to low (in the vein) o The pressure gradient causes the blood to flow through both the pulmonary and systematic circulation - Blood flows through vessels as a result of the pressure gradient - It encounters resistance as it flows o The resistance is the result of the blood “dragging” along the walls of the vessels The higher the resistance that the blood encounters the lower the flow As a result, blood flows through a vessel called laminar (streamlined) flow There are thin “layers” of flow whose velocity varies across the vessel – flow is slower at the edges and faster in the center In order to examine blood flow through a vessel we have to consider the pressure gradient and resistance encountered by the fluid o P1-P2 is the pressure gradient o R is the resistance Describe the changes to pressure and resistance throughout the circulatory system and explain why pressure and resistance are different in different vascular beds. Several factors that can affect resistance: 1. The thickness or viscosity of the fluid in the tube will affect resistance – thicker fluid = higher resistance – viscosity generally does not change 2. The length of the vessel – the longer the blood vessel the higher the resistance; since the vessels are of constant length and do not change over short period of time, the length of the vessel is not a big factor 3. The most important factor is diameter (or radius) of the vessel – the smaller the inside diameter the higher the resistance ***Explain what would happen to blood pressure above and below a constriction. Describe the structural features (amount of muscle, elastic tissue, and fibrous tissue) of all the different blood vessels and how these features contribute to the specific characteristics of these vessels ("stretchability" and so on). Structure of the Blood Vessels The main purpose of the cardiovascular system is to deliver the oxygen and nutrient rich blood to the cells of the body and to remove carbon dioxide and waste Arteries and Veins: Contain three layers in their walls Tunica Externa: outermost layer; composed mostly of fibrous connective tissue Tunica Media: middle layer; consist of smooth muscle and elastic tissue Tunica Interna: innermost layer; composed of endothelial cells Veins also contains valves to ensure blood flows in one direction – back to the heart Capillaries are composed entirely of a single layer of endothelial cells the thin walls permit the diffusion of substances in and out of the blood o These walls contain a larger proportion of elastic tissue, these vessels must be able to withstand and absorb the large pulsatile pressure changes during contractions of the heart o Vein walls are thinner than arteries – contain some smooth muscle and a little elastic tissue; makes them more flexible and distensible and therefore are able to contain 70% of the total blood volume o The small amount of muscle tissue and the presence of valves allows these vessels to constrict propelling blood back to the heart Describe the lymphatic system and explain how it regulates the interstitial body fluid and how it is related to the Starling Forces. HYDROSTATIC PRESSURES 1. Capillary (blood) hydrostatic pressure (Pc): pressure on the fluid forcing it outward on the walls of the capillaries, pressure is roughly 35mmHg at the arterial end of the capillary and 15mmHg at the venous end of the capillary – this causes filtration – resistance causes this decrease in pressure along capillary 2. Interstitial-fluid hydrostatic pressure (PIF): is the pressure from the fluid in the interstitial compartment pushing back on the capillary – pressure varies from organ to organ from -6mmHg (in subcutaneous tissue) to +6mmHg (in the brain and kidneys) – assume there is no hydrostatic pressure in the interstitial fluid OSMOTIC FORCES 3. The osmotic forces at the right are caused by the presence of large proteins in the plasma (generally albumin) and in the interstitial fluid – these large proteins are unable to move across the capillary and will cause osmosis 4. The osmotic force of plasma (Pp)– will draw fluid back into the capillary, causing reabsorption, since the plasma contains a lot of proteins this force is high at 28mmHg a. The osmotic force of proteins in the interstitial space will pull fluid out of the capillary causing filtration, since the interstitial fluid contains little proteins, this force is low, 3mmHg NET FILTRATION PRESSURE - In order to determine the NET direction of fluid movement we need to calculate the NET filtration pressure (NFP) using the following equation NFP = (Pc – PIF) – (Pp – Pif) NFP = [(35 – 0) – (23 – 3)] = +10mmHg o Because the value is positive there is a net filtration of fluid out of the capillary into the interstitial space with a pressure of 10mmHg o Pc from the venous end (15mmHg) would have a net filtration pressure of – 10mmHg reabsorbing fluid back into the capillary and moving back in at the venous end Describe and explain all of the Starling Forces that contribute to the movement of fluid across a capillary. Capillaries have small clefts and fenestrations through which water and dissolved solutes can pass. Filtration – the process whereby fluid moves from the capillary out to the interstitial space Reabsorption – is the movement of fluid from the interstitial space back into the capillary List and explain the factors that contribute to edema. Edema: the accumulation of fluid in the interstitial fluid causing swelling - Under normal circumstances, edema does not occur because the lymphatic system can remove any excess fluid - Certain conditions cause the accumulation of fluid producing edema FACTORS: 1. Increase in the capillary hydrostatic pressure cases by increased blood pressure; occur during weight lifting when muscles – which remain contracted for a long period and do not relax until the weight is put down – pinch off the veins and cause the blood pressure to increase in the capillaries a. This edema in the muscles causes the “pumped up feeling” you get immediately after lifting weights, then disappears once the lymphatics can pick up this excess fluid 2. Decrease in the plasma osmotic force; this occurs in the cases of severe malnutrition leading to a decrease in the amount of plasma proteins – with less water moving back into the capillaries, fluid accumulates in the interstitial space and can result in the bloated abdomen of malnourished children 3. A blockage or disruption of the lymphatic system; after a radical mastectomy that removes the lymph nodes in and around the arms, because excess fluid in the arms cannot be removed by the disrupted lymphatic drainage, edema results in the hands and upper limbs Describe and explain in detail the control of the cardiovascular system. Control and Regulation of the Cardiovascular System 1. Local control mechanisms in the organ themselves 2. Humoral mechanisms that rely on chemical in the blood 3. The autonomic nervous system (ANS), which alters the cardiac output and blood flow to organs *In order to change the blood flow to an organ you can either alter the pressure change, the resistance or radius of the vessel as shown by equations 1 and 4 Explain the (local) myogenic and metabolic theories as well as the humoral and neural control mechanisms. Autoregulation is the process by which individual capillary beds maintain a relatively constant blood flow when moderate changes occur in blood pressure. The mechanisms responsible for local control are explained in two ways … 1. The myogenic theory o Changes in blood flow produced by contraction and relaxation of the smooth muscle in the walls of the blood vessels o A sudden increase in blood pressure to a vital organ will cause blood vessels feeding that organ to briefly dilate This vasodilation in turn causes a reflex contraction of the smooth muscle in the walls of arterioles supplying the organ The contraction of the smooth muscle causes a vasoconstriction, decreasing the blood pressure and flow This mechanism protects the delicate capillary network in vital organs from the sudden increases in pressure 2. The metabolic theory o Changing the metabolic activity will also change blood flow to that organ EX. during exercise the working muscle heats up, uses oxygen and produces cardon dioxide, lactic acid and adenosine (from the breakdown of ATP) These metabolic by-products act locally on the blood vessels, causing vasodilation and increased blood flow to the active tissue Once the exercise stops and these metabolites are washed out, the vessel will return to its original size and blood flow decreases to normal List the agents responsible for vasodilation and vasoconstriction. Vasoconstrictors Epinephrine – released from the adrenal gland in response to fight or flight – has a weak effect on blood vessels of the intestine Angiotensin ll – is one of the most powerful vasoconstrictors in the body Vasopressin – known as antidiuretic hormone ADH – another hormone important in the renal system Vasodilators Epinephrine causes vasodilation of blood vessels in skeletal and cardiac muscle Kinins are a family of hormones formed in the plasma and tissue Histamine – released from cells after they have been damaged Atrial natriuretic factor (ANF) which is produced by atrial muscle cells Describe the Baroreceptor reflex and how it regulates blood pressure. The Baroreceptor Reflex Example of a negative feedback mechanism - Relies on special stretch receptors called baroreceptors located in the walls of the aortic arch and carotid sinuses - These receptors are sensitive to any stretching of the wall of these blood vessels - An increase in blood pressure will stretch the vessel walls, and activating these receptors will send an action potential to the cardioregulatory and vasomotor centers in the medulla oblongata - These centers will take the appropriate steps to return blood pressure to normal by changing the heart rate, force of contraction and the diameter of blood vessels A sudden increase In blood pressure will dilate almost all blood vessels, walls will stretch activating the baroreceptors in the aortic arch and carotid sinus. Module 11: Renal System Describe homeostasis as it applies to body fluids and osmolarity. List the functions of the kidney. BASIC FUNCTION: remove nonessential substances from the plasma, including waste metabolites, excess water and electrolytes and to recover any essential substance like glucose - Play major role in regulating the water levels, the chemical concentration of the body fluid compartments and pH of the blood o The kidneys do not produce water or electrolytes but conserve them by reducing the amount removed from the body The elimination of waste or foreign substances is an important function of the kidneys Removal of drugs, food, additives, and vitamins that are excreted in the urine o Also act as an endocrine gland producing hormones or components of hormonal systems such as erythropoietin, renin, vitamin D and stanniocalcin Draw a diagram of the kidney and label the major components. Roughly the size of a fist, the outer renal cortex, middle renal medulla and inner calyces drain into a central renal pelvis. The renal pelvis drains into the ureter. Located within the renal pyramids are the functional units of the kidneys – the nephrons. Each nephron drains through a collecting duct into a calyx. Consists of the following: - Calyx(ces) - Collecting Duct(s) - Nephron(s) - Renal Arter(ies) - Renal Cortex - Renal Medulla - Renal Pyramids - Renal Papilla(e) - Renal Pelvis - Renal Vein(s) - Ureter Draw a diagram of the kidney blood flow. Blood flows to the kidneys through the renal artery. This artery branches into many interlobar arteries that branch into arcuate arteries. The blood in the arcuate arteries flows through the interlobular arteries to supply the nephron. The blood supply to the nephron drains into the interlobular vein, the arcua vein and the interlobar vein and then into the renal vein. Distinguish between filtration, reabsorption, secretion, and excretion. Each section of the nephron has different functions: - Filtration: the movement of fluid through the glomerular capillary due to hydrostatic pressures - Filtrate: the solution created by filtration, generally composed of water plus all the dissolved solutes in the blood (except for proteins that are too big to be filtered) - Reabsorption: the movement of a substance from the lumen of the nephron back into the blood - Secretion: the movement of a substance from the blood into the lumen of the nephron - Excretion: the removal of a substance from the body Explain glomerular filtration and list the factors that affect it. - Bulk flow of fluid from the blood into the glomerular capsule The filtrate contains the same substances as plasma with the exception of large proteins and red blood cells Affected by the extremely permeable capillaries that make up the glomerulus and Starling Forces Podocytes: surround the capillaries, have large filtration slits that are formed between pedicles Explain Starling Forces and list the four Starling Forces. Starling Forces: cause the bulk movement of fluid across capillaries due to a combination of hydrostatic and colloid osmotic forces, the glomerular capillary is similar, although the pressure of each force is different The blood hydrostatic pressure is roughly 60mmHg – twice that of a regular capillary, causing filtration of fluid into the glomerular capsule. Pressure is due to the difference in diameter between the afferent (large) and efferent (small) arterioles. The colloid osmotic pressure due to plasma proteins is – 32 mmHg, causing reabsorption of fluid into plasma. The capsular hydrostatic pressure is -18 mmHg, causes the reabsorption of fluid. There is no colloid osmotic force in the glomerular capsule since very few proteins are filtered. The resulting net filtration pressure is 10 mmHg out of the glomerulus into the capsular space. Describe filtered load and distinguish it from glomerular filtration. Glomerular Filtration Rate and Filtered Load The kidneys filter a lot of fluid every day – this GFR is the volume of fluid that is filtered by the glomerulus during a certain time period. The filtered load equation can be calculated … Filter Load = GFR X Plasma Concentration of the substance - Also, important to be able to calculate urine concentration and the amount of solute excreted Tells important information about the health of the kidneys Urine concentration is the amount of the solute that is excreted per unit volume of urine (g/L) The amount of solute excreted is the actual amount (in grams) of solute that is excreted in the urine and can be calculated using this equation: Equation 2: Amount Excreted = Urine Concentration X Amount of Water Excreted per Day (1.8L/day) Equation 3: Amount Reabsorbed = Filtered Load – Amount Excreted Equation 4: Fraction Excreted = (Amount Excreted / Filtered Load) X 100% List and describe all the tubular transport mechanisms involved in the movement of ions and fluid along the nephron. Tubular Transport Mechanisms – Reabsorption - Over 99% of the substances filtered in the glomerulus are reabsorbed back into the circulation at different sites along the nephron - When molecules are reabsorbed from the filtrate back into the circulation there are two transport routes that can be taken – paracellular transport and/or transcellular transport - The tubular cells are joined together by tight junctions shown at right - Generally, they do not allow substances to cross between the cells - Along the nephron the junctions can vary and can be quite leaky - Some substances can diffuse between the tubular cells by a process called paracellular transport Reabsorption Occurs By: 1. Paracellular transport 2. Transcellular or transepithelial transport a. Tight junctions b. Tubular cell i. Peritubular capillaries Lumen of nephron Interstitial space of kidney Tubular Transport Mechanisms – The Na+/K+ Pump - Many of the transport mechanisms along the nephron rely upon the Na+/K+ Pump that we have seen many times before o Active Transport Mechanism: requires ATP in order to move 3 Na+ out of the cell and 2 K+ into the cell, helps establish a concentration gradient for both ions across the cell membrane – a high concentration of Na+ outside the cell and a low inside, and a high concentration of K+ inside the cell and low outside Tubular Transport Mechanisms – Reabsorption – Secondary Active Transport - In secondary active transport the Na+ concentration gradient that is established by Na+/K+ pump is used to power other transporters - As Na+ moves into the cell down its concentration gradient other substances will either move in with the Na+ or will move out in exchange with the incoming Na+ - SAT includes the Na+/Glucose co-transporter and the Na+/H+ exchanger - The Na+/Glucose co-transporter is located on the luminal side of tubule cells - With this transporter each Na+ diffuses into the cell, a single glucose molecule is carried in along with it - The Na+/H+ exchanger moves one H+ out of the cell for every Na+ that diffuses in it – also located on the luminal side of the cells Tubular Transport Mechanisms – Secretion - The process by which the kidneys remove unwanted substances from the blood into the lumen of the nephron - Secretion is generally a hormonally regulated process, it can occur without any hormone control (non-regulated) - Most substances that are secreted are eventually excreted in the urine - Secreted substances include H+ and K+ o Secretion of K+ into the lumen of the nephron: the process relies on the presence of the Na+/K+ pump Na+: reabsorption takes place in the proximal tubule, ascending limb of the loop of Henle and early distal tubule – mostly by non-regulated mechanisms, can also be regulated by the hormone angiotensin II, and by the hormone aldosterone in the late distal tubule and collecting duct – in a healthy person all the glucose that is filtered at the glomerulus is reabsorbed in the proximal tubule, amino acids (building blocks of proteins) are also reabsorbed in the proximal tubule H20: water reabsorption takes place in the proximal tubule and descending limb of the loop of Henle through nonregulated mechanisms, no water is reabsorbed in the ascending limb of the loop of Henle, it is regulated by antidiuretic hormone ADH in the late distal tubule and collecting duct K+: reabsorption takes place in the proximal tubule and the ascending limb of the loop of Henle, secretion of K+ occurs in small amounts of the ascending limb of the loop of Henle, larger amounts of this ion are secreted in the late section of the distal tubule and collecting duct under the influence of the hormone aldosterone H+: secretion occurs in the proximal tubule and the ascending limb of the loop of Henle – it can be both regulated and non-regulated, hydrogen ions are also secreted in the late distal tubule and collecting duct – complex mechanism Describe the reabsorption of sodium, glucose, amino acids, potassium, chloride and water and the secretion of hydrogen ions in the proximal tubule. Proximal Convoluted Tubule – Potassium and Chloride - 65% of all the filtered K+ and Cl- are reabsorbed in the proximal tubule - All of this reabsorption is through two types of paracellular transport – both of which are not regulated - Recall that the tubule cells are joined together by right junctions and that these junctions can be leaky - Chloride ions are also reabsorbed in the proximal tubule by transcellular transport that uses a complex mechanism Proximal Convoluted Tubule – Potassium and Chloride Reabsorption - Reabsorption of K+ and Cl- occurs by two paracellular mechanisms – solvent drag and simple diffusion o Solvent drag: involves the reabsorption of K+ with the movement of water o o Water is reabsorbed by osmosis between the tubule cells As this water moves between the cells it also carries some of the dissolved substances in the filtrate including K+ - this movement of a solute in a solvent is known as solvent drag Reabsorption of Filtrate Back into the Circulation - The cells lining the proximal tubule reabsorb a great deal of material – including Na+, glucose and water from the lumen of the nephron - The material must first leave the cells and enter the interstitial space o Na+ will leave the tubule cells by the Na+/K+ pump o Glucose and Amino Acids are transported across the basal membrane of the cells by specific facilitated diffusion transporters K+ are reabsorbed by paracellular transport so they are already in the interstitial fluid Once in the interstitial fluid all these substances are reabsorbed into the circulation by Starling Forces in the peritubular capillaries The pressures from these Starling Forces around the tubule cells are much different than those around a typical capillary In the kidney the capillary hydrostatic force (Pc) is roughly 13 mmHg, the interstitial hydrostatic force (PIF) is roughly 6 mmHg, osmotic force due to proteins in the plasma is roughly 32 mmHg and the interstitial osmotic force is roughly 15 mmHg o Result: the Net Filtration Pressure moving the fluid is calculated to be – 10 mmHg back into the capillary *Large osmotic pressure caused by plasma in proteins* Describe the reabsorption of water in the descending limb and the reabsorption of sodium, chloride, potassium and water in the ascending limb of the loop of Henle. Descending Limb – Reabsorption of Ions and Water - Descending loop is very permeable to water and not very permeable to any ion - With this and the large concentration gradient in the interstitium, water will move out of the filtrate by osmosis into the interstitial space - Very few ions will diffuse across the lumen cells down their concentration gradient because of the impermeable nature of the descending limb o End Result: loss of water from filtrate Increasing the concentration of the filtrate to almost 1200 mOsm/kg water by the time it reaches the ascending limb –Ascending Limb – Reabsorption of Sodium, Potassium, Chloride and Water - The ascending loop of Henle is not permeable to water, so no water is reabsorbed along this section of the nephron - However, is it permeable to Na+, K+ and Cl- The transport of these ions depends on the presence of the Na+/K+ pumps on the tubule cells in the loop of Henle - These Na+/K+ pumps will create a concentration gradient from Na+ from the filtrate into the tubule cells – similar to proximal tubule - The Na+ concentration gradient drives a special co-transporter o Carries all ions into the tubule calls at the same time o K+ concentration decreases dramatically due to ion activity K+ will be secreted back out into the filtrate by simple diffusion through leaky channels Describe the reabsorption of sodium and water and the secretion of potassium in the distal tubule of the nephron. Reabsorption of Na+ and Water The distal convoluted tubule is a short section of the nephron between the loop of Henle and the collecting duct - 12% of the sodium that was filtered at the glomerulus is reabsorbed in the distal tubule - The reabsorption of water here is controlled by the antidiuretic hormone (ADH, also called vasopressin) and will depend on the level of hydration of the individual o The amount of water varies between 0 to 15% of the original filtrate Reabsorption of Na+ Sodium ions diffuse into the tubule cells due to the Na+/K+ pump which established a concentration gradient – early segments In late segments, closer to the collecting duct, Na+ reabsorption is regulated by the hormone aldosterone ALDOSTERONE: increases the activity of the Na+/K+ pump o Decreases concentration of Na+ in the cell o Cause the cell to manufacture more Na+ channels on the luminal side of membrane o Result: more Na+ will diffuse into the cells down it’s concentration gradient o The Na+ will become transported out by the increased pump activity Secretion of K+ K+ are secreted into the lumen of the nephron in response to aldosterone Increase the concentration of K+ inside the cell, as well as number of K+ channels Result: K+ will be secreted into the lumen of the late distal tubule in response to aldosterone Describe the reabsorption of sodium and water and the secretion of potassium in the collecting duct. Reabsorption of Na+ and Water - Collects the filtrate from many nephrons and is the final area for processing the filtrate into urine o Plays important role in determining the final concentration of the urine - Only 10% of all of the filtered Na+ and water is reabsorbed here, always under hormone control - Na+ reabsorption is controlled by the hormone aldosterone o Water reabsorption depends on antidiuretic hormone (ADH) An increase in aldosterone or ADH will increase the reabsorption of Na+ or water Secretion of K+ o K+ secretion takes places in the collecting duct due to the presence of aldosterone Describe the concept of water balance and how the kidneys regulate it. Introduction In order for the body to function properly, the conditions in the internal environment must be maintained at relatively constant levels. - To have water balance, the water loss must be balanced by the water gained o Water is gained drinking, eating and by the metabolism of energy stores, while water can be lost through urine, sweating, lungs and feces Regulation - Regulating the amount of water in the body is one of the main functions of the kidneys o The kidneys “recycle” or reabsorb the water that is in the filtrate before it goes to the bladder Regulated by antidiuretic hormone ADH – a.k.a. vasopressin ADH is produced in the hypothalamus of the brain and is released from the posterior pituitary, relies on negative feedback Describe the control and release of antidiuretic hormone (ADH) and its effect on the kidneys. Antidiuretic Hormone (ADH) - Dehydration will concentrate the body fluids (increase their osmolarity) causes the osmoreceptors to lose water by osmosis and shrink o The shrinking osmoreceptors will signal the posterior pituitary to release ADH o This will then cause the kidneys to reabsorb water from the distal tubule and collecting ducts Result in a lower blood volume and lower blood pressure - Overhydration will dilute the body fluids, decreasing their osmolarity and causing the osmoreceptors to swell o Less ADH will be released, less water will be reabsorbed in the distal tubule and collecting duct, and more water will be excreted in the urine Increase in blood volume and pressure - The change in blood volume is detected by volume receptors that are located in the wall of the left atrium, blood pressure is detected by the baroreceptors found in the aortic arch and carotid sinus o Lower blood volume will cause the release of the ADH, while an increased blood volume will decrease the ADH release ADH’s Effect on the Cells - ADH causes water reabsorption by the distal convoluted tubule and the collecting duct by acting directly on the cells of these regions - Stimulates the cells to manufacture special water channels called aquaporins, which insert themselves into the luminal membrane o Due to the existing concentration gradient across the luminal cells – low solutes on the outside and high solute concentration on the inside – more water will be reabsorbed by osmosis and less excreted in the urine The reabsorbed water will then enter the peritubular capillaries due to Starling Forces Describe the renin-angiotensin system and the production of angiotensin II and its effects on the kidneys The Renin-Angiotensin System The RAS also regulated Na+ balance in the body by increasing the reabsorption of Na+ in the proximal convoluted tubule of the nephron. - Involves a series of chemical reactions that converts the inactive protein angiotensinogen to the active hormone angiotensin II - Angiotensinogen – produced in the liver – reacts with renin produced in the juxtaglomerular cells, which are located in the walls of the afferent and efferent arterioles just before and after the glomerular capsule o Renin – released when blood pressure or plasma Na+ levels are low, converts the angiotensinogen to angiotensin I (Ang I), which is then converted to the active hormone angiotensin II by angiotensin converting enzyme (ACE) – which is produced in the lungs Final product of RAS, angiotensin II (Ang II) increases the reabsorption of Na+ in the proximal convoluted tubule and ascending limb of the loop of Henle Acts directly on the cells of these nephron regions to increase the activity of the Na+/H+ exchanger, reabsorbing more Na+ and secreting H+ o Ang II also stimulates the secretion of aldosterone from the adrenal gland, which acts on the cells of the distal tubule and collecting duct to reabsorb sodium and secrete potassium Module 12: Acid Base/Homeostasis Define acid and base. An Acid: is any molecule that will release hydrogen ions when put in a solution - Free H+ increases acidity of solution - Less free H+ decreases the acidity making the solution more basic/alkaline A base: is any molecule that will accept a hydrogen ion - With less free H+ the acidity of the solution will decrease and become more basic or alkaline Describe pH, how it is calculated, and the normal pH of the body. The pH Scale – a way of quantifying the concentration of H+ in any solution - pH is the negative logarithm (to the base 10) of the hydrogen ion concentration - Because it is a negative logarithm, the more free H+ the lower the pH and vice versa o The more free H+ there are in solution, the more acidic the solution and the LOWER the pH This pH scale goes from 0 to 14 with neutral pH at 7 A solution with a pH below 7 is acidic A solution with a pH above 7 is alkaline or basic The normal pH of body fluids varies slightly between 7.35 and 7.45 and has an average of 7.4 Arterial blood has a pH of 7.45 while venous blood has a pH of 7.35 Describe and understand the relationship between free hydrogen ion concentration, acid, and pH. The Source of Acid in the Body - When the cells in the body make energy (ATP) they will produce CO2 as a byproduct - This CO2 with the help of the enzyme carbonic anhydrase, combine with water in red blood cells to produce carbonic acid, H2CO3 - The carbonic aid will dissociate into free H+ and bicarbonate ions HC03- In the lungs the reaction will then reverse – carbonic acid will reform o It will then convert to CO2 and H2O and the CO2 will be removed and exhaled As a result, there is generally no NET increase in free H+ in the plasma Explain what a volatile acid is, what a nonvolatile acid is, and where they come from. - Because the carbonic acid reforms into CO2, which is then removed by the lungs, carbonic acid is known as volatile acid - The metabolic breakdown of various proteins will produce a number of acids including sulphuric acid, phosphoric acid, lactic acid, and other organic acids. The stomach is a large source of hydrochloric acid. These acids cannot be removed by the lungs and are therefore called nonvolatile acids. These acids are a significant source of free H+ and are constantly being produced throughout the body. As a result, they must be dealt with in order to maintain a constant pH. List the three ways the body regulates against increases in free hydrogen ions (H +). MECHANISMS THAT REGULATE H+ CONCENTRATIONS 1. Buffers in the body fluids (including the blood) bind free H+. This system reacts almost immediately to sudden, brief changes in free H+, and, consequently, is the body’s first line of defense. It is very important to note that buffers do not directly remove H+ from the body nor do they alter the pH. Instead, they “bind up” free H+, stabilizing the pH, until balance can be reestablished by the next two systems. 2. The respiratory system can regulate H+ concentration from volatile acids within seconds to minutes. Recall that volatile acids include carbonic acid formed when CO2 combines with water. 3. The kidneys, which respond more slowly – over a period of hours or days – have an extremely powerful control over H+ concentrations, particularly from nonvolatile acids. Explain how buffers work to help maintain pH when the levels of H+ change. Regulation of H+ Concentration – Buffers A buffer is any molecule that can reversible bind (or release) free H+ - Help to stabilize the pH REACTION The buffer, “X”, combines with free H+ to make XH With less free H+ the pH of the solution is stabilized Buffers do not prevent the pH from changing, they only help to minimize any pH change until the free H+ can be removed from the body by either the lungs or kidneys o Some buffers seen include bicarbonate ions and hemoglobin (Hb) Free H+ can bind with buffers in both the intracellular and extracellular fluid. - Intracellular buffers include phosphates and intracellular proteins – hemoglobin inside red blood cells - Most powerful extracellular buffer is the bicarbonate ion, HCO3o Hemoglobin can also bind to CO2 to reduce the potential acidity should the CO2 combine with H2O to form carbonic acid H2CO3 Buffers do not directly remove free H+ from the body They only tie up the free H+ until they can be removed in another manner – the respiratory system Explain how the respiratory system regulates the levels of volatile acids in the body. Regulation of H+ Concentration – Respiratory System - The second system guarding against changes in free H+ is texcrehe respiratory system - Regulation of CO2 levels in the blood (and pH) involves detection of this gas by central and peripheral chemoreceptors when CO2 levels increase, both of these receptors detect the change and cause an increase in ventilation - The increased ventilation causes more CO2 to be removed at the lungs, which will then return blood CO2 levels to normal Describe how the kidneys regulate pH by excreting H+ and reabsorbing bicarbonate ions. This is one of the functions of the kidneys 1. They excrete H+ that come from non-volatile acids 2. Attempt to reabsorb all the bicarbonate ions that are filtered at the glomerulus 3. They create new bicarbonate ions which then get absorbed into the circulation - Roughly 90% of the bicarbonate that is filtered at the glomerulus is reabsorbed in the proximal tubule - Hydrogen ions are secreted into the filtrate in the proximal tubule by the Na+-/H+- exchanger and in the later section of the distal tubule and the collecting duct by a H+- ATP pump HOW DO THE KIDNEYS REGULATE pH BY REABSORBING, SECRETING, OR EXCRETING SUBSTANCES? o If the amount of H+ excreted in the urine exceeds the amount of bicarbonate excreted then there will be a net loss of acid from the body and the pH in the body will increase, becoming more basic o If the amount of bicarbonate excreted in the urine exceeds the amount of H+ excreted, then there will be a net loss of base from the body leaving H+ behind. As a result, the pH in the body will decrease (more acidic) The most important thing to keep in mind is that the body is constantly producing metabolic acid from the breakdown of various substances. In order to prevent the accumulation of these acids and the consequent drop in pH, the kidneys excrete the H+ from these acids while reabsorbing the bicarbonate to help buffer the blood Define alkalosis and acidosis. Acidosis: can occur when there is too much acid (H+) in the body or too little bicarbonate ion (HCO3-) the most common base in the body Alkalosis: can occur when there is too much HCO3- in the body or too little acid (H+) - Acidosis – used to describe body fluids when the pH is below 7.4 while alkalosis occurs when the pH above 7.4 – when the body fluids is below 6.8 or above 7.8 for a long time, death will occur Describe the types of alkalosis and acidosis and their causes. - in the brain stem are damaged or from lung damage resulting in a decreased ability to remove CO2 from the blood o Counteracted by buffers in the blood and by excretion of excess H+ by the kidney - Respiratory Alkalosis: is causes by an increase in ventilation and decreased PCO2, infrequent, caused by stress or emotionally induced hyperventilation o Hyperventilation will result in increased removal of CO2 from the blood causing a decrease in POC2 o High altitudes can also cause this o Compensated for by the excretion of bicarbonate from the kidney Module 13: Endocrinology Define endocrine gland and hormone and explain the general role of the endocrine glands. - An endocrine gland is a group of specialized cells that synthesize store and release a very special chemical into blood – called a hormone FUNCTION 1. Maintenance of the internal environment 2. Adaptation to stress 3. Control of growth and metabolism 4. Control of reproduction - The hormone will then have its effect on the target cell and either stimulate or inhibit the activity of the cell o Thyroid gland o Adrenal gland o Pancreas o Gonads (ovaries in female and testes in male) List the characteristic functions of hormones. All hormones can be divided into three basic categories based on their chemical makeup: Hormones are derived from the amino acid tyrosine (thyroxine, triiodothyronine) which are secreted from the thyroid gland Hormones are derived from proteins: calcitonin, parathyroid hormone, the pituitary and pancreatic hormones, and most of the releasing and inhibiting hormones from the hypothalamus The steroid hormones cortisol, aldosterone, estrogen, progesterone and testosterone, which are all derived from cholesterol Identify the three chemical types into which hormones fall. - Hydrophilic - Hydrophobic - Receptor Describe how the hormones are secreted, how they exert their effects, and how they are inactivated. - Hormones are secreted into the blood in “pulses” by a very specific stimulus (neutral or blood-borne) and in amounts that vary with the strength of the stimulus - Once secreted by the gland, hormones are present in very small concentrations in the blood They exert their specific effects by binding to receptors on or in the target cells and generally act by regulating pre-existing reactions ****Describe the chemical nature of the three types of hormones and the significance of the chemical structure to how the hormone performs its function. Define hormone receptors, identify where they are found, and describe their functions. - A receptor is a unique structure in or on a cell that interacts with a chemical (in this case the hormone) in a particular way; much like a specific key will open a specific lock, a specific hormone will bind to a specific receptor - The type of hormone will determine where the receptor is located – either on the membrane, in the cytoplasm or in the nucleus - This interaction between receptor and hormone will then trigger a response in the cell Explain how the three chemical types of hormones each affect their target cells (that is, their mechanism of action). Hydrophobic - Since hydrophobic (lipid soluble) hormones (steroid and thyroid) can diffuse through the cell membrane, the receptor will be located in the cytoplasm or in the nucleus o The hormone first must be released by its carrier protein before it can enter the cell o Once the hormone is inside the cell, it will bind with its receptor – either in the cytoplasm or in the nucleus o This new hormone/receptor complex will then bind to the DNA within the nucleus to eventually alter various activities of the cell These could be to increase or decrease production of proteins Hydrophilic - Hydrophilic hormones are unable to diffuse through the membrane and therefore must be able to alter the activity of the cell from “outside” - The receptors for protein hormones are located on the cell membrane - When the hormone attached to the receptor, it initiates a sequence of chemical reactions that will eventually alter the activity of the cell - There are three ways in which the receptor can affect the cell: through a second messenger system, through tyrosine kinase, and through G-proteins Explain how hormones are metabolized/removed from the circulation. Ion Channels - When the hormone attaches to its receptor, a G-protein is activated that lies within the cell membrane - This G-protein can then open adjacent ion channels - If the ion is calcium (Ca++) it can act as a second messenger to alter existing proteins once it diffuses into the cell - Once hormones have had their effects on their target tissue, they are broken down by different systems in the body - Hormones are removed from the blood by the same mechanisms as any other substance: metabolic destruction in the blood or by tissues (mainly liver and kidney) excretion by the liver into the bile, or excretion by the kidneys into the urine Identify the control mechanism responsible for regulating hormone secretion and explain how it works. - Secretion of most hormones is controlled by negative feedback - Negative feedback is involved throughout the endocrine system in controlling the secretion of almost all hormones Describe the location and general structure of the hypothalamus. List the functions of the hypothalamus as they pertain to maintaining homeostasis in the body. - The hypothalamus is located at the base of the brain just above the pituitary gland and below the thalamus Because of its central location, it can receive information from all over the brain Composed of many regions made up of groups of nerve cell bodies, which are called nuclei Several of these nuclei control the release of hormones from the pituitary gland o Involved in some of the body’s homeostatic mechanisms including the regulation of body temperature, water balance, and energy production o Involved in regulating the behavioral drives of thirst, hunger and sexual behavior o In order to perform all of these functions – the hypothalamus receives large amounts of information from all around the body, including metabolic, hormonal, temperature and neural information List the hormones that are secreted by the hypothalamus. - The hypothalamus secretes many types of hormones – sometimes called releasing factors into a special portal system, these include: o Prolactin Releasing Hormone (PRH) o Prolactin Inhibiting Hormone (PIH) o Thyrotropin Releasing Hormone (TRH) o Corticotropin Releasing Hormone (CRH) o Growth Hormone Releasing Hormone (GHRH) o Growth Hormone Inhibiting Hormone (GHIH) o Gonadotropin Releasing Hormone (GnRH) - These are called releasing or inhibiting because they cause the release or inhibition of a hormone from the anterior pituitary gland Draw a picture of the pituitary gland, showing the anterior and posterior sections. Explain how these sections are related to the hypothalamus. Explain why the pituitary is considered the master gland of the body. - The hormones of the anterior pituitary control many metabolic functions throughout the body - Two other anterior hormones control growth of the ovaries and testes and regulate their reproductive functions - Antidiuretic hormone from the posterior pituitary regulates water reabsorption in the kidney - Oxytocin – from posterior pituitary – regulates milk release from the breasts and causes the contraction of the uterus during labor List the hormones that are produced by the anterior and posterior pituitary and their ultimate sites of action. o Anterior Develops from tissue that forms the roof of the mouth Made up of endocrine tissue The endocrine cells in this area secrete pituitary hormones directly into the blood This part of the pituitary is regulated by the hypothalamus through a very special circulatory system called the hypothalamic-hypophyseal portal system The hypothalamus communicated with the anterior pituitary by secreting the releasing or inhibiting hormones into this portal system These hormones travel to the anterior pituitary to either stimulate or inhibit the release of the pituitary hormones o Posterior Developed from neural tissue at the base of the brain It contains the axons and nerve terminals of neurons whose cell bodies lie in the hypothalamus This tract of neurons is sometimes referred to as the hypothalamic-hypophyseal tract These neurons produce neurohormones (antidiuretic hormone and oxytocin) in the hypothalamus that are secreted into the blood from the posterior pituitary in response to action potentials Explain how the hormones of the pituitary are regulated. - TRH from the hypothalamus causes the release TSH from the anterior pituitary - TSH stimulates the thyroid gland to secrete the two thyroid hormones, T3 and T4 CRH stimulates the release of andrenocorticotropic hormone (ACTH) from the anterior pituitary ACTH then principally stimulates the adrenal glands to secrete cortisol ACTH also has a minor effect in the secretion of adrenal androgens and aldosterone The hormones secreted from the posterior pituitary are manufactured by nerve cells whose cell bodies lie in the hypothalamus The hormones are carried down to the terminal end of the nerve and are released in response to action potentials – much like neurotransmitters are released The two hormones released by the posterior pituitary are ADH and oxytocin o Oxytocin is responsible for the ejection of milk from the breasts and causes the uterus contract during birth Describe the location of the thyroid and its general structure. - Lies directly below the larynx (or voice box) and consists of two lobes that almost completely surround the trachea - Made up of follicles – functional units of the gland o Consist of a central region of colloid surrounded by epithelial cells o Lying between follicles are parafollicular cells or C cells List the two hormones produced by the thyroid gland and describe how they are formed. - Produced inside the follicles of the thyroid gland by combining iodine and tyrosine with the help of a glycoprotein thyroglobulin - The epithelial cells take up molecules of tyrosine from the circulation – here they combine thyroglobulin which is produced within the cells - The epithelial cells also actively take up iodine which is absorbed in the diet - As the tyrosine-thyroglobulin complex is secreted into the colloid, one or two molecules of iodine attach to each tyrosine - In the colloid, two tyrosine molecules will join together while attached to the thyroglobulin - The number of iodine molecules attached to the tyrosine will produce either T3 – three iodine molecules or T4 – 4 iodine molecules Describe how the hormones of the thyroid gland are secreted and the regulation of that secretion. - TSH released from the anterior pituitary gland will bind to a receptor on the membrane of the epithelial cell which will stimulate a number of reactions - These include – trapping and taking up of circulating iodine in order to form the hormones stimulating endocytosis of the T3 and T4-thyroglobulin complex into the cells - The enzymatic removal of the thyroglobulin from T3 and T4 in the epithelial cells and stimulating the secretion of T3 and T4 into the blood - TSH also stimulates the thyroid to grow – hyperplasia o The T3 and T4 hormones will feed back to the hypothalamus and pituitary to ultimately inhibit the release of thyrotropin releasing hormone and thyroid stimulating hormone o With less TSH circulating to the thyroid, less T3 and T4 will be released into the blood - Roughly 90% of the hormones released from the thyroid gland consist of thyroxine (T4) while about 10% is T3 - Both T3 and T4 are hydrophobic hormones - They circulate in the blood attached to blood proteins o Even though the thyroid secretes mostly T4, much of it is converted to T3 which is by far the more biologically active of the two hormones List the effects of T3 and T4 on the body. - Since T3 and T4 are hydrophobic, they can diffuse through the cell membrane - The receptors for these hormones are found within the nucleus of almost all cells in the body and can alter the transcription of genes to form many different proteins o Many of these proteins are enzymes that enhance the metabolic activity of these cells Result: T3 and T4 are responsible for regulating the body’s basal metabolic rate (BMR) BMR – the amount of oxygen and energy that the body is using at rest or essentially, the least amount of energy that a person will use T3 and T4 are also responsible for proper development in the nervous system in the fetus – help to maintain a person’s alertness, responsiveness and emotional state An increase in the thyroid hormones will do the following: - Increase body temperature - Increase cardiac output - Increase ventilation - Increase food intake - Increase the breakdown of energy stores (carbs, fat, protein) Describe the diseases of the thyroid gland. - Excess or insufficient amounts of the thyroid hormones can lead to serious diseases in infants and adults o Cretinism – a disease characterized by dwarfism and mental retardation and can be prevented with thyroid hormone treatments Hypothyroidism – insufficient thyroid hormone Hyperthyroidism – excess thyroid hormone secretion Describe the location and general structure of the adrenal glands, including a description of the different layers that make it up. Explain the origin of each layer and the systems of the body that control them. - The body has two adrenal glands, each resting on top of a kidney - Like the pituitary gland, they consist of neural tissue and glandular tissue - The inner medulla is composed of neural tissue that is under the control of the sympathetic nervous system, while the outer cortex is endocrine in nature and is under the control of pituitary hormones o The adrenal cortex is divided into three different layers: 1. The outer zona glomerulus: secretes the hormone aldosterone a mineralocorticoid that helps to regulate mineral and fluid volume by the kidney 2. The middle zona fasciculata: secretes the glucocorticoid hormone cortisol, which helps in glucose metabolism 3. The inner zona reticularis: secretes small amounts of androgens (a general term for the sex steroids) Each layer looks different under a microscope because each contains a different cell type that secretes a different hormone - The medulla of the adrenal gland secretes the hormone epinephrine (also called adrenaline) o Adrenal gland is under the influence of the sympathetic nervous system List the hormones that are secreted by the adrenal gland and the type of hormone each is considered to be. - When stimulated by the sympathetic nervous system, epinephrine is secreted from the adrenal medulla into the blood - The SYN is activated in fight or flight situations - The epinephrine will increase heart rate and force of contraction as well as increase blood flow to the heart and skeletal muscle - Aldosterone is secreted by the adrenal glands in response to angiotensin II, low Na+ levels and high K+ levels in the blood, as well as adrenocorticotropic hormone (ACTH) - Aldosterone, as you will recall from the renal section, stimulates the reabsorption, stimulates the reabsorption of Na+ in the nephron o Androgens – (sex steroids) are released from the zona reticularis in response to ACTH Explain the important function of cortisol, how it is secreted, and its effects on the body. - Cortisol is always being secreted from the adrenal glands in small amounts - Certain conditions like stress, increase its production and secretion - - - Stress can be physical (extreme hot or cold), physiological (pain, loss of blood, or low blood sugar), emotional (fear or anxiety) or social (personal conflicts) Stress stimulates the hypothalamus to secrete corticotropin releasing hormone (CRH) which causes the anterior pituitary gland to secrete adrenocortricotropic hormone (ACTH) – in turn stimulates the adrenal gland to produce cortisol (as well as aldosterone and androgens) Cortisol can feed back to the hypothalamus and anterior pituitary to decrease the release of CRH and ACTH respectively Cortisol is a steroid hormone which means that it is hydrophobic and is carried in the blood attached to proteins In order to have its biological effect, it must be released from these protein carriers so it can diffuse through the cell membrane and attach to receptors in the cytoplasm This cortisol-receptor complex then translocates (moves) to the nucleus of the cell where it will alter the activity of the cell Its concentration in the blood will vary throughout the say even without stress due to the body’s circadian rhythm o This is a built-in metabolic and behavioral cycle that repeats every 24 hours o The cortisol levels in the blood are relatively low throughout most of the day and evening o Around 2-4 AM, the levels begin to increase and peak just before waking Reason for this cycling is unclear Cortisol is involved with glucose metabolism that it comes from the adrenal cortex and that is a steroid hormone Generally, cortisol protects against low blood glucose levels or hypoglycemia and It is considered to be catabolic Cause the breakdown of metabolic substrates such as carbohydrates to glucose proteins to amino acids and fat into fatty acids and glycerol in order to maintain proper levels of blood glucose In the liver it will: - Increase gluconeogenesis (the production of glucose molecules from non-carbohydrates like fats and amino acids) In the skeletal muscle it will: - Decrease protein synthesis - Increase the breakdown of proteins - Decrease glucose uptake In adipose (fat) tissue it will: - Decrease lipid (fat) synthesis - Increase lipolysis, or breakdown of fat (except in the abdomen and cheeks, where it will increase fat deposits) Explain what Cushing's Syndrome is and its effects on the body. Excess secretion of cortisol results in Cushing’s Syndrome. Recall that cortisol is essentially catabolic, promoting the breakdown of most energy stores including protein and fat. The following symptoms of Cushing’s Syndrome include the following: o Wasting of muscles, resulting in weakness o Thin skin, resulting in easy bruisability o Poor wound healing o Fat deposits in cheek resulting in “moon face” o Fat deposits in abdomen, resulting in obesity o Depression Describe the structure and function of the pancreas. - Lies parallel to and beneath the stomach - Contains both endocrine tissue, secreting hormones into the blood, and exocrine tissue, secreting chemcials through a duct into the digestive tract - The endocrine portion consist of 1 million to 2 million pancreatic islets about 0.3 mm in diameter - These islets which surround small capillaries, contain three principal types of cells: 1. Alpha cells – make up 255 of the islets and secrete glucagon - 2. Beta cells – make up 60% of the islets and secrete insulin and amylin and 3. Delta cells – make up 10% of the islets and secrete somatostatin The exocrine portion consists of pancreatic acinar cells and ducts Describe the release of insulin, glucagon and somatostatin and their effects on the body. Insulin - A protein hormone secreted by the beta cells of the pancreas - Primary function is to cause cells throughout the body to rapidly take up, store and use glucose – as a result, it will cause glucose levels in the blood to decrease - Secreted when glucose levels in the blood increase o A small increase in glucose is all that is required to cause the beta cells to release large amounts of insulin o Once released, insulin circulates in the blood and stimulates glucose uptake and storage The storage from of glucose is called glycogen Although virtually all cells of the body respond to insulin, the liver, muscle and adipose tissue respond maximally to it Glucagon - Another protein hormone, works in opposition to insulin - Primary function: to increase blood glucose concentrations, which is opposite to insulin’s effects of decreasing blood glucose levels - Secreted when blood glucose levels decrease and when amino acid levels in the blood rise - Once in the blood it will primarily stimulate the liver where it will cause both … o Glycogenolysis – the breakdown of glycogen into glucose o Gluconeogenesis – the formation of new glucose molecules from non-glucose fuel sources - Also stimulated during exercise, particularly long, exhaustive exercise where it can increase four to five times the normal amount - Glucagon can cause the release of fatty acids from fatty tissues - These fatty acids can be used by muscle as a source of fuel during these long bouts of exercise - Believed that the sympathetic nervous system – activated during exercise – stimulates the release of glucagon Somatostatin - Protein hormones secreted by the delta cells of the pancreas - Released in the digestive tract and by the hypothalamus, where it is referred to as growth hormone inhibiting hormone - It is released from the pancreas when blood glucose levels ride, when amino acid levels in the blood increase and when there is an increase in blood born fats (called fatty acids) – all things that are related to the ingestion of food - Its primary function seems to be to reduce the secretion of BOTH insulin and glucagon - The exact reason for this is not clear because insulin is attempting to store and decrease blood glucose levels while glucagon is trying to increase blood glucose levels - Believed that somatostatin is trying to prevent the extremely rapid storage of food and trying to make it available to the entire body for a longer period of time Distinguish between type I and type II diabetes mellitus. Type I Diabetes Mellitus - Insulin-dependent diabetes - Involves the damage of the insulin-producing beta cells leading to a lack of insulin production - Usually occurs around the age of 14, also called juvenile diabetes mellitus o Exact trigger is unclear – understood that a person’s immune system attacks and destroys the insulin producing beta cells of the pancreas o o o Without the ability to produce insulin, glucose cannot be taken up by cells, causing blood glucose levels to rise will above normal – can reach as high as 1200mg/100 ml of blood Since cells are unable to use glucose as energy, they must then rely on fats and amino acids as a fuel source Both the increased blood glucose levels and the use of fats and amino acids as fuel have serious consequences Type II Diabetes Mellitus - Most common form accounting for roughly 80 to 90 percent of all diabetes - Onset occurs usually after the age of 40, referred to as adult-onset diabetes o Insulin has little effect on cells throughout the body – it is as if the cells are resistant to insulin’s usual uptake and storage effects o Why they become resistant is not clear o Since the cells no longer respond to the insulin, blood glucose levels increase o This triggers the release of more insulin until the beta cells become depleted o This is believed to be the reason why there is decreased insulin release in type 2 diabetes which is found in later stages o Most people with this condition are obese and it can be controlled through diet Module 14: Reproduction Describe the fetal development of the male and female reproductive systems. - Each cell in the body contains 23 pairs of chromosomes includes a pair of sex chromosomes - The sex chromosomes consist of a large X chromosome and a smaller Y chromosome - All eggs contain an X chromosome while the sperm can carry either an X or Y chromosome - The sex of the future baby is determined at the point of fertilization o If a sperm carrying the X chromosomes penetrates the egg carrying the X chromosome, then a female will develop (XX) o If a sperm carrying the Y chromosomes fertilizes the X chromosome bearing egg, then a male will develop (XY) The development of each respective reproductive tract does not begin immediately after fertilization - During the first 6 weeks of development, male and female embryos contain common gonads - These structures will eventually form the testes in the male or the ovaries in the female - There are two sets of primitive reproductive tracts – the mesonephric or Wolffian Duct and the paramesonephric – Mullerian Duct - With the correct cues, these structures will form either the male or female reproductive tracts o In the developing male embryo at roughly 6 to 7 weeks the presence of the Y chromosome causes the indifferent gonads to develop into the testes o In the developing female embryo at about 9 weeks of development the XX chromosomes are activated, and ovaries develop Once the testes or ovaries have developing, the reproductive tracts and external genitalia follow The reproductive tracts develop from two primitive ducts, the Wolffian duct or the Mullerian duct - In the developing male fetus, at 7 weeks testicular cells begin to produce Mullerian Inhibiting Hormone (MIH) which causes the Mullerian duct to regress - Then at 9 weeks, testicular cells begin to produce testosterone - This small surge in testosterone stimulates the Wolffian duct to develop into the epididymis, vas deferens, seminal vesicles and the urethra – structures we will see in more detail in a moment - The presence of testosterone also causes the development of the male external genitalia - The development of the female reproductive tract and external genitalia requires no hormonal control o In Mullerian Inhibiting Hormone – the Mullerian duct develops into the fallopian tubes, uterus, cervix and part of the vagina Since no testosterone is produced in the female fetus, the Wolffian duct regresses and female external genitalia develop Draw a diagram of the male reproductive system, showing all the structures. - The external genitalia of the male consists of the penis and scrotum - The penis is made up of the urethra, glans penis and the erectile tissue corpus spongiosum and corpus cavernosum - The scrotum contains the testes where sperm and testosterone are produced - After production, the sperm is stores in the epididymis - During ejaculation, sperm travels through the ductus deferens (or vas deferens) mixes with fluid from the seminal vesicles, passes through the prostate, receives more fluid from the bulbourethral (Cowper’s) gland, enters the urethra, and passes our through the penis List the functions of each of the male reproductive organs. Seminiferous Tubules – the site of spermatogenesis Sertoli Cell – regulate spermatogenesis and maintain the developing sperm cells o Produce the hormone inhibin, secrete fluid that pushes the immature sperm to the epididymis and form what is called the blood-testis barrier The BTB isolates the developing sperm cells from the blood so that immune cells do not attack these genetically different cells If the BTB did not develop properly, immune cells would not develop properly, immune cells would attack and destroy the developing sperm resulting in sterility Leydig Cells – located in the interstitial space between the seminiferous tubules, produce testosterone Epididymis – final maturation area and storage site for sperm The Vas (or ductus) Deferens – carries the sperm from the epididymis to the ejaculatory duct Ejaculatory Duct – drains into the urethra Seminal Vesicles – contribute a large amount of fluid to the semen during ejaculation, the fluid is rich in fructose and enzymes, helps to maintain and nourish the sperm Prostate Gland (Cowper’s Gland) – secretes a fluid that helps to naturalize the pH and lubricate the urethra and vagina to create an optimal environment for the sperm Urethra – transports the sperm during ejaculation and drains the bladder during urination Define spermatogenesis and describe the sequence of events involved in the entire process. - As the male begins puberty and starts producing testosterone sperm production begins - The spermatogonia – germ cells – contain 46 chromosomes and are located at the outer edge of the seminiferous tubules o They divide by mitosis into two cells One will continue as a spermatogonia and the other will develop into a primary spermatocyte – each still containing 46 chromosomes The primary spermatocyte divided by meiosis into two secondary spermatocyte (during first meiotic division) and then into four spermatid (during second meiotic division) Throughout this process the dividing cells – which are surrounded and nourished by the Sertoli cells – work their way to the centre of the tubule The spermatids develop into sperm cells where they are released by the Sertoli cells into the lumen of the seminiferous tubules o This whole process takes 64 days to complete and ends with 4 sperm cells that contain 23 chromosomes each – half of the original number - Although not fully mature and able to swim, the sperm cell contains a head with an acrosome and nucleus, a midpiece with mitochondria, and a long tail or flagellum that will propel the sperm once it fully matures - Complete maturation of the sperm takes another 12 days and occurs as the sperm are moved to the epididymis by the fluid that is secreted by the Sertoli cells Explain the control and regulation of the male reproductive system, including spermatogenesis and testosterone production. - The functions of the testes are controlled by follicle stimulating hormone (FSH) and luteinizing hormone (LH – sometimes called interstitial cell stimulating hormone or ICSH) released by the anterior pituitary gland in response to gonadotropin releasing hormone (GnRH) from the hypothalamus - FSH acts on the Sertoli cells to promote spermatogenesis while also producing the hormone inhibin - Inhibin feeds back to the anterior pituitary to decrease the release of LH and FSH - LH stimulates the Leydig cells to produce the male sex hormone testosterone o Testosterone – essential for spermatogenesis – will feed back to both the - Testosterone is a steroid hormone produced by the Leydig cells in the testes - Testosterone production involves a series of complex reactions that begins with cholesterol and the formation of several intermediates ending in the production of testosterone List the functions of testosterone. 1. Development of male reproductive tract and external genitalia in the embryo 2. Growth and development of all male reproductive organs at puberty 3. The development of the male secondary sex characteristics at puberty (muscle growth, hair growth on face and around genitalia and deep voice) 4. Sex drive at puberty 5. Bone and skeletal muscle growth 6. Increases aggressiveness Draw a diagram of the female reproductive system, showing all the structures. - The external genitalia of the female are collectively called the vulva - They include the clitoris, which is a small mound of erectile tissue that is derived from the same embryonic tissue as the penis - The vulva also includes the labium majus (or labia majora) which surround the labia minus (also called the labia minora – also part of the vulva) - Both of these are folds of skin derived from the same embryonic tissue as the scrotum and the shaft of the penis - The labium minora encloses the vaginal orifice – the opening of the vagina - The female internal genitalia includes o The vagina – the canal that receives the penis during intercourse and where sperm is deposited o The sperm will travel through the cervix into the uterus (also called the womb) which is a muscular walled, hollow organ o The sperm will continue to the Fallopian tubes – also called uterine tubes – roughly 20 cm long and end at the fimbria o The egg, produced in the ovaries, is released and travels through the fimbria to the fallopian tubes to meet the sperm List the functions of each of the female reproductive organs. The Vagina (birth canal) – receives the penis and the sperm during copulation, allows for the discharge of fluid during menstruation, and the birth of the baby The Cervix – secretes mucus that varies during the menstrual cycle – from thin (facilitate sperm entry) to thick (prevent sperm entry) The Uterus – the stie of implantation of the fertilized egg and is where the developing embryo is nourished and maintained o During the menstrual cycle, the uterine lining undergoes several phases under hormonal control The Fallopian Tubes – the site of fertilization of the egg, they contain cilia that pass the egg from the fimbria to the uterus The Fimbriae – “capture” the egg after it is expelled from the ovaries and funnel it into the infundibulum The Ovaries – produce eggs (oogenesis) as well as the hormones estrogen and progesterone Define oogenesis and describe the sequence of events involved in the entire process. - Similar to spermatogenesis – the egg undergoes several stages of development - The egg is contained in a structure called the follicle - The first stage begins with the production of several million oogonia in the developing female embryo - These develop into a primary follicle that consists of a single outer layer of granulosa calls that contain the primary oocyte - The granulose cells secrete a fluid into the interior of the follicle, which forms into the antrum - The primary oocyte and follicle remain in this form until puberty - At puberty the ovaries are activated by the gonadotropic hormones LH (luteinizing hormone) and FSH (follicle stimulating hormone) - By this time, only several hundred thousand primary oocytes and follicles have survived - The female also begins her menstrual cycle, during which time a few primary follicles will begin to grow - After puberty the primary follicle develops another ring of cells called theca cells – which lie outside the granulosa cells - The primary follicle slowly enlarges and develops into a mature follicle - The oocyte will separate from the granulosa cells and will float freely in the antrum immediately before ovulation o Oogenesis results in the production of only one viable oocyte, unlike spermatogenesis where millions of sperm are produced List the hormones of the ovaries and explain their function. - The role of luteinizing hormone (LH) and follicle stimulating hormone (FSH) which are involved in the development of the follicle and the production of estrogen - It should be noted that “estrogen” refers to a group of hormones that includes 17B – estradiol, estrone and estriol - The principle estrogen secreted by the ovaries in humans is estradiol – which is much more potent than either estrone or estriol - The production of estrogen by the ovaries requires the uptake of cholesterol by the theca cells - LH stimulates the theca cells to convert the cholesterol into the hormone androstenedione (a hormone that has testosterone-like effects) - A very small amount of androstenedione is converted to estradiol by the theca cells and released into the circulation o The majority of androstenedione is secreted and taken up by the adjacent granulosa calls to convert this androstenedione into more estradiol – which is then secreted into the blood - The formation of testosterone involves a series of steps that begins with cholesterol and the formation of several intermediates ending in the production of testosterone - The formation of estrogen is almost identical o The difference is that estrogen is a continuation of this series of reactions and is formed from androstenedione Progesterone is also a steroid hormone – produced from cholesterol very early in the series of reactions Progesterone is produced in small quantities by both the granulosa cells and the theca cells before ovulation Luteinizing hormone stimulates both of these cells to produce the progesterone After ovulation of the oocyte the follicle degenerates into the corpus luteum The corpus luteum will continue to secrete both estrogen and progesterone After ovulation when the mature follicle degenerates into the corpus luteum it continues to secrete estrogen and large amount of progesterone in order to prepare the lining of the uterus for the implantation of the fertilized egg Should the egg fail to be fertilized, the corpus luteum will develop into scare tissue called the corpus albicans o Progesterone levels will vary during the menstrual cycle List the events in the menstrual cycle and describe how each hormone is involved in this cycle. The Proliferative Phase – day 7 to 14: the follicle increases production of estrogen causing luteinizing hormone (LH) to surge. The follicle ruptures and the egg is expelled. Estrogen and progesterone stimulate growth of the uterine lining The Secretory/Lutealphase – day 14 to 28: the follicle develops into corpus luteum and increases production of progesterone that prepares the uterus for implantation. If fertilization and implantation do not occur, the corpus luteum degenerates into scar tissue called the corpus albicans and progesterone levels drop Menses – day 0 to 7: levels of LH, FSH, estrogen and progesterone are low. The lining of the uterus cannot be maintained, and the uterine lining is lost The Cycle repeats Module 15: Digestive System List the building blocks for carbohydrates, proteins, and lipids. The basic functions of the structures at right are summarized below: 1. In the mouth, food is broken up by chewing (mastication) and is mixed with saliva 2. The salivary glands produce saliva to moisten and begin digesting some food particles 3. The esophagus is a straight muscular tube that connects the mouth and pharynx to the stomach 4. The stomach stores, mixes and digest some food and delivers food to the small intestine 5. The liver has many functions, but for digestion it produces and secretes bile Draw and label a picture of the digestive system. - Digestion of your meal begins in the mouth where it is broken down by chewing (mastication) and is mixed with saliva to form a bolus - The saliva consists mostly of water (99.5%) with ions and proteins (0.5%) and is secreted by three glands o Parotid o Submandibular o Sublingual Can produce up to 2 liters of saliva each day - Saliva helps to lubricate the bolus of food and begins digesting carbohydrates because it contains the enzyme amyla - The production and secretion of saliva under the control of the autonomic nervous system ***List the names of the salivary glands and describe their functions. Describe the sequence of events in swallowing. - Once the bolus of food has been formed and sufficiently lubricated with the saliva, it will be pushed to the back of the mouth by the tongue and the swallowing reflex will be initiated - The uvula of the soft palate closes over the nasopharynx - The larynx is lifted by muscles in the neck and the epiglottis bends back over the glottis, covering the larynx - The bolus moves down the esophagus through the cardiac orifice (lower esophageal sphincter) and into the stomach by a wave of smooth muscle contraction called peristalsis Draw and label a diagram of the stomach and list the function and secretions from each part. The stomach is divided into three general areas: 1. The upper – dome-shaped fundus 2. The middle body – comprises the largest part of the stomach 3. The lower – antrum (pyloric region) o The pyloric sphincter located at the distal portion, regulates the emptying of the stomach into the first part of the small intestine, the duodenum o The stomach (when empty) is thrown into folds, or rugae, which increase the surface area and allow for expansion of the stomach as it fills with food - The stomach liquefies, mixes and stores each bolus of food from the meal – chyme This is slowly released into the small intestine, where most of the digestion and absorption takes place This regulates the amount of food entering the small intestine so that it can be fully digested and then absorbed Some digestion does take place in the stomach Proteins begin to be digested in the stomach by the enzyme pepsin o Very little absorption takes place here Only certain substances like alcohol and aspirin can cross the lining of the stomach to be absorbed into the bloodstream o The mixing of the chyme is achieved by peristaltic contraction of the stomach walls that begin at the fundus and end at the antrum o These contractions also help to move the chyme through the pyloric sphincter into the small intestine where most of the digestion and absorption take place The muscle activity that causes the movement of the substances through the digestive tract is called motility Draw and label a diagram of the small intestine and the intestinal villi. - The stomach contents empty through the pyloric sphincter into the small intestine - This is the longest section of the digestive tract – 9 meters (30 ft) in length - It ends at the ileocecal sphincter where it empties into the ascending colon of the large intestine - It is divided into three segments 1. Duodenum – shortest 2. Jejunum 3. Ileum – longest, makes up 50% of small intestine - The inner wall of the small intestine is thrown into folds - The folds in turn contain fingerlike projections called villi - The end result is a large surface area with which the food comes into contact - The villi contain a capillary network and lymphatic lacteal to absorb the digested material - A layer of epithelial cells secrete digestive enzymes, covers the villi - These cells have microvilli that face out onto the lumen of the intestine, forming a brush border List the different types of carbohydrates. - Carbohydrates come in a variety of forms - Some carbohydrates are made up of a single building block called monosaccharides like glucose and fructose - Other carbohydrates called disaccharides consist of two monosaccharides - These include maltose – carbohydrate found in germinating barely, lactose – found in milk, sucrose – table sugar - Carbohydrates made up of more than two units are called polysaccharides - The most common polysaccharides are starch and glycogen o In order to absorb the larger carbohydrates, polysaccharides must all be broken down into monosaccharides o Once in this form, they can be absorbed by transport systems in the wall of the small intestine 1. Digestion of carbohydrates begins in the mouth with the salivary enzyme amylase 2. This enzyme breaks up the large polysaccharides into smaller polysaccharides and maltose 3. Once the food reaches the stomach, the digestion of the carbohydrates essentially stops because of the acidic environment (low pH), which denatures the salivary amylase Describe the sequence of events in carbohydrate digestion and absorption. - When the food reaches the small intestine, digestion of the carbohydrates begins again because the pancreas secretes amylase into the duodenum - The pancreas also secretes bicarbonate ions which neutralize the acid from the stomach - The neutralized environment permits the pancreatic amylase to perform its digestive function - The pancreatic amylase digests the polysaccharide maltose - This disaccharide cannot be absorbed yet because it still must be digested to a monosaccharide The process of carbohydrate absorption is almost identical to the process of glucose reabsorption in the kidneys - The intestinal epithelial cells contain Na+/K+ pumps on their basal aide that establish a concentration gradient for Na+ o High on the outside and low on the inside - This gradient powers the Na+/glucose co-transported (type of secondary active transport mechanism located on the luminal side of the cell - This transported moves glucose into the cell as Na+ move in, down their concentration gradient - Once glucose is inside the cell it will diffuse out through the basal side by facilitated diffusion Describe the sequence of events in protein digestion and absorption. - Proteins consist of long chains of amino acids linked together - There are 20 different amino acids o 11 nonessential amino acids that can be produced by the body o 9 essential amino acids that must come from the diet - Just like carbohydrates, the different groups of amino acids require different enzymes to break them apart - Likewise, the proteins must be broken down into the amino acids building blocks before they can be absorbed by transport systems in the small intestine - Digestion of proteins begins in the stomach - Hydrochloric acid converts the inactive pepsinogen to active enzyme pepsin - The HCL also helps to uncoil the long, twisted strands of proteins - This unfolding of the protein gives the pepsin access to the long protein chains in order to digest them into smaller chains called polypeptides - These polypeptides then pass through the pyloric sphincter into the small intestine where they continue to be digested and absorbed into the body - The pancreatic enzymes that will continue protein digestion must have an environment with a neutral pH in order to work optimally o The chyme from the acidic stomach must be neutralized o This is achieved by bicarbonate which is secreted from the pancreas - As a result of the neutral pH environment, the pepsin, which was secreted by the stomach to begin the process of digestion, now become inactivated - Now the enzymes trypsin and chymotrypsin from the pancreas continue the job in the small intestine that was begun by pepsin in the stomach - A class of enzymes called proteases can continue digesting protein into amino acids - These enzymes are produced in the pancreas and are secreted into the small intestine - Some proteases are found along the brush border of the intestinal epithelial cells - There are two different classes of protease enzymes, each of which is responsible for breaking apart amino acids located in different parts of the protein - The endopeptidases break the bonds between amino acids in the inner part of the protein - Exopeptidases break the bonds between amino acids at the end of the protein Now that the proteins are broken into single amino acids with a few remaining very small polypeptides, absorption can take place … Much like carbohydrates, the absorption of amino acids is through secondary active transport requiring the presence of Na+ concentration gradient As Na+ move into the intestinal epithelial cell and down their concentration gradient, they power a cotransporter that also moves the amino acids into the cell The remaining small peptides are absorbed by endocytosis Describe the sequence of events in lipid digestion and absorption. - The fat droplets can contain different types of lipids, including phospholipids and cholesterol - The pancreatic lipase attacks the phospholipids and removes two fatty acid chains, leaving monoglycerides behind - As the lipase slowly digests the lipid interior of the fat droplets, the droplets get smaller and smaller - Eventually, they form small sphere-shaped structures called micelles that consist of a single layer of bile salts surrounding a very small lipid droplet - These micelles help to ferry the lipid droplets to the intestinal epithelial cells where lipids are absorbed - The fatty acids and the monoglycerides – which are both lipid soluble – can diffuse directly through the membrane of the epithelial cells that line the small intestine The cholesterol molecules are transported into the cells by a specific active transport system What gets left behind after the lipids are absorbed is the bile salt that kept the lipid droplets emulsified The bile salts are reabsorbed by a transport system in the cells in the ileum; this is the very end of the small intestine The bile salts are then returned to the liver where they are reused The absorbed lips are still inside the intestinal epithelial cells The monoglycerides and fatty acids will enter the smooth endoplasmic reticulum where they will combine with cholesterol and proteins to form chylomicrons These chylomicrons are packaged up into secretory vesicles by the golgi apparatus From here, the chylomicrons leave the cell and enter the lacteals of the lymphatic system, which eventually drains into the circulatory system Describe the site where bile is produced and list its function. - Bile is produced in the liver and is transported into the gallbladder where it is stored and concentrated - Bile is not a digestive enzyme;2342 rather, it is a substance that contains water, bile salts (most abundant), cholesterol, fatty acids and many ions - The gallbladder releases bile into the duodenum of the small intestine during a meal - The bile salts keep the lipid droplets emulsified Preventing them from forming back into large droplets Describe the absorption of vitamins. - The absorption of Na+ is much the same as it is in the kidney; it occurs with the help of Na+/K+ pump located on the basal lateral surface of the intestinal cells - This pump establishes a concentration gradient for Na+ - low on the inside and high on the outside - Na+ will therefore move into the cell and down their concentration gradient from the lumen of the intestine - In addition, Na+ will be absorbed along with carbohydrates and amino acids which require the presence of Na+ for their absorption o Potassium is passively absorbed o As the intestinal contents (including water) are slowly absorbed, the concentration of K+ increases in the lumen and creates a concentration gradient favoring the passive diffusion of K+ into the cells List the amount of water absorbed in the different sections of the digestive tract and describe the process of water absorption. - The total amount of water absorbed by the intestine is roughly 9 liters (roughly 2.5 gallons) a day - Not all of this water comes from drinking and eating - Approximately 80% of the water (7 liters, 1.8 gallons) is reabsorbed from water contained in saliva, the digestive enzymes from the stomach, pancreas, bile and the secretions from the intestine - The remaining 20% (2 liters, 0.5 gallons) comes from drinking and food - The amount of water absorbed in the intestine varies along its length - The first half the small intestine, the duodenum and jejunum, absorb 44% (4 liters, one gallon) - The last half of the small intestine, the ileum, absorbs roughly 38% (3.5 liters, 1 gallon) and the large intestine absorbs roughly 1.5% (1.4 liters, 0.4 gallon) The remaining 100 ml (3 ounces) is excreted in the feces Water is absorbed in the small intestine much in the same way as it is in the kidney Describe the relationship of the enteric nervous system to the divisions of the autonomic nervous system and list the enteric nervous system's functions. Both branches of the ANS – sympathetic and parasympathetic – can influence the activity of the digestive tract - The ANS performs this function by altering the activity of the nerves in the enteric nervous system - These nerves will then affect the smooth muscle in the walls of the digestive tract, the enzyme-secreting cells, endocrine cells (enteroendocrine) and the blood vessels of the tract - The enteric systems functions through two types of reflex loops – long loops that travel through the central nervous system (CNS) and short loops that travel only locally within the digestive system Describe the long loop and short loop reflexes of the enteric nervous system and their effects on the digestive tract. - Short loops begin by a mechanical distension (stretching) of the digestive tract or chemical changes such as pH or osmolarity within the tract - These changes are detected by sensors of the enteric nervous system that initiate a reflex - The reflex activates effector organs, such as the secretory cells or smooth muscle in the walls of the tract, causing the release of enzymes or altering gastric motility, respectively - Long loop reflexes include input from the higher brain centers - The stimulus may be sight or smell of food, which would be detected by their respective sensors - Signals are then sent through the parasympathetic nervous system to the enteric nervous system to alter the digestive function – enzyme release and gastric motility Describe the basal electrical rhythms of the digestive tract and how they can alter motility. - Surrounding the digestive tract are specialized smooth muscle cells called interstitial cells that act very much like the pacemaker cells of the heart - These cells spontaneously alter their membrane potentials o Producing basal electrical rhythms or BERs – also called slow waves that travel down the digestive tract These membrane potentials do not cause the muscles to contract because, for the most part, they do not reach threshold These slow waves travel from smooth muscle cell to smooth muscle cell through gap junctions, much like in the heart The frequency of these BERs varies; in the stomach their frequency is 3 waves per minute, while in the duodenum they are 12 waves per minute o As long as the BERs stay below the threshold of the smooth muscle cells, there will be no contraction along the digestive tract o If the peak of the slow waves reaches the threshold, however, the smooth muscle will contract o Reaching threshold requires an additional stimulus in the form of mechanical, nervous or hormonal input o These additional signals will cause the BERs to reach threshold and fire action potentials, which will then cause muscular contractions of the smooth muscle o The contractions will then travel down the intestine in a wave-like fashion List the hormones of the intestine and stomach and describe their functions. Hormones released by the intestine can also regulate gastric motility and the secretion of digestive enzymes - The hormone secretin is released in response to the presence of acid in the intestine o It inhibits emptying from the stomach; but at the same time, it causes the release of pancreatic bicarbonate and bile from the liver As a result of the bicarbonate release from the pancreas, the acid from the stomach is neutralized and the intestinal digestive enzymes can function optimally - The hormone cholecystokinin (CCK) is released in the pancreas of fats o - It slows the emptying from the stomach, stimulates the pancreas to release digestive enzymes, and causes the gallbladder to contract, releasing bile o Remember that the digestion of fat can take longer than carbohydrates and proteins o Therefore, the release of fatty chyme from the stomach must be carefully regulated Glucose-dependent insulinotropic peptide is secreted in response to glucose and amino acids o It also stimulates the release of insulin from the pancreas and may inhibit emptying of the stomach The food in the intestine causes the release of one or more hormones, depending on the type of food present The hormones will, in turn, cause the release of particular digestive enzymes to deal with the type of food present In addition, the hormones will slow the output of the stomach, allowing for this food to be properly digested and absorbed before more food is released into the intestine from the stomach Describe the three phases of gastric acid secretion and how they are regulated. Three Phases of Gastric Acid Secretion 1. Cephalic phase refers to the brain o The increased gastric acid secretion during this phase is initiated in response to the sight, smell, taste and chewing of the food o This is an anticipatory response to the act of eating and involves the activation of the enteric nervous system through the long loop reflex o The sight, smell and taste of the food trigger the parasympathetic nervous system o Then activates the enteric nervous system, causing the parietal cells to release HCI and the G cells to release gastrin o The motility of the stomach will also increase 2. Gastric phase refers to the stomach o Once the food is swallowed, the gastric phase of acid secretion begins o The stimulus is the presence of food in the stomach that distend the walls (mechanical stimulus) and the presence of amino acids (chemical stimulus) form the breakdown of proteins o These stimuli trigger a short loop reflex involving the enteric nervous system, which will cause the release of HCI, gastrin, and pepsinogen and will increase gastric motility 3. Intestinal phase refers to the intestine o Now that the food has left the stomach and has entered the intestine, the intestinal phase of gastric secretion begins o This is the location where most of the digestive and absorptive processes take place and it is important that it is carefully regulated o The stimulus for the intestinal phase is the presence of glucose, fat and acidic chyme in the intestine o The overall effect of the intestinal phase is to decrease the motility and to inhibit the secretions in the stomach o This is performed by the enteric nervous system as well as by the hormones as well as by the hormones secretin, CCK and glucose-dependent insulinotropic peptide Module 16: Metabolism List the building blocks of all the main food groups as well as their storage forms in the body. Recall: the food we saw in the digestive module is made up of smaller building blocks - Triglycerides which make up most of the fat found in the body, consist of three fatty acid chains attached to one molecule of glycerol - Proteins consist of long chains of amino acids linked together and carbohydrates are long chains of monosaccharides (like glucose) joined together - Once in the body, some molecules may partially reform while others stay as building blocks - These building blocks are circulating in the body and can be used to create new structures in the cell or to form ATP, or they can be stored for later use o Their storage form may not be the same as their circulating form - The carbohydrate glucose is stored inside muscle and liver cells in the form of glycogen Fats stored as triglycerides inside fatty tissue called adipose tissue The amino acids become structural or functional proteins inside the muscle cells Describe the three chemical reactions/metabolic pathways in the body that produce ATP. List how much ATP each can form, which one requires oxygen, and where the reactions take place in the cell. Energy Production o All of the molecules we have just seen can be used to produce energy in the form of ATP o Glucose contributes to 1% of the total energy requirements of the body and it reserves (in the form of glycogen) can last for roughly a day o Fatty Acids contribute to 77% of the total energy produced and can last for up to two months depending on the individual o Amino Acids stored as proteins are not usually used to create energy but can account for 22% of the body’s fuel requirements if absolutely necessary Describe where each fuel source enters the metabolic pathways. - There are three primary chemical reactions to take place within the cell to produce energy from the breakdown of food molecules - The first, glycolysis, is a series of reactions that occurs in the cytoplasm o It does not require oxygen and is therefore considered an anaerobic reaction o Glycolysis can produce two molecules of ATP very quickly from one molecule of glucose - The second series of reactions is called the citric acid cycle (CAC or Krebs Cycle) o This reaction takes place inside the mitochondria, requires the presence of oxygen and therefore is an aerobic reaction o It can produce two molecules of ATP per molecule of glucose - The third series of reactions is closely linked to the citric acid cycle and is called oxidative phosphorylation (sometimes referred to as the electron transport chain) o This reaction can produce 34 molecules of ATP from one molecule of glucose o It also occurs in the mitochondria of the cell and requires oxygen Each of the food molecules can enter one or more of these reactions to make energy (ATP) - Glucose can enter glycolysis at the beginning of this reaction - Amino acids can be converted to pyruvate to enter glycolysis or can be converted to acetyl coenzyme A (acetyl CoA) to enter the citric acid cycle (CAC) to produce ATP - Fats (triglycerides) can be broken down to glycerol and free fatty acids - The glycerol molecules can enter glycolysis, and the fatty acids can be converted to acetyl CoA to enter the CAC Describe in detail the full metabolism of glucose by glycolysis and the citric acid cycle (in the presence of oxygen and without oxygen). Glucose is a monosaccharide and is stored as glycogen in most cells of the body Most glycogen stores can be found in the liver and skeletal muscle Glucose is a common fuel source for all the cells in the body, but it is one of the only fuel sources for the brain – unlike most other cells in the body, which can use fays and amino acids as well as glucose The liver stores glucose for the brain, which cannot store any for when blood glucose levels get low Glycolysis o Glucose will enter a cell and will be almost immediately converted to glucose-6-phosphate (G-6-P) o From here, G-6-P can enter glycolysis to produce ATP, or it can be converted to glycogen and then stored o When necessary, glycogen can be converted back to G-6-P to enter glycolysis to produce energy o In glycolysis, G-6-P will undergo a series of reactions that will result in the production of ATP and the end product of pyruvate The pyruvate can then undergo two possible reactions – it can either enter the citric acid cycle and produce lots of ATP – with the help of oxidative phosphorylation Or it can enter another shorter reaction to produce a small amount of ATP and the by-product lactate – a.k.a. lactic acid WHICH REACTION WILL PYRUVATE TAKE? o This depends on whether oxygen is present or not o If there is sufficient oxygen, then most of the pyruvate will enter the CAC o Since it is an aerobic pathway, it requires O2 o If there is not enough O2 present, then the CAC will not be running at full capacity and the pyruvate will be converted to lactic acid The Citric Acid Cycle o If there is a sufficient supply of oxygen, then the citric acid cycle can function at full capacity o The pyruvate from glycolysis is converted to acetyl coenzyme A which then enters the CAC o The CAC in conjunction with oxidative phosphorylation together produce a total of 36 molecules of ATP from one molecule of glucose 2 ATP from CAC and 34 from oxidative phosphorylation o They also produce the by-products CO2 and H2O The CO2 will diffuse into the blood and leaves the body and the lungs Describe in detail the full metabolism of fats and amino acids. o Amino acids are stored in cells as proteins, while fats are mostly stored as triglycerides o These can also be metabolized to create ATP by cells, but each one enters the metabolic pathways at different points Amino acids can be converted to either pyruvate or acetyl CoA to enter glycolysis or the citric acid cycle respectively Triglycerides are broken down to glycerol and free fatty acids The glycerol can enter glycolysis and the fatty acids are converted to acetyl CoA to enter the CAC o These molecules can either produce ATP or can be converted to glycogen and stored in the cell in much the same way as glucose Explain all the processes involved in the fed state of metabolism and how insulin is involved in this process and all its functions. When are these molecules stores and when are they converted to ATP? - The fed state (also called the absorptive state) is the condition the body is in after the meal – when the levels of nutrients in the blood are quite high - During this period, the body’s primary goal is to store all this new fuel (amino acids, fats, and glucose) for later use The Fed State o Once your body has eaten, it is time to store all nutrients o Glucose will be stored in the muscle and liver as glycogen o Any excess amounts of glucose are converted to fatty acids by the liver o These fatty acids are released into the circulation and taken up by adipose (fat) tissue and stored as triglycerides for later use o Amino acids from the digestion of protein are taken up by the cells in the body for protein synthesis o This could include the building of muscle proteins or for use in making new protein carriers o Any excess amino acids are converted to fatty acids Explain all the processes involved in the fasted state of metabolism and how glucagon is involved in this process and all its functions. - Between meals – particularly in the morning before breakfast – the nutrient levels in the blood are very low o This is the fasted state (or post absorptive state) and the body’s goal is to maintain blood glucose levels In order to do this, the body will be utilizing its stored nutrients, including fats and glycogen The Fasted State o It is 4pm and you are hungry, you have not eaten since breakfast – body is in the fasted state Glycogen stores in your cells last less than a fay – your fat stores, can last up to two months o Most of the cells in your body can use different nutrient molecules to make energy The brain, which can normally only use glucose, is an exception Therefore, it is important to keep the glucose concentrations in the blood from dropping too low o In order to maintain circulating glucose levels, the liver will produce and release glucose into the blood from its own glycogen stores o The liver can make new molecules of glucose from glycerol, amino acids, pyruvate and lactate – process called gluconeogenesis o Muscle cells cannot produce glucose from their stores of glycogen Muscle cells will produce pyruvate or lactate from glycolysis and release these molecules into blood Then they will be converted to glucose by the liver for use by the brain List all the other hormones that help to regulate metabolism and explain how they perform their function. Insulin o Insulin is the hormones of the fed state o It is secreted from cells in the pancreas called beta cells in response to high levels of glucose in the blood o It has an effect on most cells in the body (with the exception of the brain and red blood cells) but its major target site is muscle, liver, and adipose (fat) tissue o Insulin’s primary effect is to promote the storage of food nutrients while at the same time inhibiting their release from storage in muscle, liver and adipose tissue When insulin is released from the pancreatic beta cells, it will cause the following: - Increased glucose uptake and utilization by cells - Increased glycogen formation (glucose storage) - Increased triglyceride formation (fat storage) - Increased protein synthesis (protein storage) Lactic Acid o o o o o o During strenuous exercise your cardiovascular system may not be able to supply sufficient oxygen to your working muscle cells to produce ATP via the CAC Since glycolysis is anaerobic, this reaction can continue without oxygen to produce ATP and the end product pyruvate With insufficient oxygen, the CAC will not work at full capacity and pyruvate will start to accumulate If too much pyruvate accumulates, then even glycolysis will be slowed In order to keep glycolysis working so it can produce ATP for the muscles, pyruvate will be converted to lactic acid The accumulation of lactic acid causes the “burning” sensation in the muscle and is believed to interfere with the contractile proteins causing fatigue The accumulation of lactic acid will cause the blood vessels to dilate, and the decreasing pH will unload more oxygen from hemoglobin These mechanisms will help to increase blood flow and increase oxygen delivery to this working tissue to reduce the buildup of lactic acid NOTE: all reactions this far are reversible FED STATE Food is digested and high levels of glucose are circulating in the blood Regulated by insulin Glucose uptake and use by the cells Glycogen formation (glucose storage in the cell) Triglyceride formation (fat storage in the cell) Increased protein synthesis (protein storage in the cell) Storage in the cell results in less of these molecules circulating in the blood FASTED STATE Occurs when circulating levels of blood glucose is low Regulated by glucagon Increased glycogenolysis Increased gluconeogenesis Increased lipolysis Results in increased circulating glucose Increased levels of fatty acid in the blood